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. Fri, 19 Mar 2010 13:40:17 +0100 http://www.medworm.com/index.php?rid=3374697&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%3D20227268%26dopt%3DAbstract Authors: Malin S, McManus S, Busslinger M Early B cell development depends on a network of transcription factors, whereby E2A and EBF1 regulate B cell specification and Pax5 controls B-lineage commitment. In contrast, activation of the transcription factor STAT5 in response to IL-7R signaling promotes cell survival by activating the prosurvival gene Mcl1 and orders immunoglobulin gene rearrangement by repressing Igk recombination in pro-B cells. Subsequently, it cooperates with the pre-B cell receptor to facilitate pre-B cell expansion. STAT5 also plays a key role in the generation of B cell precursor acute lymphoblastic leukemia, whereby the BCR-ABL1 translocation or the collaboration of JAK2 mutations with overexpression of the thymic stromal lymphopoietin receptor CRLF2 results in c... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3374697 Thu, 11 Mar 2010 00:00:00 +0100 3374697 http://www.medworm.com/index.php?rid=3374700&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%3D20226643%26dopt%3DAbstract Authors: Jenkins MR, Griffiths GM Cytotoxic T lymphocytes (CTLs) rapidly kill target cells via the release of lytic granules into the immunological synapse, a process directed by the docking of the centrosome at the plasma membrane. New evidence highlights how signal strength and avidity influence the recruitment of cytolytic machinery to the synapse, and the role of each synaptic compartment. Release of cytolytic effector proteins, including perforin and FasL, is controlled at multiple levels and is also influenced by the avidity of the interaction. New imaging technologies and the use of photoactivatable peptides have allowed the dissection of signalling molecules involved in each step of the cytolytic process. This review highlights the important role of avidity in controlling how a... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3374700 Wed, 10 Mar 2010 00:00:00 +0100 3374700 http://www.medworm.com/index.php?rid=3374699&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%3D20226644%26dopt%3DAbstract Authors: Palucka K, Ueno H, Zurawski G, Fay J, Banchereau J T cells can reject established tumors when adoptively transferred into patients, thereby demonstrating that the immune system can be harnessed for cancer therapy. However, such passive immunotherapy is unlikely to maintain memory T cells that might control tumor outgrowth on the long term. Active immunotherapy with vaccines has the potential to induce tumor-specific effector and memory T cells. Vaccines act through dendritic cells (DCs) which induce, regulate, and maintain T cell immunity. Clinical trials testing first generation DC vaccines pulsed with tumor antigens provided a proof-of-principle that therapeutic immunity can be elicited. The increased knowledge of the DC system, including the existence of distinct DC subsets... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3374699 Wed, 10 Mar 2010 00:00:00 +0100 3374699 http://www.medworm.com/index.php?rid=3374698&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%3D20226645%26dopt%3DAbstract Authors: Cuddapah S, Barski A, Zhao K Activation of T cells is an essential step in the immunological response to infection. Although activation of naïve T cells results in proliferation and slow differentiation into cytokine-producing effector cells, antigen engagement with memory cells leads to cytokine production immediately. Even though the cell surface signaling events are similar in both the cases, the outcome is different, suggesting that distinct regulatory mechanisms may exist downstream of the activation signals. Recent advances in the understanding of global epigenetic patterns in T cells have resulted in the appreciation of the role of epigenetic mechanisms in processes such as activation and differentiation. In this review we discuss recent data suggesting that na&#xE... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3374698 Wed, 10 Mar 2010 00:00:00 +0100 3374698 http://www.medworm.com/index.php?rid=3355207&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%3D20207527%26dopt%3DAbstract Authors: Kim PS, Ahmed R Ever since T cell exhaustion was initially characterized and thoroughly analyzed in the murine LCMV model, such a functional impairment has been validated in other chronic viral infections such as HIV, HCV, and HBV. In tumor immunology, it has always been postulated that tumor-reactive T cells could also become functionally exhausted owing to the high tumor-antigen load and accompanying inhibitory mechanisms. However, the empirical evidences for this hypothesis have not been as extensive as in chronic infection perhaps because much of the focus on T cell dysfunction in tumor immunology has been, and appropriately so, on breaking or bypassing immune tolerance and anergy to tumor/self antigens. On the basis of recent reports, it is becoming clear that T cell exha... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3355207 Fri, 05 Mar 2010 00:00:00 +0100 3355207 http://www.medworm.com/index.php?rid=3355206&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%3D20207528%26dopt%3DAbstract Authors: Bryder D, Sigvardsson M Even though the development of B lymphoid cells from hematopoietic stem cells is one of the most carefully investigated models of cell differentiation in adult mammalians, a set of recent findings has to a large extent increased our understanding for how B lymphoid commitment is achieved. These include the identification of IKAROS, PU.1 and E2A as transcription factors responsible for lymphoid lineage priming in multipotent cells, as well as the identification of EBF1 dependent B lineage restricted progenitors among cells lacking expression of the classical B lineage markers CD19 or B220. The insight that the B cell identity may be defined at an earlier stage then previously thought, allows for an increased understanding of B lymphoid development likely... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3355206 Fri, 05 Mar 2010 00:00:00 +0100 3355206 http://www.medworm.com/index.php?rid=3355205&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%3D20207529%26dopt%3DAbstract Authors: Ramírez J, Lukin K, Hagman J The generation of B lymphocytes from hematopoietic progenitors requires lineage-specific transcription factors that progressively direct cell fate choices. Differentiation of hematopoietic stem cells to lymphoid progenitors requires Ikaros-dependent lineage priming and graded levels of PU.1, which are controlled by Ikaros and Gfi1. E2A drives expression of EBF1, which initiates B lineage specification. EBF1, in addition to Pax5, is necessary for commitment to the B cell lineage. As a model of gene activation in early B lymphopoiesis, mb-1 genes are activated sequentially by factors (e.g. EBF1) that initiate chromatin modifications before transcription. This review highlights the requisite interplay between transcription factors and epigenetic ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3355205 Fri, 05 Mar 2010 00:00:00 +0100 3355205 http://www.medworm.com/index.php?rid=3355208&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%3D20207124%26dopt%3DAbstract Authors: Bindea G, Mlecnik B, Fridman WH, Pagès F, Galon J The evolution of cancer reflects intricate cellular and molecular interactions of tumor cells with the tumor microenvironment. Novel systems biology approaches are emerging to analyze the complex interaction between tumors and host-immune response in humans. The opposing host-protective and tumor-promoting roles of the immune system reflect the disparate effects of immunity on tumorigenesis. Global analysis of tumor microenvironment showed that a strong adaptive immune reaction within primary human tumors reduced the risk of relapse events. Recent advances support the existence of immunosurveillance in human cancer. The major role of the intratumoral immune reaction could advance our understanding of tumor evolution and ha... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3355208 Thu, 04 Mar 2010 00:00:00 +0100 3355208 http://www.medworm.com/index.php?rid=3322908&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%3D20189791%26dopt%3DAbstract Authors: Pearce EL When naïve or memory T cells encounter foreign antigen along with proper co-stimulation they undergo rapid and extensive clonal expansion. In mammals, this type of proliferation is fairly unique to cells of the adaptive immune system and requires a considerable expenditure of energy and cellular resources. While research has often focused on the roles of cytokines, antigenic signals, and co-stimulation in guiding T cell responses, data indicate that, at a fundamental level, it is cellular metabolism that regulates T cell function and differentiation and therefore influences the final outcome of the adaptive immune response. This review will focus on some earlier fundamental observations regarding T cell bioenergetics and its role in regulating cellular function,... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3322908 Fri, 26 Feb 2010 00:00:00 +0100 3322908 http://www.medworm.com/index.php?rid=3295279&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%3D20172702%26dopt%3DAbstract Authors: Mellman I, Cresswell P PMID: 20172702 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3295279 Fri, 19 Feb 2010 00:00:00 +0100 3295279 http://www.medworm.com/index.php?rid=3295277&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%3D20172703%26dopt%3DAbstract Authors: Stevenson FK, Ottensmeier CH, Rice J Genetic technology allows construction of DNA vaccines encoding selected tumor antigens together with molecules to direct and amplify the desired effector pathways. Their enormous promise has been marred by a problem of scaling up to human subjects. This is now largely overcome by electroporation, which increases both antigen expression and the inflammatory milieu. While the principles of vaccine design can be developed in mouse models, the real operative test is in the clinic, using patients in temporary remission. Monitoring of induced immunity, although commonly limited to blood, is providing objective qualitative and quantitative data on T-cell and antibody responses. Prolongation of remission is the goal and an activated immune system ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3295277 Fri, 19 Feb 2010 00:00:00 +0100 3295277 http://www.medworm.com/index.php?rid=3295285&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%3D20171861%26dopt%3DAbstract Authors: Hand T, Belkaid Y The human intestine harbors and is in constant contact with 1000 trillion microbes, composed of an estimated 15,000 strains [1]. Recent studies have changed our perspective of commensal microbes from benign but inert passengers, to active participants in the processing of food into useful metabolic components, the postnatal development of mucosal and systemic immunity, and in its long-term steady state function. Although mucosal surfaces have to constitutively integrate a multitude of microbial derived signals, new evidence suggests that defined bacteria or microbial products can play a dominant role in the induction of distinct class of immune responses. In this review we will focus on recent findings associating microbes that colonize or invade the gut, spe... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3295285 Thu, 18 Feb 2010 00:00:00 +0100 3295285 http://www.medworm.com/index.php?rid=3295283&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%3D20171862%26dopt%3DAbstract Authors: Giodini A, Albert ML This is the tale of murder, suicide, evolution, and resurrection, taking place in four parts, and all in the name of antigen cross-priming. We invite you to explore the dark mysteries lurking within each of us as you are guided through circuitous cellular pathways in a merciless fight for survival... with viral immunity being the grand finale?! PMID: 20171862 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3295283 Thu, 18 Feb 2010 00:00:00 +0100 3295283 http://www.medworm.com/index.php?rid=3295281&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%3D20171863%26dopt%3DAbstract Authors: Amigorena S, Savina A The induction of most CD8+ T cell responses by dendritic cells (DCs) requires the presentation of peptides from internalized antigen by class I MHC molecules. Increasing number of reports have shown that cross presentation is involved in transplant rejection, in immune responses to viral infections, in certain autoimmune diseases and cancer. The precise role of cross presentation in the initiation of immune responses in vivo, however, remains a matter of debate. This ongoing controversy is, at least in part, due to a lack of understanding of the molecular machinery that determine cross presentation pathways in terms of cell biology. The present review aims to summarize recent insights and advances that help enlighten the intracellular steps of antigen cro... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3295281 Thu, 18 Feb 2010 00:00:00 +0100 3295281 http://www.medworm.com/index.php?rid=3295288&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%3D20171073%26dopt%3DAbstract Authors: D'Cruz LM, Yang CY, Goldrath AW NKT cells comprise a distinct T cell subset that acquires effector function during development and prior to antigen exposure. NKT cells are of limited antigen specificity but possess the ability to be recruited into an immune response without the need for further differentiation or proliferation and thus may be considered to function as memory cells or as part of the innate immune system. Although the development and maturation of NKT cells share some similarities with conventional T cell populations, many transcriptional regulators and signaling molecules are known to be uniquely required for NKT cell development. Recently, new transcription factors that specify NKT lineage and effector function and novel roles for previously identified transcr... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3295288 Wed, 17 Feb 2010 00:00:00 +0100 3295288 http://www.medworm.com/index.php?rid=3295287&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%3D20171074%26dopt%3DAbstract Authors: Brenner MK, Heslop HE Adoptive transfer of T cells specific for antigens expressed on tumor cells is an attractive strategy for producing targeted and long-lived anti-tumor activity. T cell therapies have shown activity in selected clinical applications but broader application is limited by inadequate persistence of transferred T cells and by tumor-evasion strategies. Current research focuses on defining the optimum type of cell for transfer, genetically modifying infused T cells to augment function and overcome tumor evasion strategies and modulating the host environment. PMID: 20171074 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3295287 Wed, 17 Feb 2010 00:00:00 +0100 3295287 http://www.medworm.com/index.php?rid=3295286&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%3D20171075%26dopt%3DAbstract Authors: Peranzoni E, Zilio S, Marigo I, Dolcetti L, Zanovello P, Mandruzzato S, Bronte V Myeloid derived suppressor cells (MDSCs) are defined in mice on the basis of CD11b and Gr-1 marker expression and the functional ability to inhibit T lymphocyte activation. Nevertheless the term 'heterogeneous' remains the first, informal feature commonly attributed to this population. It is clear that CD11b(+)Gr-1(+) cells are part of a myeloid macropopulation, which comprises at least two subsets of polymorphonuclear and monocytic cells with different immunosuppressive properties. While recent literature shows substantial agreement on the immunoregulatory property of the monocytic MDSC subset, there is still contrasting evidence on the role of the granulocytic fraction. Moreover, this dichotomy ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3295286 Wed, 17 Feb 2010 00:00:00 +0100 3295286 http://www.medworm.com/index.php?rid=3291833&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%3D20167462%26dopt%3DAbstract Authors: Artis D, Tschopp J PMID: 20167462 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3291833 Tue, 16 Feb 2010 00:00:00 +0100 3291833 http://www.medworm.com/index.php?rid=3280421&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%3D20153622%26dopt%3DAbstract Authors: Kanther M, Rawls JF The amenability of the zebrafish to in vivo imaging and genetic analysis has fueled expanded use of this vertebrate model to investigate the molecular and cellular foundations of host-microbe relationships. Study of microbial encounters in zebrafish hosts has concentrated on developing embryonic and larval stages, when the advantages of the zebrafish model are maximized. A comprehensive understanding of these host-microbe interactions requires appreciation of the developmental context into which a microbe is introduced, as well as the effects of that microbial challenge on host ontogeny. In this review, we discuss how in vivo imaging and genetic analysis in zebrafish has advanced our knowledge of host-microbe interactions in the context of a developing vert... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3280421 Thu, 11 Feb 2010 00:00:00 +0100 3280421 http://www.medworm.com/index.php?rid=3280422&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%3D20153156%26dopt%3DAbstract Authors: Goldszmid RS, Sher A Control of parasitic protozoan infections requires the generation of efficient innate and adaptive immune responses, and in most cases both CD8 and CD4 T cells are necessary for host survival. Since intracellular protozoa remodel the vacuolar compartments in which they reside, it is not obvious how their antigens enter the MHC class I and class II pathways. Studies using genetically engineered parasites have shown that host cell targeting, intracellular compartmentalization, subcellular localization of antigen within the parasite, and mechanism of invasion are important factors determining the presentation pathway utilized. The recent identification of endogenous parasite-derived CD8 T cell epitopes have helped confirm these concepts as well as provided ne... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3280422 Wed, 10 Feb 2010 00:00:00 +0100 3280422 http://www.medworm.com/index.php?rid=3270164&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%3D20149615%26dopt%3DAbstract Authors: Münz C T cells monitor intracellular and extracellular protein composition via proteolytic products that are displayed to them on major histocompatibility complex (MHC) molecules. For this purpose it has been documented that MHC class II molecules, which were originally thought to just display lysosomal products of endocytosed proteins to CD4(+) helper T cells, can also present intracellular substrates of autophagic pathways. This has triggered the interest of immunologists into the role of autophagy in antigen processing in general, and recently additional autophagic mechanisms for intracellular and extracellular antigen processing onto MHC class I molecules for presentation to CD8(+) cytolytic T cells have been revealed. Here, I will review the contribution of autophagy... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3270164 Mon, 08 Feb 2010 00:00:00 +0100 3270164 http://www.medworm.com/index.php?rid=3270163&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%3D20149616%26dopt%3DAbstract Authors: Williams A, Flavell RA, Eisenbarth SC Not only does the innate immune system represent the first line of defense against invading pathogens, but it is also responsible for instructing appropriate adaptive immune responses. Pattern recognition receptors (PRR) detect the presence of invading pathogens and are paramount in innate instruction of the adaptive immune response. A diverse class of PRRs, the NOD-like Receptors (NLR), has recently been implicated in the regulation of processes ranging from anti-tumor immunity to the adjuvant action of aluminum hydroxide. In this review we will highlight many of the recent findings in the NLR field with a particular focus on NLR influence of adaptive immune responses. PMID: 20149616 [PubMed - as supplied by publisher] (Source: Curren... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3270163 Mon, 08 Feb 2010 00:00:00 +0100 3270163 http://www.medworm.com/index.php?rid=3263455&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%3D20144853%26dopt%3DAbstract Authors: Reizis B Plasmacytoid dendritic cells (PDC) represent a distinct immune cell type specialized in direct virus recognition and rapid secretion of type I interferon. The origin and lineage affiliation of PDC have been controversial, partly because PDC show features of both lymphocytes and dendritic cells (DC). Recent studies helped elucidate the cellular and molecular basis of PDC development. In particular, the common developmental origin and genetic similarity of PDC and classical antigen-presenting DC have been established. In addition, E protein transcription factor E2-2 was shown to control lineage commitment and gene expression program of PDC. Because E proteins are essential regulators of lymphocyte development, E2-2 activity may underlie the distinct 'lymphoid' features ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3263455 Mon, 08 Feb 2010 00:00:00 +0100 3263455 http://www.medworm.com/index.php?rid=3263454&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%3D20144854%26dopt%3DAbstract Authors: Mandel EM, Grosschedl R Differentiation of B lymphocytes involves the step-wise acquisition of a specialized phenotype that depends on the expression of lineage-specific genes and the repression of genes characteristic of multipotent progenitors and alternate lineages. The early steps of B lineage specification and commitment are, partly, controlled by the well-characterized transcription factors Ikaros, Pu.1, E2A, early B cell factor-1, and Pax5 that act in a complex regulatory network. However, our understanding of B cell differentiation is far from complete. Recent work has shed light on the mechanisms by which transcription factors implement cell type-specific gene expression patterns and epigenetic changes in chromatin that allow for B lineage specification and commitment... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3263454 Mon, 08 Feb 2010 00:00:00 +0100 3263454 http://www.medworm.com/index.php?rid=3263453&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%3D20144855%26dopt%3DAbstract Authors: Sokol CL, Medzhitov R Long appreciated for their role as Type-2 effector cells, basophils have recently come into the spotlight for their role in the initiation of Type-2 immunity. Via an assortment of different activation pathways, basophils produce cytokines such as IL-4 that promote Th2 differentiation. Furthermore, recent studies using different experimental systems have shown that basophils can act as antigen presenting cells both in vitro and in vivo. In addition, basophils shape the Type-2 immune response by guiding antibody production and the memory response. PMID: 20144855 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3263453 Mon, 08 Feb 2010 00:00:00 +0100 3263453 http://www.medworm.com/index.php?rid=3263452&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%3D20144856%26dopt%3DAbstract Authors: Mantovani A, Sica A Smouldering inflammation is a component of the tumor microenvironment and represents the 7(th) hallmark of cancer. Tumor-associated macrophages (TAM) have served as a paradigm for cancer promoting inflammation. Tumor-associated macrophages orchestrate various aspects of cancer, including: diversion and skewing of adaptive responses; cell growth; angiogenesis; matrix deposition and remodelling; the construction of a metastatic niche and actual metastasis; response to hormones and chemotherapeutic agents. T and B cells or cancer cell-derived signals orchestrate the functional reprogramming of TAM. In general TAM acquire M2-like properties and resemble 'tolerant' macrophages, though there is diversity in pathways and phenotypes in different tumors. TAM can als... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3263452 Mon, 08 Feb 2010 00:00:00 +0100 3263452 http://www.medworm.com/index.php?rid=3263451&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%3D20144857%26dopt%3DAbstract Authors: Dhodapkar MV A growing body of data points to not only intraclonal heterogeneity and hierarchy of growth potential, but also plasticity of cellular differentiation within human tumors. Recent studies have also identified surprising overlap between pathways that regulate pluripotency in embryonal stem (ES) cells and oncogenesis. While there is a long history of targeting embryonal tissues toward cancer vaccines, recent identification of crucial stemness pathways in ES cells as well as putative cancer stem cells (CSCs) provides novel opportunities for antigen-specific targeted therapy. Here we discuss recent insights into the capacity of the immune system to target these pathways. Immunologic targeting of pathways associated with stemness has implications for both immune regulat... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3263451 Mon, 08 Feb 2010 00:00:00 +0100 3263451 http://www.medworm.com/index.php?rid=3255528&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%3D20137905%26dopt%3DAbstract Authors: Torchinsky MB, Garaude J, Blander JM While inflammatory phagocytosis of microbial pathogens and non-inflammatory phagocytosis of apoptotic cells have each been studied extensively, the consequences of innate immune recognition of host cells undergoing apoptosis as a direct result of infection are unclear. In this situation, the innate immune system is confronted with mixed signals, those from apoptotic cells and those from the infecting pathogen. Nuclear receptor activation has been implicated downstream of apoptotic cell recognition while Toll-like receptors are the prototypical inflammatory receptors engaged during infection. When the two signals combine, a new set of events takes place beginning with transrepression of a subset of inflammatory-response genes and ending with... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3255528 Wed, 03 Feb 2010 00:00:00 +0100 3255528 http://www.medworm.com/index.php?rid=3255527&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%3D20137906%26dopt%3DAbstract Authors: Sabin LR, Hanna SL, Cherry S The study of Drosophila, and other genetically tractable insects, has expanded our understanding of innate immunity and more recently antiviral innate mechanisms. The Drosophila antiviral program includes inflammatory signaling cascades as well as antiviral RNA silencing and autophagy. This review will highlight the recent discoveries in antiviral immunity in insects and will reveal some of the lessons learned. PMID: 20137906 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3255527 Wed, 03 Feb 2010 00:00:00 +0100 3255527 http://www.medworm.com/index.php?rid=3232045&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%3D20116984%26dopt%3DAbstract Authors: Robson NC, Hoves S, Maraskovsky E, Schnurr M The use of dendritic cells (DCs) for the generation of anti-tumour immunity has been the focus of a vast array of scientific and clinical studies. The ability of DCs to present protein tumour antigens (T-Ags) to CD4(+) and CD8(+) T cells is pivotal to the success of therapeutic cancer vaccines. DC's specialised capacity to cross-present exogenous Ags onto major histocompatibility (MHC) class I molecules for the generation of T-Ag-specific cytotoxic T lymphocytes (CTLs) has made these cells the focal point of vaccine-based immunotherapy of cancer. However, although DC-based strategies can induce T cell responses in cancer patients, recent reviews of clinical studies demonstrate that DC-based approaches have essentially failed to meet... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3232045 Thu, 28 Jan 2010 00:00:00 +0100 3232045 http://www.medworm.com/index.php?rid=3232044&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%3D20116985%26dopt%3DAbstract Authors: Simpson TR, Quezada SA, Allison JP Inducible costimulator (ICOS), a member of the CD28 family of costimulatory molecules, is upregulated on the surface of T cells following T cell activation and upon binding to its ligand (ICOSL), initiates a cascade of events that can shape key aspects of the immune response. Although initial studies focused on determining the role of ICOS in Th1 versus T helper 2 (Th2) responses, new insights into its biology have revealed the contribution of ICOS to germinal center formation and isotype switching, as well as its relevance to the fate and function of effector and regulatory CD4(+) T cells in the response against self (i.e., tumors) and non-self (i.e., bacterial, worm, and viral infections). This multiplicity of roles positions ICOS at the ce... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3232044 Thu, 28 Jan 2010 00:00:00 +0100 3232044 http://www.medworm.com/index.php?rid=3189634&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%3D20083398%26dopt%3DAbstract Authors: Watts C, West MA, Zaru R Recent evidence suggests that TLR signalling in dendritic cells (DCs) transiently enhances antigen endocytosis and autophagy, augments the assembly of key antigen transport and processing systems, qualitatively modulates protein translation and induces a temporary cessation of DC motility. These rapid changes require activation of the MAP kinases, PI3-kinase and downstream signalling pathways and are observed in both myeloid DC and, with variations on the theme, in plasmacytoid DC. PMID: 20083398 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3189634 Sat, 16 Jan 2010 00:00:00 +0100 3189634 http://www.medworm.com/index.php?rid=3189636&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%3D20080040%26dopt%3DAbstract Authors: Mueller SN, Hickman HD The induction and execution of a successful anti-pathogen immune response requires a consecutive series of cellular interactions that begin in lymphoid environments and later extend into the periphery. Much of our current knowledge of these events has been gained using ex vivo approaches that yield important static information but do not convey the dynamic nature of cellular behavior in vivo. The application of multiphoton-laser based microscopic analysis to the ongoing immune response has provided new insight into cellular interactions leading to T cell activation and the behavior of primed immune effectors. Here we discuss recent insights on anti-pathogen immune responses revealed using live imaging of both lymphoid and non-lymphoid tissues. PMID: ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3189636 Thu, 14 Jan 2010 00:00:00 +0100 3189636 http://www.medworm.com/index.php?rid=3189635&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%3D20080041%26dopt%3DAbstract Authors: Salio M, Silk JD, Cerundolo V It is well established that different populations of alphabeta T lymphocytes can recognize not only peptides in the context of MHC class I and class II molecules, but also foreign and self-lipids in association with CD1 proteins, which share structural similarities with MHC class I molecules. CD1 molecules are comprised of five isoforms, known as group 1 (CD1a, b, c, e) and group 2 (CD1d) CD1, presenting lipid antigens to conventional T lymphocytes or innate-like T cells bearing an invariant T cell receptor (TCR) and known as invariant NKT (iNKT) cells. During the last couple of years, several papers have been published describing important aspects of the mechanisms controlling the processing and presentation of endogenous and exogenous CD1 lipid ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3189635 Thu, 14 Jan 2010 00:00:00 +0100 3189635 http://www.medworm.com/index.php?rid=3179432&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%3D20074925%26dopt%3DAbstract Authors: Kreslavsky T, Gleimer M, von Boehmer H alphabeta and gammadelta T cells develop in the thymus from a common precursor. Although lineages initially were defined by the type of TCR they express, it soon became clear that the TCR type per se does not play a deterministic role in the lineage decision, since in various transgenic and knockout models, as well as in a small fraction of cells in wt mice, the TCRgammadelta can drive the differentiation of alphabeta lineage cells and the TCRalphabeta can drive differentiation of gammadelta lineage cells. Thus until recently it was unclear what determines lineage choice and at which stage the two lineages diverge. Recent observations suggest that TCR signal strength determines lineage fate and that lineage choice is made at or shortly af... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3179432 Tue, 12 Jan 2010 00:00:00 +0100 3179432 http://www.medworm.com/index.php?rid=3164731&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%3D20061127%26dopt%3DAbstract Authors: Wilkins C, Gale M The immune response to virus infection is initiated when pathogen recognition receptors (PRRs) of the host cell recognize specific nonself-motifs within viral products (known as a pathogen-associated molecular pattern or PAMP) to trigger intracellular signaling events that induce innate immunity, the front line of defense against microbial infection. The replication program of all viruses includes a cytosolic phase of genome amplification and/or mRNA metabolism and viral protein expression. Cytosolic recognition of viral infection by specific PRRs takes advantage of the dependence of viruses on the cytosolic component of their replication programs. Such PRR-PAMP interactions lead to PRR-dependent nonself-recognition and the downstream induction of type I inte... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3164731 Fri, 08 Jan 2010 00:00:00 +0100 3164731 http://www.medworm.com/index.php?rid=3164733&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%3D20060698%26dopt%3DAbstract Authors: Rescigno M Recent advances have highlighted that antigen presentation in the gastrointestinal tract is carried out by different specialized immune and non-immune cells. This is required in order to achieve tolerance towards self and non-self harmless antigens and immunity towards pathogenic microorganisms. In this review we will discuss the role of different players in these responses, including dendritic cells, macrophages, B cells and basophils as professional antigen presenting cells (APCs), and stromal cells and epithelial cells as non-professional APCs. The interaction between these cell types is required for the dynamic regulation of the immune response. PMID: 20060698 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3164733 Thu, 07 Jan 2010 00:00:00 +0100 3164733 http://www.medworm.com/index.php?rid=3164732&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%3D20060699%26dopt%3DAbstract Authors: Latz E In response to injurious or infectious agents caspase-1 activating multiprotein complexes, termed inflammasomes, assemble in the cytoplasm of cells. Activated caspase-1 cleaves the proforms of the interleukin-1 cytokine family members leading to their activation and secretion. The IL-1 family cytokines have multiple proinflammatory activities implicating them in the pathogenesis of many inflammatory diseases. While defined ligands have been identified for the NLRP1, IPAF, and AIM2 inflammasomes, little is known about the activation mechanisms of the NLRP3 inflammasome. Numerous different molecular entities, such as various crystals, pore-forming toxins, or extracellular ATP can trigger the NLRP3 inflammasome. Recent work proposes that NLRP3 is activated indirectly by ho... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3164732 Thu, 07 Jan 2010 00:00:00 +0100 3164732 http://www.medworm.com/index.php?rid=3164735&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%3D20060278%26dopt%3DAbstract Authors: McGettrick AF, O'Neill LA In recent years the importance of the localisation and trafficking of Toll-like receptors (TLRs) and their adaptors within the cell has become apparent. Localisation and trafficking of both cell surface and endosomal TLRs, alongside their adaptors, appears to play an important role not only in ligand recognition but also in the downregulation of signaling following ligand stimulation. Chaperones, such as gp96, PRAT4A and Unc93B1 play a role in TLR localisation. TLR4 cycles between the Golgi and the plasma membrane until engaged by LPS. The MyD88-dependent pathway is then initiated at the plasma membrane, followed by the movement of the TLR4 complex into the endosome where the MyD88-independent pathway is activated. Several proteins, including Triad3A ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3164735 Wed, 06 Jan 2010 00:00:00 +0100 3164735 http://www.medworm.com/index.php?rid=3164734&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%3D20060279%26dopt%3DAbstract Authors: Modlin RL Investigation into the innate immune response in leprosy has provided insight into immunoregulation in human infectious disease. Key advances include the role of pattern recognition receptors in recognizing pathogen-associated molecular patterns of Mycobacterium leprae, cytokine release by innate immune cells, macrophage and dendritic cell differentiation, as well as antimicrobial effector pathways. These insights provide targets for therapeutic intervention in modulating the course of leprosy and other chronic infectious diseases. PMID: 20060279 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=3164734 Wed, 06 Jan 2010 00:00:00 +0100 3164734 http://www.medworm.com/index.php?rid=2970480&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%3D19892538%26dopt%3DAbstract Authors: Flodström-Tullberg M, Bryceson YT, Shi FD, Höglund P, Ljunggren HG Natural killer (NK) cells are innate immune cells. Although NK cells are best characterized for their ability to control tumors and infections, recent data have indicated that they also are important regulatory cells by virtue of interactions with many types of immune and nonimmune cells. Thereby, they can affect the outcome of adaptive immune responses and maintain immune homeostasis. Thus, NK cells can either exacerbate or limit immune responses, including those to autoantigens. Here, we discuss current insights into the role of NK cells in human autoimmunity. PMID: 19892538 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2970480 Tue, 03 Nov 2009 00:00:00 +0100 2970480 http://www.medworm.com/index.php?rid=2955321&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%3D19879742%26dopt%3DAbstract Authors: Bluestone JA, Kuchroo V PMID: 19879742 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2955321 Thu, 29 Oct 2009 00:00:00 +0100 2955321 http://www.medworm.com/index.php?rid=2955320&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%3D19879743%26dopt%3DAbstract Authors: Rothenberg ME, Daëron M PMID: 19879743 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2955320 Thu, 29 Oct 2009 00:00:00 +0100 2955320 http://www.medworm.com/index.php?rid=2929741&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%3D19854631%26dopt%3DAbstract Authors: Bettini M, Vignali DA Foxp3(+) regulatory T cells (T(regs)) contribute significantly to the maintenance of peripheral tolerance, but they ultimately fail in autoimmune diseases. The events that lead to T(reg) failure in controlling autoreactive effector T cells (T(effs)) during autoimmunity are not completely understood. In this review, we discuss possible mechanisms for this subversion as they relate to type 1 diabetes (T1D) and multiple sclerosis (MS). Recent studies emphasize firstly, the role of inflammatory cytokines, such as IL-6, in inhibiting or subverting T(reg) function; secondly, the issue of T(reg) plasticity; thirdly, the possible resistance of autoimmune T cells to T(reg)-mediated control; and fourthly, T(reg)-associated inhibitory cytokines TGFbeta, IL-10 and IL... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2929741 Fri, 23 Oct 2009 00:00:00 +0100 2929741 http://www.medworm.com/index.php?rid=2902287&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%3D19833494%26dopt%3DAbstract Authors: Gardner JM, Fletcher AL, Anderson MS, Turley SJ The maintenance of immunologic self-tolerance requires the coordination of multiple complementary systems. Studies of the Autoimmune Regulator (Aire) gene have revealed that Aire promotes self-tolerance partly by inducing the transcription of a wide array of tissue-specific antigens (TSAs), particularly in the thymus. The importance of Aire is highlighted by the fact that patients and mice defective in Aire expression develop a multi-organ autoimmune syndrome. In this review we discuss recent progress in our understanding of Aire's control of immune tolerance at the cellular and molecular levels, and also address the potential importance of Aire expression both in the thymus and in the peripheral lymphoid organs. The detection of... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2902287 Mon, 12 Oct 2009 23:00:00 +0100 2902287 http://www.medworm.com/index.php?rid=2896215&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%3D19828303%26dopt%3DAbstract Authors: Takeda K, Gelfand EW The increasing prevalence of allergic diseases worldwide is posing significant socio-economic challenges. The pathogenesis of these diseases reflects a complex interaction of genetic and environmental factors. The heterogeneity of disease phenotypes challenges the concept of single mechanisms of disease. As human experimentation is limited, animal models have been developed to provide insights into pathogenesis and potential for discovery of novel therapeutics. Mice have served in models of many of the allergic diseases including asthma, allergic rhinitis, food allergy, atopic dermatitis (AD), and allergic conjunctivitis. Although much has been learned from these investigations, there are limitations when these models are translated to the human diseases. ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2896215 Mon, 12 Oct 2009 23:00:00 +0100 2896215 http://www.medworm.com/index.php?rid=2896214&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%3D19828304%26dopt%3DAbstract Authors: Kawakami T, Ando T, Kimura M, Wilson BS, Kawakami Y Mast cells play as the major effector cells in immediate hypersensitivity through activation via the high-affinity IgE receptor, FcvarepsilonRI, although many other functions have recently been discovered for this cell type. Given the broad array of proinflammatory mediators secreted from FcvarepsilonRI-activated mast cells, as well as sensitization to allergens, IgE elevation, and increased mast cells in a majority of atopic dermatitis patients, mast cells are believed to be involved in the pathogenesis of atopic dermatitis. Numerous animal models have been used to study this epidemic disease. Here we review the recent progress to synthesize our current understanding of this disease and potential mechanisms for a mast cell's... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2896214 Mon, 12 Oct 2009 23:00:00 +0100 2896214 http://www.medworm.com/index.php?rid=2896219&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%3D19828300%26dopt%3DAbstract Authors: St Clair EW The emergence of new targeted therapies is rapidly improving the treatment of autoimmune disease. These drugs have been variably designed to deplete specific T and B cell subsets, interrupt receptor-ligand interactions, and inhibit the activity of inflammatory mediators relevant to immune function. Abatacept, a co-stimulatory blocker, and rituximab, a B cell depleting antibody, are among the approved therapies seeking new indications, while the newer therapies include Fc receptor-non-binding CD3-specific antibodies, IL-12/23 antibodies, an IL-6 receptor antagonist, a sphingosine-1-phosphate agonist, and small molecule inhibitors of intracellular protein kinases. Antigen-specific therapies are in their infancy, but the latest results administering glutamic acid dehy... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2896219 Sun, 11 Oct 2009 23:00:00 +0100 2896219 http://www.medworm.com/index.php?rid=2896217&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%3D19828301%26dopt%3DAbstract Authors: Hofmann AM, Abraham SN Mast cells (MCs) have primarily been associated with mediating the pathological secondary responses to allergens in sensitized hosts. In view of the recent evidence for a MC role in modulating primary immune responses to pathogens, the likelihood for a role of MCs in influencing primary immune response to allergens has grown. New evidence suggests that MCs drive the development of Th2 responses to allergens, particularly when allergen exposure occurs concomitantly with exposure to pathogen products present in the environment. These new roles for MCs in allergy and infection suggest additional drug targets to prevent the development of allergic disease and allergic exacerbations of established disease. PMID: 19828301 [PubMed - as supplied by publisher... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2896217 Sun, 11 Oct 2009 23:00:00 +0100 2896217 http://www.medworm.com/index.php?rid=2896216&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%3D19828302%26dopt%3DAbstract Authors: Metz M, Maurer M The skin as an organ has many functions of which the protection against environmental threats may be the most important. Recent investigations have broadened our understanding of the cellular mechanisms of host defense responses of the skin. Interestingly, the three key effector cells of cutaneous innate immunity, that is keratinocytes, dendritic cells, and mast cells, are also critically involved in the elicitation of allergic reactions. Keratinocytes keep bacteria and other pathogens from invading the host, but they can also promote the development of allergic asthma by releasing thymic stromal lymphopoietin. Dendritic cells in the skin are crucial for the detection and processing of allergens and thus for the development of allergies, but they are also esse... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2896216 Sun, 11 Oct 2009 23:00:00 +0100 2896216 http://www.medworm.com/index.php?rid=2866223&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%3D19800208%26dopt%3DAbstract Authors: Shlomchik MJ A recent advance in the treatment and understanding of autoimmune disease has been the efficacy of B-cell-targeted therapy. Such therapies are effective for several such diseases, with systemic autoimmunity being a prototypical example. The mechanism of action is not fully defined, but blocking B cell Ag presentation to T cells is likely to be important. T-B interactions probably engender a positive feedback loop that amplifies and sustains autoimmunity. But how is self-tolerance first broken to initiate this loop? I propose, based on recent data, a model in which autoreactive B cells are activated first, independent of T cells, but dependent upon BCR and TLR signals. These activated B cells then break T cell tolerance, resulting in full-blown autoimmunity. PM... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2866223 Tue, 29 Sep 2009 23:00:00 +0100 2866223 http://www.medworm.com/index.php?rid=2866222&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%3D19800209%26dopt%3DAbstract Authors: Li Pira G, Kapp M, Manca F, Einsele H Cellular immune functions are impaired in hemopoietic stem cell and solid organ transplantation or in cancer and autoimmune diseases treated with intensified immunosuppression. Thus, control of opportunistic pathogens is lost and severe infections break out. Defective cellular immunity can be restored upon endogenous immunoreconstitution or, if delayed, exogenous immunoreconstitution with pathogen specific T-lymphocytes selected or expanded from appropriate donors can be applied. Here we describe how recent developments in basic immunology knowledge and techniques have accelerated progresses of clinical trials in this attractive field. In particular, methods for the identification of appropriate antigens, for selection and expansion of spe... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2866222 Tue, 29 Sep 2009 23:00:00 +0100 2866222 http://www.medworm.com/index.php?rid=2856292&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%3D19796925%26dopt%3DAbstract Authors: Trapnell BC, Carey BC, Uchida K, Suzuki T Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of pulmonary surfactant, respiratory insufficiency, and increased infections. It occurs in various clinical settings that disrupt surfactant catabolism in alveolar macrophages, including a relatively more common autoimmune disease caused by GM-CSF autoantibodies and a rare congenital disease caused by CSF2RA mutations. Recent results demonstrate that GM-CSF is crucial for alveolar macrophage terminal differentiation and immune functions, pulmonary surfactant homeostasis, and lung host defense. GM-CSF is also required to determine the basal functional capacity of circulating neutrophils, including adhesion, phagocytosis, and microbial killing. PAP rese... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2856292 Mon, 28 Sep 2009 23:00:00 +0100 2856292 http://www.medworm.com/index.php?rid=2856291&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%3D19796926%26dopt%3DAbstract Authors: Notarangelo LD, Casanova JL PMID: 19796926 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2856291 Mon, 28 Sep 2009 23:00:00 +0100 2856291 http://www.medworm.com/index.php?rid=2842281&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%3D19782548%26dopt%3DAbstract Authors: Christiansen FT, Velardi A PMID: 19782548 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2842281 Wed, 23 Sep 2009 23:00:00 +0100 2842281 http://www.medworm.com/index.php?rid=2842280&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%3D19782549%26dopt%3DAbstract Authors: Boztug K, Klein C Severe congenital neutropenia (SCN) comprises a heterogenous group of primary immunodeficiency disorders collectively characterized by paucity of mature neutrophils. In recent years, progress has been made with respect to the elucidation of genetic causes underlying syndromic and non-syndromic variants of SCN. Most cases of autosomal dominant SCN are associated with mutations in the neutrophil elastase (ELA-2/ELANE) gene, autosomal recessive forms of this disorder can be caused by mutations in the gene encoding the mitochondrial protein HAX-1. Rarely, SCN can be caused by mutations in the gene encoding the transcription factor GFI1 or activating mutations in the Wiskott-Aldrich syndrome (WAS) gene, respectively. More recently, a complex disorder associating S... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2842280 Wed, 23 Sep 2009 23:00:00 +0100 2842280 http://www.medworm.com/index.php?rid=2825048&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%3D19766472%26dopt%3DAbstract Authors: Cavazzana-Calvo M, André-Schmutz I, Dal Cortivo L, Neven B, Hacein-Bey-Abina S, Fischer A Improvement of immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a key issue determining the clinical outcome of this widely used therapeutic approach. To this end, new strategies have been prompted by recent discoveries in immunology. In the setting of human leukocyte antigen (HLA) geno(pheno)identical HSCT, better prevention and treatment of acute and chronic graft-versus-host disease (GvHD) could significantly attenuate the thymic epithelium damage responsible for delayed and incomplete T-cell reconstitution. In a haploidentical setting, methods that would significantly accelerate neothymopoiesis in the months following injection of highly purified CD3... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2825048 Wed, 16 Sep 2009 23:00:00 +0100 2825048 http://www.medworm.com/index.php?rid=2825050&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%3D19765964%26dopt%3DAbstract Authors: Witt CS Numerous retrospective studies have been reported analysing the role of HLA mismatches that confer donor NK alloreactivity towards the recipient on the outcome of haematopoietic stem cell transplantation. A bewildering variety of findings have been observed with different studies showing either beneficial or deleterious effects on outcome. This review organises the reports into those that use similar definitions of NK alloreactivity, suggests possible reasons for such disparate results and assesses whether any recommendations can be made in relation to donor selection. There is growing evidence that the effect of human NK alloreactivity on outcome is transplant protocol dependent. Protocol variables most likely to affect outcome are those that influence donor T cell nu... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2825050 Tue, 15 Sep 2009 23:00:00 +0100 2825050 http://www.medworm.com/index.php?rid=2825049&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%3D19765965%26dopt%3DAbstract Authors: Tait BD The complement dependent microlymphocytotoxicity assay has been used for over 40 years for detecting HLA antibodies in transplant patients. This method has been replaced recently by more sensitive solid phase assays such as ELISA and bead based technology including the Luminex method. The introduction of these techniques into clinical practice has revealed previously undetected sensitisation in some patients and allowed the accurate assignment of antibody specificities directed at HLA-DQ and HLA-DP which was not previously possible. However it is emerging that despite the advantage of sensitivity some HLA antibodies defined by these assays are not associated with hyperacute or acute rejection. The role in allograft rejection of antibody titre and non-complement fixing ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2825049 Tue, 15 Sep 2009 23:00:00 +0100 2825049 http://www.medworm.com/index.php?rid=2800845&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%3D19748769%26dopt%3DAbstract Authors: Li F, Atz ME, Reed EF Transplant recipients exhibiting posttransplant antibodies are at a higher risk for acute and chronic antibody mediated rejection (AMR). The primary alloantigens recognized by antibodies in recipients with AMR are the highly polymorphic HLA class I and class II molecules expressed on the surface of the endothelial cells (ECs) of the graft. Traditionally, anti-HLA antibodies were thought to mediate graft injury through complement-dependent mechanisms. However, recent studies indicate that antibodies can also contribute to alterations in EC function through complement-independent mechanisms by transducing intracellular signals. Anti-HLA antibodies transduce signals that are both pro-inflammatory and pro-proliferative suggesting mechanistic roles in acute an... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2800845 Thu, 10 Sep 2009 23:00:00 +0100 2800845 http://www.medworm.com/index.php?rid=2800846&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%3D19747810%26dopt%3DAbstract Authors: Chervonsky A Cells of the adaptive immune system (T and B cells) causing autoimmunity require activation signals that are normally provided by the innate immune system. Innate signaling receptors are obvious candidates for participation in the induction of autoimmunity, and the nature of these receptors suggests that microbes could be the triggers. Recent publications describing the development of autoimmunity in sterile conditions and in animals deficient in innate signaling question the requirement of these receptors for initiation of autoimmunity. In addition, the role of the non-pathogenic (commensal) microbiota as a regulator of autoimmunity has come into the spotlight. In this review we discuss recent reports that deal with the link between innate signaling receptors and... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2800846 Tue, 08 Sep 2009 23:00:00 +0100 2800846 http://www.medworm.com/index.php?rid=2775617&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%3D19735996%26dopt%3DAbstract Authors: van Rood JJ, Oudshoorn M Until now, hematopoietic stem cell (HSC) donor selection has been almost exclusively based on selecting a (near) HLA identical donor but many patients fail to find a suitable donor. However all donors have been exposed during fetal life and by breastfeeding to microchimeric maternal cells and molecules, which may induce long lasting T regulator cells. Likewise fetal cells invade the maternal circulation and one-third of the mothers are immunized to the paternal antigens of the child, while part of the mothers become tolerant to them. By taking the alloimmune status of the HSC donor into account, HLA mismatched grafts are an attractive alternative for those patients who do not have an HLA identical sibling donor. PMID: 19735996 [PubMed - as supplied... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2775617 Fri, 04 Sep 2009 23:00:00 +0100 2775617 http://www.medworm.com/index.php?rid=2752804&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%3D19717292%26dopt%3DAbstract Authors: Minegishi Y Hyper-IgE syndrome (HIES) is a complex primary immunodeficiency characterized by atopic dermatitis associated with extremely high serum IgE levels and susceptibility to infections with extracellular bacteria. Nonimmunological abnormalities, including a distinctive facial appearance, fracture following minor trauma, scoliosis, hyperextensive joints, and the retention of deciduous teeth are also observed in most patients. Recent studies have demonstrated that dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3) gene result in the classical multisystem form of HIES, whereas a null mutation in the tyrosine kinase 2 (TYK2) gene causes an autosomal recessive HIES associated with viral and mycobacterial infections. In both patients... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2752804 Thu, 27 Aug 2009 23:00:00 +0100 2752804 http://www.medworm.com/index.php?rid=2752803&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%3D19717293%26dopt%3DAbstract Authors: Velardi A, Ruggeri L, Mancusi A, Aversa F, Christiansen FT Donor-versus-recipient natural killer (NK) cell alloreactivity has been established as a key therapeutic element in HLA haplotype mismatched hematopoietic transplants in adult AML and pediatric ALL and as a possible beneficial effector in cord blood transplant for AML. It is effected by functional NK cells which express inhibitory killer cell immunoglobulin-like receptor(s) (KIR) for self-class I ligand(s), sense missing expression of donor KIR ligand(s) in the recipient and mediate alloreactions. At present NK cell allotherapy for leukemia is deployed through stem cell transplantation (and ensuing NK cell reconstitution) across KIR ligand mismatches. Studies have been performed to infuse NK cells for immunotherapy out... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2752803 Thu, 27 Aug 2009 23:00:00 +0100 2752803 http://www.medworm.com/index.php?rid=2745951&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%3D19713093%26dopt%3DAbstract Authors: Nickerson P Transplantation has emerged as the therapy of choice for many patients with end organ failure. One of the major goals is to tailor immunosuppressive therapy to the individual needs of every patient to balance the risk for rejection and over-immunosuppression. This will require diagnostic tools that can detect harmful processes in the allograft early, and that can be measured repeatedly. This review will consider recent advances in our understanding of the molecular nature of these processes and how this information is being utilized to design novel diagnostic assays to non-invasively monitor allografts. Highlighted is the need for large-scale prospective multi-centre studies to validate assays that show early promise in single centre studies. PMID: 19713093 [Pu... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2745951 Tue, 25 Aug 2009 23:00:00 +0100 2745951 http://www.medworm.com/index.php?rid=2743227&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%3D19709867%26dopt%3DAbstract Authors: Neves JS, Weller PF Human eosinophils contain within their cytoplasmic granules multiple preformed proteins, including over three dozen cytokines with nominal Th1, Th2 and immunoregulatory capabilities, and four distinctive cationic proteins. The secretion of these granule-derived proteins within eosinophils occurs principally by a mechanism whereby selected proteins are mobilized into vesicles for transport to and release at the cell surface. In contrast, the enigmatic presence of membrane-bound cell-free granules extruded from eosinophils has been long recognized in tissues associated with eosinophilia, including allergic diseases and responses to helminths. Functional capabilities for extracellular granules have recently been demonstrated. Eosinophil granules express cytoki... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2743227 Sun, 23 Aug 2009 23:00:00 +0100 2743227 http://www.medworm.com/index.php?rid=2730802&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%3D19700272%26dopt%3DAbstract Authors: Akdis M Research on the mechanisms of immune regulation in allergy and asthma has shown substantial progress in recent years and has led to a variety of allergen-specific therapeutic and preventive approaches. Studies on the area of allergen-specific immunotherapy (allergen-SIT) have provided substantial knowledge on the mechanisms of allergic disease with novel developments for treatment and prevention. Several studies have demonstrated that increased numbers and the activation of allergen-specific T regulatory cells correlate with successful allergen-SIT. Particularly, targeting of the molecular mechanisms of immune tolerance and reciprocal regulation of effector and regulatory T-cell subsets are foreseen for the development of new strategies for immune intervention. This re... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2730802 Thu, 20 Aug 2009 23:00:00 +0100 2730802 http://www.medworm.com/index.php?rid=2730803&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%3D19699075%26dopt%3DAbstract Authors: Wucherpfennig KW, Call MJ, Deng L, Mariuzza R The crystal structures of five autoimmune T cell receptor (TCR)-peptide-MHC complexes reveal substantial structural alterations compared to antimicrobial TCRs. The two human TCRs bind their self-peptide-MHC ligands with an altered topology, while the three mouse receptors recognize a self-peptide that only partially fills the MHC-binding groove. In most cases the peptide is contacted only by a subset of available TCR complementarity-determining loops and there is a paucity of hydrogen bonds from TCR to peptide. These suboptimal binding properties may have enabled escape from negative thymic selection. While only minute amounts of antigen are typically available for negative selection, the antigens recognized by many autoimmune TCRs... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2730803 Tue, 18 Aug 2009 23:00:00 +0100 2730803 http://www.medworm.com/index.php?rid=2713560&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%3D19683910%26dopt%3DAbstract Authors: Veldhoen M The classification of T helper (T(H)) cells in subsets has progressively expanded and more effector subsets, besides T(H)1 and T(H)2, have been documented. These include follicular helper T cells (T(FH)), and the more recent T(H)17, 'T(H)9', and 'T(H)22'. In addition, T(H) are no longer thought of as terminally committed effector cells, with plasticity now recognized. Identification of the molecular mechanisms that drive differentiation of T(H) cells has established a link between environmental factors and T(H) subsets, with regard to both the initiation and severity of immune disorders. The role of T(H) in autoimmune-disorders and allergic-disorders is now re-evaluated, with current data suggesting a central role for T(H)17 in orchestrating adaptive-immune response... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2713560 Thu, 13 Aug 2009 23:00:00 +0100 2713560 http://www.medworm.com/index.php?rid=2713561&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%3D19682882%26dopt%3DAbstract Authors: Claas FH, Doxiadis II One of the major challenges in the current era of organ transplantation is to find suitable organs for highly sensitized patients. Different approaches have been successful in a proportion of the patients. Several organ exchange organizations are currently implementing an acceptable mismatch program similar to the one developed by Eurotransplant. The basis of such a program is the accurate definition of those HLA antigens or epitopes toward which the patient did not form antibodies. Donors, who are compatible with the combination of the HLA type of the recipient and these acceptable HLA mismatches, will have a negative crossmatch and are allocated with the highest priority to the highly sensitized patient. Such an approach has shown to increase the transp... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2713561 Tue, 11 Aug 2009 23:00:00 +0100 2713561 http://www.medworm.com/index.php?rid=2692474&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%3D19665880%26dopt%3DAbstract Authors: Sewell GW, Marks DJ, Segal AW The pathogenesis of Crohn's disease (CD) has remained an enigma for at least a century. There was considerable optimism that genetic linkage and genome-wide association (GWA) studies had identified genes causally responsible. However, the realisation that these genes make a relatively minor contribution to the development of CD has led to the acceptance of a 'missing heritability'. In contrast to the weak genetic effects, patients with CD almost without exception exhibit a gross phenotype, namely a profound systemic failure of the acute inflammatory response. This results in markedly delayed clearance of bacteria from the tissues, leading to local chronic granulomatous inflammation and compensatory adaptive immunological changes, as well as consti... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2692474 Thu, 06 Aug 2009 23:00:00 +0100 2692474 http://www.medworm.com/index.php?rid=2671250&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%3D19651503%26dopt%3DAbstract Authors: Conley ME In the past, immunodeficiencies were categorized based on clinical and laboratory findings in the affected patient. Now we are more likely to define them based on the specific gene involved. One might expect this shift to increase the precision and clarity of diagnosis but in the last few years it has become increasingly clear that identification of a mutation in a specific gene may not tell the whole story. Some gene defects may reliably result in clinical disease, others may act as susceptibility factors that are more common in patients with immunodeficiency but can also be found in otherwise healthy individuals. Distinguishing between these two types of gene defects is essential for informative genetic counseling. PMID: 19651503 [PubMed - as supplied by publis... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2671250 Fri, 31 Jul 2009 23:00:00 +0100 2671250 http://www.medworm.com/index.php?rid=2671251&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%3D19647987%26dopt%3DAbstract Authors: Etzioni A Up to now three distinct syndromes affecting several steps in the leukocyte adhesion cascade have been described. In LAD I the firm adhesion of leukocyte to the endothelium is defective, because of mutations in the gene encoding the beta(2)-integrin. Recent works both in human and animal models shed light on various mutations and their physiological importance. Furthermore, the beneficial effect of gene therapy is also becoming clear. LAD II which involved the first phase of the cascade, the rolling phase, is caused by mutations in the specific fucose transporter to the Golgi apparatus. Gene targeted mice were able to demonstrate indeed the role of this transporter in the adhesion process and long-term follow-up of patients showed that while in childhood immunodefici... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2671251 Thu, 30 Jul 2009 23:00:00 +0100 2671251 http://www.medworm.com/index.php?rid=2671255&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%3D19646850%26dopt%3DAbstract Authors: Kronenberg M, Kinjo Y Invariant natural killer T cells (iNKT cells) express a restricted T cell antigen receptor (TCR) repertoire and they respond rapidly to glycolipid antigens presented by CD1d. These glycolipid antigens have hexose sugars in alpha-linkage to two types of lipids that can bind to CD1d. Recent work has shown that the responses of iNKT cells to antigen-bearing microbes can have a profound impact on the development of inflammatory diseases. iNKT cells overcome the limitation of their limited TCR diversity by also responding in a foreign antigen-independent fashion to some infectious agents, similar to NK cells. Recent results demonstrate several mechanisms for the indirect activation of iNKT cells by viruses or TLR ligands, dependent on self-antigen recognition ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2671255 Tue, 28 Jul 2009 23:00:00 +0100 2671255 http://www.medworm.com/index.php?rid=2671254&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%3D19646851%26dopt%3DAbstract Authors: Cooper AM There has been an increase in our understanding of the complexity of the T cell response to mycobacterial infection recently. Improved tools have allowed the determination of the location and kinetics of naïve T cell activation in the mouse as well the variety of function of mycobacteria-specific cells in humans. There is also an increased appreciation of the balance required during mycobacterial infection between anti-bacterial activity and control of the immunopathologic response. The integration of the T cell functional data with the consequences of infection should improve rational vaccine design. PMID: 19646851 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2671254 Tue, 28 Jul 2009 23:00:00 +0100 2671254 http://www.medworm.com/index.php?rid=2671253&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%3D19646852%26dopt%3DAbstract Authors: Dorhoi A, Kaufmann SH Adequate control of infection relies on development of a tailored immune response according to the requirements of a given infection. This is achieved by the continuous crosstalk between innate and adaptive immunity. Pathogen diversity is deciphered via a plethora of receptors converging signals to adaptor molecules; tissue sites and environment generate additional signals that further influence T cell lineage decisions. Within this continuum of interactions, fine-tuning of the ensuing T cell responses together with plasticity of the committed T cells ensure development of balanced immune responses maintaining homeostasis. This review focuses on the multiple mechanisms that govern T cell differentiation during infection. PMID: 19646852 [PubMed - as su... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2671253 Tue, 28 Jul 2009 23:00:00 +0100 2671253 http://www.medworm.com/index.php?rid=2671252&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%3D19646853%26dopt%3DAbstract Authors: Padilla AM, Bustamante JM, Tarleton RL CD8(+) T cells have emerged as crucial players in the control of a number of protozoan pathogens, including Trypanosoma cruzi, the agent of human Chagas disease. The recent identification of the dominant targets of T. cruzi-specific T cells has allowed investigators to follow the generation of and document the functionality of T cell responses in both mice and humans. Although slow to develop in the early stages of the infection, T. cruzi-specific CD8(+) T cells reach prodigious levels and remain highly functional throughout chronic infections in mice. Following drug-induced cure during either the acute or chronic stage, these immunodominant T cells persist as stable, antigen-independent memory populations. T. cruzi-specific CD8(+) T cell... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2671252 Tue, 28 Jul 2009 23:00:00 +0100 2671252 http://www.medworm.com/index.php?rid=2661115&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%3D19643590%26dopt%3DAbstract Authors: Modlin RL, Brenner MB PMID: 19643590 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2661115 Mon, 27 Jul 2009 23:00:00 +0100 2661115 http://www.medworm.com/index.php?rid=2646461&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%3D19632102%26dopt%3DAbstract Authors: Dorshkind K, Swain S PMID: 19632102 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2646461 Wed, 22 Jul 2009 23:00:00 +0100 2646461 http://www.medworm.com/index.php?rid=2615659&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%3D19608393%26dopt%3DAbstract Authors: Frasca D, Blomberg BB Ability to make an optimal immune response to vaccines and infectious agents declines with age in humans and animal models. Recent advances have shown intrinsic B cell defects in aged mice and humans, including decreases in Ig class switch recombination (CSR), activation-induced cytidine deaminase (AID), and E47 transcription factor. Effects on somatic hypermutation (SHM) have been varied depending on the system studied. Increase of AID in mice has shown improved CSR but not SHM. The reported microarray analysis of human B cell subsets may now be used to delineate B cell defects with aging and all the advances presented should lead to selecting agents for improved immune response in the elderly. PMID: 19608393 [PubMed - as supplied by publisher] (Sour... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2615659 Mon, 13 Jul 2009 23:00:00 +0100 2615659 http://www.medworm.com/index.php?rid=2615658&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%3D19608394%26dopt%3DAbstract Authors: Holland AM, van den Brink MR The elderly face significant risk for susceptibility to infection and cancer because of declining immune function. Various agents used in the setting of bone marrow transplantation and aging studies represent promising approaches to combating T cell defects in the aging population. Preclinical and clinical studies on the T cell reconstitution effects of sex steroid ablation, keratinocyte growth factor, the growth hormone pathway, and the cytokines interleukin-7, interleukin-12, and interleukin-15 indicate that these strategies may be used to alleviate the effects of T cell deficiencies in the elderly. PMID: 19608394 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2615658 Mon, 13 Jul 2009 23:00:00 +0100 2615658 http://www.medworm.com/index.php?rid=2573717&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%3D19570667%26dopt%3DAbstract Authors: McElhaney JE, Effros RB The most profound consequences of immune senescence with respect to human health are the increased susceptibility to infectious diseases and decreased vaccine efficacy. Changes in both innate and adaptive immune function converge in the reduced response to vaccination and protection against infection and related diseases. The decline in thymic output of naïve T cells diminishes responses to novel antigens, such as West Nile Virus, while clonal expansions leading to defects in the T cell repertoire are associated with blunted responses of memory T cells to conserved epitopes of the influenza virus. Recent studies on how immunologic mechanisms of protection change during aging have led to novel strategies for improving vaccine responsiveness and outc... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2573717 Sun, 28 Jun 2009 23:00:00 +0100 2573717 http://www.medworm.com/index.php?rid=2557172&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%3D19559585%26dopt%3DAbstract Authors: Pays E, Vanhollebeke B Humans are naturally resistant to infection by the African trypanosome prototype Trypanosoma brucei brucei, and only two variant clones of this parasite can avoid this innate immunity and cause sleeping sickness. The resistance to T. brucei is due to serum complexes associating apolipoprotein A-1 (apoA1) with two primate-specific proteins, apolipoprotein L-1 (apoL1) and haptoglobin-related protein (Hpr). We discuss recent advances on the respective functions of apoL1 and Hpr in this system. ApoL1 was found to share structural and functional similarities with proteins of the apoptotic Bcl2 family, and to kill trypanosomes through anionic pore formation in the lysosomal membrane of the parasite. In association with hemoglobin (Hb), Hpr was found to promote... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2557172 Tue, 23 Jun 2009 23:00:00 +0100 2557172 http://www.medworm.com/index.php?rid=2529024&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%3D19541469%26dopt%3DAbstract Authors: Kasmar A, Van Rhijn I, Moody DB CD1 proteins display lipid antigens to T cell receptors. Studies using CD1d tetramers and CD1d-deficient mice provide important insight into the immunological functions of invariant NK T cells (iNKT) during viral and bacterial infections. However, the mouse CD1 locus is atypical because it encodes only CD1d, whereas most mammalian species have retained many CD1 genes. Viewed from the perspective that CD1 is a diverse gene family that activates several of classes of T cells, new insights into lipid loading and infection response are emerging. PMID: 19541469 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529024 Thu, 18 Jun 2009 23:00:00 +0100 2529024 http://www.medworm.com/index.php?rid=2529026&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%3D19535233%26dopt%3DAbstract Authors: Derhovanessian E, Larbi A, Pawelec G Age-associated failing systemic immunity, loosely termed 'immunosenescence', is thought to contribute to the increased incidence and severity of infectious disease in old people. It would therefore be of great practical as well as academic interest to accurately identify which of the multitude of alterations to immune parameters thus far reported are causally related to a person's clinically unfavourable health status, in order to identify the mechanisms of immune ageing and intervene to restore appropriate immunity. This is an enormous current challenge, as it requires longitudinal studies in a very long-lived species. Circumstantial evidence and longitudinal studies limited to the very elderly have begun to reveal 'immune signatures' or b... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529026 Sun, 14 Jun 2009 23:00:00 +0100 2529026 http://www.medworm.com/index.php?rid=2529025&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%3D19535234%26dopt%3DAbstract Authors: Liu Y, Sharpless NE The cancer-aging hypothesis suggests that the activation of some tumor suppressor mechanisms beneficially prevents cancer but also untowardly promotes mammalian aging. Along these lines, activation of tumor suppressor mechanisms that inhibit the cell cycle (e.g. p16(INK4a) and p53) in response to DNA damage and other age-promoting stimuli has taken center stage in immune-aging research. Immune cells are intrinsically susceptible to transforming events due to V(D)J recombination, a high rate of cellular turnover and requisite long-term self-renewal. Therefore, the DNA damage response and cell cycle regulation play a clear role in maintaining homeostasis without neoplastic progression. Here we will argue on the basis of recent advances in our understanding of... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529025 Sun, 14 Jun 2009 23:00:00 +0100 2529025 http://www.medworm.com/index.php?rid=2529040&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%3D19500962%26dopt%3DAbstract Authors: Waterstrat A, Van Zant G Although relationships between cellular and organismal aging are not well understood, several studies describe age-related changes in hematopoietic stem cells (HSCs) with functional consequences for the hematopoietic system. Importantly, aged hematopoietic stem and progenitor cells (HSPCs) differ from their younger counterparts in functional capacity, the complement of proteins on the cell surface, transcriptional activity, and genome integrity. These changes, however, are likely the result of a combination of cell-intrinsic and microenvironment-derived influences. Evolving views of the composition of the HSC compartment suggest that changes in HSCs may reflect the effects of the aging process on individual HSCs or a shift in the clonal composition of ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529040 Tue, 02 Jun 2009 23:00:00 +0100 2529040 http://www.medworm.com/index.php?rid=2529039&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%3D19500963%26dopt%3DAbstract Authors: Fraga MF Many age-associated conditions, such as the decrease in regenerative capacity of tissues, appear to be determined by a decline in the function of specific somatic stem cells. Although it is obvious that the genotype determines the average lifespan of different species, the variation in lifespan of individuals within a species seems to be more affected by the accumulation over time of molecular errors that compromise adult stem cell function. These molecular alterations can occur at both the genetic and epigenetic levels and depend on hereditary, environmental, and stochastic factors. This complex multifactorial mixture determines characteristics, such as longevity and a healthy life, that are central concerns of human existence. PMID: 19500963 [PubMed - as supplie... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529039 Tue, 02 Jun 2009 23:00:00 +0100 2529039 http://www.medworm.com/index.php?rid=2529035&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%3D19500967%26dopt%3DAbstract Authors: Haynes L, Maue AC Immunosenescence influences many components of the immune system. Most importantly, profound changes in T cell function are evident in older individuals. The impact of aging on specific T cell subsets has been difficult to examine, but recent advances in murine model systems and new insights into T cell function have allowed for the more precise examination of how T cell responses change with aging. Importantly, recent studies have shown that age-related enhancement of both Th17 generation and regulatory T cell function may contribute to significant changes in immune function. In this review, we summarize the current views on how aging influences the factors that impact T cell function and how this can affect the immune response to infections, vaccinations, a... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529035 Tue, 02 Jun 2009 23:00:00 +0100 2529035 http://www.medworm.com/index.php?rid=2529048&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%3D19481917%26dopt%3DAbstract Authors: Phan TG, Gray EE, Cyster JG The logistic problem of B cell antigen encounter in the lymph node has recently been studied by dynamic imaging using two-photon microscopy. These studies combined with the early studies of antigen transport have yielded a more complete picture of the orchestration of B cell activation in vivo. Here we summarize the recent advances and focus on the specialized macrophages that are critical to this process and the role of B cells themselves as antigen transporting cells. PMID: 19481917 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529048 Sun, 31 May 2009 23:00:00 +0100 2529048 http://www.medworm.com/index.php?rid=2529047&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%3D19482462%26dopt%3DAbstract Authors: Kayed R, Jackson GR Alzheimer disease (AD) is the most common neurodegenerative disorder. Currently available therapies may slow cognitive decline but do not alter underlying disease processes. Considerable effort over the last decade has been directed toward the development of vaccines for AD; these have been primarily directed against the Abeta peptide, a component of senile plaques. More recently, alternative approaches have begun to target the microtubule binding protein tau, a component of neurofibrillary tangles. Immunotherapies based upon oligomeric species of tau represent a promising new approach for AD. PMID: 19482462 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529047 Sun, 31 May 2009 23:00:00 +0100 2529047 http://www.medworm.com/index.php?rid=2529046&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%3D19493664%26dopt%3DAbstract Authors: De Gregorio E, D'Oro U, Wack A Vaccine adjuvants target the innate immune system to enhance the immunogenicity of coadministered antigens. Dendritic cells (DCs) are responsible for antigen uptake and presentation to naïve T cells and represent a key target of adjuvant activity. Adjuvants derived from microbial components, such as Toll-like receptor (TLR) agonists, elicit innate immune receptors expressed by DCs. By contrast, particulate adjuvants, like mineral salts, oil-in-water emulsions, and microparticles, do not activate DCs directly, and their mechanism of action is poorly characterized. In the last two years it has been reported that particulate adjuvants induce chemokine production in accessory cells like macrophages, monocytes, and granulocytes, leading to cell r... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529046 Sun, 31 May 2009 23:00:00 +0100 2529046 http://www.medworm.com/index.php?rid=2529045&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%3D19493665%26dopt%3DAbstract Authors: Takahashi I, Nochi T, Yuki Y, Kiyono H Progress in the past quarter-century on understanding the molecular, cellular, and in vivo components of the mucosal immune system have allowed us to develop a practical strategy for a novel mucosal vaccine. The mucosal immune system can induce secretory IgA (SIgA) and serum IgG responses to provide two layers of defense against mucosal pathogens. For SIgA-mediated immunity in the gastrointestinal tract, the gut-associated lymphoid tissue contains both the tissue-dependent and tissue-independent IgA components. Harnessing the mucosal immune system for vaccine development may help prevent the global health problems caused by enteric infectious diseases. We have therefore combined mucosal immunology and plant biology to create a rice-based ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529045 Sun, 31 May 2009 23:00:00 +0100 2529045 http://www.medworm.com/index.php?rid=2529044&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%3D19493666%26dopt%3DAbstract Authors: Casares S, Richie TL Malaria is a deadly infectious disease that affects one to two billion people and kills up to one million children yearly. Despite decades of intensive research, we are still lacking an effective vaccine against malaria. Our efforts are being challenged by the complexity of Plasmodium's life cycle, its ability to parasitize and hide within the host cells, and its masterful ability to avoid clearance by the innate and adaptive host immune responses. In this article we will review the main mechanisms of immune evasion used by malaria parasites and discuss the implications for malaria vaccine development. PMID: 19493666 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529044 Sun, 31 May 2009 23:00:00 +0100 2529044 http://www.medworm.com/index.php?rid=2529043&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%3D19497720%26dopt%3DAbstract Authors: Parish IA, Kaech SM CD8(+) T cells are key effector cells of the adaptive immune system, however their activity must be tightly regulated to allow pathogen clearance whilst preventing immunopathology and autoimmunity. In this review, we summarise the diversity of responses that CD8(+) T cells make to antigenic stimulation with a focus on how CD8(+) T cell responses are regulated to achieve different immune outcomes. In particular, we discuss phenotypic diversity during tolerance induction as well as signals that drive effector and memory cell differentiation in response to infection. PMID: 19497720 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529043 Sun, 31 May 2009 23:00:00 +0100 2529043 http://www.medworm.com/index.php?rid=2529042&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%3D19497721%26dopt%3DAbstract Authors: Lanzavecchia A, Sallusto F Following an immune response two types of differentiated B cells persist in the memory pool: plasma cells, which confer immediate protection by the secretion of specific antibodies; and memory B cells, which confer rapid and enhanced response to secondary challenge. We will review recent advances in understanding the heterogeneity, dynamics, and persistence of human memory B cells and plasma cells as well as new methods to isolate human monoclonal antibodies. These findings offer new insights into the human B cell response, which are relevant for vaccination and therapeutic intervention. PMID: 19497721 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529042 Sun, 31 May 2009 23:00:00 +0100 2529042 http://www.medworm.com/index.php?rid=2529041&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%3D19497722%26dopt%3DAbstract Authors: Stetson DB Recent advances have revealed a fundamental contradiction in antiviral immunity: innate immune sensors that detect nucleic acids mediate both protective immunity to infection and pathological autoimmune disease. Thus, the study of the mechanics of nucleic acid detection will provide insight into how these systems are inappropriately triggered in autoimmunity, and, conversely, the study of autoimmune disease triggered by these sensors will tell us more about how they are linked to activation of adaptive immunity. PMID: 19497722 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529041 Sun, 31 May 2009 23:00:00 +0100 2529041 http://www.medworm.com/index.php?rid=2529038&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%3D19500964%26dopt%3DAbstract Authors: Lu S An effective vaccine usually requires more than one time immunization in the form of prime-boost. Traditionally the same vaccines are given multiple times as homologous boosts. New findings suggested that prime-boost can be done with different types of vaccines containing the same antigens. In many cases such heterologous prime-boost can be more immunogenic than homologous prime-boost. Heterologous prime-boost represents a new way of immunization and will stimulate better understanding on the immunological basis of vaccines. PMID: 19500964 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529038 Sun, 31 May 2009 23:00:00 +0100 2529038 http://www.medworm.com/index.php?rid=2529037&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%3D19500965%26dopt%3DAbstract Authors: Poland G, Barrett A PMID: 19500965 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529037 Sun, 31 May 2009 23:00:00 +0100 2529037 http://www.medworm.com/index.php?rid=2529036&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%3D19500966%26dopt%3DAbstract Authors: Zhou X, Bailey-Bucktrout S, Jeker LT, Bluestone JA Regulatory T (Treg) cells play an essential role in maintaining immunological tolerance. The discovery of FoxP3 as a key Treg transcription factor combined with recent advances in the development of functional reporter mice has enabled new insights into Treg biology and revealed unexpected features of this lineage. In this review, we address the stability of this population, focusing on studies that suggest that Tregs can downregulate FoxP3, lose regulatory activity and, under some conditions, become memory T cells capable of recognizing self-antigens and expressing effector cell activities including the production of IL-17 and IFNgamma. The presence of these 'exTregs' in multiple inflammatory settings suggests a potential rol... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529036 Sun, 31 May 2009 23:00:00 +0100 2529036 http://www.medworm.com/index.php?rid=2529034&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%3D19502021%26dopt%3DAbstract Authors: McHeyzer-Williams LJ, Pelletier N, Mark L, Fazilleau N, McHeyzer-Williams MG Follicular helper T (T(FH)) cells are a class of helper T cells specialized in the cognate control of antigen-specific B cell immunity. Upon first contact with antigen-primed B cells, pregerminal center effector T(FH) cells promote B cell clonal expansion, antibody isotype switch, plasma cell differentiation, and the induction of germinal centers. By contrast, within germinal centers, T(FH) cells regulate the fate of antigen-specific GC B cells expressing high-affinity variant B cell receptors to promote memory B cell and long-lived plasma cell development. Recent studies unravel multiple signals controlling T(FH) development and functional subtypes of antigen-specific T(FH) cells, including memory T(... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529034 Sun, 31 May 2009 23:00:00 +0100 2529034 http://www.medworm.com/index.php?rid=2529033&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%3D19505813%26dopt%3DAbstract Authors: Barker LF, Brennan MJ, Rosenstein PK, Sadoff JC A safe and effective vaccine to prevent tuberculosis is necessary to combat this ancient disease that kills millions worldwide. Recent advances in our understanding of the host immune response to Mycobacterium tuberculosis (Mtb) are facilitating the development of several novel vaccine approaches. New tools for measuring and characterizing cell-mediated immune responses to Mtb have furthered the assessment of these new vaccines in animal models and in human clinical studies including efficacy trials. Measurements of the relative contribution of CD4+ and CD8+ T cells, central and effector memory T cells, and regulatory T cells are being completed in these studies, as well as broad screening efforts utilizing bead array cytokine de... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529033 Sun, 31 May 2009 23:00:00 +0100 2529033 http://www.medworm.com/index.php?rid=2529032&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%3D19515546%26dopt%3DAbstract Authors: Gonzalez SF, Pitcher LA, Mempel T, Schuerpf F, Carroll MC The fate of B lymphocytes is dictated in large part by cognate antigen and the environment in which it is encountered. Yet we are only now beginning to understand where and how B cells acquire antigen. Recent studies identify multiple pathways by which lymph-borne antigens enter the B cell follicles of LNs. Size is a major factor as particulate antigens and large IC are bound by subcapsular sinus macrophages. By contrast, small antigens (under 70kDa) are rapidly channeled into follicles via conduits secreted by fibroblastic reticular cells (FRC). Interestingly, the conduits not only deliver antigen to follicular dendritic cells (FDC) but also provide a rich source of B cell chemokine, that is, CXCL-13. Thus, the follicu... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529032 Sun, 31 May 2009 23:00:00 +0100 2529032 http://www.medworm.com/index.php?rid=2529031&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%3D19520559%26dopt%3DAbstract Authors: Barrett AD, Teuwen DE Yellow fever 17D vaccine is one of the most successful vaccines ever developed and over 540 million doses have been used. Nevertheless there has been very little known about the mechanism of protection induced by the vaccine. The last couple of years have seen important advances made in understanding how the vaccine works involving studies of the innate and adaptive immune responses plus a systems biology approach. Like all vaccines, the 17D vaccine causes rare serious adverse events (SAEs) following immunization. At present, the mechanism(s) of SAEs is(are) poorly understood but our advances in understanding the immune response induced by the vaccine have promise to help elucidate the mechanism of SAEs. PMID: 19520559 [PubMed - in process] (Source: C... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529031 Sun, 31 May 2009 23:00:00 +0100 2529031 http://www.medworm.com/index.php?rid=2529030&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%3D19520560%26dopt%3DAbstract Authors: McHeyzer-Williams M, Nussenzweig MC PMID: 19520560 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529030 Sun, 31 May 2009 23:00:00 +0100 2529030 http://www.medworm.com/index.php?rid=2529029&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%3D19524427%26dopt%3DAbstract Authors: Kennedy RB, Ovsyannikova IG, Jacobson RM, Poland GA In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529029 Sun, 31 May 2009 23:00:00 +0100 2529029 http://www.medworm.com/index.php?rid=2529028&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%3D19524428%26dopt%3DAbstract Authors: Turner SJ, La Gruta NL, Kedzierska K, Thomas PG, Doherty PC Naive T cells are recruited into any given host response by recognizing a spectrum of possible antigens with 'sufficient' avidity. Does selecting a more functionally diverse array give better immune control? Perhaps low avidity 'killers' that 'kiss and run' operate optimally to eliminate virus-infected targets, while high avidity 'helpers' that stay faithfully in place produce more cytokine. Recent findings indeed suggest that the selection of a broad T cell receptor repertoire is characteristic of the initial phase following antigen contact, while continued exposure leads to further cycles of division and the progressive numerical dominance of 'best-fit' clonotypes. Here, we review recent advances demonstrating a lin... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529028 Sun, 31 May 2009 23:00:00 +0100 2529028 http://www.medworm.com/index.php?rid=2529027&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%3D19524429%26dopt%3DAbstract Authors: Lee YK, Mukasa R, Hatton RD, Weaver CT The emergence of Th17 cells as a distinct subset of effector CD4 T cells has led to a revised model of the adaptive immune system. Whereas the Th1-Th2 paradigm revolutionized our understanding of adaptive immunity by introducing the concept of alternative developmental pathways for naïve CD4 T cells induced by distinct cytokine cues from microbe-activated innate immune cells, delineation of Th17 cell differentiation has extended this concept and has led to a greater appreciation of the developmental plasticity of CD4 T cells. In contrast to Th1 and Th2 cells, which have been thought to represent terminal products of their respective developmental programs, recent studies suggest that Th17 cells are less rigid. In addition to early de... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529027 Sun, 31 May 2009 23:00:00 +0100 2529027 http://www.medworm.com/index.php?rid=2529049&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%3D19442502%26dopt%3DAbstract Authors: Allison AC The term 'innate resistance' covers mechanisms of resistance that operate early in the course of infections, preceding adaptive immune responses which exert effects after several days. The first example of genetically controlled innate resistance to human malaria was the demonstration in 1954 that sickle-cell heterozygotes have less severe Plasmodium falciparum infections than do children with normal adult hemoglobin. This observation has been repeatedly confirmed, most recently by independent studies of genome-wide associations in severe falciparum malaria, which have identified the HBB locus as the major signal of association. Other abnormal hemoglobins, glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency also confer some degree of resistan... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529049 Sun, 10 May 2009 23:00:00 +0100 2529049 http://www.medworm.com/index.php?rid=2529055&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%3D19359154%26dopt%3DAbstract Authors: Kuo TC, Schlissel MS Recombination activating genes (RAG)1 and RAG2 are expressed in developing B and T lymphocytes and are required for the rearrangement of antigen receptor genes. In turn, RAG expression is regulated by the products of these assembled immunoglobulin (Ig) and T cell receptor (TCR) genes. Upon successful assembly of Ig genes, the antigen receptor is expressed on the immature B cell surface and tested for autoreactivity leading to either maintenance or inactivation of RAG expression. Successful assembly of TCR genes is followed by surface TCR expression and testing for its ability to interact with self-MHC, which if appropriate leads to the inactivation of RAG expression. Recent studies in B and T lymphocytes demonstrate that the reduction in RAG expression at ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529055 Tue, 31 Mar 2009 23:00:00 +0100 2529055 http://www.medworm.com/index.php?rid=2529054&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%3D19361970%26dopt%3DAbstract Authors: Weaver CT, Rudensky AY PMID: 19361970 [PubMed - in process] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529054 Tue, 31 Mar 2009 23:00:00 +0100 2529054 http://www.medworm.com/index.php?rid=2529053&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%3D19361971%26dopt%3DAbstract Authors: Taniuchi I The mechanism underlying the lineage decision made by CD4(+)CD8(+) double-positive (DP) thymocytes that give rise to two T lymphocyte subset with distinct functionalities, that is, helper and cytotoxic T cells, remains a major issue in immunology. The lineage decision process involves several phases and terminates when cells loose their developmental plasticity to become the alternate lineage. A detailed picture of the transcription factor network governing helper versus cytotoxic-lineage decision has recently emerged. Studies published only past year provided new insights into how the expression of ThPOK, a central transcription factor for helper T cell development, is regulated. It has now become evident that an antagonistic interplay between ThPOK and Runx transc... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529053 Tue, 31 Mar 2009 23:00:00 +0100 2529053 http://www.medworm.com/index.php?rid=2529052&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%3D19362456%26dopt%3DAbstract Authors: Krangel MS The four T cell receptor genes (Tcra, Tcrb, Tcrg, Tcrd) are assembled by V(D)J recombination according to distinct programs during intrathymic T cell development. These programs depend on genetic factors, including gene segment order and recombination signal sequences. They also depend on epigenetic factors. Regulated changes in chromatin structure, directed by enhancers and promoter, can modify the availability of recombination signal sequences to the RAG recombinase. Regulated changes in locus conformation may control the synapsis of distant recombination signal sequences, and regulated changes in subnuclear positioning may influence locus recombination events by unknown mechanisms. Together these influences may explain the ordered activation and inactivation of T... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529052 Tue, 31 Mar 2009 23:00:00 +0100 2529052 http://www.medworm.com/index.php?rid=2529051&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%3D19362457%26dopt%3DAbstract Authors: Adamson AS, Collins K, Laurence A, O'Shea JJ Recently, our understanding of helper/effector T cell differentiation has changed significantly. New subsets of T cells continue to be recognized, including Th17, Treg, and Th9 cells. In addition, the signaling pathways that contribute to their generation continue to be refined. It has become clear that STAT family proteins play a major role in these 'new' T cell fates, along with their critical role in more classical fates. Importantly, genetic studies implicate STATs in autoimmune and primary immunodeficiency diseases in humans. Focusing on how STATs work in concert with other transcription factors will hopefully provide a better mechanistic understanding of the pathogenesis of various autoimmune diseases. PMID: 19362457 [PubM... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529051 Tue, 31 Mar 2009 23:00:00 +0100 2529051 http://www.medworm.com/index.php?rid=2529050&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%3D19375293%26dopt%3DAbstract Authors: Amsen D, Spilianakis CG, Flavell RA Differentiation of T(H)1 and T(H)2 effector cells proceeds through several phases: First, naïve CD4(+) precursor cells are instructed to differentiate as appropriate to optimally fight the infectious threat encountered. This process is governed by the IL12 and IL4 cytokines, as well as by signaling through the Notch receptor. In response to these signals, transcription is initiated of lineage specific cytokine genes including the Ifngamma and Il4 genes as well as of genes encoding transcriptional regulators, such as T-bet and Gata3. The respective differentiation programs are reinforced by both positive and negative feedback mechanisms. Furthermore, epigenetic modifications of the lineage specific genes result in the emergence of regula... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2529050 Tue, 31 Mar 2009 23:00:00 +0100 2529050 http://www.medworm.com/index.php?rid=2303375&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%3D19342209%26dopt%3DAbstract Authors: Ploegh H, Amigorena S PMID: 19342209 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2303375 Tue, 31 Mar 2009 04:00:00 +0100 2303375 http://www.medworm.com/index.php?rid=2303373&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%3D19342210%26dopt%3DAbstract Authors: Segura E, Villadangos JA Dendritic cells (DC) are heterogenous, comprising several subpopulations of migratory and lymphoid-organ-resident types. Recent studies addressing the role of each subset in antigen presentation in vivo have revealed a complex division of labor within the DC network. In addition to CD8(+) DC, migratory lung or dermal DC can cross-present antigen in vivo. Migratory DC also transport to the lymph nodes antigens that can be transferred to resident DC for presentation. In inflammatory conditions, the antigen-presentation abilities of DC can be severely impaired, but an additional population of monocyte-derived DC then comes into play. Understanding the contribution of each DC subset to a physiological immune response is particularly relevant for rational v... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2303373 Tue, 31 Mar 2009 04:00:00 +0100 2303373 http://www.medworm.com/index.php?rid=2303371&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%3D19342211%26dopt%3DAbstract Authors: Qiao SW, Sollid LM, Blumberg RS Celiac disease is caused by an inappropriate immune response to ingested gluten proteins. As a dietary antigen, gluten undergoes extensive but incomplete proteolytic digestion in the intestinal lumen. The resultant peptide fragments of gluten require deamidation, but not necessarily further intracellular processing for presentation. Recent studies reveal why the disease associated HLA-DQ2 molecule is particularly suited for binding proline-rich gluten peptides. In comparison, DQ8 exhibits different binding characteristics, which may explain the lesser risk for disease in association with this molecule. PMID: 19342211 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2303371 Tue, 31 Mar 2009 04:00:00 +0100 2303371 http://www.medworm.com/index.php?rid=2303381&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%3D19328667%26dopt%3DAbstract Authors: Pierre P The plasticity that is needed by the cell to respond to rapid changes in its environment cannot only be provided by means of transcriptional regulation, which generally confers on cells a set of stable properties. Alternatively, the control of mRNA translation allows the cell to modulate rapidly and over short period of time its gene expression program, without invoking the slower nuclear pathways for mRNA synthesis and transport. Several recent findings indicate that regulation of translation affects directly antigen presentation, cytokine production, as well as the survival of dendritic cells. I describe here some of the regulatory mechanisms that control translation in response to microbial products or cytokine exposure and their contribution to the overall immune ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2303381 Thu, 26 Mar 2009 04:00:00 +0100 2303381 http://www.medworm.com/index.php?rid=2303379&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%3D19328668%26dopt%3DAbstract Authors: Schumacher TN, Restifo NP PMID: 19328668 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2303379 Thu, 26 Mar 2009 04:00:00 +0100 2303379 http://www.medworm.com/index.php?rid=2303377&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%3D19328669%26dopt%3DAbstract Authors: Zhou L, Littman DR Upon encountering antigen in the context of antigen presenting cells, naïve CD4(+) T cells undergo differentiation into effector T helper (Th) cells, which can secrete high levels of cytokines and other immunomodulators to mediate host defense and tissue inflammation. During the past three years, the immunology field has witnessed an explosion of research advances in the biology of Th17 cells, the most recently described subset of T helper cells, which play crucial roles in host immunity and inflammation. Here we review emerging data on transcriptional regulatory networks that govern the differentiation program of Th17 cells, and focus on how the orphan nuclear receptor RORgammat coordinates this process in concert with diverse cytokine-induced transcri... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2303377 Thu, 26 Mar 2009 04:00:00 +0100 2303377 http://www.medworm.com/index.php?rid=2303383&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%3D19327974%26dopt%3DAbstract Authors: Sadelain M, Brentjens R, Rivière I One important purpose of T cell engineering is to generate tumor-targeted T cells through the genetic transfer of antigen-specific receptors, which consist of either physiological, MHC-restricted T cell receptors (TCRs) or non MHC-restricted chimeric antigen receptors (CARs). CARs combine antigen-specificity and T cell activating properties in a single fusion molecule. First generation CARs, which included as their signaling domain the cytoplasmic region of the CD3zeta or Fc receptor gamma chain, effectively redirected T cell cytotoxicity but failed to enable T cell proliferation and survival upon repeated antigen exposure. Receptors encompassing both CD28 and CD3zeta are the prototypes for second generation CARs, which are now rapidly e... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2303383 Wed, 25 Mar 2009 04:00:00 +0100 2303383 http://www.medworm.com/index.php?rid=2303386&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%3D19321326%26dopt%3DAbstract Authors: Bendle GM, Haanen JB, Schumacher TN The adoptive transfer of TCR gene-modified T cells has been developed with the aim to induce immune reactivity toward defined tumor-associated antigens to which the endogenous T cell repertoire is non-responsive. Here we discuss in which areas preclinical studies in mouse models can or cannot be expected to be of value to guide clinical trial design, and how the available data from preclinical studies should influence forthcoming clinical trials. PMID: 19321326 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2303386 Mon, 23 Mar 2009 04:00:00 +0100 2303386 http://www.medworm.com/index.php?rid=2303385&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%3D19321327%26dopt%3DAbstract Authors: Jensen KD, Chien YH gammadelta T cells contribute uniquely to host immune defense, but how they do so remains unclear. Recent work suggests that thymic selection does little to constrain gammadelta T cell antigen specificities, but instead determines their effector fate. When triggered through the T cell receptor, ligand-experienced cells make IFNgamma, whereas ligand-naïve gammadelta T cells produce IL-17, a major initiator of inflammation. These advances warrant a fresh look at how gammadelta T cells may function in the immune system. PMID: 19321327 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2303385 Mon, 23 Mar 2009 04:00:00 +0100 2303385 http://www.medworm.com/index.php?rid=2285953&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%3D19304470%26dopt%3DAbstract Authors: Berger C, Turtle CJ, Jensen MC, Riddell SR The adoptive transfer of T cells isolated or engineered to have specificity for diseased cells represents an ideal approach for the targeted therapy of human viral and malignant diseases. The therapeutic potential of adoptive T cell therapy for infections and cancer was demonstrated in rodent models long ago, but the task of translating this approach into an effective clinical therapy has not been easy. Carefully designed clinical trials have evaluated the transfer of antigen-specific T cells in humans, and provided insight into the barriers to efficacy and strategies to improve T cell therapy. The importance of altering the host environment to facilitate persistence and function of transferred T cells and intrinsic properties of T ce... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2285953 Fri, 20 Mar 2009 04:00:00 +0100 2285953 http://www.medworm.com/index.php?rid=2285952&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%3D19304471%26dopt%3DAbstract Authors: Rosenberg SA, Dudley ME Adoptive cell therapy (ACT) is the best available treatment for patients with metastatic melanoma. In a recent series of three consecutive clinical trials using increasing lymphodepletion before infusion of autologous tumor infiltrating lymphocytes (TIL), objective response rates between 49% and 72% were seen. Persistence of infused cells in the circulation at one month was highly correlated with anti-tumor response as was the mean telomere length of the cells infused and the number of CD8+ CD27+ cells infused. Responses occur at all sites and appear to be durable with many patients in ongoing response beyond three years. In the most recent trial of 25 patients receiving maximum lymphodepletion, seven of the 25 patients (28%) achieved a complete respons... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2285952 Fri, 20 Mar 2009 04:00:00 +0100 2285952 http://www.medworm.com/index.php?rid=2285954&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%3D19297140%26dopt%3DAbstract Authors: Offringa R Immunotherapy of cancer through adoptive transfer of genetically engineered T-cells constitutes a more powerful strategy than attempts to mobilize the endogenous T-cell repertoire. Application of this technology in patients offers great opportunities towards a long-awaited breakthrough in cancer immunotherapy. However, recent findings in preclinical mouse models indicate that infusion of T-cells directed against tumor-associated auto-antigens can be associated with higher 'on target' toxicity than was anticipated on the basis of anti-tumor vaccination studies. Critical evaluation of candidate target antigens is required to ensure that T-cell receptor gene therapy will result in preferential attack of tumor cells in the absence of irreversible damage to vital somatic... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2285954 Mon, 16 Mar 2009 04:00:00 +0100 2285954 http://www.medworm.com/index.php?rid=2275629&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%3D19285848%26dopt%3DAbstract Authors: Muranski P, Restifo NP CD4(+) T cells are central to the function of the immune system but their role in tumor immunity remains underappreciated. It is becoming clear that there is an enormous diversity of CD4(+) T cell polarization patterns including Th1, Th2, Th17, and regulatory T cells (Tregs). These functionally divergent T cell subsets can have opposing effects-they can trigger tumor rejection or inhibit treatment after adoptive cell transfer. Some polarized CD4(+) cells have plasticity, and their phenotypes and functions can evolve in vivo. Recent advances in understanding of polarization and differentiation of lymphocytes, as well as some intriguing developments in the clinic, indicate that the use of CD4(+) T cell subsets in the immunotherapy of cancer has unrealized ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2275629 Thu, 12 Mar 2009 04:00:00 +0100 2275629 http://www.medworm.com/index.php?rid=2262017&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%3D19282163%26dopt%3DAbstract Authors: van Leeuwen EM, Sprent J, Surh CD In the course of an immune response to an infectious microbe, pathogen-specific naïve CD4(+) T cells proliferate extensively and differentiate into effector cells. Most of these cells die rapidly, but a small fraction of effector cells persist as memory cells to confer enhanced protection against the same pathogen. Recent advances indicate that strong TCR stimulation during the primary response is essential for the generation of long-lived memory CD4(+) T cells. Memory cells appear to be derived equally from all subsets of effector cells, and memory cells can also acquire additional functional capabilities during the secondary response. Resting memory CD4(+) cells are dependent on signals from contact with IL-7 and IL-15, but not MHC clas... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2262017 Tue, 10 Mar 2009 04:00:00 +0100 2262017 http://www.medworm.com/index.php?rid=2250718&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%3D19269148%26dopt%3DAbstract Authors: Deretic V Autophagy is a cytoplasmic homeostasis pathway, enabling cells to digest their own cytosol, remove toxic protein aggregates, and eliminate defective or surplus organelles. A plenitude of studies has now expanded roles of autophagy to both effector and regulatory functions in innate and adaptive immunity. In its role of an immunological effector, autophagy plays many parts: (i) In its most primeval manifestation, it captures and digests intracellular microbes, (ii) it is an antimicrobial output of Toll-like receptor (TLR) response to pathogen associated molecular patterns (PAMP), and (iii) it is an effector of Th1-Th2 polarization in resistance or susceptibility to intracellular pathogens. As a regulator of immunity, autophagy plays a multitude of functions: (i) It ac... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2250718 Thu, 05 Mar 2009 05:00:00 +0100 2250718 http://www.medworm.com/index.php?rid=2250717&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%3D19269149%26dopt%3DAbstract Authors: Chi AW, Bell JJ, Zlotoff DA, Bhandoola A T cells develop in the thymus. Previous work suggested an early separation of lymphoid from myeloerythroid lineages during hematopoiesis and hypothesized the thymus was settled exclusively by lymphoid-restricted hematopoietic progenitors. Recent data have instead established the existence of lymphoid-myeloid progenitors, which possess lymphoid and myeloid lineage potentials but lack erythroid potential. Myeloid and lymphoid potentials are present at the clonal level in early thymic progenitors, confirming that progenitors settling the thymus include lymphoid-myeloid progenitors. These results revise our view of the T lineage branch of hematopoiesis and focus attention on the generation, circulation, and homing of lymphoid-myeloid progen... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2250717 Thu, 05 Mar 2009 05:00:00 +0100 2250717 http://www.medworm.com/index.php?rid=2249328&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%3D19264470%26dopt%3DAbstract Authors: Crawford A, Wherry EJ T cell responses are regulated by integrating positive and negative signals from costimulatory and inhibitory receptors. While the function of specific T cell costimulatory molecules during infections has been appreciated for some time, recent observations have now revealed a crucial role for inhibitory receptors in regulating T cell responses to pathogens, especially during chronic infections. A key emerging principle is that there is considerable diversity in the number and type of inhibitory receptors that can be expressed by T cells during both acute and chronic infections. These distinct inhibitory pathways appear to cooperate in regulating T cell function, could have distinct mechanisms of action, and are likely to provide novel therapeutic targets ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2249328 Wed, 04 Mar 2009 05:00:00 +0100 2249328 http://www.medworm.com/index.php?rid=2241174&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%3D19261456%26dopt%3DAbstract Authors: Procko E, Gaudet R Adaptive, cell-mediated immunity involves the presentation of antigenic peptides on class I MHC molecules at the cell surface. This requires an ABC transporter associated with antigen processing (TAP) to transport antigenic peptides generated in the cytosol into the endoplasmic reticulum (ER) for loading onto class I MHC. Recent crystal structures of bacterial ABC transporters suggest how the transmembrane domains of TAP form a peptide-binding cavity that acquires peptides from the cytosol, and following ATP-induced conformational changes, the peptide-binding cavity closes to the cytosol and instead opens to the ER lumen for peptide release. Extensive biochemical studies show how transport is driven by ATP binding and hydrolysis on an asymmetric pair of cyto... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2241174 Mon, 02 Mar 2009 05:00:00 +0100 2241174 http://www.medworm.com/index.php?rid=2222731&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%3D19246181%26dopt%3DAbstract Authors: Nedjic J, Aichinger M, Mizushima N, Klein L Functional and biochemical assays indicate a substantial contribution of intracellularly derived peptides to the MHC class II 'ligandome'. Macroautophagy, a process traditionally known for its role in cellular housekeeping and adaptation to nutrient withdrawal, is an attractive candidate pathway for endogenous MHC class II loading. Work in cell culture systems, including antigen presentation assays, co-localization studies and sequencing of MHC class II bound peptides, demonstrates that substrates of autophagy can be loaded onto MHC class II. Advances in the development of mouse models to monitor or genetically disrupt macroautophagy now provide the basis for elucidating the immunological relevance of autophagy in vivo. Here, we will... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2222731 Tue, 24 Feb 2009 05:00:00 +0100 2222731 http://www.medworm.com/index.php?rid=2222730&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%3D19246182%26dopt%3DAbstract Authors: Lambrecht BN, Kool M, Willart MA, Hammad H Aluminum-containing adjuvants continue to be the most widely used adjuvants for human use. In the last year a major breakthrough has been the realization that alum adjuvant triggers an ancient pathway of innate recognition of crystals in monocytes and triggers them to become immunogenic dendritic cells, nature's adjuvant. This recognition can occur directly, via the triggering of the NALP3 inflammasome by alum crystals, or indirectly through release of the endogenous danger signal uric acid. It is also clear now that adjuvants trigger the stromal cells at the site of injection, leading to the necessary chemokines that attract the innate immune cells to the site of injection. How exactly these pathways interact remains to be determined... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2222730 Tue, 24 Feb 2009 05:00:00 +0100 2222730 http://www.medworm.com/index.php?rid=2210811&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%3D19231148%26dopt%3DAbstract Authors: Ganz T Iron is essential for nearly all living organisms. Innate immunity effectively restricts iron availability to microbial invaders. Some microbes have evolved effective countermeasures that blunt the effect of iron restriction. Recent epidemiologic studies have highlighted the potentiating effect of iron on microbial infections. Laboratory studies have focused on specific immune mechanisms that mediate iron withholding from microbes constitutively and in response to infections. Specialized inflammation-regulated proteins chelate iron, trap siderophores, and transport iron or modulate its transport to alter its tissue distribution during infections. PMID: 19231148 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2210811 Thu, 19 Feb 2009 05:00:00 +0100 2210811 http://www.medworm.com/index.php?rid=2210812&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%3D19230638%26dopt%3DAbstract Authors: Ford JW, McVicar DW Since the discovery of triggering receptor expressed on myeloid cells (TREM)-1 in 2000, evidence documenting the profound ability of the TREM and TREM-like receptors to regulate inflammation has rapidly accumulated. Monocytes, macrophages, myeloid dendritic cells, plasmacytoid dendritic cells, neutrophils, microglia, osteoclasts, and platelets all express at least one member of the TREM family, underscoring the importance of these proteins in the regulation of innate resistance. Recent work on the TREM family includes: characterization of a new receptor expressed on plasmacytoid dendritic cells; definition of a key role for TREM in inflammatory bowel disease and multiple sclerosis; an expanded list of diseases associated with the release of soluble forms of... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2210812 Wed, 18 Feb 2009 05:00:00 +0100 2210812 http://www.medworm.com/index.php?rid=2200711&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%3D19223160%26dopt%3DAbstract Authors: Pedra JH, Cassel SL, Sutterwala FS The NLR (nucleotide-binding domain leucine-rich repeat containing) family of intracellular sensors is a crucial component of the innate immune system. A number of NLR family members can form multiprotein complexes, called inflammasomes, and are capable of activating the cysteine protease caspase-1 in response to a wide range of stimuli including both microbial and self-molecules. Caspase-1 activation leads to processing and secretion of the proinflammatory cytokines interleukin-1beta (IL-1beta) and IL-18, which play crucial roles in host defense to infectious insults. Dysregulation of the inflammasome has also been linked to a number of autoinflammatory and autoimmune disorders. Recent advances in the inflammasome field will be discussed in t... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2200711 Fri, 13 Feb 2009 05:00:00 +0100 2200711 http://www.medworm.com/index.php?rid=2200710&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%3D19223161%26dopt%3DAbstract Authors: Gordon S, Trinchieri G PMID: 19223161 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2200710 Fri, 13 Feb 2009 05:00:00 +0100 2200710 http://www.medworm.com/index.php?rid=2200709&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%3D19223162%26dopt%3DAbstract Authors: Reid DM, Gow NA, Brown GD The beta-glucan receptor Dectin-1 is an archetypical non-toll-like pattern recognition receptor expressed predominantly by myeloid cells, which can induce its own intracellular signalling and can mediate a variety of cellular responses, such as cytokine production. Recent identification of the components of these signalling pathways, such as Syk kinase, CARD9 and Raf-1, has provided novel insights into the molecular mechanisms underlying Dectin-1 function. Furthermore, a broader appreciation of the cellular responses mediated by this receptor and the effects of interactions with other receptors, including the TLRs, have greatly furthered our understanding of innate immunity and how this drives the development of adaptive immunity, particularly Th17 re... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2200709 Fri, 13 Feb 2009 05:00:00 +0100 2200709 http://www.medworm.com/index.php?rid=2200708&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%3D19223163%26dopt%3DAbstract Authors: Kemp C, Imler JL Genetic analysis of the drosophila antiviral response indicates that RNA interference plays a major role. This contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. An inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. In particular, DExD/H box helicases appear to play a crucial role in the cytosolic detection of viral RNAs in flies and mammals. PMID: 19223163 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2200708 Fri, 13 Feb 2009 05:00:00 +0100 2200708 http://www.medworm.com/index.php?rid=2200707&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%3D19223164%26dopt%3DAbstract Authors: Barclay AN SIRPalpha is an inhibitory receptor present on myeloid cells that interacts with a widely distributed membrane protein CD47. The activating member SIRPbeta, despite extensive sequence similarity to SIRPalpha in the extracellular region, shows negligible binding to CD47. The SIRPalpha/CD47 interaction is unusual in that it can lead to bidirectional signalling through both SIRPalpha and CD47. This review concentrates on the interactions of SIRPalpha with CD47 where recent data have shed light on the structure of the proteins including determining why the activating SIRPbeta does not bind CD47, evidence of extensive polymorphisms and implication for the evolution and function of this protein and paired receptors in general. The interaction may be modified by endocytosi... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2200707 Fri, 13 Feb 2009 05:00:00 +0100 2200707 http://www.medworm.com/index.php?rid=2190778&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%3D19217269%26dopt%3DAbstract Authors: Ramachandra L, Simmons D, Harding CV Macrophages and dendritic cells are phagocytic antigen presenting cells that internalize bacteria and other particulate antigens into phagosomes. The phagosome must then balance microbicidal and proteolytic degradation functions with the generation of antigenic peptides for presentation by class I and class II MHC molecules to CD8 and CD4 T cells, respectively. Understanding the host and bacterial factors that affect phagosomal antigen processing may help facilitate new strategies to eliminate pathogens. PMID: 19217269 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2190778 Wed, 11 Feb 2009 05:00:00 +0100 2190778 http://www.medworm.com/index.php?rid=2177605&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%3D19203867%26dopt%3DAbstract Authors: Ishido S, Goto E, Matsuki Y, Ohmura-Hoshino M Recently, novel E3 ubiquitin ligases that target MHC molecules for lysosomal degradation have been discovered by several groups. All these E3s are membrane-bound and possess a variant type RING domain, termed the RING-CH or RING variant (RINGv) domain. They belong to a new E3 family designated Modulator of Immune Recognition (MIR), based on the name of the first identified family members. The discovery of the MIR family has provided fresh insight into viral pathogenesis and immune regulation. PMID: 19203867 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=2177605 Sat, 07 Feb 2009 05:00:00 +0100 2177605 http://www.medworm.com/index.php?rid=1934115&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%3D18977298%26dopt%3DAbstract Authors: Pelanda R, Piccirillo CA PMID: 18977298 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=1934115 Wed, 29 Oct 2008 04:00:00 +0100 1934115 http://www.medworm.com/index.php?rid=1918089&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%3D18955138%26dopt%3DAbstract Authors: Westerberg LS, Klein C, Snapper SB A key feature of the immune system is the capacity to monitor and control infections from non-self pathogens while maintaining tolerance to self-antigens. Primary immunodeficiencies (PID) are characterized by an increased susceptibility to infections, often associated with aberrant inflammatory responses and a concomitant high prevalence of autoimmunity. Autoimmunity in PID raises a conundrum: How can an immune system fail to respond to non-self pathogens while reacting vigorously to self-antigens? Recent advances from studies of PID patients and related animal models have revealed the crucial role of Aire-induced expression of self-antigens for deletion of autoreactive T cells in the thymus (central tolerance). Moreover, lessons from PID hav... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=1918089 Fri, 24 Oct 2008 04:00:00 +0100 1918089 http://www.medworm.com/index.php?rid=1901722&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%3D18940257%26dopt%3DAbstract Authors: Strom TB, Koulmanda M In short, manipulation of cytokine pathways shows promise as a mean to tilt the balance of immunity toward tolerance. Effective and regulatory T cells vary in their response to a variety of cytokines. In particular, the ability of certain cytokines, for example, IL-2, to provide vital survival signals to regulatory cells and to trigger death of effector T cells or impede IL-15 driven expansion of memory cells has spurred several trials. The ability of IFNgamma, IL-4, TNFalpha, and lymphotoxin to exert selective effects upon crucial lymphocyte subset populations in vivo may also enable translation into potent therapies. PMID: 18940257 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=1901722 Sat, 18 Oct 2008 04:00:00 +0100 1901722 http://www.medworm.com/index.php?rid=1895144&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%3D18938241%26dopt%3DAbstract Authors: Lee CG, Da Silva CA, Lee JY, Hartl D, Elias JA Chitin, the second most abundant polysaccharide in nature, is commonly found in lower organisms such as fungi, crustaceans, and insects, but not in mammals. Although the non-specific anti-viral and anti-tumor activities of chitin/chitin derivatives were described two decades ago, the immunological effects of chitin have been only recently been addressed. Recent studies demonstrated that chitin has complex and size-dependent effects on innate and adaptive immune responses including the ability to recruit and activate innate immune cells and induce cytokine and chemokine production via a variety of cell surface receptors including macrophage mannose receptor, toll-like receptor 2 (TLR-2), and Dectin-1. They also demonstrated adjuvan... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=1895144 Fri, 17 Oct 2008 04:00:00 +0100 1895144 http://www.medworm.com/index.php?rid=1895145&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%3D18930815%26dopt%3DAbstract Authors: Bochner BS, Alam R PMID: 18930815 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology) Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=1895145 Thu, 16 Oct 2008 04:00:00 +0100 1895145 http://www.medworm.com/index.php?rid=1888324&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%3D18926906%26dopt%3DAbstract Authors: Piccirillo CA, d'Hennezel E, Sgouroudis E, Yurchenko E The immune system requires a homeostatic equilibrium between the mechanisms that assure self-tolerance, those that control the capacity to mount life-long immunity to pathogenic microbes, and those that attenuate effector mechanisms from inducing immune pathology [Sakaguchi S, Yamaguchi T, Nomura T, Ono M: Regulatory T cells and immune tolerance. Cell 2008, 133 (5):775-87; Piccirillo CA, Thornton AM: Cornerstone of peripheral tolerance: naturally occurring CD4(+)CD25(+)regulatory T cells. Trends Immunol 2004, 25:374-80]. In the past decade, an overwhelming body of literature showed that CD4(+)Foxp3(+) regulatory T (Treg) cells are a dominant mechanism regulating the decision fate of these different immunological outcomes. ... Current Opinion in Immunology journals http://www.medworm.com/rss/comments.php?id=1888324 Mon, 13 Oct 2008 04:00:00 +0100 1888324