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 'Current Opinion in Immunology' source. Wed, 08 Feb 2012 06:42:50 +0100 http://www.medworm.com/index.php?rid=5659434&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22296715%26dopt%3DAbstract Authors: Krüger E, Kloetzel PM Abstract The immunoproteasome is a specific proteasome isoform induced by interferons. Its proteolytic function has been almost exclusively connected with the adaptive immune response and improved MHC class I antigen presentation. However, IFN-signaling also exposes cells to oxidative stress with concomitant production of nascent-oxidant damaged poly-ubiquitylated proteins. Here we discuss how immunoproteasomes protect cells against accumulation of toxic protein-aggregates and how i-proteasomes dysfunction associates with different diseases. We propose that the immunoproteasome has a central function at the interface between the innate and adaptive immune response and that its predominant protective innate function determines its favorable role in th... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5659434 Mon, 30 Jan 2012 05:00:00 +0100 5659434 http://www.medworm.com/index.php?rid=5659433&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22296716%26dopt%3DAbstract Authors: Guerder S, Viret C, Luche H, Ardouin L, Malissen B Abstract The stromal network of the thymus provides a unique environment that supports the development of mature CD4(+) and CD8(+) T cells expressing a very diverse repertoire of T cell receptors (TCR) with limited reactivity to self-antigens. Thymic cortical epithelial cells (cTECs) are specialized antigen-presenting cells (APCs) that promote the positive selection of developing thymocytes while medullary thymic epithelial cells (mTECs) and thymic dendritic cells (tDCs) induce central tolerance to self-antigens. Recent studies showed that cTECs express a unique set of proteases involved in the generation of self-peptides presented by major-histocompatibility encoded molecules (pMHC) and consequently may express a unique s... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5659433 Mon, 30 Jan 2012 05:00:00 +0100 5659433 http://www.medworm.com/index.php?rid=5659436&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285892%26dopt%3DAbstract Authors: Takahama Y, Takada K, Murata S, Tanaka K Abstract Proteasomes are multisubunit proteolytic complexes that degrade cytoplasmic and nuclear proteins in eukaryotes. Proteasome-dependent proteolysis contributes to various cellular processes, including misfolded protein degradation, signal transduction, and antigen presentation. The thymoproteasome is a form of proteasome that contains the vertebrate-specific catalytic subunit β5t specifically expressed by cortical epithelial cells in the thymus. The thymoproteasome is essential for the positive selection of CD8+ T cells that carry an immunocompetent repertoire of antigen recognition specificity. Here we summarize the structure and expression of the thymoproteasome and discuss how it regulates the positive selection of CD8+ T ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5659436 Fri, 27 Jan 2012 05:00:00 +0100 5659436 http://www.medworm.com/index.php?rid=5659435&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285893%26dopt%3DAbstract Authors: Chan CJ, Andrews DM, Smyth MJ Abstract Management of an immune response is achieved through a delicate balance of pro-inflammatory and anti-inflammatory mechanisms. Controlling this response requires co-operation between a multitude of immune cells that are in turn controlled by specific receptor-ligand interactions and cytokine networks. In the context of cancer, a major mechanism by which the immune system restrains disease is through the action of cytotoxic lymphocytes that include natural killer (NK) cells and CD8 T cells. Both of these cell types express a panoply of receptors that are able to control their responses in order to heighten the specificity of their effector function. An emerging class of such receptors on cytotoxic lymphocytes are a group of immunoglobul... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5659435 Fri, 27 Jan 2012 05:00:00 +0100 5659435 http://www.medworm.com/index.php?rid=5659437&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22277983%26dopt%3DAbstract Authors: Tarakhovsky AS, Kroemer G PMID: 22277983 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5659437 Mon, 23 Jan 2012 05:00:00 +0100 5659437 http://www.medworm.com/index.php?rid=5623811&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264927%26dopt%3DAbstract Authors: Rygiel TP, Meyaard L Abstract The inhibitory CD200-CD200 receptor (CD200R) interaction is essential to prevent massive inflammatory responses and immune pathology during microbial infection. Since CD200 expression on human malignancies is associated with tumor progression, CD200 blocking antibodies are currently tested in clinical trials to boost anti-tumor responses. Here we discuss that CD200-mediated suppression of anti-tumor responses may not only be mediated by the tumor itself, but also by CD200 expressed on healthy tissue. However, in cancers that benefit from inflammation, the blockade of CD200 could result in enhanced tumor growth. We conclude that CD200 blockade forms a potential therapeutic option to strengthen anti-tumor responses which is not restricted to tre... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5623811 Thu, 19 Jan 2012 05:00:00 +0100 5623811 http://www.medworm.com/index.php?rid=5623810&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264928%26dopt%3DAbstract Authors: Rothenberg EV Abstract The T-cell development program is specifically triggered by Notch-Delta signaling, but most transcription factors needed to establish T-cell lineage identity also have crossover roles in other hematopoietic lineages. This factor sharing complicates full definition of the core gene regulatory circuits required for T-cell specification. But new advances illuminate the roles of three of the most T-cell specific transcription factors. Commitment to the T-cell lineage is now shown to depend on Bcl11b, while initiation of the T-cell differentiation program begins earlier with the induction of TCF-1 (Tcf7 gene product) and GATA-3. Several reports now reveal how TCF-1 and GATA-3 are mobilized in early T cells and the pathways for their T-lineage specific eff... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5623810 Thu, 19 Jan 2012 05:00:00 +0100 5623810 http://www.medworm.com/index.php?rid=5623809&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264929%26dopt%3DAbstract Authors: Thielens A, Vivier E, Romagné F Abstract The natural killer (NK) cell effector response towards infected cells or tumoural cells is guided by the integration of activating and inhibitory signals sensed by NK cell surface receptors. Major histocompatibility complex class I specific inhibitory receptors expressed by NK cells have two distinct roles: while allowing self tolerance, they are also needed for the acquisition of NK cell functional competence, a process termed education. In the context of allotransplantation, NK cell alloreactivity, arising from the expression on donor NK cells of inhibitory killer Ig-like receptors (KIRs) that do not recognize human leukocyte antigen from the patient, has shown clinical benefit for leukaemia patients. Based on these genetic studi... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5623809 Thu, 19 Jan 2012 05:00:00 +0100 5623809 http://www.medworm.com/index.php?rid=5602862&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245556%26dopt%3DAbstract Authors: Schaer DA, Murphy JT, Wolchok JD Abstract Modulation of co-inhibitory and co-stimulatory receptors of the immune system has become a promising new approach for immunotherapy of cancer. With the recent FDA approval of CTLA-4 blockade serving as an important proof of principal, many new targets are now being translated into the clinic. Preclinical research has demonstrated that targeting glucocorticoid-induced tumor necrosis factor (TNF) receptor related gene (GITR), a member of TNF receptor superfamily, by agonist antibodies or natural ligand, can serve as an effective anti-tumor therapy. In this review, we will cover this research and the rationale that has led to initiation of two phase 1 clinical trials targeting GITR as a new immunotherapeutic approach for cancer. P... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5602862 Thu, 12 Jan 2012 05:00:00 +0100 5602862 http://www.medworm.com/index.php?rid=5602863&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240121%26dopt%3DAbstract Authors: Bezbradica JS, Medzhitov R Abstract Diverse cell types use a small number of evolutionarily conserved signaling modules to integrate external cues and elicit distinct functions. A question thus arises as to how does a receptor, which contains a single signaling module, produce distinct outcomes to diverse signals, particularly if such module is shared amongst a family of receptors? Emerging data suggest that many immunoreceptors, all of which use a conserved ITAM-module for their signaling, can couple with members of additional classes of membrane receptors to deliver unique signal(s) to the cell. We discuss the possible biological purposes and mechanisms behind these interactions at the plasma membrane. We offer a conceptual framework to understand information processing ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5602863 Wed, 11 Jan 2012 05:00:00 +0100 5602863 http://www.medworm.com/index.php?rid=5602864&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240120%26dopt%3DAbstract Authors: Oestreich KJ, Weinmann AS Abstract Recent research has made great strides in uncovering the mechanisms by which the T helper 1 (Th1) cell gene expression program is established. In particular, studies examining the transcription factors T-bet, STAT1, and STAT4 have elucidated their roles in regulating Th1 signature genes, including Ifng, and have started to address their contributions to the epigenetic states in Th1 cells. Additionally, new findings have provided information about how the co-expression of T helper cell lineage-defining transcription factors impacts the phenotype of the cell. In this review, we will briefly highlight the research from the last few years examining the epigenetic states in T helper cells and the mechanisms by which they are established. We wi... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5602864 Tue, 10 Jan 2012 05:00:00 +0100 5602864 http://www.medworm.com/index.php?rid=5602948&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22236695%26dopt%3DAbstract Authors: Topalian SL, Drake CG, Pardoll DM Abstract Genetic alterations and epigenetic dysregulation in cancer cells create a vast array of neoepitopes potentially recognizable by the immune system. Immune checkpoint blockade has the capacity to enhance and sustain endogenous immunity against non-mutated tumor-associated antigens as well as uniquely mutant antigens, establishing durable tumor control. Recent evidence from preclinical models highlights the pivotal role of the Programmed Death-1 (PD-1) T cell co-receptor and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, in maintaining an immunosuppressive tumor microenvironment. Encouraging early clinical results using blocking agents against components of the PD-1 pathway have validated its importance as a target for cancer immunotherap... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5602948 Mon, 09 Jan 2012 05:00:00 +0100 5602948 http://www.medworm.com/index.php?rid=5602932&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22236696%26dopt%3DAbstract Authors: Zhang Q, Iida R, Shimazu T, Kincade PW Abstract The path from hematopoietic stem cells (HSCs) to functional B lymphocytes has long been appreciated as a basic model of differentiation, but much clinically relevant information has also been obtained. It is now possible to conduct single cell studies with increasingly high resolution, revealing that individual stem and progenitor cells differ from each other with respect to differentiation potential and fates. B lymphopoiesis is now seen as a gradual and unsynchronized process where progenitors eventually become B lineage restricted. Major milestones have been identified, but a precise sequence need not be followed and oscillation between states is possible. It is not yet clear if this versatility has survival value, but inf... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5602932 Mon, 09 Jan 2012 05:00:00 +0100 5602932 http://www.medworm.com/index.php?rid=5602865&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22236697%26dopt%3DAbstract Authors: Pukkila-Worley R, Ausubel FM Abstract Intestinal epithelial cells provide an essential line of defense for Caernohabditis elegans against ingested pathogens. Because nematodes consume microorganisms as their food source, there has presumably been selection pressure to evolve and maintain immune defense mechanisms within the intestinal epithelium. Here we review recent advances that further define the immune signaling network within these cells and suggest mechanisms used by the nematode to monitor for infection. In reviewing studies of pathogenesis that use this simple model system, we hope to illustrate some of the basic principles of epithelial immunity that may also be of relevance in higher order hosts. PMID: 22236697 [PubMed - as supplied by publisher] (Source: Cu... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5602865 Mon, 09 Jan 2012 05:00:00 +0100 5602865 http://www.medworm.com/index.php?rid=5578690&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22230561%26dopt%3DAbstract Authors: Smale ST Abstract In cells of the innate immune system, the transcriptional response to a microbial stimulus is tailored to both the stimulus and cell type, suggesting the existence of highly sophisticated regulatory mechanisms. Early studies suggested that specificity is dictated by sets of differentially induced transcription factors that synergistically activate target genes containing their binding sites. However, recent studies have revealed additional interrelated regulatory layers, which are the topic of this article. In particular, individual transcription factors may require different post-translational modifications and coregulatory interactions to regulate different target genes. Furthermore, competence for induction is programmed at an early stage of developmen... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5578690 Sat, 07 Jan 2012 05:00:00 +0100 5578690 http://www.medworm.com/index.php?rid=5578691&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226204%26dopt%3DAbstract Authors: Anderson AC Abstract T cell immunoglobulin-3 (Tim-3) was identified nearly 10 years ago as a negative regulator of IFN-γ-secreting CD4(+) T helper 1 and CD8(+) T cytotoxic 1 cells. Tim-3 is now classed with other inhibitory receptors, such as cytotoxic lymphocyte antigen-4 and programmed death-1 that are commonly referred to as immune checkpoint molecules. Recent studies have highlighted Tim-3 as an important player in the CD8(+) T cell exhaustion that takes place in chronic immune conditions such as chronic viral infection and cancer in both humans and experimental models. In addition to its role in exhausted T cells, recent data suggest that Tim-3 can further influence cancer outcome through its action on myeloid cells and cancer stem cells. PMID: 22226204 [PubMed -... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5578691 Wed, 04 Jan 2012 05:00:00 +0100 5578691 http://www.medworm.com/index.php?rid=5561103&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209117%26dopt%3DAbstract Authors: Aliahmad P, Seksenyan A, Kaye J Abstract TOX is a member of an evolutionarily conserved DNA-binding protein family and is expressed in several immune-relevant cell subsets. Here, we review the key role of TOX in regulating development of CD4 T cells, natural killer cells and lymphoid tissue inducer cells, the latter responsible for the generation of lymph nodes. Although the exact molecular mechanism of action of TOX remains to be elucidated, the role of TOX in establishment of gene programs in the thymus and the potential of TOX as a regulator of E protein activity are discussed. PMID: 22209117 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5561103 Fri, 30 Dec 2011 05:00:00 +0100 5561103 http://www.medworm.com/index.php?rid=5561102&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209691%26dopt%3DAbstract Authors: Doyle HA, Mamula MJ Abstract Protein targets in autoimmune disease vary in location, originating within cells as in system lupus erythematosus (SLE), or found on cell surfaces or in extracellular spaces. The term 'autoantigenesis' is first defined here as the changes that arise in self-proteins as they break self-tolerance and trigger autoimmune B and/or T cell responses. As illustrated in many studies, between 50 and 90% of the proteins in the human body acquire post-translational modification. In some cases, it may be that these modifications are necessary for the biological functions of proteins of the cells in which they reside or as extracellular mediators. Summarized herein, it is clear that some post-translational modifications can create new self-antigens by alteri... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5561102 Thu, 29 Dec 2011 05:00:00 +0100 5561102 http://www.medworm.com/index.php?rid=5561104&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206698%26dopt%3DAbstract Authors: Vigneron N, Van den Eynde BJ Abstract Protein degradation by the proteasome releases peptides that can be loaded on MHC class I molecules and presented to cytolytic T lymphocytes. Several mechanisms were recently found to increase the diversity of antigenic peptides displayed at the cell surface, thereby maximizing the efficacy of immune responses. The proteasome was shown to produce spliced antigenic peptides, which are made of two fragments initially not contiguous in the parental protein. Different proteasome subtypes also produce distinct sets of antigenic peptides: the standard proteasome and the immunoproteasome, containing different catalytic subunits, have different cleavage specificities and produce different sets of peptides. Moreover, recent work confirmed the e... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5561104 Tue, 27 Dec 2011 05:00:00 +0100 5561104 http://www.medworm.com/index.php?rid=5535827&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188798%26dopt%3DAbstract Authors: Chambers MC, Schneider DS Abstract Insects are a powerful tool for discovering and then dissecting interesting new immunology. Recent insect research has made productive forays into non-classical immune areas including tolerance, immune priming (trained immunity), and environmental effects on immunity. Environments which affect immunity not only include diet and metabolism, but also social interactions and the animal's microbiota. We argue that every process that affects immunity should be considered as part of the immune response and that it is the broad phenomena discovered in insects that will be translated to other organisms rather than fine mechanistic details. PMID: 22188798 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5535827 Mon, 19 Dec 2011 05:00:00 +0100 5535827 http://www.medworm.com/index.php?rid=5535828&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178549%26dopt%3DAbstract Authors: Calderon B, Unanue ER Abstract Antigen presenting cells (APC) be they dendritic cells (DC) or macrophages reside in all tissues. Their role varies from presenting antigen, clearing the tissue from unwanted material, helping in the remodeling that follows injury and inflammation, to a supporting or trophic function. Their features, biology, and turnover may be unique for each organ, modulated by the particular anatomy and physiology of the tissue. These features affect the handling and presentation of antigens, either exogenous such as those from viruses or bacteria, or endogenous, autologous proteins in situations of autoimmunity. Herein, we focus on the resident APC of the islets of Langerhans and their role in autoimmune diabetes. The intra-islet APC are central cells in... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5535828 Thu, 15 Dec 2011 05:00:00 +0100 5535828 http://www.medworm.com/index.php?rid=5535830&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138314%26dopt%3DAbstract Authors: Schulze MS, Wucherpfennig KW Abstract HLA-DM serves a critical function in the loading and editing of peptides on MHC class II (MHCII) molecules. Recent data showed that the interaction cycle between MHCII molecules and HLA-DM is dependent on the occupancy state of the peptide binding groove. Empty MHCII molecules form stable complexes with HLA-DM, which are disrupted by binding of high-affinity peptide. Interestingly, MHCII molecules with fully engaged peptides cannot interact with HLA-DM, and prior dissociation of the peptide N-terminus from the groove is required for HLA-DM binding. There are significant similarities to the peptide loading process for MHC class I molecules, even though it is executed by a distinct set of proteins in a different cellular compartment. ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5535830 Fri, 02 Dec 2011 05:00:00 +0100 5535830 http://www.medworm.com/index.php?rid=5535829&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138315%26dopt%3DAbstract Authors: Cloonan SM, Choi AM Abstract Mitochondrial dysfunction is associated with the manifestation and origin of a plethora of diseases and disorders. Whilst classically the role of these archetypical 'powerhouses' in many disease phenotypes has been attributed to their ability to regulate cell metabolism and cell death pathways, emerging data posit that mitochondria may also act as powerful initiators and masters of the innate immune response. This new paradigm complements the current mitochondrial dogma, whereby molecules endogenously present on or inside the mitochondria may act as immune regulators in response to stress or pathogens and may also be responsible for the initiation and/or manifestation of chronic inflammation observed in many diseases and disorders. PMID: 22... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5535829 Fri, 02 Dec 2011 05:00:00 +0100 5535829 http://www.medworm.com/index.php?rid=5456509&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118953%26dopt%3DAbstract Authors: Deretic V Abstract Autophagy is rapidly developing into a new immunological paradigm. The latest links now include overlaps between autophagy and innate immune signaling via TBK-1 and IKKα/β, and the role of autophagy in inflammation directed by the inflammasome. Autophagy's innate immunity connections include responses to pathogen and damage-associated molecular patterns including alarmins such as HMGB1 and IL-1β, Toll-like receptors, Nod-like receptors including NLRC4, NLRP3 and NLRP4, and RIG-I-like receptors. Autophagic adaptors referred to as SLRs (sequestosome 1/p62-like receptors) are themselves a category of pattern recognition receptors. SLRs empower autophagy to eliminate intracellular microbes by direct capture and by facilitating generation and delivery of a... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5456509 Thu, 24 Nov 2011 05:00:00 +0100 5456509 http://www.medworm.com/index.php?rid=5456510&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22115876%26dopt%3DAbstract Authors: Atarashi K, Honda K Abstract The composition of a host's intestinal microbiota directs the type of mucosal and systemic immune responses by affecting the proportion and number of functionally distinct T cell subsets. In particular, the microbiota composition affects the differentiation of intestinal Th17 cells and Foxp3(+) regulatory T cells, both of which play critical roles in maintaining mucosal barrier functions and in controlling immunological homeostasis. In this review, we discuss the recent advances in our understanding of how the intestinal microbiota affects T cell differentiation and host susceptibility to autoimmune disease. PMID: 22115876 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5456510 Wed, 23 Nov 2011 05:00:00 +0100 5456510 http://www.medworm.com/index.php?rid=5456508&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22119110%26dopt%3DAbstract Authors: Pillai S, Mattoo H, Cariappa A Abstract There is a growing appreciation for the role for B cells in autoimmune disorders in which inflammation is driven by T cells, in addition to the well-established role for B cells in autoimmune disorders characterized by pathogenic auto-antibodies. Current information on tolerance checkpoints in B cells, B cell depletion, BAFF blockade, regulatory B cells and clonal ignorance mediated by the SIAE/Siglec pathway will be reviewed. PMID: 22119110 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5456508 Wed, 23 Nov 2011 05:00:00 +0100 5456508 http://www.medworm.com/index.php?rid=5422214&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079134%26dopt%3DAbstract Authors: Bikard D, Marraffini LA Abstract Bacteria are constantly challenged by bacteriophages (viruses that infect bacteria), the most abundant microorganism on earth. Bacteria have evolved a variety of immunity mechanisms to resist bacteriophage infection. In response, bacteriophages can evolve counter-resistance mechanisms and launch a 'virus versus host' evolutionary arms race. In this context, rapid evolution is fundamental for the survival of the bacterial cell. Programmed genetic variation mechanisms at loci involved in immunity against bacteriophages generate diversity at a much faster rate than random point mutation and enable bacteria to quickly adapt and repel infection. Diversity-generating retroelements (DGRs) and phase variation mechanisms enhance the generic (innate)... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5422214 Fri, 11 Nov 2011 05:00:00 +0100 5422214 http://www.medworm.com/index.php?rid=5422215&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074731%26dopt%3DAbstract Authors: Willart M, Hammad H Abstract Dendritic cells (DC) have been shown to be responsible for the initiation and maintenance of adaptive Th2 responses in asthma. It is increasingly clear that DC functions are strongly influenced by crosstalk with neighboring cells like epithelial cells, which can release a number of innate cytokines promoting Th2 responses. Clinically relevant allergens often interfere directly or indirectly with the innate immune functions of airway epithelial cells and DC. A better understanding of these interactions might lead to a better prevention and ultimately to new treatments for asthma. PMID: 22074731 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5422215 Tue, 08 Nov 2011 05:00:00 +0100 5422215 http://www.medworm.com/index.php?rid=5422216&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056379%26dopt%3DAbstract Authors: Bettini M, Vignali DA Abstract The destruction of beta cells in type 1 diabetes in humans and in autoimmune diabetes in the NOD mouse model is a consequence of chronic islet inflammation in the pancreas. The T cell-driven autoimmune response is initiated by environmental triggers which are influenced by the state of intestinal homeostasis and the microbiota. The disease process can be separated into two phases: firstly, initiation of mild, controlled, long-term infiltration and secondly, propagation of invasive inflammation which quickly progresses to beta cell deletion and autoimmune diabetes. In this review, we will discuss the cellular and molecular triggers that might be required for these two phases in the context of other issues including the unique anatomical locati... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5422216 Thu, 03 Nov 2011 04:00:00 +0100 5422216 http://www.medworm.com/index.php?rid=5422217&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056155%26dopt%3DAbstract Authors: Wucherpfennig KW, Noelle RJ PMID: 22056155 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5422217 Wed, 02 Nov 2011 04:00:00 +0100 5422217 http://www.medworm.com/index.php?rid=5381677&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22051340%26dopt%3DAbstract Authors: Roep BO, Peakman M Abstract The field of Type 1 diabetes research has been quick to embrace the era of translational medicine in the recent epoch. Building upon some 30 years of intense immunological research, the past decade has been marked by a series of clinical trials designed to evaluate the potential beneficial effects of a range of immune intervention and prevention strategies [1(••),2-5]. At the heart of Type 1 diabetes is an autoimmune process, the consequence of which is immune-mediated destruction of islet β-cells. Although understanding the pathogenesis of islet autoimmunity is critical, there are also good reasons to focus research onto the β-cell destructive process itself. Measuring preservation of function of insulin-producing cells is currently the b... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5381677 Tue, 01 Nov 2011 04:00:00 +0100 5381677 http://www.medworm.com/index.php?rid=5381678&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22035810%26dopt%3DAbstract Authors: Voehringer D Abstract Basophils are rare effector cells of the innate immune system. They are generally associated with type 2 immune responses that develop during helminth infections and allergic reactions. The role of basophils for initiation and execution of allergic immune responses is not well understood. Over the past few years new tools have been generated to study the function of basophils in mouse models. Depending on the experimental systems used conflicting results were obtained with regard to the role of basophils for initiation and execution of immune responses against allergens and helminths. This review highlights the current knowledge about basophil in vivo functions with a focus on the role of basophils for allergic responses like asthma, allergic skin dis... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5381678 Thu, 27 Oct 2011 04:00:00 +0100 5381678 http://www.medworm.com/index.php?rid=5361762&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22019285%26dopt%3DAbstract Authors: Milner JD Abstract The roles of IL-17 producing cells have been the subject of significant research in the fields of autoimmunity, host defense, and recently, atopy. A substantial number of genetic disease with disruptions in the IL-17 pathway have been identified and characterized in past few years, not only enhancing our understanding, but also raising new and complex questions. The connection between IL-17 and atopic disease, in particular, is complex, but it merits further study which may ultimately lead to therapies targeting the Th17 pathway in infectious and/or allergic settings. PMID: 22019285 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5361762 Thu, 20 Oct 2011 04:00:00 +0100 5361762 http://www.medworm.com/index.php?rid=5361764&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018455%26dopt%3DAbstract Authors: Novak N, Leung DY Abstract Atopic dermatitis (AD) results from barrier defects combined with modified immune responses of the innate and the adaptive immune system to exogenous and endogenous factors. Recent research has continued to sort out the complex pathophysiologic puzzle of this frequent skin disease. However, the network of mechanisms leading to the manifestation of AD is far from being completely understood. PMID: 22018455 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5361764 Wed, 19 Oct 2011 04:00:00 +0100 5361764 http://www.medworm.com/index.php?rid=5361763&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018456%26dopt%3DAbstract Authors: Lambrecht BN, Leung DY PMID: 22018456 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5361763 Wed, 19 Oct 2011 04:00:00 +0100 5361763 http://www.medworm.com/index.php?rid=5313361&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983151%26dopt%3DAbstract Authors: von Büdingen HC, Bar-Or A, Zamvil SS Abstract Over the past two decades B cells have increasingly moved into the spotlight in multiple sclerosis (MS) research. This interest was fuelled by growing understanding and acceptance of pathological involvement of B cells and antibodies in MS. Data derived from animal models of MS, human histopathological studies, and analyses of B cells in the peripheral blood and cerebrospinal fluid (CSF) have permitted the integration of B cells in our overall picture of MS immunopathogenesis. The as yet strongest direct evidence for a central role of B cells in MS autoimmunity was the demonstration that peripheral B cell depletion leads to a rapid decline of disease-activity in MS. While lending formidable impact to peripheral blood B cells a... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5313361 Fri, 07 Oct 2011 04:00:00 +0100 5313361 http://www.medworm.com/index.php?rid=5313364&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982509%26dopt%3DAbstract Authors: Hiscott J, Ware C PMID: 21982509 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5313364 Sat, 01 Oct 2011 04:00:00 +0100 5313364 http://www.medworm.com/index.php?rid=5313363&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982510%26dopt%3DAbstract Authors: Newell KA, Phippard D, Turka LA Abstract Experimental models of transplantation provide strong support for the role of regulatory cells in tolerance. However, limited studies of humans who display sustained tolerance following transplantation have not definitively demonstrated a role for regulatory cells in this process. Rather than excluding or minimizing the contribution of regulatory cells to the development of transplantation tolerance, we suggest the possibility that multiple lineages of cells exert regulatory effects that contribute to the development of tolerance, that these regulatory effects are not constant but vary over time, and that the role of regulatory cells varies based on the organ transplanted. More detailed studies will be necessary to elucidate the rol... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5313363 Sat, 01 Oct 2011 04:00:00 +0100 5313363 http://www.medworm.com/index.php?rid=5313362&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982511%26dopt%3DAbstract Authors: Redfield RR, Rodriguez E, Parsons R, Vivek K, Mustafa MM, Noorchashm H, Naji A Abstract T lymphocytes are the primary targets of immunotherapy in clinical transplantation. However, B lymphocytes are detrimental to graft survival by virtue of their capacity to present antigen to T cells via the indirect pathway of allorecognition and the generation of donor specific alloantibody. Furthermore, the long-term survival of organ allografts remains challenged by chronic rejection, a process in which activated B cells have been found to play a significant role. Therefore, the achievement of transplantation tolerance will likely require induction of both T and B cell tolerance to alloantigens. Moreover, human and animal investigations have shown that subsets of B cells, Transitiona... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5313362 Sat, 01 Oct 2011 04:00:00 +0100 5313362 http://www.medworm.com/index.php?rid=5281728&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21943957%26dopt%3DAbstract Authors: Berin MC, Sicherer S Abstract The immunologic mechanisms responsible for the development of allergic sensitization rather than tolerance to foods are not well understood, although there have been a number of recent advances in our understanding of why some foods are inherently allergenic. In addition, the involvement of alternative routes of exposure that are not inherently tolerogenic may play a role in sensitization to foods. Although there are no currently accepted therapeutic approaches to food allergy, there are a number of approaches to treatment in preclinical or clinical trials. Here, we review selected findings published since 2009 that advance our understanding of mechanisms and new therapeutics for IgE-mediated food allergy. PMID: 21943957 [PubMed - as suppl... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5281728 Wed, 21 Sep 2011 04:00:00 +0100 5281728 http://www.medworm.com/index.php?rid=5247535&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21924887%26dopt%3DAbstract Authors: Pfaller CK, Li Z, George CX, Samuel CE Abstract Double-stranded RNA (dsRNA) plays a centrally important role in antiviral innate immunity, both for the production of interferon (IFN) and also in the actions of IFN. Among the IFN-inducible gene products are the protein kinase regulated by RNA (PKR) and the adenosine deaminase acting on RNA 1 (ADAR1). PKR is an established key player in the antiviral actions of IFN, through dsRNA-dependent activation and subsequent phosphorylation of protein synthesis initiation factor eIF2α thereby altering the translational pattern in cells. In addition, PKR plays an important role as a positive effector that amplifies the production of IFN. ADAR1 catalyzes the deamination of adenosine (A) in RNA with double-stranded (ds) character, leadi... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5247535 Thu, 15 Sep 2011 04:00:00 +0100 5247535 http://www.medworm.com/index.php?rid=5233164&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920725%26dopt%3DAbstract Authors: Silke J Abstract In the past 2 years there has been an explosion of information regarding molecules that regulate TNF-R1 signalling, and even reviews published in 2010 are out of date. TNF-R1 activation of NF-κB is a text book example of a signal transduction pathway regulated by ubiquitin and many of the concepts concerning the different roles of ubiquitin chains were first outlined in TNF-R1 signalling. What was once a very simple pathway with clearly defined roles for ubiquitin in regulating TNF-R1 signalling has, however, now become so complicated that we have 'an embarrassment of riches' [1]. The less polite might claim our pathways of TNF-R1 signalling look as complicated as a web constructed by a drug-addled spider [2]. This review will pick apart only one small st... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5233164 Tue, 13 Sep 2011 04:00:00 +0100 5233164 http://www.medworm.com/index.php?rid=5233163&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920726%26dopt%3DAbstract Authors: Ware CF, Sedý JR Abstract The herpesvirus entry mediator (HVEM; TNFRSF14) can activate either proinflammatory or inhibitory signaling pathways. HVEM engages two distinct types of ligands, the canonical TNF-related cytokines, LIGHT and Lymphotoxin-α, and the Ig-related membrane proteins, BTLA (B and T lymphocyte attenuator) and CD160. Recent evidence indicates that the signal generated by HVEM depends on the context of its ligands expressed in trans or in cis. HVEM engagement by all of its ligands in trans initiates bidirectional signaling. In contrast, naïve T cells coexpress BTLA and HVEM forming a cis-complex that interferes with the activation of HVEM by extraneous ligands in the surrounding microenvironment. The HVEM Network is emerging as a key survival system for... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5233163 Tue, 13 Sep 2011 04:00:00 +0100 5233163 http://www.medworm.com/index.php?rid=5233166&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21917438%26dopt%3DAbstract Authors: Sollid LM, Jabri B Abstract Posttranslational modification (PTM) of antigen is a way to break T-cell tolerance to self-antigens and promote autoimmunity. However, the precise mechanisms by which modifications would facilitate autoimmune T-cell responses and how they relate to particular autoimmune-associated MHC molecules remain elusive. Celiac disease is a T-cell mediated enteropathy with a strong HLA association where the immune response is directed mainly against deamidated cereal gluten peptides that have been modified by the enzyme transglutaminase 2. The disease is further characterized by autoantibodies to transglutaminase 2 that have extraordinary high disease specificity and sensitivity. There have been important advances in the knowledge of celiac disease pathoge... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5233166 Mon, 12 Sep 2011 04:00:00 +0100 5233166 http://www.medworm.com/index.php?rid=5233165&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21917439%26dopt%3DAbstract Authors: Haskins K, Cooke A Abstract Pathogenesis of type 1 diabetes (T1D) is mediated by effector T cells and CD4 Th1 and Th17T cells have important roles in this process. While effector function of Th1 cells is well established, because of their inherent plasticity Th17 cells have been more controversial. Th17 cells contribute to pathogenicity, but several studies indicate that Th17 cells transfer disease through conversion to Th1 cells in vivo. CD4T cells are attracted to islets by β-cell antigens which include insulin and the two new autoantigens, chromogranin A and islet amyloid polypeptide, all proteins of the secretory granule. Peptides of insulin and ChgA bind to the NOD class II molecule in an unconventional manner and since autoantigenic peptides may typically bind to MH... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5233165 Mon, 12 Sep 2011 04:00:00 +0100 5233165 http://www.medworm.com/index.php?rid=5219393&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907555%26dopt%3DAbstract Authors: Becher B, Segal BM Abstract It has been firmly established that IL-23 polarized T(H)17 cells are potent effectors in the pathogenesis of experimental autoimmune encephalitomyelitis (EAE). However, the relative importance of these cells in comparison to other encephalitogenic T(H) subsets, and the mechanisms that they employ to effect inflammatory demyelination, are topics of continuing investigation. Interestingly, deletion of individual 'T(H)17 cytokines', such as IL-17A, IL-17F, IL-22 and IL-21, does not phenocopy the complete EAE-resistance of IL-23-deficient mice. The instability of T(H)17 cells in vivo introduces an additional layer of complexity to their role in the context of relapsing or chronic disease. Recent data indicate that IL-23 drives the production of myel... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5219393 Thu, 08 Sep 2011 04:00:00 +0100 5219393 http://www.medworm.com/index.php?rid=5219394&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21899997%26dopt%3DAbstract Authors: Peters A, Lee Y, Kuchroo VK Abstract Th17 cells have been shown to be strong inducers of tissue inflammation and autoimmune diseases. However, not all Th17 cells are pathogenic and increasing data suggest that Th17 cells may come in different flavors. Thus, Th17 cells cannot be described using a narrow schematic, but instead Th17 cells comprise a wide spectrum with a range of effector phenotypes. Here, we review the key factors that generate such diversity, as well as the cytokines and transcription factors that are differentially expressed in pathogenic and nonpathogenic Th17 cells. This new knowledge can be used to identify molecules that make Th17 cells pathogenic and determine how these cells could be targeted to suppress autoimmune diseases. PMID: 21899997 [PubMed... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5219394 Mon, 05 Sep 2011 04:00:00 +0100 5219394 http://www.medworm.com/index.php?rid=5219395&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889323%26dopt%3DAbstract Authors: Liao W, Lin JX, Leonard WJ Abstract Interleukin-2 (IL-2) is a pleiotropic cytokine that drives T-cell growth, augments NK cytolytic activity, induces the differentiation of regulatory T cells, and mediates activation-induced cell death. Along with IL-4, IL-7, IL-9, IL-15, and IL-21, IL-2 shares the common cytokine receptor γ chain, γ(c), which is mutated in humans with X-linked severe combined immunodeficiency. Herein, we primarily focus on the recently discovered complex roles of IL-2 in broadly modulating T cells for T helper cell differentiation. IL-2 does not specify the type of Th differentiation that occurs; instead, IL-2 modulates expression of receptors for other cytokines and transcription factors, thereby either promoting or inhibiting cytokine cascades that co... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5219395 Wed, 31 Aug 2011 04:00:00 +0100 5219395 http://www.medworm.com/index.php?rid=5177034&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21865020%26dopt%3DAbstract Authors: Belgnaoui SM, Paz S, Hiscott J Abstract Sensing of RNA virus infection by the RIG-I-like receptors (RLRs) engages a complex signaling cascade that utilizes the mitochondrial antiviral signaling (MAVS) adapter protein to orchestrate the innate host response to pathogen, ultimately leading to the induction of antiviral and inflammatory responses mediated by type I interferon (IFN) and NF-κB pathways. MAVS is localized to the outer mitochondrial membrane, and has been associated with peroxisomes, the endoplasmic reticulum and autophagosomes, where it coordinates signaling events downstream of RLRs. MAVS not only plays a pivotal role in the induction of antiviral and inflammatory pathways but is also involved in the coordination of apoptotic and metabolic functions. This revi... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5177034 Sun, 21 Aug 2011 23:00:00 +0100 5177034 http://www.medworm.com/index.php?rid=5157564&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862302%26dopt%3DAbstract Authors: Rutz S, Ouyang W Abstract Interleukin (IL)-10 and IL-22 are crucial regulators of inflammation during immune responses. While IL-10 functions to prevent excessive inflammation by acting on immune cells, IL-22 elicits innate responses from tissue epithelia and promotes wound healing. Although T helper (Th) cells are a major source for both cytokines, IL-10 and IL-22 are rarely co-expressed at high levels in the same cells. Here we discuss a number of common aspects as well as crucial differences in the molecular regulation of both cytokines that might explain their broad, but distinct expression among Th cell subsets. PMID: 21862302 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5157564 Fri, 19 Aug 2011 23:00:00 +0100 5157564 http://www.medworm.com/index.php?rid=5157563&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862303%26dopt%3DAbstract Authors: Stokes JR, Casale TB Abstract Since Noon first described allergen immunotherapy a century ago the basic premise of subcutaneous injections (SCIT) of relevant aeroallergens to induce clinical tolerance has remained true [1]. Indeed, allergen immunotherapy did not change dramatically over the first 75 years, but over the past 25 years there have been a number of important advancements leading to newer approaches and novel formulations. Here we review the top 50 articles published in the past 2 years on allergens, environmental control, and immunotherapy for asthma and allergic rhinitis and the use of immunomodulators in allergic disease. PMID: 21862303 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5157563 Thu, 18 Aug 2011 23:00:00 +0100 5157563 http://www.medworm.com/index.php?rid=5157566&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856138%26dopt%3DAbstract Authors: Stappenbeck T, Kiyono H PMID: 21856138 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5157566 Tue, 16 Aug 2011 23:00:00 +0100 5157566 http://www.medworm.com/index.php?rid=5157565&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856139%26dopt%3DAbstract Authors: Chow J, Tang H, Mazmanian SK Abstract Our immune system is charged with the vital mission of identifying invading pathogens and mounting proper inflammatory responses. During the process of clearing infections, the immune system often causes considerable tissue damage. Conversely, if the target of immunity is a member of the resident microbiota, uncontrolled inflammation may lead to host pathology in the absence of infectious agents. Recent evidence suggests that several inflammatory disorders may be caused by specific bacterial species found in most healthy hosts. Although the mechanisms that mediate pathology remain largely unclear, it appears that genetic defects and/or environmental factors may predispose mammals to immune-mediated diseases triggered by potentially pat... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5157565 Tue, 16 Aug 2011 23:00:00 +0100 5157565 http://www.medworm.com/index.php?rid=5157568&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21852079%26dopt%3DAbstract Authors: Delgoffe GM, Murray PJ, Vignali DA Abstract Cytokines are essential for the activation, differentiation and control of the immune system. Many cytokines, alone or in combination with other cytokines, have multiple functions and can often act on many different cell types with distinct developmental or functional consequences. Despite the myriad of cytokines and cytokine receptors, there are relatively few signaling molecules that transduce these diverse cytokine signals. In this review, we will discuss the potential mechanisms used by cytokines to mediate distinct cellular outcomes from a small number of signaling molecules. Understanding this paradigm in cytokine signaling can aid in the development of potential therapeutic approaches involving cytokine targeting or use. ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5157568 Mon, 15 Aug 2011 23:00:00 +0100 5157568 http://www.medworm.com/index.php?rid=5157567&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21852080%26dopt%3DAbstract Authors: Gaffen SL Abstract The IL-17/IL-17 receptor family is the newest and least understood of the cytokine subclasses. Composed of ligands IL-17A-IL-17F and receptors IL-17RA-IL-17RE, these cytokines have many unique structural and functional features. Since the discovery of the 'Th17' subset in 2005, particular attention has been paid to IL-17A and IL-17F and their cognate receptors. To date, far less is known about the rest of the family. This review discusses recent advances in the field, with an emphasis on IL-17A biology. PMID: 21852080 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5157567 Mon, 15 Aug 2011 23:00:00 +0100 5157567 http://www.medworm.com/index.php?rid=5141757&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840693%26dopt%3DAbstract Authors: Kotenko SV Abstract For decades, type I IFNs have been considered indispensable and unique antiviral mediators for the activation of rapid innate antiviral protection. However, the recent discovery of type III IFNs is challenging this paradigm. Since their identification in 2002/2003 by two independent groups, type III IFNs or IFN-λs, also known as IL-28/29, have been the subject of increased study with consequent recognition of their importance in virology and immunology. Initial reports suggested that IFN-λs functionally resemble type I IFNs. Although IFN-λs and classical type I IFNs (IFN-α/β) utilize distinct receptor complexes for signaling, both types of IFNs activate similar intracellular signaling pathways and biological activities, including the ability to ind... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5141757 Thu, 11 Aug 2011 23:00:00 +0100 5141757 http://www.medworm.com/index.php?rid=5141760&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840184%26dopt%3DAbstract Authors: Hall BM, Verma ND, Tran GT, Hodgkinson SJ Abstract Effector T cells have functional subpopulations with distinct cytokine, cytokine receptor, chemokine receptor and transcription factors. We review how activation of antigen specific Treg induces expression of cytokines, cytokine receptors and chemokine receptors depending upon the effector lineage they are activated by. Activated Treg express receptors that are directly related to the effector T cell lineage. Other classes of Treg are induced in the periphery from effector lineage CD4(+)CD25(-)FOXP3(-)CD127(high)T cells, either by IL-10 or TGF-β or by association with activated CD4(+)CD25(+)FOXP3(+)Treg. Thus Treg are produced and adapt to the specific immune inflammatory environment they are activated within. Activated T... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5141760 Wed, 10 Aug 2011 23:00:00 +0100 5141760 http://www.medworm.com/index.php?rid=5141759&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840185%26dopt%3DAbstract Authors: Fukuyama S, Kawaoka Y Abstract Influenza viruses cause acute respiratory inflammation in humans and symptoms such as high fever, body aches, and fatigue. Usually these symptoms improve after several days; however, the 2009 pandemic H1N1 influenza virus [influenza A(H1N1) 2009] is more pathogenic than seasonal influenza viruses and the pathogenicity of highly pathogenic H5N1 viruses is still higher. The 1918 influenza pandemic virus caused severe pneumonia, resulting in an estimated 50 million deaths worldwide. Several virulence factors have been identified in these virus strains, but host factors are also responsible for the pathogenesis of infections caused by virulent viruses. Here, we review the contributions of both virus and host factors to the pathogenesis of these v... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5141759 Wed, 10 Aug 2011 23:00:00 +0100 5141759 http://www.medworm.com/index.php?rid=5141758&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840186%26dopt%3DAbstract Authors: Szefler SJ, Dakhama A Abstract Although national asthma guidelines help organize standards for asthma care, current asthma management is still primarily symptom based. Recent reports provide insights on how to improve asthma management through steps to better understand the natural history of asthma, individualize asthma care, reduce asthma exacerbations, manage inner city asthma, and some potential new ways to use available medications to improve asthma control. Despite many significant gains in managing asthma, we must now find improved strategies to prevent asthma exacerbations, alter the natural history of the disease, and to reduce health disparities in asthma care. Perhaps new directions in personalized medicine including a systems biology approach, along with improv... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5141758 Wed, 10 Aug 2011 23:00:00 +0100 5141758 http://www.medworm.com/index.php?rid=5141762&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839623%26dopt%3DAbstract Authors: Barker BR, Taxman DJ, Ting JP Abstract The inflammasome-forming NLRs are well characterized members of a protein complex mediating the activation of caspase-1 and the cleavage of pro-IL-1β and pro-IL-18 into their active, secreted forms. New data suggest that components of the inflammasome cascade may have roles in influencing inflammasome-independent pathways of cytokine production. These influences on other immune cytokine pathways are complemented by data suggesting that non-inflammasome cytokines can influence the activation of the inflammasome, either directly or by influencing transcription of inflammasome components. The crosstalk between these cytokine cascades may lead to increased abilities for the cell to respond to diverse pathogen threats. PMID: 21839623 ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5141762 Tue, 09 Aug 2011 23:00:00 +0100 5141762 http://www.medworm.com/index.php?rid=5141761&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839624%26dopt%3DAbstract Authors: Regateiro FS, Howie D, Cobbold SP, Waldmann H Abstract TGF-β is a cytokine required for the induction and maintenance of transplantation tolerance in animal models. TGF-β mediates anti-inflammatory effects by acting on many immune cell-types. Central for transplantation tolerance is the role for TGF-β in the induction of Foxp3 and regulatory capacity in CD4(+) T cells. Recently, however, the general anti-inflammatory role of TGF-β in CD4(+) T cell polarization was questioned by the discovery that, in the presence of inflammatory cytokines such as IL-6 or IL-1, TGF-β drives the differentiation of Th17 cells associated with transplant rejection. A better understanding of the factors determining TGF-β production and activation, Foxp3 induction and Treg stability is vita... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5141761 Tue, 09 Aug 2011 23:00:00 +0100 5141761 http://www.medworm.com/index.php?rid=5141763&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21831621%26dopt%3DAbstract Authors: Hancock WW, Turka LA PMID: 21831621 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5141763 Sun, 07 Aug 2011 23:00:00 +0100 5141763 http://www.medworm.com/index.php?rid=5105394&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802931%26dopt%3DAbstract Authors: Lees JR, Azimzadeh AM, Bromberg JS Myeloid derived suppressor cells (MDSC) are a heterogeneous population of hematopoietic derived cell precursors that can suppress immune responses in a variety of inflammatory settings. Here we review recent studies detailing expansion of phenotypically and functionally disparate MDSC. Findings related to MDSC accumulation, activation, and mechanisms utilized in immune suppression are presented. Further, we discuss recent reports that suggest MDSC are expanded during transplantation and that modulation of MDSC can participate in preventing graft rejection. PMID: 21802931 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5105394 Wed, 27 Jul 2011 23:00:00 +0100 5105394 http://www.medworm.com/index.php?rid=5105395&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802270%26dopt%3DAbstract Authors: Edinger M, Hoffmann P The adoptive transfer of donor-type CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) protects from graft-versus-host disease in murine bone marrow transplantation models. Results from first clinical trials exploring such strategies have recently been presented and seem to confirm the efficacy of Treg for the prevention of this severe complication after allogeneic stem cell transplantation. Further improvements in Treg isolation and in vitro expansion technologies will facilitate the broader exploration of Treg therapies, for example, for the treatment of ongoing graft-versus-host disease or the prevention of graft rejection after solid organ transplantation. PMID: 21802270 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5105395 Tue, 26 Jul 2011 23:00:00 +0100 5105395 http://www.medworm.com/index.php?rid=5105396&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21798734%26dopt%3DAbstract Authors: Beier UH, Akimova T, Liu Y, Wang L, Hancock WW Lysine ɛ-acetylation is a post-translational modification that alters the biochemical properties of many proteins. The reaction is catalyzed by histone/protein acetyltransferases (HATs), and is reversed by histone/protein deacetylases (HDACs). As a result, HATs and HDACs constitute an important, though little recognized, set of proteins that control the functions of T-regulatory (Treg) cells. Targeting certain HDACs, especially HDAC6, HDAC9, and Sirtuin-1 (Sirt1), can augment Treg suppressive potency by several distinct and potentially additive mechanisms. These involve promoting Forkhead box p3 (Foxp3) gene expression and preserving Foxp3 lysine ɛ-acetylation, which infers resistance to ubiquitination and proteasomal degradatio... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5105396 Mon, 25 Jul 2011 23:00:00 +0100 5105396 http://www.medworm.com/index.php?rid=5105397&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782404%26dopt%3DAbstract Curr Opin Immunol. 2011 Jul 20; Authors: Grubeck-Loebenstein B, Cambier J PMID: 21782404 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5105397 Tue, 19 Jul 2011 23:00:00 +0100 5105397 http://www.medworm.com/index.php?rid=5058467&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763117%26dopt%3DAbstract Authors: Ashida H, Ogawa M, Mimuro H, Kobayashi T, Sanada T, Sasakawa C The intestinal mucosa is equipped with multiple innate immune defense systems that sense bacterial infection, transmit alarm signals to the immune system, defeat intruding bacteria, and renew damaged and aging epithelial cells. Nevertheless, mucosal bacterial pathogens have versatile pathogenic mechanisms that modulate the host inflammatory and immune responses, manipulate host cell death and survival signal pathways, and renovate the injured epithelium. These properties enable pathogens to adapt to the intestinal mucosal environment, exploit cellular and immune functions, and facilitate infection. Here we review current topics on host defense mechanisms against bacterial infection and the countermeasures that Shig... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5058467 Tue, 12 Jul 2011 23:00:00 +0100 5058467 http://www.medworm.com/index.php?rid=5058466&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763118%26dopt%3DAbstract Authors: Gravekamp C Cancer vaccination is less effective at old than at young age, due to T cell unresponsiveness, caused by various age-related changes of the immune system. This includes lack of naïve T cells, defects in activation pathways of T cells and antigen-presenting cells (APC), and age-related changes in the tumor microenvironment. Although evidence exists that also natural killer (NK) and natural killer T (NKT) cells of the innate immune system change with age, comparison of various studies involving adaptive and innate immune responses in elderly and cancer patients, as well as cancer vaccination at young and old age in this review, indicates that also innate immune responses should be tested as a potential candidate to improve immunotherapy against cancer at older age. ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5058466 Tue, 12 Jul 2011 23:00:00 +0100 5058466 http://www.medworm.com/index.php?rid=5058470&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752617%26dopt%3DAbstract Authors: López CB, Hermesh T Type I IFNs are well known for their role in controlling virus replication and spread. Type I IFNs produced by the infected tissue also signal beyond the boundaries of the infection to regulate different elements of the anti-viral immune response. Recent reports show that type I IFNs directly condition naive monocytes residing in the distal bone marrow (BM) and induce the expression of effector molecules in memory T cells, before their recruitment to the infected site. In addition, hematopoietic stem cells (HSCs) were shown to enter the cell cycle in response to systemically distributed type I IFNs. These discoveries expand our understanding of the pleiotropic effects of type I IFNs during infection and highlight the critical role of systemic signals in th... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5058470 Sun, 10 Jul 2011 23:00:00 +0100 5058470 http://www.medworm.com/index.php?rid=5058469&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752618%26dopt%3DAbstract Authors: Sauce D, Appay V The thymus is responsible for the maturation of lymphoid precursors into T cells, and is necessary to establish the T cell pool during prenatal and early postnatal life in humans. With the years, it undergoes a natural shrinking process, referred to as involution, suspected to be central in the decline of immune competence with aging, or immunosenescence. Here, we review the recent studies focusing on the immunological consequences of abnormal thymic development and thymectomy shortly after birth. These works highlight the importance of the thymic function in preserving immune efficacy throughout life, and provide insights into the development of immune aging. PMID: 21752618 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5058469 Sun, 10 Jul 2011 23:00:00 +0100 5058469 http://www.medworm.com/index.php?rid=5058468&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752619%26dopt%3DAbstract Authors: Issa F, Chandrasekharan D, Wood KJ Chronic allograft dysfunction (CAD) in solid organ transplantation is a principal cause of patient morbidity and late allograft loss. The pathogenesis of CAD is largely secondary to chronic damage by the adaptive immune system and long-term immunosuppression. Manipulating these factors may be possible with the use of regulatory T cells (Treg), which have the ability to suppress specific immune responses and therefore potentially remove the need for immunosuppressive drugs. Studies of CAD in experimental models have demonstrated the capacity for both mouse and human Treg cellular therapy to prevent the development of some manifestations of CAD. Furthermore, a role for Treg has been demonstrated in clinically tolerant transplant patients. Certa... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5058468 Sun, 10 Jul 2011 23:00:00 +0100 5058468 http://www.medworm.com/index.php?rid=5010461&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726990%26dopt%3DAbstract Authors: Huynh KK, Joshi SA, Brown EJ Mycobacterium tuberculosis is an enormously successful human pathogen that can infect its host for decades without causing clinical disease, only to reactivate when host immunity is compromised. A normal immune response thus contains bacterial spread without inducing sterilizing immunity, therefore benefitting both host and pathogen. Recent work has begun to outline the complexity of this host-pathogen interaction and to reveal how the homeostatic balance between the two is achieved. This review focuses on two significant aspects of this delicate dance: the host's initial innate response and the mature granuloma that later contains the pathogen. Here, we review the fine balance of inflammatory events triggered or controlled by both the host and bac... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5010461 Fri, 01 Jul 2011 23:00:00 +0100 5010461 http://www.medworm.com/index.php?rid=5010460&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726991%26dopt%3DAbstract Authors: Kaiser P, Hardt WD The mammalian intestine is a complex biological system composed of the epithelium, the gut associated immune system, a commensal microbial community of approx. 10(10) cells per gram of content ('microbiota') and an occasional onslaught by pathogens. The mechanisms governing homeostasis and immune defense are of great importance, but incompletely understood. This is explained by the system's sheer complexity. So far, no single study has considered all relevant parameters, that is (i) innate and adaptive mucosal immune responses; (ii) mucosa cell gene expression; (iii) community composition of the microbiota; (iv) microbiota gene expression; (v) genetic profiling of the host; (vi) the virulence complement expressed by the pathogen in vivo. This exquisite compl... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5010460 Fri, 01 Jul 2011 23:00:00 +0100 5010460 http://www.medworm.com/index.php?rid=5010462&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21719266%26dopt%3DAbstract Authors: Borrmann S, Matuschewski K Plasmodium undergoes an obligate liver phase before the onset of malaria, which is caused exclusively by cyclic propagation of the parasite inside erythrocytes. The diagnostically inaccessible and clinically silent pre-erythrocytic expansion phase is a promising target for inducing sterilizing immunity against reinfections. Recent studies in rodent and human malaria models called attention to the induction of potent protective immunity by administration of anti-malarial drugs during sporozoite exposure. Here, we review the concept of drug-mediated pathogen arrest as a natural immunization strategy. This previously unrecognized immunological benefit might also open new opportunities for population-wide presumptive drug administration as an adjunct mal... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5010462 Mon, 27 Jun 2011 23:00:00 +0100 5010462 http://www.medworm.com/index.php?rid=5010465&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21703838%26dopt%3DAbstract Authors: Holtzman MJ, Patel DA, Zhang Y, Patel AC Research on the pathogenesis of asthma has concentrated on initial stimuli, genetic susceptibilities, adaptive immune responses, and end-organ alterations (particularly in airway mucous cells and smooth muscle) as critical steps leading to disease. Recent evidence indicates that the innate immune cell response to respiratory viruses also contributes to the development of inflammatory airway disease. We further develop this concept by raising the issue that the interaction between host airway epithelial cells and respiratory viruses is another aspect of innate immunity that is also a critical determinant of asthma. We also introduce a rationale for how antiviral performance at the epithelial cell level might be improved to prevent acute ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5010465 Tue, 21 Jun 2011 23:00:00 +0100 5010465 http://www.medworm.com/index.php?rid=5010464&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21703839%26dopt%3DAbstract Authors: Lepperdinger G In adults, mesenchymal stromal cells contain tissue-specific multipotent stem cells, MSC, which can be found throughout the body. With advancing age, tight controls of regulatory networks, which guide MSC biology, gradually deteriorate. Aberrations within the MSC microenvironment such as chronic inflammation eventually lead to adverse manifestations, such as the accumulation of fat deposits in bone and muscles, impaired healing and fibrosis after severe injury, or altered hematopoiesis and autoimmunity. MSC can also specifically interact with a large variety of immune cells, and in doing so, they secrete cytoprotective and immunoregulatory molecules, which together with intercellular contacts mediate immune modulatory processes. This review comprehends the curre... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5010464 Tue, 21 Jun 2011 23:00:00 +0100 5010464 http://www.medworm.com/index.php?rid=5010463&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21703840%26dopt%3DAbstract Authors: Vukmanovic-Stejic M, Rustin MH, Nikolich-Zugich J, Akbar AN A marked increase in the susceptibility to cutaneous infections and malignancies has been observed in older humans indicating that cutaneous immunity becomes defective with age. In this review we will focus on recent developments in the understanding of age-related changes in immune function of the skin with a particular emphasis on how alterations in the interaction between cells involved in innate and adaptive immunity leads to decreased cutaneous antigen-specific T cell immunosurveillance. PMID: 21703840 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=5010463 Tue, 21 Jun 2011 23:00:00 +0100 5010463 http://www.medworm.com/index.php?rid=4962865&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664807%26dopt%3DAbstract We present novel insights gained by studying the antigen-driven differentiation of single CD8(+) T cells in young hosts and discuss possible implications of these insights for therapeutic support of the thinned-out clonal T cell repertoire of the elderly by vaccination or adoptive cell therapy. PMID: 21664807 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4962865 Wed, 08 Jun 2011 23:00:00 +0100 4962865 http://www.medworm.com/index.php?rid=4962866&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664115%26dopt%3DAbstract Authors: Woolthuis CM, de Haan G, Huls G During development hematopoietic stem cells (HSCs) expand in number and persist throughout life by undergoing self-renewing divisions. Nevertheless, the hematopoietic system does not escape the negative effects of aging, suggesting that self-renewal is not complete. A fundamental issue in stem cell biology relates to such age-dependent loss of stem cell activity. Both stem cell intrinsic factors and extrinsic factors associated with an aging micro-environment could contribute to aging of the hematopoietic system. Recently, changes in the clonal composition of the HSC compartment during aging have been put forward as a key factor. Here, we discuss these recent developments and speculate how they may be of clinical relevance. PMID: 21664115 [P... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4962866 Tue, 07 Jun 2011 23:00:00 +0100 4962866 http://www.medworm.com/index.php?rid=4915687&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21652194%26dopt%3DAbstract Authors: Blackman MA, Woodland DL Immune function declines progressively with age, resulting in increased susceptibility of the elderly to infection and impaired responses to vaccines. A diverse repertoire of T cells is essential for a vigorous immune response, and an important manifestation of immune aging is the progressive loss of repertoire diversity, predominantly among CD8 T cells in both mice and humans. Importantly, perturbations in the peripheral T cell repertoire, including reduction of the CD4:CD8 ratio and cytomegalovirus-driven T cell clonal expansions, make a major contribution to the 'immune risk phenotype' defined for humans, which predicts two-year mortality in very old individuals. PMID: 21652194 [PubMed - as supplied by publisher] (Source: Current Opinion in Immu... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4915687 Sun, 05 Jun 2011 23:00:00 +0100 4915687 http://www.medworm.com/index.php?rid=4866611&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21600751%26dopt%3DAbstract Authors: Corti D, Sallusto F, Lanzavecchia A There is growing consensus for an urgent need to develop efficient methods to analyze the human T and B cell response in order to understand its regulation, to unravel host-pathogen interactions and to design better vaccines. In this review we will consider different methods that have been developed to analyze human T and B cells and focus in particular on those based on high-throughput cell culture, such as memory B cell immortalization, plasma cell cultures and libraries of naïve or memory T cells. These culture-based methods can be used to interrogate with high efficiency the immune repertoires in order to characterize the frequency, function and specificity of naïve or memory T cells and to isolate potent and broadly neutralizing monoc... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4866611 Tue, 17 May 2011 23:00:00 +0100 4866611 http://www.medworm.com/index.php?rid=4866612&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21570272%26dopt%3DAbstract Authors: Oberg AL, Kennedy RB, Li P, Ovsyannikova IG, Poland GA The current 'isolate, inactivate, inject' vaccine development strategy has served the field of vaccinology well, and such empirical vaccine candidate development has even led to the eradication of smallpox. However, such an approach suffers from limitations, and as an empirical approach, does not fully utilize our knowledge of immunology and genetics. A more complete understanding of the biological processes culminating in disease resistance is needed. The advent of high-dimensional assay technology and 'systems biology' along with a vaccinomics approach [1,2(•)] is spawning a new era in the science of vaccine development. Here we review recent developments in systems biology and strategies for applying this approach and... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4866612 Tue, 10 May 2011 23:00:00 +0100 4866612 http://www.medworm.com/index.php?rid=4866613&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561752%26dopt%3DAbstract Authors: Cornelissen F, Domingo PA, Reijmers RM, Cupedo T Innate lymphoid cells expressing the nuclear hormone receptor RORC have emerged as important players in human mucosal immunity. These cells combine innate modes of activation such as Toll-like receptor signaling with secretion of adaptive effector molecules including IL-2, BAFF and the Th17 cytokines IL-17 and IL-22. This endows these cells with the ability to rapidly respond to changes in cytokine milieu as well as changes in microbial composition and to affect both intestinal homeostasis and activation of adaptive immune cells. PMID: 21561752 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4866613 Sun, 08 May 2011 23:00:00 +0100 4866613 http://www.medworm.com/index.php?rid=4653808&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21439803%26dopt%3DAbstract Authors: Storck S, Aoufouchi S, Weill JC, Reynaud CA Post-rearrangement diversification of the antibody repertoire relies on a DNA editing factor, the cytidine deaminase AID. How B lymphocytes avoid generalized mutagenesis while expressing high levels of AID remained a long-standing question. Genome-wide studies of AID targeting combined to the discovery of several co-factors controlling its recruitment and its local activity shed new light on this enigma. PMID: 21439803 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4653808 Wed, 23 Mar 2011 00:00:00 +0100 4653808 http://www.medworm.com/index.php?rid=4591874&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21353514%26dopt%3DAbstract Authors: Belver L, Papavasiliou FN, Ramiro AR MicroRNAs (miRNAs) are a class of endogenous, non-coding regulatory RNAs that control gene regulation by guiding silencing protein complexes to mRNA in a sequence-dependent manner. In this way miRNAs are able to repress gene expression post-transcriptionally by affecting mRNA stability or translation. These ubiquitous molecules play central roles in a wide range of biological processes, including cell proliferation, differentiation and apoptosis. Within the context of the immune system, genetic studies have identified distinct roles for specific miRNAs in gene regulation during development, activation and maturation. Conversely, dysregulation of miRNA expression has been specifically correlated with cancer. This review outlines our current ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4591874 Thu, 24 Feb 2011 00:00:00 +0100 4591874 http://www.medworm.com/index.php?rid=4591873&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21353515%26dopt%3DAbstract Authors: Chen K, Cerutti A Recent discoveries of IgD in ancient vertebrates suggest that IgD has been preserved in evolution from fish to human for important immunological functions. A non-canonical form of class switching from IgM to IgD occurs in the human upper respiratory mucosa to generate IgD-secreting B cells that bind respiratory bacteria and their products. In addition to enhancing mucosal immunity, IgD class-switched B cells enter the circulation to 'arm' basophils and other innate immune cells with secreted IgD. Although the nature of the IgD receptor remains elusive, cross-linking of IgD on basophils stimulates release of immunoactivating, proinflammatory and antimicrobial mediators. This pathway is dysregulated in autoinflammatory disorders such as hyper-IgD syndrome, indi... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4591873 Thu, 24 Feb 2011 00:00:00 +0100 4591873 http://www.medworm.com/index.php?rid=4591875&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21324660%26dopt%3DAbstract Authors: Engels N, Wienands J Triggering lymphocyte effector functions is controlled by a diverse array of immune cell coreceptors that dampen or potentiate the primary activation signal from antigen receptors. Attenuation of lymphocyte activation has been shown to be accomplished by immunoreceptor tyrosine-based inhibition motifs that upon phosphorylation recruit protein or lipid phosphatases. By contrast, a general concept of signal amplification and/or diversification is still out. However, the recent discovery of antigen receptor-intrinsic costimulation by membrane-bound immunoglobulins in class-switched memory B cells identified a consensus phosphorylation motif that can boost antigen-induced signal chains and is also employed by costimulatory receptors on T and Natural Killer cel... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4591875 Mon, 14 Feb 2011 00:00:00 +0100 4591875 http://www.medworm.com/index.php?rid=4477746&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21300532%26dopt%3DAbstract Authors: Oltz E, Hogquist K PMID: 21300532 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4477746 Sat, 05 Feb 2011 00:00:00 +0100 4477746 http://www.medworm.com/index.php?rid=4477747&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21295956%26dopt%3DAbstract Authors: Lampen MH, van Hall T Defects in MHC-I antigen presentation represent a common feature of cancer and allow evasion from T cell recognition. Recent findings from immunotherapy in melanoma suggested that irreversible MHC-I defects enable escape from immune pressure. Although loss of antigen presentation is known for many years, strategies to counteract these defects are scarce and largely unexamined. Now that the first forms of T-cell-based immunotherapy show clinical efficacy and reach FDA approval, this issue deserves urgent awareness. Here we describe possible roads leading to corrections of MHC-I defects in tumors and describe a salvage pathway for CTL by targeting novel tumor antigens that we recently uncovered. PMID: 21295956 [PubMed - as supplied by publisher] (Source... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4477747 Thu, 03 Feb 2011 00:00:00 +0100 4477747 http://www.medworm.com/index.php?rid=4477748&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21295456%26dopt%3DAbstract Authors: Kothapalli NR, Fugmann SD Activation-induced cytidine deaminase (AID) is a key enzyme for antibody-mediated immune responses. Antibodies are encoded by the immunoglobulin genes and AID acts as a transcription-dependent DNA mutator on these genes to improve antibody affinity and effector functions. An emerging theme in field is that many transcribed genes are potential targets of AID, presenting an obvious danger to genomic integrity. Thus there are mechanisms in place to ensure that mutagenic outcomes of AID activity are specifically restricted to the immunoglobulin loci. Cis-regulatory targeting elements mediate this effect and their mode of action is probably a combination of immunoglobulin gene specific activation of AID and a perversion of faithful DNA repair towards error... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4477748 Wed, 02 Feb 2011 00:00:00 +0100 4477748 http://www.medworm.com/index.php?rid=4477749&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21292460%26dopt%3DAbstract Authors: Melief CJ, Finn OJ PMID: 21292460 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4477749 Tue, 01 Feb 2011 00:00:00 +0100 4477749 http://www.medworm.com/index.php?rid=4477751&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277760%26dopt%3DAbstract Authors: Baracho G, Miletic A, Omori S, Cato M, Rickert R Phosphoinositide 3-kinase (PI3K) defines a family of lipid kinases that direct a wide range of cellular processes and cell fate decisions. Since its discovery, and that of its enzymatic antagonist PTEN, much of the focus on PI3K has been on its oncogenic potential. In recent years, studies on PI3K signaling in B lymphocytes have established the importance of this pathway in effecting B cell differentiation and associated molecular events such as V(D)J recombination and class switch recombination. Intriguing new findings also indicate that there is specificity in the PI3K pathway in B cells, including preferential expression or usage of particular PI3K isoforms and counter-regulation by the PTEN and SHIP phosphatases. The role of... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4477751 Fri, 28 Jan 2011 00:00:00 +0100 4477751 http://www.medworm.com/index.php?rid=4477750&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277761%26dopt%3DAbstract Authors: Cramer DW, Finn OJ Common 'themes' in epidemiology related to cancer risk beg a comprehensive mechanistic explanation. As people age, risk for cancer increases. Obesity and smoking increase the risk for many types of cancer. History of febrile childhood diseases lowers the risk for melanomas, leukemias, non-Hodgkin's lymphoma (NHL), and ovarian cancer. Increasing number of ovulatory cycles uninterrupted by pregnancies correlate positively with breast, endometrial, and ovarian cancer risk while pregnancies and breastfeeding lower the risk for these cancers as well as cancers of the colon, lung, pancreas, and NHL. Chronic inflammatory events such as endometriosis or mucosal exposure to talc increase the risk for several types of cancer. Mechanisms so far considered are site spec... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4477750 Fri, 28 Jan 2011 00:00:00 +0100 4477750 http://www.medworm.com/index.php?rid=4412618&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21269819%26dopt%3DAbstract Authors: Long HM, Taylor GS, Rickinson AB Epstein-Barr virus (EBV), a B-lymphotropic herpesvirus widespread in the human population and normally contained as an asymptomatic infection by T cell surveillance, nevertheless causes infectious mononucleosis and is strongly linked to several types of human cancer. Here we describe new findings on the range of cellular immune responses induced by EBV infection, on viral strategies to evade those responses and on the links between HLA gene loci and EBV-induced disease. The success of adoptive T cell therapy for EBV-driven post-transplant lymphoproliferative disease is stimulating efforts to target other EBV-associated tumours by immunotherapeutic means, and has reawakened interest in the ultimate intervention strategy, a prophylactic EBV vacci... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4412618 Mon, 24 Jan 2011 00:00:00 +0100 4412618 http://www.medworm.com/index.php?rid=4412620&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21257299%26dopt%3DAbstract Authors: Alonzo ES, Sant'angelo DB Recent studies have shown that the transcriptional regulator promyelocytic leukemia zinc finger (PLZF) controls the development of essentially all of the innate-like features of invariant Natural Killer T (NKT) cells. For example, PLZF-deficient NKT cells do not acquire an 'activated' phenotype nor do they acquire the capacity to secrete multiple cytokines upon primary stimulation. The function of a subset of γδ T cells has now also been shown to be dependent upon expression of PLZF. Furthermore, IL-4 produced by PLZF-expressing cells causes some CD8 T cells to acquire innate-like features. Therefore, it is becoming clear that PLZF has a broad impact on the immune response. Here we discuss the current understanding of how expression of PLZF, the inn... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4412620 Fri, 21 Jan 2011 00:00:00 +0100 4412620 http://www.medworm.com/index.php?rid=4412619&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21257300%26dopt%3DAbstract Authors: Huang LM, Lu CY, Chen DS Hepatitis B virus (HBV) infection is a global health problem. There are >350 million of people chronically infected with this virus worldwide. Hepatitis B vaccines are effective in preventing the infection. Humoral immunity is the key factor in conferring the protection. Hepatitis B surface antibody titers of ≥10mIU/mL are protective. Chronic carriage of HBV is related to the age when the infection occurs, the younger the age the higher the chronicity rate. Hence, vaccination should be given in early childhood. People vaccinated in infancy have a protection of >20 years, and hepatocellular carcinoma decreases in them. Although the vaccine-conferred immunity wanes by time, a universal booster is not recommended at present. PMID: 21257300 [Pu... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4412619 Fri, 21 Jan 2011 00:00:00 +0100 4412619 http://www.medworm.com/index.php?rid=4412621&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21242076%26dopt%3DAbstract Authors: Gascoigne NR, Palmer E T cell receptor signaling allows the developing thymocyte to undergo positive or negative selection, which is required for the formation of a useful mature T cell repertoire. Recent developments include the finding that much of the Lck kinase (required to initiate T cell signaling) is already in an active configuration before signaling. The analog strength of antigen binding to the T cell receptor binding may be translated into a digital signal by the amount of time the TCR is paired with a co-receptor carrying Lck. Downstream, the cellular localization of MAP kinase signaling is determined by the strength of the signal and in turn predicts positive or negative selection. A novel protein, Themis, is important in crossing the positive selection developmen... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4412621 Sat, 15 Jan 2011 00:00:00 +0100 4412621 http://www.medworm.com/index.php?rid=4412622&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239155%26dopt%3DAbstract Authors: Barber GN The early detection of microbes is the responsibility of the innate immune system which has evolved to sense pathogen derived molecules such as lipopolysaccharides and non-self nucleic acid, to trigger host defense countermeasures. These sensors include the RIG-I-like helicase (RLH) family that specifically recognizes viral RNA, as well as the cytoplasmic, nucleotide binding oligermerization domain (NOD)-like receptor and Toll-like receptor (TLR) pathways that sense a variety of microbial derived molecules. Comprehending how the cell senses foreign DNA, generated by certain viruses, bacteria and possibly parasites has proven elusive but is of significant importance since such information could shed insight into the causes of microbial related disease, including viral... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4412622 Fri, 14 Jan 2011 00:00:00 +0100 4412622 http://www.medworm.com/index.php?rid=4412625&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21237630%26dopt%3DAbstract Authors: Turtle CJ, Riddell SR The extraordinary sensitivity and specificity of T cells for their cognate antigen make them a highly attractive cancer therapeutic. However, the rarity of tumor-reactive T cells in cancer patients, the difficulty isolating them in sufficient numbers for adoptive immunotherapy, and the unpredictable persistence of transferred cells have been significant obstacles to broad application. Technologies that enable genetic modification of T cells have been refined and are being used to redirect the specificity of T cells to tumor antigens. An issue the field is now grappling with is how the diverse phenotypic and functional heterogeneity in T cells that could potentially be genetically modified can be capitalized upon to enhance the efficacy, safety, and reprod... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4412625 Thu, 13 Jan 2011 00:00:00 +0100 4412625 http://www.medworm.com/index.php?rid=4412624&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21237631%26dopt%3DAbstract Authors: Fridman WH, Mlecnik B, Bindea G, Pagès F, Galon J Immunosurveillance of infections and therefore of viral-induced cancers is well admitted but that of nonviral cancers is a matter of hot debate. In the recent years, data collected from large libraries of human cancers demonstrated that the immune contexture of the primary tumors is an essential prognostic factor for patients' disease-free and overall survival. The location in the tumor's center and invasive margin, the coordination of a memory Th1/cytotoxic T cell infiltrate, and the expression of genes involved in angiogenesis, chemotaxis, and cell adhesion are key factors for an immune control of disease progression. Systems biology predicted markers shaping an efficient immune reaction can serve as tools and targets for no... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4412624 Thu, 13 Jan 2011 00:00:00 +0100 4412624 http://www.medworm.com/index.php?rid=4412623&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21237632%26dopt%3DAbstract Authors: van der Burg SH, Melief CJ Human Papilloma Virus (HPV)-induced (pre-)malignancies offer an excellent case for the rational design of immunotherapeutic strategies against cancer. Transformed cells express tumor-specific antigens of viral origin while the spontaneous antitumor response and the immunological make up of HPV-induced tumors do not differ from other immunogenic epithelial tumors. A first clinically active therapeutic HPV vaccine has been developed and clear links were found between the type and kinetics of vaccine-induced T-cell immunity. Here, we will review the mechanisms determining the success and failure of therapeutic vaccines against HPV-induced tumors, with particular emphasis on the immunological setting in which these vaccines need to work. The recent progr... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4412623 Thu, 13 Jan 2011 00:00:00 +0100 4412623 http://www.medworm.com/index.php?rid=4412626&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21236654%26dopt%3DAbstract Authors: Santos PM, Borghesi L The progression of hematopoietic stem cells (HSCs) to the B lymphocyte lineage requires that uncommitted progenitors successfully negotiate the transition from multipotency to unipotency, including the loss of self-renewal potential. Previous work identified essential transcription factors that mediate B lineage development. Major advances build on this knowledge and reveal coordinated changes in gene expression occurring within single cells at sequential stages in the B cell differentiation pathway. Recent studies on epigenetic mechanisms also provide a framework within which transcription factor activity, chromatin modifications, and gene expression patterns can be viewed at hierarchical levels to link genotype and phenotype. PMID: 21236654 [PubMed ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4412626 Wed, 12 Jan 2011 00:00:00 +0100 4412626 http://www.medworm.com/index.php?rid=4349732&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21227670%26dopt%3DAbstract Authors: Sonda N, Chioda M, Zilio S, Simonato F, Bronte V In normal hematopoiesis, differentiation and maturation of cell populations belonging to various lineages are tightly regulated by the interaction of many transcription factors. The relative numbers of different myeloid cells depends on their proliferative/apoptotic rate, while their identity relates to their recruitment to the sites of action and the expression of specific genes regulating their function. Under pathological conditions, as during chronic inflammation and cancer development, an aberrant hematopoiesis occurs, with the consequent expansion of myeloid-derived suppressor cells (MDSCs). These cells have distinctive properties that determine their ability to tune down the immune system by principally inactivating CD8(+... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4349732 Mon, 10 Jan 2011 00:00:00 +0100 4349732 http://www.medworm.com/index.php?rid=4349730&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21227671%26dopt%3DAbstract Authors: Hsu E Lamprey and hagfish are surviving representatives of the most ancient vertebrates. They possess adaptive immune systems based on a vast, somatically diversified repertoire of lymphocyte-bound antigen receptors. Despite these similarities to antibody and T cell receptors (TCR) of later vertebrates, the variable lymphocyte receptors (VLR) are not related to the immunoglobulin (Ig)-superfamily of genes; and instead of V(D)J recombination VLR are somatically assembled by a gene conversion process. However, recent studies have revealed two lamprey lymphocyte subsets so closely resembling B cells and T cells that separate lymphocyte lineages must have already existed in the ancestral vertebrate, before Ig/TCR emergence. VLR and Ig/TCR arose independently, but the convergent ev... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4349730 Mon, 10 Jan 2011 00:00:00 +0100 4349730 http://www.medworm.com/index.php?rid=4349734&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216580%26dopt%3DAbstract Authors: Feeney AJ Recent studies of the regulation of antigen receptor rearrangement have revealed several completely new levels of control. Not only do antigen receptor loci undergo changes in histone modifications as they become accessible for recombination, but also the number of different histone modifications and the variation at different parts of each receptor locus reveal great complexity. RAG2 is now known to bind to one of these histone modifications, H3K4me3, and this targets the initial RAG binding events to the J genes. The large megabase receptor loci undergo 3D changes in their structure during rearrangement, and receptor loci move throughout the nucleus, transiently binding to heterochromatin, and transiently pairing with each other. RAG-mediated DNA breaks promote som... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4349734 Fri, 07 Jan 2011 00:00:00 +0100 4349734 http://www.medworm.com/index.php?rid=4349736&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21194915%26dopt%3DAbstract Authors: Nitta T, Ohigashi I, Nakagawa Y, Takahama Y The medullary microenvironment of the thymus plays a crucial role in the establishment of self-tolerance through the deletion of self-reactive thymocytes and the generation of regulatory T cells. Crosstalk or bidirectional signal exchanges between developing thymocytes and medullary thymic epithelial cells (mTECs) contribute to the formation of the thymic medulla. Recent studies have identified the molecules that mediate thymic crosstalk. Tumor necrosis factor superfamily cytokines, including RANKL, CD40L, and lymphotoxin, produced by positively selected thymocytes and lymphoid tissue inducer cells promote the proliferation and differentiation of mTECs. In return, CCR7 ligand chemokines produced by mTECs facilitate the migration of p... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4349736 Wed, 29 Dec 2010 00:00:00 +0100 4349736 http://www.medworm.com/index.php?rid=4349740&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21190820%26dopt%3DAbstract Authors: van den Elsen PJ, McCluskey J PMID: 21190820 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4349740 Mon, 27 Dec 2010 00:00:00 +0100 4349740 http://www.medworm.com/index.php?rid=4349738&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21190821%26dopt%3DAbstract Authors: Magalhaes JG, Sorbara MT, Girardin SE, Philpott DJ Over the last few years, much research has focused on determining the function of members of the cytosolic Nod-like receptor (NLR) family in terms of their triggers and the signaling pathways that they control. Members of this family include the NLRP proteins, which play a role in sensing both microbial and danger signals and triggering the caspase-1 dependent inflammasome, and the Nod subfamily characterized by proteins with a caspase-activating and recruitment domain (CARD) or a so-called 'X' domain. Nod1, Nod2, NLRX1 and NLRC5 are all members of this subfamily and in this review, we will focus on recent work that has shown the importance of these molecules in both pathogen sensing and regulation of innate and adaptive immun... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4349738 Mon, 27 Dec 2010 00:00:00 +0100 4349738 http://www.medworm.com/index.php?rid=4349746&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21185705%26dopt%3DAbstract Authors: Gajewski TF, Fuertes M, Spaapen R, Zheng Y, Kline J The molecular identification of tumor antigens initially catalyzed substantial enthusiasm for the development of tumor antigen-based vaccines for the treatment of cancer. However, numerous vaccine approaches in melanoma and other cancers have yielded a low rate of clinical response, despite frequent induction of specific T cells as detected in the peripheral blood. This observation has prompted several investigators to begin interrogating the tumor microenvironment for biologic correlates to tumor response versus resistance. Evidence is beginning to emerge suggesting that distinct subsets of tumors may exist that reflect distinct categories of immune escape. Lack of chemokine-mediated trafficking, poor innate immune cell acti... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4349746 Thu, 23 Dec 2010 00:00:00 +0100 4349746 http://www.medworm.com/index.php?rid=4349743&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21185706%26dopt%3DAbstract Authors: Kwak K, Yemelyanova A, Roden RB Oncogenic human papillomaviruses (HPVs) are exclusively mucosal pathogens that are noncytopathic and the basal epithelial cells harboring and maintaining an infection do not produce either capsid antigen or virus. The efficacy of the licensed L1 virus-like particle (VLP) vaccines has encouraged development of several second generation vaccines aimed at expanding the coverage to all oncogenic HPV types and reducing barriers to global implementation. Currently there is no defined immune correlate of protection that can be used to determine if an individual patient is protected and for the evaluation of these second generation vaccines. Surprisingly, passive transfer of neutralizing serum antibody is protective in animal models. Recent studies sugg... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4349743 Thu, 23 Dec 2010 00:00:00 +0100 4349743 http://www.medworm.com/index.php?rid=4349742&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21185707%26dopt%3DAbstract Authors: Glimcher LH, Martinon F, Modlin RL PMID: 21185707 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4349742 Thu, 23 Dec 2010 00:00:00 +0100 4349742 http://www.medworm.com/index.php?rid=4280996&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21169001%26dopt%3DAbstract Authors: Unger WW, van Kooyk Y Current strategies in immunotherapy for the treatment of tumors or autoimmunity focus on direct in vivo targeting of antigens to dendritic cells (DC), as these cells are the key regulators of immune responses. Multiple DC subsets can be distinguished in both humans and mice, based on phenotype and location. Moreover, recent data show that these subsets have distinct functions. All these features have implications for the design of DC-targeting vaccines. In this review we integrate recent knowledge on the different DC subsets in human and mice and how DC-expressed C-type lectin receptors (CLR) can be exploited for the induction of either antigen-specific immunity or tolerance. PMID: 21169001 [PubMed - as supplied by publisher] (Source: Current Opinion ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4280996 Fri, 17 Dec 2010 00:00:00 +0100 4280996 http://www.medworm.com/index.php?rid=4280997&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21168318%26dopt%3DAbstract Authors: Lukacs-Kornek V, Turley SJ The induction and maintenance of T cell tolerance is essential to prevent autoimmunity. A combination of central and peripheral mechanisms acts to control autoreactive T cells. In secondary lymphoid organs, dendritic cells (DCs) presenting self-antigen were thought to play a major role in the induction of peripheral T cell tolerance. Multiple recent studies have demonstrated that DCs are not absolutely essential to induce and maintain tolerance. Furthermore, it has also been recently shown that non-hematopoietic stromal cells expressing peripheral tissue-restricted antigens can induce T cell tolerance, independently of DCs. Together these studies imply that peripheral tolerance is more complex than previously thought and a consequence of the toleroge... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4280997 Thu, 16 Dec 2010 00:00:00 +0100 4280997 http://www.medworm.com/index.php?rid=4280998&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21163636%26dopt%3DAbstract Authors: Anderson MS, Su MA In the thymus, developing T cells that react against self-antigens with high affinity are deleted in the process of negative selection. An essential component of this process is the display of self-antigens, including those whose expression are usually restricted to specific tissues, to developing T cells within the thymus. The Autoimmune Regulator (Aire) gene plays a crucial role in the expression of tissue specific self-antigens within the thymus, and disruption of Aire function results in spontaneous autoimmunity in both humans and mice. Recent advances have been made in our understanding of how Aire influences the expression of thousands of tissue-specific antigens in the thymus. Additional roles of Aire, including roles in chemokine and cytokine express... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4280998 Tue, 14 Dec 2010 00:00:00 +0100 4280998 http://www.medworm.com/index.php?rid=4280999&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21159498%26dopt%3DAbstract Authors: Held W, Kijima M, Angelov GS, Bessoles S The effector response of natural killer (NK) cells is determined by opposing signals received through activating and inhibitory receptors. A process termed NK cell education, which is guided by the recognition of Major Histocompatibility Complex class I (MHC-I) molecules, determines how efficiently activating receptors respond to stimulation. This ensures NK cell tolerance to healthy tissues while allowing robust responses to diseased host cells. It was thought that NK cells are educated during their development in the bone marrow and that education fixes the NK cells' functional properties. However, recent findings suggest that the function of mature peripheral NK cells can adapt to changes in their environment and that the persistent ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4280999 Mon, 13 Dec 2010 00:00:00 +0100 4280999 http://www.medworm.com/index.php?rid=4281001&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21146971%26dopt%3DAbstract Authors: Ewald SE, Barton GM Trafficking and activation of the nucleic acid sensing TLRs is subject to unique regulatory requirements imposed by the risk of self-recognition. Like all TLRs these receptors traffick through the Golgi, however, access to the secretory pathway is controlled by a binding partner present in the ER. Receptor activation in the endolysosome is regulated through a proteolytic mechanism that requires activity of compartment-resident proteases, thereby preventing activation in other regions of the cell. Advances in our understanding of the cell biology of these receptors have been paralleled by efforts to understand their precise roles in autoimmunity. Mouse models have revealed that TLR7 and TLR9 make unique contributions to the types of self-molecules recognized... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4281001 Fri, 10 Dec 2010 00:00:00 +0100 4281001 http://www.medworm.com/index.php?rid=4281000&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21146972%26dopt%3DAbstract Authors: Lio CW, Hsieh CS The generation of Foxp3(+) regulatory T (Treg) cells in the thymus is essential for immune homeostasis. In the past several years, substantial progress has been made in understanding the mechanisms by which a minor portion of developing thymocytes are selected to become Treg cells. Although previously controversial, recent data support the importance of TCR specificity as a primary determinant for selecting self-reactive thymocytes to become Treg cells in a multi-step process involving cytokines, co-stimulatory molecules, and a variety of antigen-presenting cells. Importantly, the antigenic niche for Treg cell development appears to be typically quite small, implying the recognition of tissue-specific, rather than ubiquitous, self-antigens. Finally, it appears... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4281000 Fri, 10 Dec 2010 00:00:00 +0100 4281000 http://www.medworm.com/index.php?rid=4281002&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21146386%26dopt%3DAbstract Authors: Horst D, Verweij MC, Davison AJ, Ressing ME, Wiertz EJ Upon infecting a host, viruses are confronted by a coordinated and multi-faceted immune response. Indeed, evolutionary combat between virus and host has contributed signally to the host's development of a formidable innate and adaptive immune defense arsenal, and to the virus' acquisition of effective means to evade it. Cytotoxic T lymphocytes play a key role in the elimination of virus-infected cells, which they detect through recognition of virus-derived peptides displayed at the cell surface in the context of MHC class I molecules. This highly sensitive recognition system is a prime target for immune evasion strategies deployed by many viruses, particularly large DNA viruses such as herpesviruses and poxviruses. Elucida... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4281002 Thu, 09 Dec 2010 00:00:00 +0100 4281002 http://www.medworm.com/index.php?rid=4252667&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21131187%26dopt%3DAbstract Authors: McNab FW, Rajsbaum R, Stoye JP, O'Garra A The tripartite motif containing (TRIM) proteins are a family of proteins that have been implicated in many biological processes including cell differentiation, apoptosis, transcriptional regulation and signaling pathways. Many TRIM proteins are upregulated by the immunologically important Type I and Type II interferons and several, including TRIM5α and TRIM19/PML, restrict viral replication. There is growing evidence that TRIMs also play an important role in the broader immune response through regulating signaling pathways such as the RIG-I pathway. In this review we discuss recent research elucidating TRIM regulation of a number of pathways important in immunity and review the latest findings relating to viral restriction by TRIMs. ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4252667 Fri, 03 Dec 2010 00:00:00 +0100 4252667 http://www.medworm.com/index.php?rid=4252669&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21123040%26dopt%3DAbstract Authors: Yan N, Lieberman J During the first week after sexual exposure to HIV, HIV infection does not appear to trigger a strong innate immune response. Here we describe some recent studies that show that HIV may avoid triggering antiviral innate immune responses by not replicating efficiently in dendritic cells and by avoiding detection in infected CD4 T cells and macrophages by harnessing a host cytoplasmic DNase TREX1 to digest nonproductive HIV reverse transcripts. PMID: 21123040 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4252669 Mon, 29 Nov 2010 00:00:00 +0100 4252669 http://www.medworm.com/index.php?rid=4252668&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21123041%26dopt%3DAbstract Authors: Liu SY, Sanchez DJ, Cheng G Type I interferons (IFNs) are cytokines of the innate immune system that induce antiviral protein expression in response to viral infection. Various proteins and pathways have been shown to recognize nucleic acid ligands especially from RNA viruses. Here, we will review recent developments including transcription of DNA virus genomes into RNA ligands, and the recognition of viruses by TLR2 for interferon induction. The induced IFNs activate many interferon stimulated genes (ISGs) that have direct antiviral effects. Recent studies have identified IFITM proteins as the first ISG to inhibit viral entry processes and revealed mechanistic understanding of known antiviral ISGs such as ISG15 and Viperin. PMID: 21123041 [PubMed - as supplied by publishe... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4252668 Mon, 29 Nov 2010 00:00:00 +0100 4252668 http://www.medworm.com/index.php?rid=4222094&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112755%26dopt%3DAbstract Authors: Bedoui S, Gebhardt T Effective viral immunity depends on the activation of T cells by professional antigen presenting cells, such as dendritic cells (DC). The remarkable heterogeneity of the DC network allows the immune system to respond specifically to various infection strategies by different viruses. As a consequence, DC-T cell interactions resulting in optimal virus-specific T cell priming are highly flexible and involve different types of DC. Further highlighting this complexity, recent lines of evidence suggest that presentation of viral antigen by DC is not only restricted to lymphoid organs, but instead also occurs at peripheral sites of infection. Here we discuss the multifaceted interactions between DC and T cells during peripheral virus infections in both lymphoid o... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4222094 Fri, 26 Nov 2010 00:00:00 +0100 4222094 http://www.medworm.com/index.php?rid=4222095&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112200%26dopt%3DAbstract Authors: van den Hoorn T, Paul P, Jongsma ML, Neefjes J MHC class II molecules (MHC-II) present antigenic fragments acquired in the endocytic route to the immune system for recognition and activation of CD4+ T cells. This ignites a series of immune responses. MHC-II strongly correlates to most autoimmune diseases. Understanding the biology of MHC-II is therefore expected to translate into novel means of autoimmunity control or immune response improvement. Although the basic cell biology of MHC-II antigen presentation is well understood, many novel aspects have been uncovered in recent years including means of antigen delivery, preparation for MHC-II loading, transport processes and vaccination strategies. We will discuss past, present and future of these insights into the biology of MH... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4222095 Thu, 25 Nov 2010 00:00:00 +0100 4222095 http://www.medworm.com/index.php?rid=4222096&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21111589%26dopt%3DAbstract Authors: Shapira SD, Hacohen N Advances in experimental tools have allowed for the systematic identification of components and biological processes as well as quantification of their activities over time. Together with computational analysis, these measurement and perturbation technologies have given rise to the field of systems biology, which seeks to discover, analyze and model the interactions of physical components in a biological system. Although in its infancy, recent application of this approach has resulted in novel insights into the machinery that regulates and modifies innate immune cell functions. Here, we summarize contributions that have been made through the unbiased interrogation of the mammalian innate immune system, emphasizing the importance of integrating orthogonal ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4222096 Wed, 24 Nov 2010 00:00:00 +0100 4222096 http://www.medworm.com/index.php?rid=4222097&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21109412%26dopt%3DAbstract Authors: Ziegler SF The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies, in both humans and mouse models, have implicated TSLP in the development and progression of atopy and atopic diseases. This review will discuss this work and place TSLP in the inflammatory cascade that leads to allergic disease. PMID: 21109412 [PubMed - as supplied by publisher] (Source: Current ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4222097 Tue, 23 Nov 2010 00:00:00 +0100 4222097 http://www.medworm.com/index.php?rid=4203120&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21106358%26dopt%3DAbstract Authors: Strickland DH, Upham JW, Holt PG Airway epithelial cells act through multiple mechanisms to function as an important component of the pulmonary defence strategy that is crucial to the maintenance of immune homeostasis. Dendritic cells are uniquely potent inducers of immune responses and it is increasingly clear that epithelium has the capacity to modulate the functional activity of dendritic cells, and vice versa, through production of a diverse array of mediators. Bidirectional interactions between epithelial cells and dendritic cell networks can thus impact upon the development and progression of immunity/tolerance in respiratory tissues. In this brief review we highlight the most recent advances in understanding how airway epithelial/dendritic cell interactions contribute t... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4203120 Mon, 22 Nov 2010 00:00:00 +0100 4203120 http://www.medworm.com/index.php?rid=4203121&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21095110%26dopt%3DAbstract Authors: Nakanishi K Basophils are important effector cells, which contribute to protection against helminths and execute proinflammatory effector function during allergic inflammation. Basophils are also regulators of Th2 responses in helminth-infected hosts and in allergen-injected animals. Recently, three groups using different experimental systems have shown that basophils are antigen-presenting cells (APC), which induce Th2 cells both in vitro and in vivo. Basophils express MHC class II and CD80/86, have the potential to take-up and process protein antigen (Ag), particularly Ag-IgE complexes, and to present peptide with MHC class II and produce IL-4. However, relevance of basophils as Th2 cell-inducing APC in vivo has been challenged by several recent reports that favor the concep... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4203121 Sat, 20 Nov 2010 00:00:00 +0100 4203121 http://www.medworm.com/index.php?rid=4203123&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21094031%26dopt%3DAbstract Authors: Martinon F, Glimcher LH The innate immune system has evolved the capacity to detect specific pathogens and to interrogate cell and tissue integrity in order to mount an appropriate immune response. Loss of homeostasis in the endoplasmic reticulum (ER) triggers the ER-stress response, a hallmark of many inflammatory and infectious diseases. The IRE1/XBP1 branch of the ER-stress signaling pathway has been recently shown to regulate and be regulated by innate immune signaling pathways in both the presence and absence of ER-stress. By contrast, innate immune pathways negatively affect the activation of two other branches of the ER-stress response as evidenced by reduced expression of the pro-apoptotic transcription factor CHOP. Here we will discuss how innate immune pathways and E... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4203123 Thu, 18 Nov 2010 00:00:00 +0100 4203123 http://www.medworm.com/index.php?rid=4203122&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21094032%26dopt%3DAbstract Authors: Wang A, Batteux F, Wakeland EK The SLAM/CD2 gene family encodes receptors that play important roles in regulating multiple cellular interactions in the adaptive and innate immune systems. Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations. Polymorphisms of Ly108 in mice strongly impact central tolerance in both B and T cell development, predominantly by modulating apoptosis, anergy, and cell-cycle progression. In addition, Ly108 and CD84, together with their downstream signaling adaptor SLAM-associated protein (SAP), have emerged as key players in B-T interactions during the formation of germinal centers. Interestingly, several indepe... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4203122 Thu, 18 Nov 2010 00:00:00 +0100 4203122 http://www.medworm.com/index.php?rid=4203126&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21093237%26dopt%3DAbstract Authors: Yamamoto K, Shlomchik M PMID: 21093237 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4203126 Wed, 17 Nov 2010 00:00:00 +0100 4203126 http://www.medworm.com/index.php?rid=4203125&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21093238%26dopt%3DAbstract Authors: Wills-Karp M Allergic diseases continue to plague modernized societies, underscoring the need to identify the molecular basis for the propensity of a small number of environmental proteins to provoke maladaptive, allergic responses. Recent data suggest that the ability of allergenic proteins to drive allergic responses in susceptible hosts is driven by their unique innate immune activating capabilities. Although the identification of allergen-specific pattern recognition receptors is in its infancy, studies to date have shown that allergens drive Th2-biased immune responses via directly engaging C-type lectin receptors (dectin-2, DC-SIGN, and mannose receptor) on dendritic cells and/or mimicking toll-like receptor 4 signaling complex molecules expressed on airway structural ce... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4203125 Wed, 17 Nov 2010 00:00:00 +0100 4203125 http://www.medworm.com/index.php?rid=4203124&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21093239%26dopt%3DAbstract Authors: Uccelli A, Prockop DJ The adult stem/progenitor cells from bone marrow and other tissues referred to as mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) display a significant therapeutic plasticity as reflected by their ability to enhance tissue repair and influence the immune response both in vitro and in vivo. In this review we will focus on the paradigmatic preclinical experience achieved testing MSCs in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. We will emphasize how the paradigm changed over time from the original prediction that MSCs would enhance tissue repair through their transdifferentiation into somatic cells to the current paradigm that they can produce therapeutic benefits without engraftment into the inj... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4203124 Wed, 17 Nov 2010 00:00:00 +0100 4203124 http://www.medworm.com/index.php?rid=4187344&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21087847%26dopt%3DAbstract Authors: Mauri C Compelling evidence has demonstrated that IL-10-producing regulatory B cells (B(regs)) are specialized to suppress immune responses and control various immunopathologies. Several reports have provided information on the phenotype, generation, and mechanism of action of B(regs). Recent work has also identified B(regs) in humans and has begun to unravel their phenotype and mode of suppression. A complete analysis of their function in immune-mediated diseases is required for possible future use of B(regs) as a part of new clinical strategies for treating autoimmune diseases and in the induction of transplant tolerance. PMID: 21087847 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4187344 Wed, 17 Nov 2010 00:00:00 +0100 4187344 http://www.medworm.com/index.php?rid=4187340&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21087848%26dopt%3DAbstract Authors: Souwer Y, Szegedi K, Kapsenberg ML, de Jong EC A long standing paradigm is that antigen-specific Th2 cells and their cytokines such as IL-4, IL-5, and IL-13 orchestrate the characteristic features of atopic allergy. The discovery of a role for IL-17-producing (Th17) and IL-22-producing (Th22) T helper cells in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogenesis of allergic diseases. Here we re-evaluate the role of T helper cells, with special focus on the Th17 and Th22 subsets in allergic asthma and atopic dermatitis. Whereas sparse data point to a protective role of the increasing amounts of Th22 cells that are found in chronic stages of both allergies, the data on Th17 cells paint different pictures for the contribution ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4187340 Wed, 17 Nov 2010 00:00:00 +0100 4187340 http://www.medworm.com/index.php?rid=4169698&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071193%26dopt%3DAbstract Authors: Wills-Karp M, Kapsenberg M PMID: 21071193 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4169698 Tue, 09 Nov 2010 00:00:00 +0100 4169698 http://www.medworm.com/index.php?rid=4169697&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071194%26dopt%3DAbstract Authors: Lloyd CM The discovery of IL-33 as the ligand for the orphan Th2 associated receptor ST2 has uncovered a whole range of different avenues for this pathway. Although the extracellular functions of ST2 as a marker for Th2 cell and mast cell activity were well defined, the complexities of IL-33 regulation, nuclear function and secretion are only just being realised. The well documented expression pattern of ST2 has identified a role for the IL-33/ST2 axis in the classical Th2 cell and mast cell driven pathogenesis of asthma and anaphylaxis. However, the induction of IL-33 expression by environmental or endogenous triggers now suggests a wider role for the pathway during infection, inflammation and tissue damage. PMID: 21071194 [PubMed - as supplied by publisher] (Source: Curr... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4169697 Tue, 09 Nov 2010 00:00:00 +0100 4169697 http://www.medworm.com/index.php?rid=4169696&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071195%26dopt%3DAbstract Authors: Fabri M, Realegeno SE, Jo EK, Modlin RL There is compelling evidence demonstrating a key role for autophagy in host defense against microbial infections. Induction and regulation of autophagy involves complex pathways including signaling molecules that have widespread roles in cell biological functions. For example, inhibiting mTOR by rapamycin, the most widely used chemical approach to induce autophagy, can also result in immunosupression. Nevertheless, advances in our understanding of autophagy provide a new opportunity to modulate host cellular responses as a potential therapeutic strategy to combat microbial infections in humans. PMID: 21071195 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4169696 Tue, 09 Nov 2010 00:00:00 +0100 4169696 http://www.medworm.com/index.php?rid=4140085&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21051210%26dopt%3DAbstract Authors: Finkelman FD Peanuts are a frequent cause of food allergy and the most common cause of fatal food-induced anaphylaxis in the U.S. Advances during the past two years have promoted our understanding of peanut allergens and peanut allergy prevalence, etiology, diagnosis, and therapy. The advances highlighted in this review include evidence that the peanut allergens most important in disease differ in different parts of the world, that early oral exposure to peanuts may decrease the frequency of peanut allergy, while early nonoral exposure may have the opposite effect, that complement activation by peanut constituents appears to promote peanut-induced anaphylaxis and that oral immunotherapy, anti-IgE antibody, and a herbal formulation are promising approaches for the treatment of ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4140085 Tue, 02 Nov 2010 00:00:00 +0100 4140085 http://www.medworm.com/index.php?rid=4140096&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21050736%26dopt%3DAbstract Authors: Wong FS, Hu C, Xiang Y, Wen L B cells have a vitally important function to produce antibodies which are directly pathogenic in some autoimmune diseases. However, it is clear that a number of other B cell functions are also critical in the pathogenesis of organ-specific autoimmune diseases that were previously thought to be mainly T cell mediated. Therapeutic agents that target B cells and their functions may therefore be of considerable importance in these autoimmune diseases. In this review, we will focus on B cell characteristics and functions that contribute to type 1 diabetes (T1D) and discuss why anti-B cell treatment may be effective in T1D, a disease that was previously considered to be primarily T cell mediated. PMID: 21050736 [PubMed - as supplied by publisher] (S... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4140096 Mon, 01 Nov 2010 00:00:00 +0100 4140096 http://www.medworm.com/index.php?rid=4140091&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21050737%26dopt%3DAbstract Authors: Espeli M, Niederer HA, Traherne JA, Trowsdale J, Smith KG Recent work has emphasised the marked genetic variability that exists in the Fc receptor locus. This variation can contribute to the risk of autoimmune disease in both mice and humans, but can also have a profound impact on defence against infection. Using FcγRIIB and FcγRIIIB as examples, we demonstrate that variations associated with increased susceptibility to autoimmunity may be maintained in populations for their beneficial effect against infection. We examine the KIR locus from the same perspective and highlight similarities between the two loci. Intense selection pressure by pathogens presumably accounts for the marked variability within both regions and leads to susceptibility to autoimmunity for some alleles.... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4140091 Mon, 01 Nov 2010 00:00:00 +0100 4140091 http://www.medworm.com/index.php?rid=4125424&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21030229%26dopt%3DAbstract Authors: Rothlin CV, Lemke G The TAM receptor tyrosine kinases Tyro3, Axl, and Mer and their ligands Gas6 and Protein S are essential for the phagocytosis of apoptotic cells and membranes in the adult immune, nervous, and reproductive systems. Genetic studies indicate that this receptor-ligand system is central to apoptotic cell engulfment that is triggered by the 'eat-me' signal phosphatidylserine (PtdSer). At the same time, TAM signaling is normally activated by Toll-like receptor (TLR) and type I interferon signaling, as part of the innate inflammatory response in dendritic cells (DCs) and macrophages, where it inhibits this response. Deficiencies in TAM signaling result in human retinal dystrophies and may contribute to lupus and other human autoimmune diseases. PMID: 21030229 ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4125424 Tue, 26 Oct 2010 00:00:00 +0100 4125424 http://www.medworm.com/index.php?rid=4108445&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970972%26dopt%3DAbstract Authors: Choi NM, Majumder P, Boss JM The major histocompatibility complex class II (MHC-II) genes are regulated at the level of transcription. Recent studies have shown that chromatin modification is critical for efficient transcription of these genes, and a number of chromatin modifying complexes recruited to MHC-II genes have been described. The MHC-II genes are segregated from each other by a series of chromatin elements, termed MHC-II insulators. Interactions between MHC-insulators and the promoters of MHC-II genes are mediated by the insulator factor CCCTC-binding factor and are critical for efficient expression. This regulatory mechanism provides a novel view of how the entire MHC-II locus is assembled architecturally and can be coordinately controlled. PMID: 20970972 [PubMe... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4108445 Wed, 20 Oct 2010 23:00:00 +0100 4108445 http://www.medworm.com/index.php?rid=4108444&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970973%26dopt%3DAbstract Authors: Ma Y, Aymeric L, Locher C, Kroemer G, Zitvogel L The question as to whether the tumor grows because of or despite the host immune system is being progressively addressed with refined technology, gene targeting in mice and human translational research. The productive interplay between major actors of the antitumor immunity is actively compromised by the tumor microenvironment subverting the links between innate and cognate immunity and/or generating devastating new players. The complexity of the host-tumor equilibrium could be dissected at the reduced level of the dialogue between professional antigen presenting cells (APC), more precisely dendritic cells, and tumor cells that may profoundly dictate the outcome of the neoplasma. This review will summarize the novel mechanisms b... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4108444 Wed, 20 Oct 2010 23:00:00 +0100 4108444 http://www.medworm.com/index.php?rid=4108443&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970974%26dopt%3DAbstract Authors: Hofstetter AR, Sullivan LC, Lukacher AE, Brooks AG While the prime function of classical MHC class I molecules (MHC-I) is to present peptide antigens to pathogen-specific cytotoxic T cells, non-classical MHC-I antigens perform a diverse array of functions in both innate and adaptive immunity. In this review we summarize recent evidence that non classical MHC-I molecules are not only recognized by pathogen-specific T cells but that they also serve as immunoregulatory molecules by stimulating a number of distinct non-conventional T cell subsets. PMID: 20970974 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4108443 Wed, 20 Oct 2010 23:00:00 +0100 4108443 http://www.medworm.com/index.php?rid=4108442&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970975%26dopt%3DAbstract Authors: Davidson A BAFF and APRIL are TNF-like cytokines that support survival and differentiation of B cells. The early appreciation that overexpression of BAFF leads to B cell expansion and a lupus-like syndrome in mice, and the demonstration that BAFF inhibition delays lupus onset in spontaneous mouse models of SLE and other autoimmune diseases has rapidly led to the development of strategies for inhibiting both BAFF and APRIL. The commercialization of this new class of drugs has proceeded in parallel with the continuing elucidation of the biology of the cytokines and their receptors. Recent studies have uncovered a role for BAFF in enhancing both innate and adaptive immune responses and in amplifying aberrant pathways that arise during inflammation. Two phase III studies of an ant... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4108442 Wed, 20 Oct 2010 23:00:00 +0100 4108442 http://www.medworm.com/index.php?rid=4090510&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20956073%26dopt%3DAbstract Authors: Greene MI, Waldmann H PMID: 20956073 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4090510 Fri, 15 Oct 2010 23:00:00 +0100 4090510 http://www.medworm.com/index.php?rid=4078310&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20952173%26dopt%3DAbstract Authors: Gill RG NK cells constitute an innate MHC class I-reactive lymphoid population that rapidly responds to infection, injury, or cell distress. In the transplant field, NK cells have most often been associated with pro-inflammatory immunity resulting in the exacerbation of allograft injury. Despite this general view of NK cell reactivity, it has been challenging to assign unambiguous obligate roles for NK cells in the allograft response. While recent reports continue to provide evidence supporting a role for NK cells in promoting both acute and chronic rejection, there are also a growing number of studies that illustrate an alternative role for NK cells in promoting allograft survival and tolerance. This review addresses the plasticity of NK responses in transplantation by sugges... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4078310 Thu, 14 Oct 2010 23:00:00 +0100 4078310 http://www.medworm.com/index.php?rid=4078311&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951016%26dopt%3DAbstract Authors: Lundie RJ Understanding the initiation of cellular immune responses during blood-stage malaria infection is essential for the development of an effective vaccine that improves upon the naturally acquired immune response and induces rapid and long-lasting protection against disease. Recent studies have identified the dendritic cell (DC) subtypes responsible for priming Plasmodium-specific T cells that mediate protection and/or pathology during blood-stage infection. Significant progress has also been made towards understanding DC recognition of Plasmodium parasites through engagement of TLR signalling pathways, as well as the potential for non-TLR ligands to mediate Plasmodium-induced suppression of DC antigen presentation. PMID: 20951016 [PubMed - as supplied by publisher]... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4078311 Tue, 12 Oct 2010 23:00:00 +0100 4078311 http://www.medworm.com/index.php?rid=4066026&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933376%26dopt%3DAbstract Authors: Kirk A, Strom TB PMID: 20933376 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4066026 Tue, 05 Oct 2010 23:00:00 +0100 4066026 http://www.medworm.com/index.php?rid=4066025&cid=s_35493_3_f&fid=35493&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933377%26dopt%3DAbstract Authors: Delgado-Vega A, Sánchez E, Löfgren S, Castillejo-López C, Alarcón-Riquelme ME Association studies of over 1 million SNPs capturing most of the human genome common variation became possible thanks to the information provided by the HapMap International project and the development of high-throughput genotyping technologies at accessible prices. Genome-wide scans analyzing thousands of individuals have now identified most if not all of the major genes involved in susceptibility for several systemic autoimmune diseases. In particular, results for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) are reviewed here. While most genes are shared between diseases, few seem to be unique reflecting that we still are long before knowing all ge... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=4066025 Tue, 05 Oct 2010 23:00:00 +0100 4066025