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Immune Recognition (immune + recognition)
Selected AbstractsImmune recognition of fungal ,-glucansCELLULAR MICROBIOLOGY, Issue 4 2005Gordon D. Brown Summary The recognition of conserved microbial structures is a key aspect of metazoan immunity, and ,-glucans are emerging as a major target for the recognition of fungal pathogens. A number of receptors for these carbohydrates have been identified, which upon recognition, trigger a variety of immune responses. In contrast to many other systems, there is little apparent conservation in these mechanisms between vertebrates and invertebrates. In this review, we will highlight all the known receptors for ,-glucans and will discuss the various immune responses they can initiate, with reference to fungal infection, in both vertebrates and invertebrates. [source] A role for innate immunity in type 1 diabetes?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2003H. Beyan Abstract Two arms of the immune system, innate and adaptive immunity, differ in their mode of immune recognition. The innate immune system recognizes a few highly conserved structures on a broad range of microorganisms. On the other hand, recognition of self or autoreactivity is generally confined to the adaptive immune response. Whilst autoimmune features are relatively common, they should be distinguished from autoimmune disease that is infrequent. Type 1 diabetes is an immune-mediated disease due to the destruction of insulin secreting cells mediated by aggressive immune responses, including activation of the adaptive immune system following genetic and environmental interaction. Hypotheses for the cause of the immune dysfunction leading to type 1 diabetes include self-reactive T-cell clones that (1) escape deletion in the thymus, (2) escape from peripheral tolerance or (3) escape from homeostatic control with an alteration in the immune balance leading to autoimmunity. Evidence, outlined in this review, raises the possibility that changes in the innate immune system could lead to autoimmunity, by either priming or promoting aggressive adaptive immune responses. Hostile microorganisms are identified by genetically determined surface receptors on innate effector cells, thereby promoting clearance of these invaders. These innate effectors include a few relatively inflexible cell populations such as monocytes/macrophages, dendritic cells (DC), natural killer (NK) cells, natural killer T (NKT) cells and ,, T cells. Recent studies have identified abnormalities in some of these cells both in patients with type 1 diabetes and in those at risk of the disease. However, it remains unclear whether these abnormalities in innate effector cells predispose to autoimmune disease. If they were to do so, then modulation of the innate immune system could be of therapeutic value in preventing immune-mediated diseases such as type 1 diabetes. Copyright © 2002 John Wiley & Sons, Ltd. [source] Roles of Toll-like receptors in innate immune responsesGENES TO CELLS, Issue 9 2001Kiyoshi Takeda Innate immunity recognizes invading micro-organisms and triggers a host defence response. However, the molecular mechanism for innate immune recognition was unclear. Recently, a family of Toll-like receptors (TLRs) was identified, and crucial roles for these receptors in the recognition of microbial components have been elucidated. The TLR family consists of 10 members and will be expanding. Each TLR distinguishes between specific patterns of microbial components to provoke innate immune responses. The activation of innate immunity then leads to the development of antigen-specific adaptive immunity. Thus, TLRs control both innate and adaptive immune responses. [source] Cytotoxic T lymphocytes recognize and lyse chondrocytes under inflammatory, but not non-inflammatory conditionsIMMUNOLOGY, Issue 1 2003E. Suzanne Cohen Summary The human major histocompatibility complex (MHC) class I allele HLA-B27 is strongly associated with seronegative spondyloarthropathies including ankylosing spondylitis and reactive arthritis. Although of unknown aetiology, one hypothesis suggests that a cytotoxic T cell (CTL) response against a self-antigen at sites of inflammation, such as entheses or joints may be involved. The chondrocyte is one of the major specialized cell types found both in articular cartilage and cartilaginous entheses and therefore is a possible source of such an antigen. CTL recognition of these cells is a potential mechanism for inflammation and cartilage damage, both through direct lysis of chondrocytes and the secretion of pro-inflammatory cytokines such as tumour necrosis factor and interferon-, (IFN-,). We test the feasibility of this hypothesis by examining the ability of chondrocytes to present antigen to CTL in vitro. Chondrocytes isolated from the ribcages of mice did not constitutively express detectable levels of MHC class I by fluorescence-activated cell sorting analysis. In addition, they were resistant to lysis by alloreactive and influenza A virus nucleoprotein (NP)-specific CTL. However, treatment of chondrocytes with IFN-, up-regulated MHC class I expression and rendered the cells susceptible to lysis by CTL. Similarly, IFN-,-treated chondrocytes infected with influenza A virus were recognized by NP-specific CTL, though with variable efficiency. Thus, we suggest that under certain circumstances CTL-mediated lysis of chondrocytes is potentially a potent mechanism for cartilage damage in vivo, but that low levels of MHC class I on healthy chondrocytes protects from immune recognition in health. [source] B and CTL responses to the ALK protein in patients with ALK-positive ALCLINTERNATIONAL JOURNAL OF CANCER, Issue 3 2006Kamel Ait-Tahar Abstract Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) has a good prognosis compared to ALK-negative ALCL, possibly as a result of the immune recognition of the ALK proteins. The aim of our study was to investigate the presence of both a B and cytotoxic T cell (CTL) response to ALK in ALK-positive ALCL. We confirmed the presence of an antibody response to ALK in all 9 ALK-positive ALCL patients investigated. An ELISpot assay was used to detect a ,-interferon (IFN) T cell response after short term culture of mononuclear blood cells with 2 ALK-derived HLA-A*0201 restricted peptides: ALKa and ALKb. A significant ,-IFN response was identified in all 7 HLA-A*0201-positive ALK-positive ALCL patients but not in ALK-negative ALCL patients (n = 2) or normal subjects (n = 6). CTL lines (>95% CD8-positive) raised from 2 ALK-positive ALCL patients lysed ALK-positive ALCL derived cell lines in a MHC-Class I restricted manner. This is the first report of both a B cell and CTL response to ALK in patients with ALK-positive ALCL. This response persisted during long-term remission. The use of modified vaccinia virus Ankara (MVA) to express ALK is also described. Our findings are of potential prognostic value and open up therapeutic options for those ALK-positive patients who do not respond to conventional treatment. © 2005 Wiley-Liss, Inc. [source] HLA-G polymorphism in a Chinese Han population with recurrent spontaneous abortionINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2006W. H. Yan Summary Reproduction is an important biological phenomenon posing an immunological paradox because the semiallogeneic fetus survives by evading maternal immune recognition. The detailed mechanisms behind this maternal,fetal immunotolerance remain elusive. Human leucocyte antigen (HLA)-G, a non-classical HLA class I antigen, initially identified as a molecule selectively expressed on extravillous cytotrophoblasts and first studied in the context of pregnancy, has long been supposed to play a critical role in fetal,maternal immunotolerance. To investigate the role of HLA-G polymorphism in this process and whether the HLA-G genotype is associated with an increased risk for a subsequent miscarriage, 69 women with three or more recurrent spontaneous abortions (RSA) and 146 fertile control women were genotyped for the HLA-G locus in this study. To our knowledge, this is the first report on HLA-G polymorphism in RSA and in normal fertile women from a Chinese Han population. Nine HLA-G alleles were detected in the fertile control group; however, the allele HLA-G*0103 was absent in the RSA group. No statistical significance was observed in the distribution of HLA-G alleles between the two groups. The frequency of the null allele HLA-G*0105 N in the RSA group and in normal fertile women is 0.7% and 1.4%, respectively. Our data suggested that there was no association of HLA-G polymorphism with RSA. [source] Alcohol and Hepatitis C Virus,Interactions in Immune Dysfunctions and Liver DamageALCOHOLISM, Issue 10 2010Gyongyi Szabo Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)-TLR4 signaling, and reactive oxygen species (ROS) production. LPS-induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation. [source] Association of antibodies to hepatitis C virus glycoproteins 1 and 2 (anti-E1E2) with HCV diseaseJOURNAL OF VIRAL HEPATITIS, Issue 5 2008M. R. B. Hamed Summary., Hepatitis C virus (HCV) causes acute and chronic liver diseases in humans. Its two envelope glycoproteins, E1 and E2, provide a target for host immune recognition. HCV genotypes are classified into six genetic groups. To study the role of anti-HCV E1 and E2 (anti-E1E2) in HCV disease, the correlation between antibody level and viral load, genotype, disease severity and response to treatment was investigated. The levels of antibodies to HCV glycoproteins E1 and E2 antibodies were evaluated in 230 sera of patients with chronic hepatitis C by enzyme-linked immunosorbent assay. The antigens used were recombinant HCV glycoproteins derived from genotype 1 (H77c) and genotype 3 (UKN3A1.28). Seroreactivity was greater when sera were tested against antigen derived from their homologous genotype than against heterologous antigen. Reactivity against UKN3A1.28 in sera from patients infected with genotype 3 was significantly higher than corresponding reactivity between patients infected with genotype 1 and H77c. The seroreactivity was inversely proportional to the viral load and to the degree of liver fibrosis. The pre-treatment level of anti-E1E2 was higher in sustained responders to combination therapy. These results demonstrate that seroreactivity against E1E2 depends upon the genotypic origin of the E1E2 antigens and the infecting genotype, and suggest a possible protective effect of anti-E1E2 against disease progression. [source] A previous infection with Toxoplasma gondii does not protect against a challenge with Neospora caninum in pregnant sheepPARASITE IMMUNOLOGY, Issue 3 2001E.A. Innes Sheep immunized with Toxoplasma gondii (Toxovax®) prior to pregnancy were tested for their ability to withstand a challenge at 90 days gestation with 107 Neospora caninum (NC1) tachyzoites. The antibody responses in sheep following immunization with T. gondi were specific for T. gondii whereas peripheral blood mononuclear cells responded to both T. gondii and caninum antigen in vitro. This suggested that there was induction of crossreactive immune recognition in the sheep, at least at the cellular level. Following challenge of sheep at mid-gestation with N caninum, no febrile responses were recorded in the group of sheep which had previously received Toxovax® while significant febrile responses were recorded in the group of sheep which received N challenge alone. Antibody responses to N developed in all sheep following challenge and antibody responses to T,gondii were boosted in the group of sheep which had previously been immunized with Toxovax®. No antibodies to were observed in the sheep which received the challenge alone. Peripheral blood mononuclear cells from both groups of sheep responded to T.gondii N.caninum antigen invitro and interferon gamma was present in the cell-free supernatant from activated cells. However despite evidence of the induction of crossreactive immunity between T.gondii N.caninum this was not sufficient to prevent foetal death. The group of sheep which had received Toxovax® prior to pregnancy and the group of sheep which only received the N.caninum challenge experienced 100% foetal death compared with 0% in the unchallenged control group. Vaccination prior to pregnancy with Toxovax® did protect against foetal death following oral challenge at 90 days with 2000 oocysts which caused 100% foetal death in a control challenge group. [source] A novel heat-shock protein coinducer boosts stress protein Hsp70 to activate T cell regulation of inflammation in autoimmune arthritisARTHRITIS & RHEUMATISM, Issue 4 2010Lotte Wieten Objective Stress proteins, such as members of the heat-shock protein (HSP) family, are up-regulated by cells in inflamed tissue and can be viewed functionally as "biomarkers" for the immune system to monitor inflammation. Exogenous administration of stress proteins has induced immunoregulation in various models of inflammation and has also been shown to be effective in clinical trials in humans. This study was undertaken to test the hypothesis that boosting of endogenous HSP expression can restore effective immunoregulation through T cells specific for stress proteins. Methods Stress protein expression was manipulated in vivo and in vitro with a food component (carvacrol), and immune recognition of stress proteins was studied. Results Carvacrol, a major compound in the oil of many Origanum species, had a notable capacity to coinduce cellular Hsp70 expression in vitro and, upon intragastric administration, in Peyer's patches of mice in vivo. As a consequence, carvacrol specifically promoted T cell recognition of endogenous Hsp70, as demonstrated in vitro by the activation of an Hsp70-specific T cell hybridoma and in vivo by amplified T cell responses to Hsp70. Carvacrol administration also increased the number of CD4+CD25+FoxP3+ T cells, systemically in the spleen and locally in the joint, and almost completely suppressed proteoglycan-induced experimental arthritis. Furthermore, protection against arthritis could be transferred with T cells isolated from carvacrol-fed mice. Conclusion These findings illustrate that a food component can boost protective T cell responses to a self stress protein and down-regulate inflammatory disease, i.e., that the immune system can respond to diet. [source] PAN,DR-Binding Hsp60 self epitopes induce an interleukin-10,mediated immune response in rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 7 2009Huib de Jong Objective Human Hsp60 is expressed in the joints of patients with rheumatoid arthritis (RA) and can elicit a regulatory T cell response in the peripheral blood and synovial fluid. However, Hsp60 can also trigger strong proinflammatory pathways. Thus, to understand the nature of these Hsp60-directed responses in RA, it is necessary to study such responses at the molecular, epitope-specific level. This study was undertaken to characterize the disease specificity and function of pan,DR-binding Hsp60,derived epitopes as possible modulators of autoimmune inflammation in RA. Methods Lymphocyte proliferation assays (using 3H-thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester [CFSE] staining) and measurement of cytokine production (using multiplex immunoassay and intracellular staining) were performed after in vitro activation of peripheral blood mononuclear cells from patients with RA, compared with healthy controls. Results A disease (RA),specific immune recognition, characterized by T cell proliferation as well as increased production of tumor necrosis factor , (TNF,), interleukin-1, (IL-1,), and IL-10, was found for 3 of the 8 selected peptides in patients with RA as compared with healthy controls (P < 0.05). Intracellular cytokine staining and CFSE labeling showed that CD4+ T cells were the subset primarily responsible for both the T cell proliferation and the cytokine production in RA. Interestingly, the human peptides had a remarkably different phenotype, with a 5,10-fold higher IL-10:TNF, ratio, compared with that of the microbial peptides. Conclusion These results suggest a disease-specific immune-modulatory role of epitope-specific T cells in the inflammatory processes of RA. Therefore, these pan,DR-binding epitopes could be used as a tool to study the autoreactive T cell response in RA and might be suitable candidates for use in immunotherapy. [source] First steps towards effective methods in exploiting high-throughput technologies for the determination of human protein structures of high biomedical valueACTA CRYSTALLOGRAPHICA SECTION D, Issue 10 2006L. Banci The EC `Structural Proteomics In Europe' contract is aimed specifically at the atomic resolution structure determination of human protein targets closely linked to health, with a focus on cancer (kinesins, kinases, proteins from the ubiquitin pathway), neurological development and neurodegenerative diseases and immune recognition. Despite the challenging nature of the analysis of such targets, ,170 structures have been determined to date. Here, the impact of high-throughput technologies, such as parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens or the use of mass spectrometry to assist sample preparation, on the structural biology of mammalian protein targets is illustrated through selected examples. [source] ER quality control of immune receptors and regulators in plantsCELLULAR MICROBIOLOGY, Issue 6 2010Yusuke Saijo Summary Like in animals, cell surface and intracellular receptors mediate immune recognition of potential microbial intruders in plants. Membrane-localized pattern recognition receptors (PRRs) initiate immune responses upon perception of cognate microbe-associated molecular patterns (MAMPs). MAMP-triggered immunity provides a first line of defence that restricts the invasion and propagation of both adapted and non-adapted pathogens. The Leu-rich repeat (LRR) receptor protein kinases (RKs) define a major class of trans-membrane receptors in plants, of which some members are engaged in MAMP recognition and/or defence signalling. The endoplasmic reticulum (ER) quality control (QC) systems monitor N-glycosylation and folding states of the extracellular, ligand-binding LRR domains of LRR-RKs. Recent progress reveals a critical role of evolutionarily conserved ERQC components for different layers of plant immunity. N-glycosylation appears to play a role in ERQC fidelity rather than in ligand binding of LRR-RKs. Moreover, even closely related PRRs show receptor-specific requirements for N-glycosylation. These findings are reminiscent of the earlier defined function of the cytosolic chaperon complex for LRR domain-containing intracellular immune receptors. QC of the LRR domains might provide a basis not only for the maintenance but also for diversification of recognition specificities for immune receptors in plants. [source] | |||||||||||||