自身耐受和免疫异常与免疫介导的炎症性疾病.pptVIP

自身耐受和免疫调节异常与免疫介导的炎症性疾病 吕昌龙 中国医科大学免疫研究所 免疫调节的方式 免疫耐受 中枢性耐受 外周性耐受 免疫细胞调节 —— 调节性T细胞作用 Genetics of autoimmunity: recent successes of genomics NOD2: polymorphism associated with ~25% of Crohn’s disease Microbial sensor PTPN22: commonest autoimmunity-associated gene; polymorphism in RA, SLE, others Phosphatase CD25 (IL-2R?): associated with MS, others; genome-wide association mapping Role in Tregs 卫生假说的内容 卫生假说指出，过敏性疾病的发病率不断上升与现代生活方式有关。高水平的生活环境和卫生条件同过敏性疾病发生的危险性增加密切相关。由于暴露于环境中微生物及其产物机会的减少，这些环境因素对过敏性疾病的预防潜能无论在质还是量方面都不能足够存在，结果导致免疫系统功能失衡，过敏性疾病发生。因此说，过敏性疾病的发生是基于患者同环境因素之间复杂相互作用的结果。 The nature of the disease is determined by the type of dominant immune response Th1 response: inflammation, autoantibody production; autoimmune diseases Th2 response: IgE+eosinophil-mediated inflammation; allergic reactions Th17 response: acute (and chronic?) inflammation; increasingly recognized in immune-mediated diseases After a microbial infection, activa-ted microbe-speci-fic TH1 (mTH1) cells migrate to the infected organ. A. Molecular mimicry. B. Epitope spre-ading. C. Bystander activation. D. Cryptic antigen. Pathogenesis of organ-specific autoimmunity Current therapies target late stages of the reaction (lymphocyte activation, inflammation). Ultimate goal should be to tackle the underlying cause and restore control of the abnormally directed response Treatment of autoimmune disease (cont’d) Reduce inflammation TNF-alpha blockers (RA, Crohn’s dis., psoriasis) e.g., Enbrel, Remicade, Humira IL-1 receptor antagonist (RA) Ab’s against IL6R and IL-15R Statins, shown to lower CRP (RA, MS) Rituxin = monoclonal Ab = anti-CD20 Eliminates B cells in non-Hodgkins lymphoma (maybe also RA, and other Ab-mediated autoimmune diseases) Possible experimental approaches T cell vaccines (against activated Ag-specific T cells) Interfere with antigen presentation (anti-MHC) Monoclonal antibodies against a