分子免疫学Hypersensitivity an autoimmunity Chinese.ppt

* * 髓鞘碱性蛋白（MBP），CNS中枢神经系统，脱髓鞘疾病MS，实验性变态反应性脑脊髓炎（EAE） * 感染与自身免疫 Infection ?development and exacerbation of autoimmunity Local immune responses ?activate tissue APCs ? breakdown of T cell tolerance (bystander activation) Molecular mimicry: rheumatic fever, anti-streptococcal Abs cross-react with myocardial proteins?myocarditis Some infections may protect against autoimmunity: NOD mice 自身免疫的其它因素 Anatomic alterations in tissues, caused by inflammation, ischemic injury or trauma, may lead to the exposure of self antigens that are normally concealed from the immune system. Hormonal influences play a role in some autoimmune diseases Selected immunologic diseases: pathogenesis and therapeutic strategies SLE RA MS or EAE Type I diabetes mellitus IBD 系统性红斑狼疮Systemic lupus erythematosus (SLE) Immune complex-mediated disease 1:700 women (20-60y), female:male=10:1 Rashes, arthritis and glomerulonephritis Autoantibodies, antinuclear, anti-DNA, ribonucleoproteins, histones, nucleolar Ags Test: anti-double stranded native DNA Pathogenesis of SLE HLA-DR2, DR3 Complement deficiency FcγRIIB UV light IFN-α produced by pDC TLR9 and TLR7 Therapies: anti-IFNα, anti-CD20, anti-Baff UV… Apoptosis Complement Nuclear Ags T B Ab FcγRIIB IC IFN-α Tissue damage 类风湿性关节炎Rheumatoid arthritis (RA) Joint inflammation Cell-mediated and humoral immune response Th1, Th17, B, macrophages, lymphoid follicles IL-1, Il-8, TNF, IL-6, IL-17, IFN-g Joint destruction (collagenase, osteoclast) Rheumatoid factors (anti-IgG Fc Ab) Anti-CCP (cyclic citrullinated peptides) Ab (Arginine?citrulline) RA 患者手指关节实质性损伤 Pathogenesis of RA HLA-DR4 PTPN22 CCP Therapies:anti-TNF, anti-IL1, anti-IL-6R, CTLA-4, anti-IL-17, anti-CD40 Multiple sclerosis and experimental autoimmune encephalomyelitis Th1 and Th17 against myelin EAE model, Ags in CNS myelin+ adjuvant, T cell mediated Viral infection ?activates self myelin-reactive T cells by molecular mimicry Genetic factors, HLA-DR2, CD25 Myelin-specific T cells ?CNS?release cy