自身耐受和免疫异常与免疫介导的炎症性疾病.pptxVIP

自身耐受和免疫异常与免疫介导的炎症性疾病;;免疫调节的重要性 ;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;免疫耐受;自身免疫;第7页/共36页;The principal fate of lymphocytes that recognize self antigens in the generative organs is death (deletion), BUT: Some B cells may change their specificity (called “receptor editing”) Some CD4 T cells may differentiate into regulatory (suppressive) T lymphocytes;Consequences of self antigen recognition in thymus;第10页/共36页;第11页/共36页;;T cell anergy;“Activation-induced cell death”: death of mature T cells upon recognition of self antigens;Regulatory T cells ;T Regulatory Cell Properties;Peripheral (adaptive, inducible) regulatory T cells;Signals for the generation and maintenance of regulatory T cells ;cellular therapy with Regulatory T cells?;Immune-mediated inflammatory diseases;Pathogenesis of autoimmunity;Genetics of autoimmunity;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;Infections and autoimmunity;卫生假说的内容;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;;Immunological diseases tend to be chronic and self-perpetuating, because – The initiating trigger can often not be eliminated (self antigen, commensal microbes) The immune system contains many built-in amplification mechanisms whose normal function is to optimize our ability to combat infections “Epitope spreading” “Molecular minicry”;Amplification loop in cell-mediated immunity;After a microbial infection, activa-ted microbe-speci-fic TH1 (mTH1) cells migrate to the infected organ. A. Molecula