免疫耐受及自身免疫.ppt

* * * 辅助刺激分子表达异常 感染(微生物及其产物)刺激APC异常表达 MHC-Ⅱ、粘附分子和共刺激分子（B7、CD40L) 等。 细胞因子产生的失调 细胞因子异常可以诱导MHCII类分子异常 表达或粘附分子表达上调， 引用抗细胞因子或抗细胞因子受体的抗体， 可能防治某些自身免疫病 * Th1与Th2细胞功能失调 * IL-17: The Autoimmunity Cytokine? IL-17 KO mice – less susceptible to autoimmunity – especially MS and RA * MDSC in Autoimmunity ?Int Immunopharnacol. 2011 Jul;11(7):789-93.? * Regulatory T-cells in autoimmunity * CD103+ dendritic cells in the intestinal mucosal immune system * Cytokine Dysregulation in Autoimmunity CD = Crohn’s Disease * ●自身免疫相关的遗传因素 MHC 病名 HLA抗原 相对危险值 性别比(♀:♂) 强直性脊柱炎 B27 87. 4 0.3 急性前葡萄膜炎 B27 10.04 〈0.5 多发性硬化 DR2 4.8 10 Goodpasture综合症 DR2 15.9 ～1 Graves病 DR3 (A8) 3.7 4-5 重症肌无力 DR3 2.5 ～1 SLE DR3 5.8 10-20 类风湿关节炎 DR4 4.2 3 桥本氏甲状腺炎 DR5 3.2 4-5 胰岛素依赖性糖尿病 DR3 ,DR4 3.2 ～1 * II类反式激活蛋白(CII TA) CTLA-4 Fas/FasL 免疫分子基因 * T cell activation eventually gets down-modulated by expression on activated T cells of CTLA4, which competes for binding to B7 and which carries an inhibitory signal. Normal function of CTLA 4: limiting T cell costimulation * CTLA 4-deficient mice Mice die at 3-4 weeks of systemic T cell activation and infiltration of multiple organs Elevated antibodies, and autoantibodies * Along with its role in cell killing, FasL is important in eliminating activated T cells T cells T cell T cell * Fas deficiency leads to autoimmune lymphoproliferative syndrome * FasL expression may play a role in “immune privilege“(免疫赦免) FasL expression in brain, eye, placenta, and reproductive organs is believed to contribute to immunological privilege. Aberrant FasL expression may also be an adaptation of tumors to evade immune surveillance. * 自身免疫病的组织损伤机制 ●自身抗体的致病作用 1.抗体依赖