MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Advances in Immunology' source. Wed, 08 Feb 2012 06:42:43 +0100 http://www.medworm.com/index.php?rid=5604081&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244575%26dopt%3DAbstract Authors: Unanue ER, Carrero JA PMID: 22244575 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5604081 Wed, 18 Jan 2012 22:54:02 +0100 5604081 http://www.medworm.com/index.php?rid=5604080&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244576%26dopt%3DAbstract Authors: Lam GY, Czuczman MA, Higgins DE, Brumell JH Abstract Macrophages are immune cells that participate in the host defense against bacterial pathogens. These cells mediate bacterial clearance by internalizing bacteria into a phagosome, which ultimately fuses with lysosomes to kill bacteria. One bacterial strategy to evade killing in the phagosome is to escape from this compartment prior to lysosomal fusion. Listeria monocytogenes is a classic example of a "cytosol-adapted pathogen" in that it can rapidly escape from the phagosome in macrophages (and other cell types) and replicate rapidly in the cytosol. Phagosome escape also enables cell-to-cell spread by the bacteria through a bacterial driven actin-based motility mechanism. How the bacteria escape the phagosome and evade ho... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5604080 Wed, 18 Jan 2012 22:54:02 +0100 5604080 http://www.medworm.com/index.php?rid=5604079&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244577%26dopt%3DAbstract Authors: Mostowy S, Cossart P Abstract The Gram-positive bacterial pathogen Listeria monocytogenes has become one of the best studied models in infection biology. This review will update our knowledge of Listeria virulence factors and highlight their role during the Listeria infection process. PMID: 22244577 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5604079 Wed, 18 Jan 2012 22:54:02 +0100 5604079 http://www.medworm.com/index.php?rid=5604078&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244578%26dopt%3DAbstract Authors: Edelson BT Abstract Dendritic cells (DCs) represent a unique collection of innate immune cells present throughout the body as distinct subpopulations generally sharing the functions of pathogen recognition, cytokine production, and antigen presentation. A large body of work in recent years has examined DC functions during infection with Listeria monocytogenes (Lm), particularly in the murine model. Here, I review several aspects of DC biology in this model, with particular emphasis on the role DCs play in the establishment of a productive Lm infection and the role of DCs as cytokine producers and antigen-presenting cells in this system. PMID: 22244578 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5604078 Wed, 18 Jan 2012 22:54:02 +0100 5604078 http://www.medworm.com/index.php?rid=5604077&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244579%26dopt%3DAbstract Authors: Condotta SA, Richer MJ, Badovinac VP, Harty JT Abstract CD8 T cells play a critical role in the control and eradication of intracellular pathogens. Increased understanding of CD8 T cell biology provides insight that can be translated into improved vaccination strategies. The intracellular bacterium, Listeria monocytogenes, has been used as a model organism to study every phase of the CD8 T cell response to intracellular bacterial infection. Infection of laboratory mice with L. monocytogenes has provided insight into the factors that are involved in primary T cell responses, memory CD8 T cell generation, maintenance, functionality, and diversification following repeated pathogenic challenges. In this review, we will focus on work from our laboratories utilizing the murine m... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5604077 Wed, 18 Jan 2012 22:54:02 +0100 5604077 http://www.medworm.com/index.php?rid=5604076&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244580%26dopt%3DAbstract We describe their development as vectors to carry protein tumor antigen and eukaryotic DNA plasmids to antigen-presenting cells and efforts to harness their tumor-homing properties. We also describe their use as vectors of angiogenic molecules to induce an immune response that will destroy tumor vasculature. The background knowledge necessary to understand the biology behind the rationale to develop Listeria as a vaccine vector for tumor immunotherapy is included as well as a brief summary of the major therapies that have used this approach thus far. PMID: 22244580 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5604076 Wed, 18 Jan 2012 22:54:02 +0100 5604076 http://www.medworm.com/index.php?rid=5604075&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244581%26dopt%3DAbstract Authors: Serbina NV, Shi C, Pamer EG Abstract Infection of mice with Listeria monocytogenes induces a robust innate inflammatory response that restricts bacterial growth in the liver and spleen prior to the development of protective T cell responses. Ly6C(hi) monocytes contribute to the innate immune response following L. monocytogenes infection and in their absence, mice rapidly succumb to infection. Emigration of Ly6C(hi) monocytes from the bone marrow into the circulation is the first step in their recruitment to sites of L. monocytogenes infection and is triggered by CCL2- and CCL7-mediated stimulation of CCR2 chemokine receptors on monocytes. CCL2 expression by mesenchymal stem cells in the bone marrow, in response to TLR stimulation, drives monocyte emigration from cellular c... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5604075 Wed, 18 Jan 2012 22:54:02 +0100 5604075 http://www.medworm.com/index.php?rid=5604073&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244582%26dopt%3DAbstract Authors: Witte CE, Archer KA, Rae CS, Sauer JD, Woodward JJ, Portnoy DA Abstract Acquired cell-mediated immunity to Listeria monocytogenes is induced by infection with live, replicating bacteria that grow in the host cell cytosol, whereas killed bacteria, or those trapped in a phagosome, fail to induce protective immunity. In this chapter, we focus on how L. monocytogenes is sensed by the innate immune system, with the presumption that innate immunity affects the development of acquired immunity. Infection by L. monocytogenes induces three innate immune pathways: an MyD88-dependent pathway emanating from a phagosome leading to expression of inflammatory cytokines; a STING/IRF3-dependent pathway emanating from the cytosol leading to the expression of IFN-β and coregulated genes; an... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5604073 Wed, 18 Jan 2012 22:54:02 +0100 5604073 http://www.medworm.com/index.php?rid=5604072&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244583%26dopt%3DAbstract Authors: Carrero JA, Unanue ER Abstract Infection with Listeria monocytogenes shows an early stage of lymphocyte apoptosis. This is an obligatory stage the extent of which depends on infective dose. Lymphocyte apoptosis occurs early and is rapidly superseded, yet it has a strong biological consequence. The immunological effect of lymphocyte apoptosis following infection is increased susceptibility to L. monocytogenes infection due, in part, to upregulation of IL-10 on macrophages and DC. Lymphocyte apoptosis is dependent on bacterial expression of the pore-forming toxin listeriolysin O (LLO). Also, purified LLO can lead to the induction of death pathways similar to infection, demonstrating that it is a killer agent generated by L. monocytogenes. Signaling through the type I interfe... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5604072 Wed, 18 Jan 2012 22:54:02 +0100 5604072 http://www.medworm.com/index.php?rid=5457439&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118405%26dopt%3DAbstract Authors: Hori S Abstract Regulatory T (Treg) cells expressing the transcription factor Foxp3 constitute a unique T-cell lineage committed to suppressive functions and play a central role in maintaining self-tolerance and immune homeostasis. While their differentiation state is remarkably stable in the face of various perturbations from the extracellular environment, recent studies have also revealed their adaptability to the changing environment; in response to extrinsic cues, Treg cells differentiate further into distinct substates to regulate different classes of immune responses effectively. In contrast, some other recent studies have challenged this notion of a committed Treg cell lineage and suggested that Treg cells might lose their identity and be reprogrammed to various eff... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5457439 Thu, 01 Dec 2011 02:36:02 +0100 5457439 http://www.medworm.com/index.php?rid=5457435&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118406%26dopt%3DAbstract Authors: Lee HM, Bautista JL, Hsieh CS Abstract The development of regulatory T (Treg) cells is essential for the maintenance of immune tolerance and homeostasis. Here, we review recent studies that have advanced our understanding of Treg cell differentiation. In the thymus, TCR specificity to self-antigen appears to be a primary determinant for Treg cell lineage commitment, with c-Rel being an important factor that links T cell receptor (TCR) engagement and Foxp3 expression, along with cytokines and costimulatory molecules. It is also clear that postthymic events shape the peripheral Treg cell population. This includes preferential maintenance of Treg cells specific to self-antigens presented in the periphery, as well as the de novo generation of Treg cells from conventional Foxp3... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5457435 Thu, 01 Dec 2011 02:36:02 +0100 5457435 http://www.medworm.com/index.php?rid=5457253&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118407%26dopt%3DAbstract Authors: Maizels RM, Smith KA Abstract Infectious agents have intimately co-evolved with the host immune system, acquiring a portfolio of highly sophisticated mechanisms to modulate immunity. Among the common strategies developed by viruses, bacteria, protozoa, helminths, and fungi is the manipulation of the regulatory T cell network in order to favor pathogen survival and transmission. Treg activity also benefits the host in many circumstances by controlling immunopathogenic reactions to infection. Interestingly, some pathogens are able to directly induce the conversion of naive T cells into suppressive Foxp3-expressing Tregs, while others activate pre-existing natural Tregs, in both cases repressing pathogen-specific effector responses. However, Tregs can also act to promote immu... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5457253 Thu, 01 Dec 2011 02:36:02 +0100 5457253 http://www.medworm.com/index.php?rid=5457252&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118408%26dopt%3DAbstract Authors: Shevach EM Abstract The subpopulation of CD4(+) T lymphocytes that co-express the transcription factor Foxp3 plays a unique role as regulatory T lymphocytes (Tregs) that modulate many aspects of the immune response. Multiple mechanisms have been proposed for the suppressor function of CD4(+)Foxp3(+) T cells based on in vitro studies, but much less is known about how Tregs suppress immune responses in vivo. Both polyclonal Tregs and antigen-specific Tregs are capable of exerting potent suppressive effects in vivo, and it is likely that they mediate their biologic functions using different mechanisms. Antigen-specific Tregs primarily target dendritic cells and inhibit dendritic cell functions including the expression of costimulatory molecules and the presentation of antigen... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5457252 Thu, 01 Dec 2011 02:36:02 +0100 5457252 http://www.medworm.com/index.php?rid=5457251&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118409%26dopt%3DAbstract Authors: Daniel C, von Boehmer H Abstract Fopx3(+) expressing regulatory T cells (Tregs) function as an indispensable cellular constituent of the immune system by establishing and maintaining immunological self-tolerance. T cell receptor (TCR) ligands of high agonist activity, when applied in vivo under subimmunogenic conditions, convert naive but not activated T cells into stable Tregs expressing Foxp3. Tolerogenic vaccination with strong-agonist mimetopes of self-antigens may function as a safe and highly specific instrument in the prevention of autoimmune disease by promoting self-antigen-specific tolerance. In this review, we address the requirements for generation of dominant tolerance exerted by Foxp3(+) Tregs in autoimmune disease with special focus on type 1 diabetes (T1D).... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5457251 Thu, 01 Dec 2011 02:36:02 +0100 5457251 http://www.medworm.com/index.php?rid=5298741&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21970951%26dopt%3DAbstract Authors: Roulland S, Faroudi M, Mamessier E, Sungalee S, Salles G, Nadel B Abstract Follicular lymphoma (FL) pathogenesis is a complex and fascinating multi-hit process, escalating along successive derailments of the distinctive molecular and cellular mechanisms paving B-cell differentiation and activation. This progressive subversion of B-cell receptor diversification mechanisms and B-cell homeostasis likely occurs during a protracted preclinical phase of asymptomatic growth, in which premalignant clones already disseminate and establish "niches" in secondary lymphoid organs. Following FL diagnosis, a parallel indolent behavior is observed in most patients, slowly progressing over a period of many years, to eventually generate a highly refractory (and in some case transform into a... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5298741 Sun, 09 Oct 2011 19:10:02 +0100 5298741 http://www.medworm.com/index.php?rid=5298740&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21970952%26dopt%3DAbstract "A Rose is a Rose is a Rose," but CVID is Not CVID Common Variable Immune Deficiency (CVID), What do we Know in 2011? Adv Immunol. 2011;111:47-107 Authors: Yong PF, Thaventhiran JE, Grimbacher B Abstract Common variable immune deficiency (CVID) is the commonest symptomatic primary immunodeficiency and represents a heterogenous collection of disorders resulting mostly in antibody deficiency and recurrent infections. However, autoimmunity, granulomatous inflammation and malignancy frequently occur as part of the syndrome. The etiology of the condition has been poorly understood although in recent years, significant progress has been made in elucidating genetic mechanisms that can result in a CVID phenotype. In parallel to this, advances in treatment of the condition have also... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5298740 Sun, 09 Oct 2011 19:10:02 +0100 5298740 http://www.medworm.com/index.php?rid=5298739&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21970953%26dopt%3DAbstract Authors: Marusawa H, Takai A, Chiba T Abstract Human cancer is a genetic disease resulting from the stepwise accumulation of genetic alterations in various tumor-related genes. Normal mutation rates, however, cannot account for the abundant genetic changes accumulated in tumor cells, suggesting that certain molecular mechanisms underlie such a large number of genetic alterations. Activation-induced cytidine deaminase (AID), a nucleotide-editing enzyme that triggers DNA alterations and double-strand DNA breaks in the immunoglobulin gene, has been identified in activated B lymphocytes. Recent studies revealed that AID-mediated genotoxic effects target not only immunoglobulin genes but also a variety of other genes in both B lymphocytes and non-lymphoid cells. Consistent with the find... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5298739 Sun, 09 Oct 2011 19:10:02 +0100 5298739 http://www.medworm.com/index.php?rid=5298738&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21970954%26dopt%3DAbstract Authors: Das S, Hirano M, McCallister C, Tako R, Nikolaidis N Abstract The immunoglobulins (Igs or antibodies) as an integral part of the tetrapod adaptive immune response system have evolved toward producing highly diversified molecules that recognize a remarkably large number of different antigens. Antibodies and their respective encoding loci have been shaped by different and often contrasting evolutionary forces, some of which aim to conserve an established pattern or mechanism and others to generate alternative and diversified structural and functional configurations. The genomic organization, gene content, ratio between functional genes and pseudogenes, number and position of recombining genetic elements, and the different levels of divergence present at the germline of the I... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5298738 Sun, 09 Oct 2011 19:10:02 +0100 5298738 http://www.medworm.com/index.php?rid=5298737&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21970955%26dopt%3DAbstract Authors: Medvedovic J, Ebert A, Tagoh H, Busslinger M Abstract The B cell lineage of the hematopoietic system is responsible for the generation of high-affinity antibodies, which provide humoral immunity for protection against foreign pathogens. B cell commitment and development depend on many transcription factors including Pax5. Here, we review the different functions of Pax5 in regulating various aspects of B lymphopoiesis. At B cell commitment, Pax5 restricts the developmental potential of lymphoid progenitors to the B cell pathway by repressing B-lineage-inappropriate genes, while it simultaneously promotes B cell development by activating B-lymphoid-specific genes. Pax5 thereby controls gene transcription by recruiting chromatin-remodeling, histone-modifying, and basal transc... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5298737 Sun, 09 Oct 2011 19:10:02 +0100 5298737 http://www.medworm.com/index.php?rid=5058893&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21762814%26dopt%3DAbstract Authors: Pavri R, Nussenzweig MC Antibody maturation requires class switch recombination (CSR) and somatic hypermutation (SHM), both of which are initiated by activation-induced cytidine deaminase (AID). AID deaminates cytosine residues resulting in mismatches that are differentially processed to produce double-strand breaks in Ig switch (S) regions that lead to CSR, or to point mutations in variable (V) exons resulting in SHM. Although AID was first thought to be Ig-specific, recent work indicates that it also targets a diverse group of non-Ig loci, including genes such as Bcl6 and c-myc, whose modification by AID results in lymphoma-associated mutations and translocations. Here, we review the recent literature on AID targeting and the role for transcriptional stalling in recruitment ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5058893 Mon, 25 Jul 2011 12:00:06 +0100 5058893 http://www.medworm.com/index.php?rid=5058892&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21762815%26dopt%3DAbstract Authors: Pinaud E, Marquet M, Fiancette R, Péron S, Vincent-Fabert C, Denizot Y, Cogné M Antigen receptor gene loci are among the most complex in mammals. The IgH locus, encoding the immunoglobulin heavy chain (IgH) in B-lineage cells, undergoes major transcription-dependent DNA remodeling events, namely V(D)J recombination, Ig class-switch recombination (CSR), and somatic hypermutation (SHM). Various cis-regulatory elements (encompassing promoters, enhancers, and chromatin insulators) recruit multiple nuclear factors in order to ensure IgH locus regulation by tightly orchestrated physical and/or functional interactions. Among major IgH cis-acting regions, the large 3' regulatory region (3'RR) located at the 3' boundary of the locus includes several enhancers and harbors an intriguin... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5058892 Mon, 25 Jul 2011 12:00:06 +0100 5058892 http://www.medworm.com/index.php?rid=5058891&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21762816%26dopt%3DAbstract Authors: Taniuchi I, Ellmeier W The helper versus cytotoxic-lineage choice of CD4(+)CD8(+) DP thymocytes correlates with MHC restriction of their T cell receptors and the termination of either CD8 or CD4 coreceptor expression. It has been hypothesized that transcription factors regulating the expression of the Cd4/Cd8 coreceptor genes must play a role in regulating the lineage decision of DP thymocytes. Indeed, progress made during the past decade led to the identification of several transcription factors that regulate CD4/CD8 expression that are as well important regulators of helper/cytotoxic cell fate choice. These studies provided insight into the molecular link between the regulation of coreceptor expression and lineage decision. However, studies initiated by the identification of... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5058891 Mon, 25 Jul 2011 12:00:06 +0100 5058891 http://www.medworm.com/index.php?rid=5058890&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21762817%26dopt%3DAbstract Authors: Kurschus FC, Wörtge S, Waisman A The recent decades have shown that multiple sclerosis (MS) is not a uniform disease entity with common etiology, but rather a disease or syndrome characterized by a heterogeneous pattern of manifestations and pathological principles. Apart from the older distinctions of the Devic's disease from the standard Western form of relapsing remitting MS or the more Asian form of opticospinal MS, specific pathological patterns indicating distinct etiologies have been established by analyses of biopsies and autopsies. Further, the distinct responses of patients to drugs targeting either specific cell types or immunoregulatory mechanisms such as Rituximab or IFNβ clearly demonstrate the heterogeneity of the disease and their driving mechanisms. Finally,... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5058890 Mon, 25 Jul 2011 12:00:06 +0100 5058890 http://www.medworm.com/index.php?rid=5058889&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21762818%26dopt%3DAbstract Authors: Nagata S, Kawane K In various mammalian developmental processes such as programmed cell death, erythropoiesis, and lens-cell differentiation, chromosomal DNA is degraded into nucleotides by a set of specific nucleases. If this process does not proceed smoothly, the undigested DNA causes various problems. For example, when chromosomal DNA is not degraded in the lens cells, cataracts form. In other cases, undigested DNA in macrophages activates the innate immune system, like a DNA virus, and causes strong inflammation, resulting in anemia, arthritis, and lymphopenia. Here, we discuss when, where, and how DNA is degraded to maintain mammalian homeostasis. PMID: 21762818 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=5058889 Mon, 25 Jul 2011 12:00:06 +0100 5058889 http://www.medworm.com/index.php?rid=4871979&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21569911%26dopt%3DAbstract Authors: Ladygina N, Martin BR, Altman A Although protein S-palmitoylation was first characterized >30years ago, and is implicated in the function, trafficking, and localization of many proteins, little is known about the regulation and physiological implications of this posttranslational modification. Palmitoylation of various signaling proteins required for TCR-induced T cell activation is also necessary for their proper function. Linker for activation of T cells (LAT) is an essential scaffolding protein involved in T cell development and activation, and we found that its palmitoylation is selectively impaired in anergic T cells. The recent discovery of the DHHC family of palmitoyl acyl transferases and the establishment of sensitive and quantitative proteomics-based methods for g... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4871979 Sat, 28 May 2011 03:30:03 +0100 4871979 http://www.medworm.com/index.php?rid=4871978&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21569912%26dopt%3DAbstract Authors: Hesslein DG, Lanier LL Natural killer (NK) cells play an important role in host defense against tumors and viruses and other infectious diseases. NK cell development is regulated by mechanisms that are both shared with and separate from other hematopoietic cell lineages. Functionally, NK cells use activating and inhibitory receptors to recognize both healthy and altered cells such as transformed or infected cells. Upon activation, NK cells produce cytokines and cytotoxic granules using mechanisms similar to other hematopoietic cell lineages especially cytotoxic T cells. Here we review the transcription factors that control NK cell development and function. Although many of these transcription factors are shared with other hematopoietic cell lineages, they control unexpected an... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4871978 Sat, 28 May 2011 03:30:03 +0100 4871978 http://www.medworm.com/index.php?rid=4871977&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21569913%26dopt%3DAbstract Authors: Schenten D, Medzhitov R The mammalian immune system comprises an adaptive and an innate component. The innate immune system employs a limited number of germ-line-encoded pattern-recognition receptors (PRRs) that recognize invariant pathogen-associated molecular patterns (PAMPs). In contrast, the adaptive immune system depends on the generation of a diverse repertoire of antigen receptors on T and B lymphocytes and subsequent activation and clonal expansion of cells carrying the appropriate antigen-specific receptors. Induction of adaptive immunity not only depends on direct antigen recognition by the antigen receptors but also relies on essential signals that are delivered by the innate immune system. In recent years, we have witnessed the discovery of a still expanding array ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4871977 Sat, 28 May 2011 03:30:03 +0100 4871977 http://www.medworm.com/index.php?rid=4871976&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21569914%26dopt%3DAbstract Authors: Hirano M, Das S, Guo P, Cooper MD Approximately 500 million years ago, two types of recombinatorial adaptive immune systems (AISs) arose in vertebrates. The jawed vertebrates diversify their repertoire of immunoglobulin domain-based T and B cell antigen receptors mainly through the rearrangement of V(D)J gene segments and somatic hypermutation, but none of the fundamental AIS recognition elements in jawed vertebrates have been found in jawless vertebrates. Instead, the AIS of jawless vertebrates is based on variable lymphocyte receptors (VLRs) that are generated through recombinatorial usage of a large panel of highly diverse leucine-rich-repeat (LRR) sequences. Whereas the appearance of transposon-like, recombination-activating genes contributed uniquely to the origin of the ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4871976 Sat, 28 May 2011 03:30:03 +0100 4871976 http://www.medworm.com/index.php?rid=4871975&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21569915%26dopt%3DAbstract Authors: Zygmunt B, Veldhoen M CD4(+) T helper (T(H)) cells play a critical role in orchestrating a pleiotropy of immune activities against a large variety of pathogens. It is generally thought that this is achieved through the acquisition of highly specialized functions after activation followed by the differentiation into various functional subsets. The differentiation process of naive precursor T(H) cells into defined effector subsets is controlled by cells of the innate immune system and their complex array of effector molecules such as secreted cytokines and membrane bound costimulatory molecules. These provide a unique quantitative or qualitative signal initiating T(H) development, which is subsequently reinforced via T cell-mediated feedback signals and selective survival and pr... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4871975 Sat, 28 May 2011 03:30:03 +0100 4871975 http://www.medworm.com/index.php?rid=4170527&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21056727%26dopt%3DAbstract Authors: Valledor AF, Comalada M, Santamaría-Babi LF, Lloberas J, Celada A Macrophages play key roles in inflammation. During the onset of the inflammatory process, these phagocytic cells become activated and have destructive effects. Macrophage activation, which involves the induction of more than 400 genes, results in an increased capacity to eliminate bacteria and to regulate many other cells through the release of cytokines and chemokines. However, excessive activation has damaging effects, such as septic shock, which can lead to multiple organ dysfunction syndrome and death. In other situations, persistence of proinflammatory activity results in the development of chronic inflammation, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. To prevent undesirable... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4170527 Tue, 16 Nov 2010 16:05:06 +0100 4170527 http://www.medworm.com/index.php?rid=4170526&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21056728%26dopt%3DAbstract Authors: Koyasu S, Moro K, Tanabe M, Takeuchi T The Th2-type immune response, characterized by the production of IL-4, IL-5, and IL-13, is a critical immune response against helminths invading cutaneous or mucosal sites. Th2 cytokines are induced soon after helminth infection, even before a pathogen-specific adaptive immune response is established. Although the expulsion and clearance of helminths usually requires pathogen-specific Th2-mediated immunity, early induction of Th2 cytokines during the innate immune phase is important for host protection from helminth invasion. Recent studies have shed light on such Th2 cytokine production by formerly uncharacterized innate immune cells such as a newly identified natural helper cell. We discuss here the mechanisms of innate production of Th... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4170526 Tue, 16 Nov 2010 16:05:06 +0100 4170526 http://www.medworm.com/index.php?rid=4170525&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21056729%26dopt%3DAbstract Authors: Stavnezer J, Björkman A, Du L, Cagigi A, Pan-Hammarström Q Class switch recombination (CSR) is induced upon B cell activation and occurs within special DNA regions, termed switch (S) regions, which consist of tandem repeats of G-rich sequences. CSR occurs by introduction of double-strand breaks (DSBs) into each S region, and recombination by nonhomologous end-joining (NHEJ). The recombination event occurs during the G1 phase of the cell cycle in cells that are rapidly dividing. By examination of patients and mouse knock-out strains lacking various DNA-damage response factors and enzymes involved in DNA repair, much has been learned about which factors are important for CSR, how DSBs are introduced into S regions, and how the donor and acceptor S regions are then recombined. ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4170525 Tue, 16 Nov 2010 16:05:06 +0100 4170525 http://www.medworm.com/index.php?rid=4170524&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21056730%26dopt%3DAbstract Authors: Maldonado RA, von Andrian UH Since their discovery by Steinman and Cohn in 1973, dendritic cells (DCs) have become increasingly recognized for their crucial role as regulators of innate and adaptive immunity. DCs are exquisitely adept at acquiring, processing, and presenting antigens to T cells. They also adjust the context (and hence the outcome) of antigen presentation in response to a plethora of environmental inputs that signal the occurrence of pathogens or tissue damage. Such signals generally boost DC maturation, which promotes their migration from peripheral tissues into and within secondary lymphoid organs and their capacity to induce and regulate effector T cell responses. Conversely, more recent observations indicate that DCs are also crucial to ensure immunological... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4170524 Tue, 16 Nov 2010 16:05:06 +0100 4170524 http://www.medworm.com/index.php?rid=4140223&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034968%26dopt%3DAbstract Authors: Fagarasan S, Cerutti A PMID: 21034968 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4140223 Sun, 07 Nov 2010 07:55:03 +0100 4140223 http://www.medworm.com/index.php?rid=4140222&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034969%26dopt%3DAbstract Authors: Sonnenberg GF, Fouser LA, Artis D Expression of interleukin (IL)-22, a member of the IL-10 cytokine family, has recently been reported in a number of human diseases, including mucosal-associated infections and inflammatory disorders of the intestine, skin, and joints. Both T cells and an emerging category of innate lymphoid cells are sources of IL-22, while the IL-22 receptor complex is reported to be restricted to cells of nonhematopoietic origin. The ligand-receptor distribution of IL-22-IL-22R permits immune cells to regulate responses of epithelial cells, endothelial cells, fibroblasts, and other tissue-resident stromal cells. This pathway appears to be critically important at barrier surfaces where epithelial cells play an active role in the initiation, regulation, and re... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4140222 Sun, 07 Nov 2010 07:55:03 +0100 4140222 http://www.medworm.com/index.php?rid=4140221&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034970%26dopt%3DAbstract Authors: Chorny A, Puga I, Cerutti A The past 20 years have seen a growing interest over the control of adaptive immune responses by the innate immune system. In particular, considerable attention has been paid to the mechanisms by which antigen-primed dendritic cells orchestrate the differentiation of T cells. Additional studies have elucidated the pathways followed by T cells to initiate immunoglobulin responses in B cells. In this review, we discuss recent advances on the mechanisms by which intestinal bacteria, epithelial cells, dendritic cells, and macrophages cross talk with intestinal T cells and B cells to induce frontline immunoglobulin A class switching and production. PMID: 21034970 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4140221 Sun, 07 Nov 2010 07:55:03 +0100 4140221 http://www.medworm.com/index.php?rid=4140220&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034971%26dopt%3DAbstract Authors: Peterson DA, Jimenez Cardona RA The adaptive immune response to normal gut bacteria is part of a homeostatic process that is neither ignorance nor tolerance. Through both targeted and meta-genome sequencing of the gut microbiota, we now know more about the microbial population that inhabits the gut environment than any previous generation. Defining the specificity of the adaptive immune response to gut symbionts and the impact of this specificity on the gut barrier function is still limited by lack of comprehensive data. The evolution of the gut microbiota over millenia with its host provides stability to the present-day microbiota in the presence and absence of the adaptive and innate immune system. Intrinsic factors within each member of the microbiota modulate the immunosti... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4140220 Sun, 07 Nov 2010 07:55:03 +0100 4140220 http://www.medworm.com/index.php?rid=4140219&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034972%26dopt%3DAbstract Authors: Rescigno M Dendritic cells (DCs) are specialized antigen-presenting cells that orchestrate innate and adaptive immune responses. The intestinal mucosa contains numerous DCs that are highly specialized in function. Mucosal DCs display a unique response to toll-like receptor ligands, are capable of driving immunoglobulin isotype switching to IgA, can imprint gut-homing receptors on T and B cells, and drive either T regulatory or Th17 cells depending on the analyzed subtype. These functions are partly cell autonomous and partly conferred by the local microenvironment. In this review, we will summarize the different DC subtypes present in the intestine and in the gut-associated lymphoid tissue (GALT), the unique characteristics of these subtypes, and how the local microenvironment... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4140219 Sun, 07 Nov 2010 07:55:03 +0100 4140219 http://www.medworm.com/index.php?rid=4140218&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034973%26dopt%3DAbstract Authors: Mucida D, Cheroutre H Recent advances in stem cell research have redefined previous concepts of hematopoietic hierarchy, lineage commitment, and cell fate. The immune system is comprised of several well-defined cell lineages of which many exhibit high levels of plasticity or capacity in changing their phenotype. The CD4 T helper cells provide a peculiar example of apparently defined cell subsets, at times described as lineages, but also highly sensitive to tissue environmental cues that may change their fate. The classical Th1/Th2 CD4 T cell differentiation referred to for many years as the main CD4 T cell fate dichotomy and the later additions of CD4 helper T cell variants, such as T helper 17 (Th17) and induced regulatory T cells (iTreg), have added complexity but also doubt... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4140218 Sun, 07 Nov 2010 07:55:03 +0100 4140218 http://www.medworm.com/index.php?rid=4140217&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034974%26dopt%3DAbstract Authors: Suzuki K, Kawamoto S, Maruya M, Fagarasan S Since its discovery more than four decades ago, immunoglobulin (Ig) A has been the subject of continuous and intensive studies. The major concepts derived were that the precursors of IgA plasma cells are generated in follicular organized structures with the help of T cells and the secreted IgAs provide protection against mucosal pathogens. However, only recently we began to appreciate that IgAs play key roles in regulation of bacterial communities in the intestine and that the repertoire of gut microbiota is closely linked to the proper functioning of the immune system. In this review, we highlight the complex and dynamic mutualistic relationships between bacteria and immune cells and discuss the sites and pathways leading to IgA syn... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4140217 Sun, 07 Nov 2010 07:55:03 +0100 4140217 http://www.medworm.com/index.php?rid=4140216&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034975%26dopt%3DAbstract Authors: Randall TD Bronchus-associated lymphoid tissue (BALT) is a constitutive mucosal lymphoid tissue adjacent to major airways in some mammalian species, including rats and rabbits, but not humans or mice. A related tissue, inducible BALT (iBALT), is an ectopic lymphoid tissue that is formed upon inflammation or infection in both mice and humans and can be found throughout the lung. Both BALT and iBALT acquire antigens from the airways and initiate local immune responses and maintain memory cells in the lungs. Here, we discuss the development and function of BALT and iBALT in the context of pulmonary immunity to infectious agents, tumors, and allergens as well as autoimmunity and inflammatory diseases of the lung. PMID: 21034975 [PubMed - in process] (Source: Advances in Immuno... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4140216 Sun, 07 Nov 2010 07:55:03 +0100 4140216 http://www.medworm.com/index.php?rid=4140215&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034976%26dopt%3DAbstract Authors: Chow J, Lee SM, Shen Y, Khosravi A, Mazmanian SK All animals live in symbiosis. Shaped by eons of co-evolution, host-bacterial associations have developed into prosperous relationships creating mechanisms for mutual benefits to both microbe and host. No better example exists in biology than the astounding numbers of bacteria harbored by the lower gastrointestinal tract of mammals. The mammalian gut represents a complex ecosystem consisting of an extraordinary number of resident commensal bacteria existing in homeostasis with the host's immune system. Most impressive about this relationship may be the concept that the host not only tolerates, but has evolved to require colonization by beneficial microorganisms, known as commensals, for various aspects of immune development and ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=4140215 Sun, 07 Nov 2010 07:55:03 +0100 4140215 http://www.medworm.com/index.php?rid=3903167&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20728022%26dopt%3DAbstract Authors: Gonzalez SF, Kuligowski MP, Pitcher LA, Roozendaal R, Carroll MC Over the past decade, it has become apparent that B cells acquire antigens primarily from membrane surfaces and that uptake is an active process involving a synapse between the B cell receptor, coreceptor, and the antigen surface. However, understanding how antigens are delivered to follicular dendritic cells (FDC), which are the primary depot for B cell antigen within the lymph node follicles, is only recently beginning to be dissected. The application of fluorescent-based imaging techniques such as multiphoton intravital microscopy to visualize trafficking of B cells and antigens into draining lymph nodes has provide insights that would not otherwise be made. At least three novel pathways for transport of lymph... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3903167 Thu, 26 Aug 2010 10:57:04 +0100 3903167 http://www.medworm.com/index.php?rid=3903166&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20728023%26dopt%3DAbstract Authors: Saijo K, Crotti A, Glass CK Chronic inflammation is associated with many neurodegenerative diseases, including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Increasing evidence that neuroinflammation contributes to disease severity has generated considerable interest in determining whether inhibition of inflammation pathways might be of therapeutic benefit. One potential avenue of intervention is provided by members of the nuclear receptor superfamily of ligand-dependent transcription factors that exert anti-inflammatory effects in many cell types. Here, we review recent studies providing insights into the distinct mechanisms that enable nuclear receptors to modulate immune responses, describe inflammatory components of neurodegenerative diseases, and discu... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3903166 Thu, 26 Aug 2010 10:57:04 +0100 3903166 http://www.medworm.com/index.php?rid=3903165&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20728024%26dopt%3DAbstract Authors: Dasgupta S, Kasper DL The intestinal microflora of mammals includes organisms with many unique molecules that enable them to modulate their immediate environment and thus to survive and reside successfully in the gut. Little is known about how individual molecules from these microbes affect the host's health and development, but the microbiome is considered a crucial factor in intestinal homeostasis. The literature highlights numerous ways in which the microflora stimulates the mammalian host's immune system, starting with its development and continuing to the initiation and resolution of inflammation. The influence of the microflora on the host's immune system is mediated principally by interactions with various antigen-presenting cells of the gut; these interactions result i... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3903165 Thu, 26 Aug 2010 10:57:04 +0100 3903165 http://www.medworm.com/index.php?rid=3903164&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20728025%26dopt%3DAbstract Authors: Zhang Y, Gostissa M, Hildebrand DG, Becker MS, Boboila C, Chiarle R, Lewis S, Alt FW Recurrent chromosomal abnormalities, especially chromosomal translocations, are strongly associated with certain subtypes of leukemia, lymphoma and solid tumors. The appearance of particular translocations or associated genomic alterations can be important indicators of disease prognosis, and in some cases, certain translocations may indicate appropriate therapy protocols. To date, most of our knowledge about chromosomal translocations has derived from characterization of the highly selected recurrent translocations found in certain cancers. Until recently, mechanisms that promote or suppress chromosomal translocations, in particular, those responsible for their initiation, have not been addre... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3903164 Thu, 26 Aug 2010 10:57:04 +0100 3903164 http://www.medworm.com/index.php?rid=3618344&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20510728%26dopt%3DAbstract Authors: Montoya D, Modlin RL Investigation into the innate immune response in leprosy has provided insight into host defense and immunopathology in human infectious disease. A key advance has been the delineation of pattern recognition receptors that detect pathogen-associated molecular patterns of the bacterium that causes leprosy, Mycobacterium leprae. From this knowledge, it has been possible to determine the cytokine responses as well as macrophage and dendritic cell differentiation programs that contribute to host defense and tissue injury in leprosy. These insights provide targets for therapeutic intervention to modulate innate immune responses against microbial infection in humans. PMID: 20510728 [PubMed - as supplied by publisher] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3618344 Tue, 01 Jun 2010 21:57:03 +0100 3618344 http://www.medworm.com/index.php?rid=3618343&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20510729%26dopt%3DAbstract Authors: Darmoise A, Maschmeyer P, Winau F Saposins or sphingolipid activator proteins (SAPs) are small, nonenzymatic glycoproteins that are ubiquitously present in lysosomes. SAPs comprise the five molecules saposins A-D and the GM2 activator protein. Saposins are essential for sphingolipid degradation and membrane digestion. On the one hand, they bind the respective hydrolases required to catabolize sphingolipid molecules; on the other hand, saposins can interact with intralysosomal membrane structures to render lipids accessible to their degrading enzymes. Thus, saposins bridge the physicochemical gap between lipid substrate and hydrophilic hydrolases. Accordingly, defects in saposin function can lead to lysosomal lipid accumulation. In addition to their specific functions in sphing... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3618343 Tue, 01 Jun 2010 21:57:03 +0100 3618343 http://www.medworm.com/index.php?rid=3618342&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20510730%26dopt%3DAbstract Authors: Ishii N, Takahashi T, Soroosh P, Sugamura K T-cell activation is mediated not only by antigen stimulation through T-cell receptors but also by costimulatory signals through costimulatory molecules. Among several costimulatory molecules, the tumor necrosis factor (TNF) receptor family member OX40 plays a key role in the survival and homeostasis of effector and memory T cells. According to the conventional understanding of OX40 costimulation, an interaction between OX40 and OX40 ligand (OX40L) occurs when activated T cells bind to professional antigen-presenting cells (APCs). The T-cell functions, including cytokine production, expansion, and survival, are then enhanced by the OX40 costimulatory signals. Over the last half-decade, evidence has accumulated that OX40 signals are c... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3618342 Tue, 01 Jun 2010 21:57:03 +0100 3618342 http://www.medworm.com/index.php?rid=3618341&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20510731%26dopt%3DAbstract Authors: Fujio K, Okamura T, Yamamoto K Regulatory T cells (Treg cells) play critical roles in the induction of peripheral tolerance to self- and foreign antigens. Naturally occurring CD4(+)CD25(+) Treg cells, which characteristically express the transcription factor forkhead box protein P3 (Foxp3), have been studied intensively because their deficiency abrogates self-tolerance and causes autoimmune disease. However, several lines of evidence suggest that additional important mechanisms other than the Foxp3 system are required to enforce immunological self-tolerance in the periphery. Interleukin-10 (IL-10) is a regulatory cytokine that plays a central role in controlling inflammatory processes, and IL-10-secreting T cells may constitute an additional mechanism that are responsible for ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3618341 Tue, 01 Jun 2010 21:57:03 +0100 3618341 http://www.medworm.com/index.php?rid=3618340&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20510732%26dopt%3DAbstract Authors: Tan JK, Watanabe T Secondary lymphoid organs such as spleen and lymph nodes are highly organized immune structures essential for the initiation of immune responses. They display distinct B cell and T cell compartments associated with specific stromal follicular dendritic cells and fibroblastic reticular cells, respectively. Interweaved through the parenchyma is a conduit system that distributes small antigens and chemokines directly to B and T cell zones. While most structural aspects between lymph nodes and spleen are common, the entry of lymphocytes, antigen-presenting cells, and antigen into lymphoid tissues is regulated differently, reflecting the specialized functions of each organ in filtering either lymph or blood. The overall organization of lymphoid tissue is vital fo... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3618340 Tue, 01 Jun 2010 21:57:03 +0100 3618340 http://www.medworm.com/index.php?rid=3618339&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20510733%26dopt%3DAbstract Authors: Maul RW, Gearhart PJ In response to an assault by foreign organisms, peripheral B cells can change their antibody affinity and isotype by somatically mutating their genomic DNA. The ability of a cell to modify its DNA is exceptional in light of the potential consequences of genetic alterations to cause human disease and cancer. Thus, as expected, this mechanism of antibody diversity is tightly regulated and coordinated through one protein, activation-induced deaminase (AID). AID produces diversity by converting cytosine to uracil within the immunoglobulin loci. The deoxyuracil residue is mutagenic when paired with deoxyguanosine, since it mimics thymidine during DNA replication. Additionally, B cells can manipulate the DNA repair pathways so that deoxyuracils are not faithfull... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3618339 Tue, 01 Jun 2010 21:57:03 +0100 3618339 http://www.medworm.com/index.php?rid=3618338&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20510734%26dopt%3DAbstract Authors: Basso K, Dalla-Favera R BCL6 is a transcriptional repressor which has emerged as a critical regulator of germinal centers (GC), the sites where B cells are selected based on the production of antibodies with high affinity for the antigen. BCL6 is also a frequently activated oncogene in the pathogenesis of human B cell lymphomas, most of which derive from the GC B cells. A thorough understanding of the biological role of BCL6 in normal B cell development and lymphomagenesis depends upon the identification of the full set of genes that are targets of its transcriptional regulatory function. Recently, the identification of BCL6 targets has been implemented with the use of genome-wide chromatin immunoprecipitation and gene expression profiling approaches. A large set of promoters ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=3618338 Tue, 01 Jun 2010 21:57:03 +0100 3618338 http://www.medworm.com/index.php?rid=2807184&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19755181%26dopt%3DAbstract Authors: Nechushtan H, Kim S, Kay G, Razin E Lysyl tRNA synthetase (LysRS) is an aminoacyl-tRNA synthetase (AaRS). This group of ancient proteins, known for their critical role in translation, was found in recent years to function in a variety of other roles. Besides its enzymatic activity in aminoacylation of tRNA, LysRS can produce dinucleotide diadenosine tetraphosphate (Ap(4)A). Intracellularly, it is found mainly in the cytoplasm as a part of a multisynthetase complex where it interacts with several proteins, most notably AIMP2. Besides its role in translation it has been demonstrated that LysRS can act as a cytokine-like molecule, secreted by cells and having distinct effects on macrophages. Moreover, LysRS can bind to the transcription factors USF2 and MITF and can influence the... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2807184 Fri, 18 Sep 2009 17:50:02 +0100 2807184 http://www.medworm.com/index.php?rid=2807183&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19755182%26dopt%3DAbstract Authors: Munford R, Lu M, Varley A We consider here a previously neglected aspect of recovery from infectious diseases: how animals dispose of the dead microbes in their tissues. For one of the most important disease-causing microorganisms, Gram-negative bacteria, there is now evidence that the host catabolism of a key microbial molecule is essential for full recovery. As might be expected, it is the same bacterial molecule that animals sense to detect the presence of Gram-negative bacteria in their tissues, the cell wall lipopolysaccharide (LPS). Here, we discuss current knowledge about LPS sensing with emphasis on the host enzyme that inactivates this microbial "messenger" molecule. We also consider the possibility that the rate at which stimulatory microbial molecules undergo inacti... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2807183 Fri, 18 Sep 2009 17:50:02 +0100 2807183 http://www.medworm.com/index.php?rid=2807182&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19755183%26dopt%3DAbstract Authors: Cassel SL, Rothman PB Cytokines are powerful mediators of the immune response that, following initial release by components of the innate system, drive effector functions as well as stimulate the additional arms of the response. Their individual functions are diverse, with stimulatory and inhibitory actions, with the resultant systemic immune response a summation of these actions. The frequently opposing effects of cytokines determine that the blockade of one results in the functional augmentation of the other. Thus, the differential regulation of cytokines profoundly influences the character of the immune response. The suppressor of cytokine signaling proteins are a family of molecules pivotal to this critical regulation. In this review, we will discuss their structural compo... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2807182 Fri, 18 Sep 2009 17:50:02 +0100 2807182 http://www.medworm.com/index.php?rid=2807180&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19755184%26dopt%3DAbstract Authors: Ward ES, Ober RJ The MHC Class I-related receptor, FcRn, transports antibodies of the immunoglobulin G (IgG) class within and across a diverse array of different cell types. Through this transport, FcRn serves multiple roles throughout adult life that extend well beyond its earlier defined function of transcytosing IgGs from mother to offspring. These roles include the maintenance of IgG levels and the delivery of antigen in the form of immune complexes to degradative compartments within cells. Recent studies have led to significant advances in knowledge of the intracellular trafficking of FcRn and (engineered) IgGs at both the molecular and cellular levels. The engineering of FcRn-IgG (or Fc) interactions to generate antibodies of increased longevity represents an area of act... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2807180 Fri, 18 Sep 2009 17:50:02 +0100 2807180 http://www.medworm.com/index.php?rid=2529080&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19477319%26dopt%3DAbstract Authors: Cohen NR, Garg S, Brenner MB The discovery of molecules capable of presenting lipid antigens, the CD1 family, and of the T cells that recognize them, has opened a new dimensionin our understanding of cell-mediated immunity against infection. Like MHC Class I molecules, CD1 isoforms (CD1a, b, c and d) are assembled in the ER and sent to the cell surface. However, in contrast to MHC molecules, CD1 complexes are then re-internalized into specific endocytic compartments where they can bind lipid antigens. These include a broad scope of both self and foreign molecules that range from simple fatty acids or phospholipids, to more complex glycolipids, isoprenoids, mycolates and lipopeptides. Lipid-loaded CD1 molecules are then delivered to the cell surface and can be surveyed by CD1-r... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2529080 Sat, 27 Jun 2009 13:08:05 +0100 2529080 http://www.medworm.com/index.php?rid=2529078&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19477320%26dopt%3DAbstract Authors: Jiang H, Chess L We propose an "Avidity Model of Self-Nonself Discrimination" in which self-nonself discrimination is achieved by both central thymic selection and peripheral immune regulation. The conceptual framework that links these two events is the understanding that both in the thymus and in the periphery the survival or the fate of T cells is determined by the avidity of the interactions between T cell receptors (TCRs) on T cells, specific to any antigens and MHC/antigen peptides presented by antigen-presenting cells (APCs). We envision that the immune system achieves self-nonself discrimination, during adaptive immunity, not by recognizing the structural differences between self versus foreign antigens, but rather by perceiving the avidity of T cell activation. Intrath... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2529078 Sat, 27 Jun 2009 13:08:05 +0100 2529078 http://www.medworm.com/index.php?rid=2529076&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19477321%26dopt%3DAbstract Authors: Oyoshi MK, He R, Kumar L, Yoon J, Geha RS Atopic dermatitis (AD) is a pruritic inflammatory skin disease associated with a personal or family history of allergy. The prevalence of AD is on the rise and estimated at approximately 17% in the USA. The fundamental lesion in AD is a defective skin barrier that results in dry itchy skin, and is aggravated by mechanical injury inflicted by scratching. This allows entry of antigens via the skin and creates a milieu that shapes the immune response to these antigens. This review discusses recent advances in our understanding of the abnormal skin barrier in AD, namely abnormalities in epidermal structural proteins, such as filaggrin, mutated in approximately 15% of patients with AD, epidermal lipids, and epidermal proteases and protease ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2529076 Sat, 27 Jun 2009 13:08:05 +0100 2529076 http://www.medworm.com/index.php?rid=2529074&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19477322%26dopt%3DAbstract Authors: Petrocca F, Lieberman J MicroRNAs (miRNAs) regulate cell fate during development and in response to environmental cues. Here, we review the emerging story of how miRNAs regulate immune cell development and function. PMID: 19477322 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2529074 Sat, 27 Jun 2009 13:08:05 +0100 2529074 http://www.medworm.com/index.php?rid=2529072&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19477323%26dopt%3DAbstract Authors: Holtzman MJ, Byers DE, Benoit LA, Battaile JT, You Y, Agapov E, Park C, Grayson MH, Kim EY, Patel AC To better understand the immune basis for chronic inflammatory lung disease, we analyzed a mouse model of lung disease that develops after respiratory viral infection. The disease that develops in this model is similar to asthma and chronic obstructive pulmonary disease (COPD) in humans and is manifested after the inciting virus has been cleared to trace levels. The model thereby mimics the relationship of paramyxoviral infection to the development of childhood asthma in humans. When the acute lung disease appears in this model (at 3 weeks after viral inoculation), it depends on an immune axis that is initiated by expression and activation of the high-affinity IgE receptor (Fcv... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2529072 Sat, 27 Jun 2009 13:08:05 +0100 2529072 http://www.medworm.com/index.php?rid=2210031&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19231591%26dopt%3DAbstract Authors: Liu YJ Dendritic cells (DCs) are professional antigen-presenting cells that have the ability to sense infection and tissue stress, sample and present antigen to T lymphocytes, and instruct the initiation of different forms of immunity and tolerance. The functional versatility of DCs depends on their remarkable ability to translate collectively the information from the invading microbes, as well as their resident tissue microenvironments. Recent progress in understanding Toll-like receptor (TLR) biology has illuminated the mechanisms by which DCs link innate and adaptive antimicrobial immune responses. However, how tissue microenvironments shape the function of DCs has remained elusive. Recent studies of TSLP (thymic stromal lymphopoietin), an epithelial cell-derived cytokine t... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2210031 Tue, 24 Feb 2009 20:27:01 +0100 2210031 http://www.medworm.com/index.php?rid=2210030&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19231592%26dopt%3DAbstract Authors: Jonsson AH, Yokoyama WM Armed with potent cytotoxic and immunostimulatory effector functions, natural killer (NK) cells have the potential to cause significant damage to normal self cells unless controlled by self-tolerance mechanisms. NK cells identify and attack target cells based on integration of signals from activation and inhibitory receptors, whose ligands exhibit complex expression and/or binding patterns. Preservation of NK cell self-tolerance must therefore go beyond mere engagement of inhibitory receptors during effector functions. Herein, we review recent work that has uncovered a number of mechanisms to ensure self-tolerance of NK cells. For example, licensing of NK cells allows only NK cells that can engage self-MHC to become functionally competent, or licensed. ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2210030 Tue, 24 Feb 2009 20:27:01 +0100 2210030 http://www.medworm.com/index.php?rid=2210029&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19231593%26dopt%3DAbstract Authors: Blanchard C, Rothenberg ME In this review, we aim to put in perspective the biology of a multifunctional leukocyte, the eosinophil, by placing it in the context of innate and adaptive immune responses. Eosinophils have a unique contribution in initiating inflammatory and adaptive responses, due to their bidirectional interactions with dendritic cells and T cells, as well as their large panel of secreted cytokines and soluble mediators. The mechanisms and consequences of eosinophil responses in experimental inflammatory models and human diseases are discussed. PMID: 19231593 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2210029 Tue, 24 Feb 2009 20:27:01 +0100 2210029 http://www.medworm.com/index.php?rid=2210028&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19231594%26dopt%3DAbstract Authors: Schroeder JT Despite being first described in humans nearly 130 years ago, the basophil granulocyte has received little recognition other than being the least common leukocyte circulating in blood. Even after its identity as the source of histamine released by blood cells in response to reaginic IgE, its role in allergic disease has largely been viewed as redundant to that of the tissue mast cell. This line of thought, however, is changing with evidence that has emerged during the last 15 years. Not only have these rare cells been shown to constitute a significant source of cytokines (IL-4 and IL-13) vital to the pathogenesis of allergic disease, but by doing so, may very well modulate T-helper 2-type inflammation at the level of T-cell/dendritic cell interactions. This novel ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2210028 Tue, 24 Feb 2009 20:27:01 +0100 2210028 http://www.medworm.com/index.php?rid=2210027&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19231595%26dopt%3DAbstract We describe properties of the S sequences, and discuss species and isotypic differences among S regions. Common properties of SHM and CSR target sequences suggest that evolution of S regions might involve the duplication and selection of SHM hotspots. PMID: 19231595 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2210027 Tue, 24 Feb 2009 20:27:01 +0100 2210027 http://www.medworm.com/index.php?rid=2210026&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19231596%26dopt%3DAbstract Authors: Takatsu K, Kouro T, Nagai Y Interleukin-5 (IL-5) is an interdigitating homodimeric glycoprotein that is initially identified by its ability to support the in vitro growth and differentiation of mouse B cells and eosinophils. IL-5 transgenic mouse shows two predominant features, remarkable increase in B-1 cells resulting in enhanced serum antibody levels, predominantly IgM, IgA, and IgE classes and in expansion of eosinophil numbers in the blood and eosinophil infiltration into various tissues. Conversely, mice lacking a functional gene for IL-5 or IL-5 receptor alpha chain (IL-5Ralpha) display a number of developmental and functional impairments in B cells and eosinophils. IL-5 receptor (IL-5R) comprises alpha and betac chains. IL-5 specifically binds to IL-5Ralpha and induces... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=2210026 Tue, 24 Feb 2009 20:27:01 +0100 2210026 http://www.medworm.com/index.php?rid=1770370&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18772002%26dopt%3DAbstract Authors: Hoehlig K, Lampropoulou V, Roch T, Neves P, Calderon-Gomez E, Anderton SM, Steinhoff U, Fillatreau S B lymphocytes contribute to immunity in multiple ways, including production of antibodies, presentation of antigen to T cells, organogenesis of secondary lymphoid organs, and secretion of cytokines. Recent clinical trials have shown that depleting B cells can be highly beneficial for patients with autoimmune diseases, implicating B cells and antibodies as key drivers of pathology. However, it should be kept in mind that B cell responses and antibodies also have important regulatory roles in limiting autoimmune pathology. Here, we analyze clinical examples illustrating the potential of antibodies as treatment for immune-mediated disorders and discuss the underlying mechanisms. F... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1770370 Sun, 07 Sep 2008 10:00:23 +0100 1770370 http://www.medworm.com/index.php?rid=1770369&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18772003%26dopt%3DAbstract Authors: Chang TW, Pan AY The human immune system evolved over many hundreds of million of years in the ancestors of vertebrates and mammals to defend them against infectious and parasitic organisms in their natural habitats. By the time the Primates and Rodentia orders diverged about 88 million years ago, the human immune system was largely configured. From about 125,000 years ago, marked by the use of fire, Homo sapiens began to make substantial changes in their living environment and lifestyle. Here, we examine those changes in two phases, before and after the Industrial Revolution, and analyze their impact on the exposure of our immune system to infectious organisms and to harmless environmental antigens. Our analyses show that the cumulative changes in environment and lifestyle in... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1770369 Sun, 07 Sep 2008 10:00:23 +0100 1770369 http://www.medworm.com/index.php?rid=1770368&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18772004%26dopt%3DAbstract Authors: Rivera J, Fierro NA, Olivera A, Suzuki R Mast cells are innate immune cells that function as regulatory or effector cells and serve to amplify adaptive immunity. In adaptive immunity these cells function primarily through cell surface Fc receptors that bind immunoglobulin antibodies. The dysregulation of their adaptive role makes them central players in allergy and asthma. Upon encountering an allergen (antigen), which is recognized by immunoglobulin E (IgE) antibodies bound to the high affinity IgE receptor (FcvarepsilonRI) expressed on their cell surface, mast cells secrete both preformed and newly synthesized mediators of the allergic response. Blocking of these responses is an objective in therapeutic intervention of allergic diseases. Thus, understanding the mechanisms by... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1770368 Sun, 07 Sep 2008 10:00:23 +0100 1770368 http://www.medworm.com/index.php?rid=1770367&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18772005%26dopt%3DAbstract Authors: McLaughlin KA, Wucherpfennig KW Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The mainstream view is that MS is caused by an autoimmune attack of the CNS myelin by myelin-specific CD4 T cells, and this perspective is supported by extensive work in the experimental autoimmune encephalomyelitis (EAE) model of MS as well as immunological and genetic studies in humans. However, it is important to keep in mind that other cell populations of the immune system are also essential in the complex series of events leading to MS, as exemplified by the profound clinical efficacy of B cell depletion with Rituximab. This review discusses the mechanisms by which B cells contribute to the pathogenesis of MS and dissects their role ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1770367 Sun, 07 Sep 2008 10:00:23 +0100 1770367 http://www.medworm.com/index.php?rid=1770366&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18772006%26dopt%3DAbstract Authors: Jackson SM, Wilson PC, James JA, Capra JD PMID: 18772006 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1770366 Sun, 07 Sep 2008 10:00:23 +0100 1770366 http://www.medworm.com/index.php?rid=1469486&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18501768%26dopt%3DAbstract Authors: Gomez TS, Billadeau DD More than a quarter of a century has passed since the observation that T cells rapidly polarize their actin and microtubule cytoskeletal systems toward antigen-presenting cells during activation. Since this initial discovery, several receptors on T cells (e.g., T cell receptor [TCR], co-receptors, integrins, and chemokine receptors) have been identified to regulate these two cytoskeletal networks through complex signaling pathways, which are still being elucidated. There is now an undeniable body of biochemical, pharmacological, and genetic evidence indicating that regulators of actin and microtubule dynamics are crucial for T cell activation and effector functions. In fact, the actin cytoskeleton participates in the initial clustering of TCR-major histo... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1469486 Tue, 27 May 2008 16:20:06 +0100 1469486 http://www.medworm.com/index.php?rid=1469485&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18501769%26dopt%3DAbstract Authors: Mangalam AK, Rajagopalan G, Taneja V, David CS Population studies have shown that among all the genetic factors linked with autoimmune disease development, MHC class II genes on chromosome 6 accounts for majority of familial clustering in the common autoimmune diseases. Despite the highly polymorphic nature of HLA class II genes, majority of autoimmune diseases are linked to a limited set of class II-DR or -DQ alleles. Thus a more detailed study of these HLA-DR and -DQ alleles were needed to understand their role in genetic predisposition and pathogenesis of autoimmune diseases. Although in vitro studies using class-II restricted CD4 T cells and purified class II molecules have helped us in understanding some aspects of HLA class-II association with disease, it is difficult to... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1469485 Tue, 27 May 2008 16:20:06 +0100 1469485 http://www.medworm.com/index.php?rid=1469484&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18501770%26dopt%3DAbstract Authors: Hirano T, Murakami M, Fukada T, Nishida K, Yamasaki S, Suzuki T Zinc (Zn) is an essential nutrient required for cell growth, differentiation, and survival, and its deficiency causes growth retardation, immunodeficiency, and other health problems. Therefore, Zn homeostasis must be tightly controlled in individual cells. Zn is known to be important in the immune system, although its precise roles and mechanisms have not yet been resolved. Zn has been suggested to act as a kind of neurotransmitter. In addition, Zn has been shown to bind and affect the activity of several signaling molecules, such as protein tyrosine phosphatases (PTPs). However, it has not been known whether Zn itself might act as an intracellular signaling molecule, that is, a molecule whose intracellular status... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1469484 Tue, 27 May 2008 16:20:06 +0100 1469484 http://www.medworm.com/index.php?rid=1469483&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18501771%26dopt%3DAbstract Authors: Calpe S, Wang N, Romero X, Berger SB, Lanyi A, Engel P, Terhorst C The nine SLAM-family genes, SLAMF1-9, a subfamily of the immunoglobulin superfamily, encode differentially expressed cell-surface receptors of hematopoietic cells. Engagement with their ligands, which are predominantly homotypic, leads to distinct signal transduction events, for instance those that occur in the T or NK cell immune synapse. Upon phosphorylation of one or more copies of a unique tyrosine-based signaling motif in their cytoplasmic tails, six of the SLAM receptors recruit the highly specific single SH2-domain adapters SLAM-associated protein (SAP), EAT-2A, and/or EAT-2B. These adapters in turn bind to the tyrosine kinase Fyn and/or other protein tyrosine kinases connecting the receptors to signal t... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1469483 Tue, 27 May 2008 16:20:06 +0100 1469483 http://www.medworm.com/index.php?rid=1469482&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18501772%26dopt%3DAbstract Authors: Engels N, Engelke M, Wienands J Over the past two decades our view of the B cell antigen receptor (BCR) has fundamentally changed. Being initially regarded as a mute antibody orphan of the B cell surface, the BCR turned out to be a complex multimolecular machine monitoring almost all stages of B cell development, selection, and activation through a plethora of ubiquitously and cell-type-specific effector proteins. A comprehensive understanding of the many BCR signaling facets is still out but a few common biochemical principles outlined in this review operate at the level of receptor activation and orchestrate specific wiring of intracellular transducer cascades. First, initiation and processing of antigen-induced signal transduction relies on transient conformational changes ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1469482 Tue, 27 May 2008 16:20:06 +0100 1469482 http://www.medworm.com/index.php?rid=1007060&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17981203%26dopt%3DAbstract Authors: Siffrin V, Brandt AU, Herz J, Zipp F Understanding the immune response in the central nervous system (CNS) is crucial for the development of new therapeutic concepts in chronic neuroinflammation, which differs considerably from other autoimmune diseases. Special immunologic properties of inflammatory processes in the CNS, which is often referred to as an immune privileged site, imply distinct features of CNS autoimmune disease in terms of disease initiation, perpetuation, and therapeutic accessibility. Furthermore, the CNS is a stress-sensitive organ with a low capacity for self-renewal and is highly prone to bystander damage caused by CNS inflammation. This leads to neuronal degeneration that contributes considerably to the phenotype of the disease. In this chapter, we discus... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1007060 Tue, 06 Nov 2007 14:24:31 +0100 1007060 http://www.medworm.com/index.php?rid=1007059&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17981204%26dopt%3DAbstract Authors: Schoenborn JR, Wilson CB Interferon-gamma (IFN-gamma) is crucial for immunity against intracellular pathogens and for tumor control. However, aberrant IFN-gamma expression has been associated with a number of autoinflammatory and autoimmune diseases. This cytokine is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response, and by Th1 CD4 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops. Herein, we briefly review the functions of IFN-gamma, the cells that produce it, the cell extrinsic signals that induce its production and influence the differentiation of naïve T cells into IFN-gamma-producing effector T cells, and the signaling pathways and transcription factors that... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1007059 Tue, 06 Nov 2007 14:24:31 +0100 1007059 http://www.medworm.com/index.php?rid=1007058&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17981205%26dopt%3DAbstract Authors: Fearon DT The biological purpose of the mature, postthymic CD8(+) T cell is to respond to microbial antigens with a developmental program of clonal expansion and concomitant differentiation leading to effector cells (T(EFF)) that provide antimicrobial defense. Because many microbial infections persist into a chronic phase, this antigen-stimulated developmental program must be capable of continually generating T(EFF), perhaps for the lifetime of the individual. This chapter proposes that the ability of a CD8(+) T cell clone to maintain the continual production of T(EFF) during periods of persistent antigenic stimulation is based on a program that has two sequential phases of clonal expansion: an initial stage that occurs mainly in the secondary lymphoid tissues and is mediated ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1007058 Tue, 06 Nov 2007 14:24:31 +0100 1007058 http://www.medworm.com/index.php?rid=1007057&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17981206%26dopt%3DAbstract Authors: Richards A, Kavanagh D, Atkinson JP In this chapter, we examine the role of complement regulatory activity in atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). These diseases are representative of two distinct types of complement-mediated injury, one being acute and self-limited, the other reflecting accumulation of chronic damage. Neither condition was previously thought to have a pathologic relationship to the immune system. However, alterations in complement regulatory protein genes have now been identified as major predisposing factors for the development of both diseases. In aHUS, heterozygous mutations leading to haploinsufficiency and function-altering polymorphisms in complement regulators have been identified, while in AMD, polymorp... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1007057 Tue, 06 Nov 2007 14:24:31 +0100 1007057 http://www.medworm.com/index.php?rid=1007056&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17981207%26dopt%3DAbstract Authors: Nimmerjahn F, Ravetch JV Receptors for immunoglobulins [Fc-receptors (FcRs)] are widely expressed throughout the immune system. By binding to the antibody Fc-portion, they provide a link between the specificity of the adaptive immune system and the powerful effector functions triggered by innate immune effector cells. By virtue of coexpression of activating and inhibitory FcRs on the same cell, they set a threshold for immune cell activation by immune complexes (ICs). Besides their involvement in the efferent phase of an immune response, they are also important for modulating adaptive immune responses by regulating B cell and dendritic cell (DC) activation. Deletion of the inhibitory FcR leads to the loss of tolerance in the humoral immune system and the development of autoimm... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=1007056 Tue, 06 Nov 2007 14:24:31 +0100 1007056 http://www.medworm.com/index.php?rid=882352&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17869609%26dopt%3DAbstract Authors: Monroe JG, Dorshkind K In adult mammals, bone marrow pluripotent hematopoietic stem cells generate B lymphoid-specified progeny that progress through a series of well-characterized stages before generating B-cell receptor expressing B lymphocytes. These functionally immature B lymphocytes then migrate to the spleen wherein they differentiate through transitional stages into follicular or marginal zone B lymphocytes capable of responding to T-dependent and -independent antigens, respectively. During the terminal stages of B lymphocyte development in the bone marrow, as well as immediately following egress into the peripheral compartments, B lymphocytes are counterselected to eliminate B lymphocytes with potentially dangerous self-reactivity. These developmental and selection ev... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=882352 Wed, 19 Sep 2007 01:06:19 +0100 882352 http://www.medworm.com/index.php?rid=882351&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17869610%26dopt%3DAbstract Authors: Carneiro-Sampaio M, Coutinho A The recent progress in the genetic characterization of many primary immunodeficiencies (PIDs) allows for a better understanding of immune molecular and cellular mechanisms. The present chapter discusses associations between PIDs and autoimmune diseases (AIDs) in this new light. PIDs are classified according to the frequency of association with AIDs, defining four groups of conditions: systematic (more than 80% of all patients), strong (10-80%), mild (less than 10%), and absent (no available descriptions). Several general conclusions could be drawn: (1) pathological autoimmune (AI) manifestations are very frequently associated with PIDs, indicating that, contrary to conventional notions, antimicrobial protection and natural tolerance to body tissu... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=882351 Wed, 19 Sep 2007 01:06:19 +0100 882351 http://www.medworm.com/index.php?rid=882350&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17869611%26dopt%3DAbstract Authors: Wardemann H, Nussenzweig MC Two mechanisms account for generation of the human antibody repertoire; V(D)J recombination during the early stages of B-cell development in the bone marrow and somatic mutation of immunoglobulin genes in mature B cells responding to antigen in the periphery. V(D)J recombination produces diversity by random joining of gene segments and somatic mutation by introducing random point mutations. Both are required to attain the degree of antigen receptor diversification that is necessary for immune protection: defects in either mechanism are associated with increased susceptibility to infection. However, the downside of producing enormous random diversity in the antibody repertoire is the generation of autoantibodies. To prevent autoimmunity B cells expre... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=882350 Wed, 19 Sep 2007 01:06:19 +0100 882350 http://www.medworm.com/index.php?rid=882349&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17869612%26dopt%3DAbstract Authors: Hünig T Suppressor or "regulatory" CD4 T cells play a key role in the control of autoimmunity and overshooting immune responses to foreign antigens, but can also obstruct effective anticancer therapies. The homeostasis and activation of these regulatory T cells (Treg cells) is tightly connected to that of effector CD4 T cells via the costimulatory receptor CD28 and the cytokine IL-2: Both subsets require costimulation to be activated by antigen, and Treg cells additionally depend on IL-2 produced by effector CD4 T cells in a costimulation-dependent fashion. Depending on the therapeutic aim, blockade, or stimulation of CD28 with monoclonal antibodies (mAb) can therefore profoundly affect the size and activity of the Treg compartment. In this chapter, experiments performed ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=882349 Wed, 19 Sep 2007 01:06:19 +0100 882349 http://www.medworm.com/index.php?rid=882348&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17869613%26dopt%3DAbstract Authors: David JP Osteoimmunology can be defined in a very broad sense as the field of research focusing on interrelations between bone and the immune system. This is a rather opened field that covers at least three different issues. The first one is developmental, that is, organogenesis of the bones and immune systems. The second is post-developmental, that is, the role of the bone in the regulation of the immune response and role of the immune cells on the regulation of bone homeostasis. The third one is related to pathologies: Can immune cells be involved in the development of bone-related pathology? Can deregulation of the bone be causing immune-related diseases? I will not review in detail the bibliography covering osteoimmunology. This has been extensively done in Immunological R... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=882348 Wed, 19 Sep 2007 01:06:19 +0100 882348 http://www.medworm.com/index.php?rid=882347&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17869614%26dopt%3DAbstract Authors: Pejler G, Abrink M, Ringvall M, Wernersson S Mast cells (MCs) are traditionally thought of as a nuisance for its host, for example, by causing many of the symptoms associated with allergic reactions. In addition, recent research has put focus on MCs for displaying harmful effects during various autoimmune disorders. On the other hand, MCs can also be beneficial for its host, for example, by contributing to the defense against insults such as bacteria, parasites, and snake venom toxins. When the MC is challenged by an external stimulus, it may respond by degranulation. In this process, a number of powerful preformed inflammatory "mediators" are released, including cytokines, histamine, serglycin proteoglycans, and several MC-specific proteases: chymases, tryptases, and carboxyp... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=882347 Wed, 19 Sep 2007 01:06:19 +0100 882347 http://www.medworm.com/index.php?rid=673860&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560269%26dopt%3DAbstract Authors: Alt FW, Honjo T PMID: 17560269 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673860 Sun, 17 Jun 2007 08:03:12 +0100 673860 http://www.medworm.com/index.php?rid=673859&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560270%26dopt%3DAbstract Authors: Muramatsu M, Nagaoka H, Shinkura R, Begum NA, Honjo T Discovery of activation-induced cytidine deaminase (AID) paved a new path to unite two genetic alterations induced by antigen stimulation; class switch recombination (CSR) and somatic hypermutation (SHM). AID is now established to cleave specific target DNA and to serve as engraver of these genetic alterations. AID of a 198-residue protein has four important domains: nuclear localization signal and SHM-specific region at the N-terminus; the alpha-helical segment (residue 47-54) responsible for dimerization; catalytic domain (residues 56-94) shared by all the other cytidine deaminase family members; and nuclear export signal overlapping with class switch-specific domain at the C-terminus. Two alternative models have been pro... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673859 Sun, 17 Jun 2007 08:03:12 +0100 673859 http://www.medworm.com/index.php?rid=673858&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560271%26dopt%3DAbstract Authors: Conticello SG, Langlois MA, Yang Z, Neuberger MS The activation-induced cytidine deaminase (AID)/apolipoprotein B RNA-editing catalytic component (APOBEC) family is a vertebrate-restricted subgrouping of a superfamily of zinc (Zn)-dependent deaminases that has members distributed throughout the biological world. AID and APOBEC2 are the oldest family members with APOBEC1 and the APOBEC3s being later arrivals restricted to placental mammals. Many AID/APOBEC family members exhibit cytidine deaminase activity on polynucleotides, although in different physiological contexts. Here, we examine the AID/APOBEC proteins in the context of the entire Zn-dependent deaminase superfamily. On the basis of secondary structure predictions, we propose that the cytosine and tRNA deaminases are li... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673858 Sun, 17 Jun 2007 08:03:12 +0100 673858 http://www.medworm.com/index.php?rid=673857&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560272%26dopt%3DAbstract Authors: Ramiro A, San-Martin BR, McBride K, Jankovic M, Barreto V, Nussenzweig A, Nussenzweig MC Although B and T lymphocytes are similar in many respects including diversification of their antigen receptor genes by V(D)J recombination, 95% of all lymphomas diagnosed in the western world are of B-cell origin. Many of these are derived from mature B cells [Kuppers, R. (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer 5, 251-262] and display hallmark chromosome translocations involving immunoglobulin genes and a proto-oncogene partner whose expression becomes deregulated as a result of the translocation reaction [Kuppers, R. (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer 5, 251-262; Kuppers, R., and Dalla-Favera, R. (2001). Mechanisms of chromoso... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673857 Sun, 17 Jun 2007 08:03:12 +0100 673857 http://www.medworm.com/index.php?rid=673856&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560273%26dopt%3DAbstract Authors: Yang SY, Schatz DG After their assembly by V(D)J recombination, immunoglobulin (Ig) genes undergo somatic hypermutation, gene conversion, and class switch recombination to generate additional antibody diversity. The three diversification processes depend on activation-induced cytidine deaminase (AID) and are tightly linked to transcription. The reactions occur primarily on Ig genes and the molecular mechanisms that underlie their targeting to Ig loci have been of intense interest. In this chapter, we discuss the evidence linking transcription and transcriptional control elements to the three diversification pathways, and we consider how various features of chromatin could render parts of the genome permissive for AID-mediated sequence diversification. PMID: 17560273 [PubMe... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673856 Sun, 17 Jun 2007 08:03:12 +0100 673856 http://www.medworm.com/index.php?rid=673855&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560274%26dopt%3DAbstract Authors: Goodman MF, Scharff MD, Romesberg FE Exposure brings risk to all living organisms. Using a remarkably effective strategy, higher vertebrates mitigate risk by mounting a complex and sophisticated immune response to counter the potentially toxic invasion by a virtually limitless army of chemical and biological antagonists. Mutations are almost always deleterious, but in the case of antibody diversification there are mutations occurring at hugely elevated rates within the variable (V) and switch regions (SR) of the immunoglobulin (Ig) genes that are responsible for binding to and neutralizing foreign antigens throughout the body. These mutations are truly purposeful. This chapter is centered on activation-induced cytidine deaminase (AID). AID is required for initiating somatic hy... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673855 Sun, 17 Jun 2007 08:03:12 +0100 673855 http://www.medworm.com/index.php?rid=673854&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560275%26dopt%3DAbstract We present a model for CSR in which transcription through S regions provides DNA substrates on which AID can generate DSB-inducing lesions. We also discuss how phosphorylation of AID may mediate interactions with cofactors that facilitate access to transcribed S regions during CSR and transcribed variable regions during the related process of somatic hypermutation (SHM). Finally, in the context of this CSR model, we further discuss current findings that suggest synapsis and joining of S region DSBs during CSR have evolved to exploit general mechanisms that function to join widely separated chromosomal DSBs. PMID: 17560275 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673854 Sun, 17 Jun 2007 08:03:12 +0100 673854 http://www.medworm.com/index.php?rid=673853&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560276%26dopt%3DAbstract Authors: Rosenberg BR, Papavasiliou FN As the primary effector of immunoglobulin somatic hypermutation (SHM) and class switch recombination (CSR), activation-induced cytidine deaminase (AID) serves an important function in the adaptive immune response. Recent advances have demonstrated that AID and a group of closely related cytidine deaminases, the APOBEC3 proteins, also act in the innate host response to viral infection. Antiviral activity was first attributed to APOBEC3G as a potent inhibitor of HIV. It is now apparent that the targets of the APOBEC3 proteins extend beyond HIV, with family members acting against a wide variety of viruses as well as host-encoded retrotransposable genetic elements. Although it appears to function through a different mechanism, AID also possesses antiv... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673853 Sun, 17 Jun 2007 08:03:12 +0100 673853 http://www.medworm.com/index.php?rid=673852&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560277%26dopt%3DAbstract Authors: Okazaki IM, Kotani A, Honjo T A hallmark of mature B-cell lymphomas is reciprocal chromosomal translocations involving the Ig locus and a proto-oncogene, which usually result in the deregulated, constitutive expression of the translocated gene. In addition to such translocations, proto-oncogenes are frequently hypermutated in germinal center (GC)-derived B-cell lymphomas. Although aberrant, mistargeted class switch recombination (CSR) and somatic hypermutation (SHM) events have long been suspected of causing chromosomal translocations and mutations in oncogenes, and thus of playing a critical role in the pathogenesis of most B-cell lymphomas, the molecular basis for such deregulation of CSR and SHM is only beginning to be elucidated by recent genetic approaches. The tumorigeni... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673852 Sun, 17 Jun 2007 08:03:12 +0100 673852 http://www.medworm.com/index.php?rid=673851&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17560278%26dopt%3DAbstract Authors: Durandy A, Taubenheim N, Peron S, Fischer A B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies, previously termed hyper-IgM syndromes, are genetically determined conditions characterized by normal or elevated serum IgM levels and an absence or very low levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the defective CSR is variably associated to a defect in the generation of somatic hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies contributed to a better delineation of the mechanisms underlying CSR and SHM, the major events of antigen-triggered antibody maturation. Four Ig-CSR deficiency phenotypes have been so far reported: the description of the activation-induced cytidine deaminase (AID) defi... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=673851 Sun, 17 Jun 2007 08:03:12 +0100 673851 http://www.medworm.com/index.php?rid=504196&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17383538%26dopt%3DAbstract Authors: Pan-Hammarström Q, Zhao Y, Hammarström L Humans and mice separated more than 60 million years ago. Since then, evolution has led to a multitude of changes in their genomic sequences. The divergence of genes has resulted in differences both in the innate and adaptive immune systems. In this chapter, we focus on species difference with regard to immunoglobulin class switch recombination (CSR). We have compared the immunoglobulin constant region gene loci from human and mouse, with an emphasis on the switch regions, germ line transcription promoters, and 3' enhancers. We have also compared pathways/factors that are involved in CSR. Although there are remarkable similarities in the cellular machinery involved in CSR, there are also a number of unique features in each species. ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=504196 Tue, 27 Mar 2007 22:32:02 +0100 504196 http://www.medworm.com/index.php?rid=504195&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17383539%26dopt%3DAbstract Authors: Chang TW, Wu PC, Hsu CL, Hung AF The pharmacological purposes of the anti-IgE therapy are to neutralize IgE and to inhibit its production to attenuate type I hypersensitivity reactions. The therapy is based on humanized IgG1antibodies that bind to free IgE and to membrane-bound IgE on B cells, but not to IgE bound by the high-affinity IgE.Fc receptors on basophils and mast cells or by the low-affinity IgE.Fc receptors on B cells. After nearly 20 years since inception, therapeutic anti-IgE antibodies (anti-IgE) have been studied in about 30 Phase II and III clinical trials in many allergy indications, and a lead antibody, omalizumab, has been approved for treating patients (12 years and older) with moderate-to-severe allergic asthma. Anti-IgE has confirmed the roles of IgE in t... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=504195 Tue, 27 Mar 2007 22:32:02 +0100 504195 http://www.medworm.com/index.php?rid=504194&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17383540%26dopt%3DAbstract Authors: Kikutani H, Suzuki K, Kumanogoh A The semaphorin family consists of soluble and membrane-bound proteins originally identified as axonal guidance cues functioning during neuronal development. However, it is becoming increasingly clear that semaphorins play diverse roles in organogenesis, vascular growth, and tumor progression. In addition, emerging evidence indicates that several semaphorins, called "immune semaphorins," play crucial roles also during immune responses. Extensive studies on the immune semaphorins have revealed not only parallels but also differences in the semaphorin functions between the immune and nervous systems, providing unexpected but meaningful insights into the biological activities of these molecules. This chapter focuses on our current understanding of... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=504194 Tue, 27 Mar 2007 22:32:02 +0100 504194 http://www.medworm.com/index.php?rid=504193&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17383541%26dopt%3DAbstract Authors: Felices M, Falk M, Kosaka Y, Berg LJ The Tec family of tyrosine kinases consists of five members (Itk, Rlk, Tec, Btk, and Bmx) that are expressed predominantly in hematopoietic cells. The exceptions, Tec and Bmx, are also found in endothelial cells. Tec kinases constitute the second largest family of cytoplasmic protein tyrosine kinases. While B cells express Btk and Tec, and T cells express Itk, Rlk, and Tec, all four of these kinases (Btk, Itk, Rlk, and Tec) can be detected in mast cells. This chapter will focus on the biochemical and cell biological data that have been accumulated regarding Itk, Rlk, Btk, and Tec. In particular, distinctions between the different Tec kinase family members will be highlighted, with a goal of providing insight into the unique functions of eac... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=504193 Tue, 27 Mar 2007 22:32:02 +0100 504193 http://www.medworm.com/index.php?rid=504192&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17383542%26dopt%3DAbstract Authors: Kinashi T High trafficking capability of lymphocytes is crucial in immune surveillance and antigen responses. Central to this regulatory process is a dynamic control of lymphocyte adhesion behavior regulated by chemokines and adhesion receptors such as integrins. Modulation of lymphocyte adhesive responses occurs in a wide range of time window from less than a second to hours, enabling rolling lymphocyte to attach to and migrate through endothelium and interact with antigen-presenting cells. While there has been a rapid progress in the understanding of integrin structure, elucidation of signaling events to relay extracellular signaling to integrins in physiological contexts has recently emerged from studies using gene-targeting and gene-silencing technique. Regulatory molecule... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=504192 Tue, 27 Mar 2007 22:32:02 +0100 504192 http://www.medworm.com/index.php?rid=504191&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17383543%26dopt%3DAbstract Authors: Minato N, Kometani K, Hattori M Rap1 (Ras-proximity 1), a member of the Ras family of small guanine triphosphatases (GTPases), is activated by diverse extracellular stimuli. While Rap1 has been discovered originally as a potential Ras antagonist, accumulating evidence indicates that Rap1 per se mediates unique signals and exerts biological functions distinctly different from Ras. Rap1 plays a dominant role in the control of cell-cell and cell-matrix interactions by regulating the function of integrins and other adhesion molecules in various cell types. Rap1 also regulates MAP kinase (MAPK) activity in a manner highly dependent on the context of cell types. Recent studies (including gene-targeting analysis) have uncovered that the Rap1 signal is integrated crucially and unpredi... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=504191 Tue, 27 Mar 2007 22:32:02 +0100 504191 http://www.medworm.com/index.php?rid=504189&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17383544%26dopt%3DAbstract Authors: Hammad H, Lambrecht BN Dendritic cells (DCs) are crucial in regulating the immune response by bridging innate and adaptive immunity. DCs are constantly migrating from the blood to the lungs and from the lungs to the draining lymph nodes. How DCs populate the lung in the absence of inflammation and how they are recruited there during inflammation remain unclear. Since DCs play a central role in immune responses, both under steady-state and inflammatory conditions, detailed characterization of their migratory behavior may be essential for the development of future therapeutic strategies. PMID: 17383544 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=504189 Tue, 27 Mar 2007 22:32:02 +0100 504189 http://www.medworm.com/index.php?rid=392819&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16682271%26dopt%3DAbstract Authors: Stoecklin G, Anderson P The inflammatory response is a complex physiologic process that requires the coordinate induction of cytokines, chemokines, angiogenic factors, effector-enzymes, and proteases. Although transcriptional activation is required to turn on the inflammatory response, recent studies have revealed that posttranscriptional mechanisms play an important role by determining the rate at which mRNAs encoding inflammatory effector proteins are translated and degraded. Most posttranscriptional control mechanisms function to dampen the expression of pro-inflammatory proteins to ensure that potentially injurious proteins are not overexpressed during an inflammatory response. Here we discuss the factors that regulate the stability and translation of mRNAs encoding pro-in... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392819 Sun, 01 Jan 2006 07:00:00 +0100 392819 http://www.medworm.com/index.php?rid=392816&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16682272%26dopt%3DAbstract Authors: Daëron M, Lesourne R Cell activation results from the transient displacement of an active balance between positive and negative signaling. This displacement depends in part on the engagement of cell surface receptors by extracellular ligands. Among these are receptors for the Fc portion of immunoglobulins (FcRs). FcRs are widely expressed by cells of hematopoietic origin. When binding antibodies, FcRs provide these cells with immunoreceptors capable of triggering numerous biological responses in response to a specific antigen. FcR-dependent cell activation is regulated by negative signals which are generated together with positive signals within signalosomes that form upon FcR engagement. Many molecules involved in positive signaling, including the FcRbeta subunit, the src ki... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392816 Sun, 01 Jan 2006 07:00:00 +0100 392816 http://www.medworm.com/index.php?rid=392813&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16682273%26dopt%3DAbstract Authors: Moody DB CD1 proteins have been conserved throughout mammalian evolution and function to present lipid antigens to T cells. Crystal structures of CD1-lipid complexes show that CD1 antigen-binding grooves are composed of four pockets and two antigen entry portals. This structural information now provides a detailed understanding of how CD1-binding grooves capture a surprisingly diverse array of lipid ligands. CD1-expressing APCs are able to acquire lipid antigens from their own pool of lipids and from exogenous sources, including microbial pathogens, bystander cells, or even the systemic circulation. CD1 proteins bind to certain antigens using high stringency loading reactions within endosomes that involve low pH, glycosidases, and lipid transfer proteins. Other antigens can di... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392813 Sun, 01 Jan 2006 07:00:00 +0100 392813 http://www.medworm.com/index.php?rid=392810&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16682274%26dopt%3DAbstract Authors: Lin DA, Boyce JA Lysophospholipids (LPLs) are lipid-derived signaling molecules exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). Originally identified as serum-associated growth factors, these mediators now are known to signal through a family of diverse G protein-coupled receptors (GPCRs). Virtually all cells that participate in the immune response express multiple receptors for LPLs. The development of antibody reagents that recognize the receptors for each LPL and the derivation of receptor-selective agonists and receptor-null mouse strains have provided insights into the widely diverse functions of LPLs in immune responses, particularly the role of S1P in lymphocyte trafficking. This review focuses on the biology of the LPLs as these molecules ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392810 Sun, 01 Jan 2006 07:00:00 +0100 392810 http://www.medworm.com/index.php?rid=392807&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16682275%26dopt%3DAbstract Authors: Robyn J, Metcalfe DD Systemic mastocytosis is a fascinating disease with diverse clinical features. There have been numerous advances in understanding the basis of clinical manifestations of this disease and of its molecular pathogenesis in the last several decades. The development of methods to study mast cell biology using cell culture and murine models has proven invaluable in this regard. Clarification of the roles of mast cells in various biological processes has expanded our understanding of their importance in innate immunity, as well as allergy. New diagnostic methods have allowed the design of detailed criteria to assist in distinguishing reactive mast cell hyperplasia from systemic mastocytosis. Variants and subvariants of systemic mastocytosis have been defined to a... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392807 Sun, 01 Jan 2006 07:00:00 +0100 392807 http://www.medworm.com/index.php?rid=392804&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16682276%26dopt%3DAbstract Authors: Lupher ML, Gallatin WM Inflammation and fibrosis are two inter-related conditions with many overlapping mechanisms. Three specific cell types, macrophages, T helper cells, and myofibroblasts, each play important roles in regulating both processes. Following tissue injury, an inflammatory stimulus is often necessary to initiate tissue repair, where cytokines released from resident and infiltrating leukocytes stimulate proliferation and activation of myofibroblasts. However, in many cases this drive stimulates an inappropriate pro-fibrotic response. In addition, activated myofibroblasts can take on the role of traditional APCs, secrete pro-inflammatory cytokines, and recruit inflammatory cells to fibrotic foci, amplifying the fibrotic response in a vicious cycle. Moreover, infla... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392804 Sun, 01 Jan 2006 07:00:00 +0100 392804 http://www.medworm.com/index.php?rid=392801&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16682277%26dopt%3DAbstract Authors: Diamond B, Kowal C, Huerta PT, Aranow C, Mackay M, DeGiorgio LA, Lee J, Triantafyllopoulou A, Cohen-Solal J, Volpe BT Classic immunologic teaching describes the brain as an immunologically privileged site. Studies of neuroimmunology have focused for many years almost exclusively on multiple sclerosis, a disease in which inflammatory cells actually infiltrate brain tissue, and the rodent model of this disease, experimental allergic encephalitis. Over the past decade, however, increasingly, brain-reactive antibodies have been demonstrated in the serum of patients with numerous neurological diseases. The contribution these antibodies make to neuronal dysfunction has, in general, not been determined. Here, we describe recent studies showing that serum antibodies to the N-methyl-D-... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392801 Sun, 01 Jan 2006 07:00:00 +0100 392801 http://www.medworm.com/index.php?rid=392798&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16682278%26dopt%3DAbstract Authors: Notarangelo LD, Gambineri E, Badolato R Far from being mutually exclusive, immunodeficiency and autoimmunity may occur simultaneously. During the last years, analysis of Autoimmune Polyendocrinopathy--Candidiasis--Ectodermal Dystrophy (APECED) and Immunodysregulation--Polyendocrinopathy--Enteropathy--X-linked (IPEX), two rare monogenic forms of immunodeficiency associated with autoimmunity, has led to the identification of Auto Immune Regulator (AIRE) and Forkhead Box P3 (FOXP3), essential transcriptional regulators, involved in central tolerance and peripheral immune homeostasis, respectively. Characterization of the molecular and cellular mechanisms involved in APECED, and recognition that AIRE expression is sustained by effective thymopoiesis, has recently allowed to define... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392798 Sun, 01 Jan 2006 07:00:00 +0100 392798 http://www.medworm.com/index.php?rid=392794&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730259%26dopt%3DAbstract Authors: PMID: 16730259 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392794 Sun, 01 Jan 2006 07:00:00 +0100 392794 http://www.medworm.com/index.php?rid=392791&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730260%26dopt%3DAbstract Authors: Smyth MJ, Dunn GP, Schreiber RD Cellular transformation and tumor development result from an accumulation of mutational and epigenetic changes that alter normal cell growth and survival pathways. For the last 100 years, there has been a vigorous debate as to whether the unmanipulated immune system can detect and eliminate such altered host derived cells despite the fact that cancer cells frequently express either abnormal proteins or abnormal levels of normal cellular proteins that function as tumor antigens. In this review, we discuss the current state of this argument and point out some of the recent key experiments demonstrating that immunity not only protects the host from cancer development (i.e., provides a cancer immunosurveillance function) but also can promote tumor g... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392791 Sun, 01 Jan 2006 07:00:00 +0100 392791 http://www.medworm.com/index.php?rid=392788&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730261%26dopt%3DAbstract Authors: Drake CG, Jaffee E, Pardoll DM In the past decade, basic studies in animal models have begun to elucidate the physiological barriers which impede a successful antitumor immune response. These barriers operate at a number of levels, and involve the tumor, the tumor microenvironment and various components of the innate and adaptive immune systems. In this review, we discuss the multiple mechanisms by which tumors evade an immune response, with an emphasis on clinically relevant strategies to overcome these inhibitory checkpoints. PMID: 16730261 [PubMed - in process] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392788 Sun, 01 Jan 2006 07:00:00 +0100 392788 http://www.medworm.com/index.php?rid=392785&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730262%26dopt%3DAbstract Authors: Waldmann TA, Morris JC Monoclonal antibodies are among the most rapidly expanding class of therapeutics for cancer treatment. Monoclonal antibodies targeting non-Hodgkin's lymphoma (NHL), Her-2/neu highly expressing metastatic breast cancer, colorectal cancer, acute myelogenous leukemia, and B-cell chronic lymphocytic leukemia (CLL) have received FDA approval. Promising new targets for antibody therapy include cellular growth factor receptors, mediators of tumor-driven neo-angiogenesis, as well as host negative immunoregulatory checkpoints that impede an effective immune response to neoplasia. Antibody efficacy has been increased by genetic engineering to humanize the antibodies and to increase their effector functions including antibody dependent cellular cytotoxicity. Furthe... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392785 Sun, 01 Jan 2006 07:00:00 +0100 392785 http://www.medworm.com/index.php?rid=392782&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730263%26dopt%3DAbstract Authors: Wu CJ, Ritz J The curative potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for many hematologic malignancies derives in large part from reconstitution of normal donor immunity and the development of a potent graft-versus-leukemia (GVL) immune response capable of rejecting tumor cell in vivo. Elucidation of the mechanisms of GVL by studies of animal models and analysis of clinical data has yielded important insights into how clinically effective tumor immunity is generated following allo-HSCT. These studies have identified NK cells and B cells as well as T cells as important mediators of the GVL response. A variety of antigenic targets of the GVL response have also been identified, and include tumor-associated antigens as well as minor histocompatibi... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392782 Sun, 01 Jan 2006 07:00:00 +0100 392782 http://www.medworm.com/index.php?rid=392779&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730264%26dopt%3DAbstract Authors: Cavallo F, Offringa R, van der Burg SH, Forni G, Melief CJ Two approaches to immunological intervention in tumor-host interactions in mouse models are discussed in this review. The first is described with reference to experiments in which CD8(+) T lymphocytes are used to kill established transplantable tumors. Peptides and their optimal presentation by dendritic cells and intervention in immune regulatory mechanisms are the key issues for efficient induction of T-killer cell-mediated tumor eradication. The time frame of tumor therapy and the threat imposed by tumor growth in transplantable models and cancer patients require the induction of a robust T-cell reaction. Prevention of the progression of small preneoplastic lesions, on the other hand, requires the significant and pr... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392779 Sun, 01 Jan 2006 07:00:00 +0100 392779 http://www.medworm.com/index.php?rid=392776&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730265%26dopt%3DAbstract Authors: Uchi H, Stan R, Turk MJ, Engelhorn ME, Rizzuto GA, Goldberg SM, Wolchok JD, Houghton AN A relationship between melanoma and vitiligo, a skin disorder characterized by the loss of melanocytes, has been postulated for many decades. In some cases, vitiligo is almost certainly a manifestation of autoimmune-mediated destruction of melanocytes. Melanocytes and melanoma cells share melanocyte differentiation antigens. Based on a number of observations, de novo vitiligo developing in patients with melanoma has been regarded as a sign of good prognosis. The immune system tolerates or ignores differentiation antigens because these antigens are self-derived. Therefore, immune tolerance or ignorance must be overcome to prime naive T and B cells to induce cancer immunity and autoimmunity a... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392776 Sun, 01 Jan 2006 07:00:00 +0100 392776 http://www.medworm.com/index.php?rid=392773&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730266%26dopt%3DAbstract Authors: Slingluff CL, Chianese-Bullock KA, Bullock TN, Grosh WW, Mullins DW, Nichols L, Olson W, Petroni G, Smolkin M, Engelhard VH The development of effective immune therapy for cancer is a central goal of immunologists in the 21st century. Our laboratories have been deeply involved in characterization of the immune response to melanoma and translation of laboratory discoveries into clinical trials. We have identified a cohort of peptide antigens presented by Major Histocompatibility Complex (MHC) molecules on melanoma cells and widely recognized by T cells from melanoma patients. These have been incorporated into peptide-based vaccines that induce CD8(+) and CD4(+) T-cell responses in 80-100% of patients. Major objective clinical tumor regressions have been observed in some patient... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392773 Sun, 01 Jan 2006 07:00:00 +0100 392773 http://www.medworm.com/index.php?rid=392770&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730267%26dopt%3DAbstract Authors: Korman AJ, Peggs KS, Allison JP The progression of a productive immune response requires that a number of immunological checkpoints be passed. Passage may require the presence of excitatory costimulatory signals or the avoidance of negative or coinhibitory signals, which act to dampen or terminate immune activity. The immunoglobulin superfamily occupies a central importance in this coordination of immune responses, and the CD28/cytotoxic T-lymphocyte antigen-4 (CTLA-4):B7.1/B7.2 receptor/ligand grouping represents the archetypal example of these immune regulators. In part the role of these checkpoints is to guard against the possibility of unwanted and harmful self-directed activities. While this is a necessary function, aiding in the prevention of autoimmunity, it may act as ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392770 Sun, 01 Jan 2006 07:00:00 +0100 392770 http://www.medworm.com/index.php?rid=392767&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16730268%26dopt%3DAbstract Authors: Hodi FS, Dranoff G The formulation of therapeutic strategies to enhance immune-mediated tumor destruction is a central goal of cancer immunology. Substantive progress toward delineating the mechanisms involved in innate and adaptive tumor immunity has improved the prospects for crafting efficacious treatments. Schemes under active clinical evaluation include cancer vaccines, monoclonal antibodies, recombinant cytokines, and adoptive cellular infusions. While these manipulations increase tumor immunity in many patients, the majority still succumbs to progressive disease. Detailed analysis of subjects on experimental protocols together with informative studies of murine tumor models have begun to clarify the parameters that determine therapeutic activity and resistance. These in... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392767 Sun, 01 Jan 2006 07:00:00 +0100 392767 http://www.medworm.com/index.php?rid=392764&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16938537%26dopt%3DAbstract Authors: Casadevall A, Pirofski LA Sometime in the mid to late twentieth century the study of antibody-mediated immunity (AMI) entered the doldrums, as many immunologists believed that the function of AMI was well understood, and was no longer deserving of intensive investigation. However, beginning in the 1990s studies using monoclonal antibodies (mAbs) revealed new functions for antibodies, including direct antimicrobial effects and their ability to modify host inflammatory and cellular responses. Furthermore, the demonstration that mAbs to several intracellular bacterial and fungal pathogens were protective issued a serious challenge to the paradigm that host defense against such microbes was strictly governed by cell-mediated immunity (CMI). Hence, a new view of AMI is emerging. Th... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392764 Sun, 01 Jan 2006 07:00:00 +0100 392764 http://www.medworm.com/index.php?rid=392759&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16938538%26dopt%3DAbstract Authors: Cobb RM, Oestreich KJ, Osipovich OA, Oltz EM Mammals contend with a universe of evolving pathogens by generating an enormous diversity of antigen receptors during lymphocyte development. Precursor B and T cells assemble functional immunoglobulin (Ig) and T cell receptor (TCR) genes via recombination of numerous variable (V), diversity (D), and joining (J) gene segments. Although this combinatorial process generates significant diversity, genetic reorganization is inherently dangerous. Thus, V(D)J recombination must be tightly regulated to ensure proper lymphocyte development and avoid chromosomal translocations that cause lymphoid tumors. Each genomic rearrangement is mediated by a common V(D)J recombinase that recognizes sequences flanking all antigen receptor gene segments. ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392759 Sun, 01 Jan 2006 07:00:00 +0100 392759 http://www.medworm.com/index.php?rid=392753&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16938539%26dopt%3DAbstract Authors: Staunton DE, Lupher ML, Liddington R, Gallatin WM Initially linked to the pathogenesis of inflammatory and hematologic diseases, integrins have become validated drug targets with the approval of five drugs. Moreover, there are several promising drug candidates in preclinical and clinical stages of development for multiple clinical indications. Integrins are attractive drug targets as their antagonism can block several steps in disease progression or maintenance. Integrin inhibitors can block the proliferation, migration, or tissue localization of inflammatory, angiogenic, and tumor cells, as well as signaling and gene expression contributing to disease. There has been a rapid increase in the elucidation of integrin structure, their allosteric mechanisms of bidirectional signal... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392753 Sun, 01 Jan 2006 07:00:00 +0100 392753 http://www.medworm.com/index.php?rid=392747&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16938540%26dopt%3DAbstract Authors: Wagner H Based on an evolutionary conserved repertoire Toll-like-receptors (TLRs) donate specificity to innate immune cells. Therefore, TLRs are considered as paradigmatic for "self" versus "non-self" discrimination. This view, however, needs to be modified since TLR's also appear to recognise "endogeneous", that is host-derived ligands, examples being host-derived DNA and -RNA. Here I discuss physiological and pathophysiological consequences of endogeneous ligand-recognition by TLRs. I conclude that endogeneous ligand recognition by TLRs drives sterile inflammation sustained by innate immune cells in certain autoimmune disorders. PMID: 16938540 [PubMed - indexed for MEDLINE] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392747 Sun, 01 Jan 2006 07:00:00 +0100 392747 http://www.medworm.com/index.php?rid=392742&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16938541%26dopt%3DAbstract Authors: Hoebe K, Jiang Z, Tabeta K, Du X, Georgel P, Crozat K, Beutler B The inflammatory response to microbes--and host perception of microbes in general--is largely initiated by a single class of receptors, named for their similarity to the prototypic Toll receptor of Drosophila. The mammalian Toll-like receptors (TLRs) are ultimately responsible for most phenomena associated with infection. This includes both "good" effects of infection (e.g., the induction of lasting specific immunity to an infectious agent) and "bad" effects of infection (systemic inflammation and shock). Although they are essential for host defense, no other endogenous proteins can match their lethal potential. The TLR complexes transduce the toxicity of lipopolysaccharide (LPS), cysteinyl lipopeptides, and many... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392742 Sun, 01 Jan 2006 07:00:00 +0100 392742 http://www.medworm.com/index.php?rid=392738&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16938542%26dopt%3DAbstract Authors: Kuchroo VK, Meyers JH, Umetsu DT, DeKruyff RH T cells on activation differentiate into different subsets (Th1 or Th2) with distinct effector functions. These T cell subsets are primarily differentiated on the basis of the cytokines that they produce, however, we have identified a novel gene family called TIM (T cell, immunoglobulin, mucin domain-containing molecules), whose members are differentially expressed on Th1 and Th2 cells. Three of the family members (Tim-1, Tim-3, and Tim-4) are conserved between mouse and man. Genomic association of the TIM family and polymorphisms in both Tim-1 and Tim-3 in different immune-mediated diseases suggest that the family may have an important role in regulating immunity, both in terms of normal immune responses and in diseases like autoi... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392738 Sun, 01 Jan 2006 07:00:00 +0100 392738 http://www.medworm.com/index.php?rid=392734&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16938543%26dopt%3DAbstract Authors: Katz HR The immune system must effectively regulate the balance between beneficial and detrimental inflammation. This process is achieved in part through cell surface receptors that rapidly integrate activating and inhibitory signals. The inhibitory members of the leukocyte Ig-like receptor (LILR) family, termed LILRBs, are broadly distributed among cell populations in the immune system and potently counterregulate cell activation induced by stimuli of innate and adaptive immune responses. Studies in mice and humans indicate that LILRBs appreciably downregulate harmful inflammatory responses induced by microbial, allergic, and cytotoxic mechanisms. Hence, the LILRBs likely play significant roles in regulating the incidence and severity of many inflammatory diseases, making the... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392734 Sun, 01 Jan 2006 07:00:00 +0100 392734 http://www.medworm.com/index.php?rid=392730&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17145301%26dopt%3DAbstract Authors: Fairhurst AM, Wandstrat AE, Wakeland EK Systemic lupus erythematosus (SLE) is a complex polygenic autoimmune disease characterized by the presence of anti-nuclear autoantibodies (ANAs) that are often detectable years prior to the onset of clinical disease. The disease is associated with a chronic activation of the immune system, with the most severe forms progressing to inflammatory damage that can impact multiple organ systems in afflicted individuals. Current therapeutic strategies poorly control disease manifestations and are generally immunosuppressive. Recent studies in human patient populations and animal models have associated elements of the innate immune system and abnormalities in the immature B lymphocyte receptor repertoires with disease initiation. A variety of cy... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392730 Sun, 01 Jan 2006 07:00:00 +0100 392730 http://www.medworm.com/index.php?rid=392722&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17145302%26dopt%3DAbstract Authors: Wick G, Andersson L, Hala K, Gershwin ME, Selmi C, Erf GF, Lamont SJ, Sgonc R Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible anymore. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models--albeit rare--reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present chapter describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroid... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392722 Sun, 01 Jan 2006 07:00:00 +0100 392722 http://www.medworm.com/index.php?rid=392717&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17145303%26dopt%3DAbstract Authors: Levings MK, Allan S, d'Hennezel E, Piccirillo CA A network of regulatory T (Treg) cells exists to downregulate immune responses in various inflammatory circumstances and ultimately assure peripheral T cell tolerance. Naturally occurring CD4(+)CD25(+) Treg cell represents a major lymphocyte population engaged in the dominant control of self-reactive T responses and maintenance of tolerance within this network. CD4(+)CD25(+) Treg cells differentiate in the normal thymus as a functionally distinct subpopulation of T cells bearing a broad T cell receptor repertoire endowing these cells with the capacity to recognize a wide spectrum of self-Ag and non-self-Ag specificities. The development of CD4(+)CD25(+) Treg cells is genetically determined, influenced by Ag-specific and nonspeci... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392717 Sun, 01 Jan 2006 07:00:00 +0100 392717 http://www.medworm.com/index.php?rid=392711&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17145304%26dopt%3DAbstract Authors: Gavrieli M, Sedy J, Nelson CA, Murphy KM Recently a new inhibitory immunoglobulin domain-containing lymphocyte receptor was identified on the basis of its T helper 1 (T(H)1)-selective expression in murine T cell lines, which was named B and T lymphocyte attenuator (BTLA). Several groups have confirmed the initial characterization of BTLA as an inhibitory receptor, which was initially inferred from the mild increases in several parameters of BTLA-deficient mice. The initial expectation that BTLA would interact with a B7 family ligand, such as the B7x protein, was surprisingly overturned with the functional cloning of the actual BTLA ligand as herpesvirus entry mediator (HVEM). This was unexpected largely due to the fact that this interaction represents the convergence of two ve... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392711 Sun, 01 Jan 2006 07:00:00 +0100 392711 http://www.medworm.com/index.php?rid=392707&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17145305%26dopt%3DAbstract Authors: Romero P, Cerottini JC, Speiser DE The cornerstone of the concept of immunosurveillance in cancer should be the experimental demonstration of immune responses able to alter the course of in vivo spontaneous tumor progression. Elegant genetic manipulation of the mouse immune system has proved this tenet. In parallel, progress in understanding human T cell mediated immunity has allowed to document the existence in cancer patients of naturally acquired T cell responses to molecularly defined tumor antigens. Various attributes of cutaneous melanoma tumors, notably their adaptability to in vitro tissue culture conditions, have contributed to convert this tumor in the prototype for studies of human antitumor immune responses. As a consequence, the first human cytolytic T lymphocyte ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392707 Sun, 01 Jan 2006 07:00:00 +0100 392707 http://www.medworm.com/index.php?rid=392888&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15705418%26dopt%3DAbstract Authors: Blackburn MR, Kellems RE Genetic deficiencies in the purine catabolic enzyme adenosine deaminase (ADA) in humans results primarily in a severe lymphopenia and immunodeficiency that can lead to the death of affected individuals early in life. The metabolic basis of the immunodeficiency is likely related to the sensitivity of lymphocytes to the accumulation of the ADA substrates adenosine and 2'-deoxyadenosine. Investigations using ADA-deficient mice have provided compelling evidence to support the hypothesis that T and B cells are sensitive to increased concentrations of 2'-deoxyadenosine that kill cells through mechanisms that involve the accumulation of dATP and the induction of apoptosis. In addition to effects on the developing immune system, ADA-deficient humans exhibit ph... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392888 Sat, 01 Jan 2005 07:00:00 +0100 392888 http://www.medworm.com/index.php?rid=392885&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15705419%26dopt%3DAbstract Authors: Dudley DD, Chaudhuri J, Bassing CH, Alt FW V(D)J recombination is the process by which the variable region exons encoding the antigen recognition sites of receptors expressed on B and T lymphocytes are generated during early development via somatic assembly of component gene segments. In response to antigen, somatic hypermutation (SHM) and class switch recombination (CSR) induce further modifications of immunoglobulin genes in B cells. CSR changes the IgH constant region for an alternate set that confers distinct antibody effector functions. SHM introduces mutations, at a high rate, into variable region exons, ultimately allowing affinity maturation. All of these genomic alteration processes require tight regulatory control mechanisms, both to ensure development of a normal im... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392885 Sat, 01 Jan 2005 07:00:00 +0100 392885 http://www.medworm.com/index.php?rid=392882&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15705420%26dopt%3DAbstract Authors: Thai TH, Kearney JF The immune system develops in a series of programmed developmental stages. Although recombination-activating gene (RAG) and nonhomologous end-joining (NHEJ) proteins are indispensable in the generation of immunoglobulins and T-cell receptors (TCRs), most CDR3 diversity is contributed by nontemplated addition of nucleotides catalyzed by the nuclear enzyme terminal deoxynucleotidyltransferase (TdT) and most nucleotide deletion is performed by exonucleases at V(D)J joins. Increasing TdT expression continuing into adult life results in N region addition and diversification of the T and B cell repertoires. In several species including mice and humans, there are multiple isoforms of TdT resulting from alternative mRNA splicing. The short form (TdTS) produces N ad... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392882 Sat, 01 Jan 2005 07:00:00 +0100 392882 http://www.medworm.com/index.php?rid=392879&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15705421%26dopt%3DAbstract Authors: Carroll MC, Holers VM The adaptive immune system has evolved highly specific pattern recognition proteins and receptors that, when triggered, provide a first line of host defense against pathogens. Studies reveal that these innate recognition proteins are also self-reactive and can initiate inflammation against self-tissues in a similar manner as with pathogens. This specific event is referred to as "innate autoimmunity." In this review, we describe two classes of autoimmune responses, that is, reperfusion injury and fetal loss syndrome, in which the recognition and injury are mediated by innate immunity. Both disorders are common and are clinically important. Reperfusion injury (RI) represents an acute inflammatory response after a reversible ischemic event and subsequent res... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392879 Sat, 01 Jan 2005 07:00:00 +0100 392879 http://www.medworm.com/index.php?rid=392876&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15705422%26dopt%3DAbstract Authors: Joseph K, Kaplan AP The plasma kinin-forming cascade can be activated by contact with negatively charged macromolecules leading to binding and autoactivation of factor XII, activation of prekallikrein to kallikrein by factor XIIa, and cleavage of high molecular weight kininogen (HK) by kallikrein to release the vasoactive peptide bradykinin. Once kallikrein formation begins, there is rapid cleavage of unactivated factor XII to factor XIIa, and this positive feedback is favored kinetically over factor XII autoactivation. Examples of surface initiators that can function in this fashion are endotoxin, sulfated mucopolysaccharides, and aggregated Abeta protein. Physiological activation appears to occur along the surface of endothelial cells both by the aforementioned contact-initi... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392876 Sat, 01 Jan 2005 07:00:00 +0100 392876 http://www.medworm.com/index.php?rid=392873&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15705423%26dopt%3DAbstract Authors: Becknell B, Caligiuri MA Natural killer (NK) cells are CD56+CD3- large granular lymphocytes that constitute a key component of the human innate immune response. In addition to their potent cytolytic activity, NK cells elaborate a host of immunoregulatory cytokines and chemokines that play a crucial role in pathogen clearance. Furthermore, interactions between NK and other immune cells are implicated in triggering the adaptive, or antigen-specific, immune response. Interleukin-2 (IL-2) and IL-15 are two distinct cytokines with partially overlapping properties that are implicated in the development, homeostasis, and function of NK cells. This review examines the pervasive effects of IL-2 and IL-15 on NK cell biology, with an emphasis on recent discoveries and lingering challenge... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392873 Sat, 01 Jan 2005 07:00:00 +0100 392873 http://www.medworm.com/index.php?rid=392870&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15705424%26dopt%3DAbstract Authors: Wilson NS, Villadangos JA Dendritic cells (DCs) are central to the maintenance of immunological tolerance and the initiation and control of immunity. The antigen-presenting properties of DCs enable them to present a sample of self and foreign proteins, contained within an organism at any given time, to the T-cell repertoire. DCs achieve this communication with T cells by displaying antigenic peptides bound to MHC I and MHC II molecules. Here we review the studies carried out over the past 15 years to characterize these antigen presentation mechanisms, emphasizing their significance in relation to DC function in vivo. The life cycles of different DC populations found in vivo are described. Furthermore, we provide a critical assessment of the studies that examine the mechanisms ... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392870 Sat, 01 Jan 2005 07:00:00 +0100 392870 http://www.medworm.com/index.php?rid=392867&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16102570%26dopt%3DAbstract Authors: Malissen B, Aguado E, Malissen M LAT (linker for activation of T cells) is an integral membrane adaptor protein that constitutes in T cells a major substrate of the ZAP-70 protein tyrosine kinase. LAT coordinates the assembly of a multiprotein signaling complex through phosphotyrosine-based motifs present within its intracytoplasmic segment. The resulting "LAT signalosome" links the TCR to the main intracellular signalling pathways that regulate T-cell development and T-cell function. Early studies using transformed T-cell lines suggested that LAT acts primarily as a positive regulator of T-cell receptor (TCR) signalling. The partial or complete inhibition of T-cell development observed in several mouse lines harboring mutant forms of LAT was congruent with that view. More rec... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392867 Sat, 01 Jan 2005 07:00:00 +0100 392867 http://www.medworm.com/index.php?rid=392864&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16102571%26dopt%3DAbstract Authors: Pennington DJ, Vermijlen D, Wise EL, Clarke SL, Tigelaar RE, Hayday AC This review builds on evidence that cell-mediated immune responses to bacteria, viruses, parasites, and tumors are an integration of conventional and unconventional T-cell activities. Whereas conventional T cells provide clonal antigen-specific responses, unconventional T cells profoundly regulate conventional T cells, often suppressing their activities such that immunopathology is limited. By extrapolation, immunopathologies and inflammatory diseases may reflect defects in regulation by unconventional T cells. To explore the function of unconventional T cells, several extensive gene expression analyses have been undertaken. These studies are reviewed in some detail, with emphasis on the mechanisms by which... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392864 Sat, 01 Jan 2005 07:00:00 +0100 392864 http://www.medworm.com/index.php?rid=392861&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16102572%26dopt%3DAbstract Authors: Naka T, Fujimoto M, Tsutsui H, Yoshimura A PMID: 16102572 [PubMed - indexed for MEDLINE] (Source: Advances in Immunology) Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392861 Sat, 01 Jan 2005 07:00:00 +0100 392861 http://www.medworm.com/index.php?rid=392858&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16102573%26dopt%3DAbstract Authors: Haskins K T-cell clones that can efficiently transfer diabetes to prediabetic nonobese diabetic (NOD) mice provide a powerful approach to dissecting the autoimmune disease process and for investigating immunoregulation. Diabetogenic T-cell clones carried in culture allow for detailed analysis of T-cell effector function and in vivo activity, and thus the contribution of a single clonotype to pathogenesis can be studied. As T cells comprising most or all of the repertoire in T-cell receptor transgenic (TCR-Tg) mice, diabetogenic T-cell clones have led to new variations on the NOD mouse model of autoimmune disease. T-cell clones are being used to screen peptide libraries and proteomic arrays to identify the autoantigens that drive these clones in vivo and to extend our knowledge... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392858 Sat, 01 Jan 2005 07:00:00 +0100 392858 http://www.medworm.com/index.php?rid=392855&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16102574%26dopt%3DAbstract Authors: Staudt LM, Dave S Gene expression profiling provides a quantitative molecular framework for the study of human lymphomas. This genomic technology has revealed that existing diagnostic categories are comprised of multiple molecularly and clinically distinct diseases. Diffuse large B-cell lymphoma (DLBCL), for example, consists of three gene expression subgroups, termed germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma (PMBL). These DLBCL subgroups arise from different stages of normal B-cell differentiation, utilize distinct oncogenic mechanisms, and differ in their ability to be cured by chemotherapy. Key regulatory factors and their target genes are differentially expressed among these subgroups, including BCL-... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392855 Sat, 01 Jan 2005 07:00:00 +0100 392855 http://www.medworm.com/index.php?rid=392852&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16102575%26dopt%3DAbstract Authors: Litman GW, Cannon JP, Rast JP The clonal commitment, selection, and expansion of B and T lymphocytes expressing diversified receptors provide the underlying basis for the jawed vertebrates adaptive immune response. At the core of this process is the rearrangement and somatic modification of segmental genetic elements that encode the constituent components of immunoglobulins and T-cell antigen receptors. No evidence has been found for a similar mechanism outside of jawed vertebrates; however, invertebrates and jawless vertebrates are subjected to continuous exposure to pathogenic bacteria, viruses, and parasites. The invertebrates and jawless vertebrates as well as jawed vertebrates all encode a variety of mediators of innate immunity. Several reports of extensive germline dive... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392852 Sat, 01 Jan 2005 07:00:00 +0100 392852 http://www.medworm.com/index.php?rid=392849&cid=s_34425_3_f&fid=34425&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16102576%26dopt%3DAbstract Authors: Revy P, Buck D, le Deist F, de Villartay JP The immune system is the site of various genotoxic stresses that occur during its maturation as well as during immune responses. These DNA lesions/modifications are primarily the consequences of specific physiological processes such as the V(D)J recombination, the immunoglobulin class switch recombination (CSR), and the generation of somatic hypermutations (SHMs) within Ig variable domains. The DNA lesions can be introduced either by specific factors (RAG1 and RAG2 in the case of V(D)J recombination and AID in the case of CSR and SHM) or during the various phases of cellular proliferation and cellular activation. All these DNA lesions are taken care of by the diverse DNA repair machineries of the cell. Several animal models as well a... Advances in Immunology journals http://www.medworm.com/rss/comments.php?id=392849 Sat, 01 Jan 2005 07:00:00 +0100 392849