医学免疫学3补体系统.ppt

3 补体系统 (Complement) 3-6 补体系统的调节机制 The explosive potential of the complement system requires that it be kept under tight control. At least 12 proteins are known that do this. Regulation of Complement Activity Factor H removes Bb from the alternative pathway C3 convertase breaking the positive feedback loop. Factor I inactivates C3b and C4b. C1 inhibitor (C1INH) binds to sites on activated C1r and C1s shutting down their proteolytic activity. 经典和 MBP 途径的调节 NH2 CL CL CL CL NH2 CL CL CL CL 补 体 抑 制 因 子 CD55 CD46 胞浆区 胞膜 GPI锚固 CD46和 CD55 CD55（DAF）是经GPI锚固于胞膜表面的75 kDa 糖蛋白，能够与C3b结合并且降解C3/C5转化酶。CD46是一个分子量为56-66 kDa的共二聚体膜蛋白，与CD55、CR1和CR2等具有同源性。能够与C3b和C4b结合并使之被I因子降解。 * * Jules Bodet (1870-1961), Discoverer of complement 3补体系统 (Complement) Jules Bodet (1870-1961), Discoverer of complement Complement refers, historically, to fresh serum capable of lysing Ab-coated cells. This activity is destroyed (inactivated) by heating serum at 560C for 30 minutes. 3-1 补体系统的组成及一般特点 生 化 级 联 反 应 I Ia Ib II IIb IIa III IIIa IIIb 发挥生物学效应 补体反应实际上是一系列酶促反应，其最终结果是在靶细胞膜表面形成MACs，同时产生具有生物学活性的补体小分段。 启动 扩增 效应 调控 Classical MBP Alternative （C3转化酶） （C3、C5转化酶） （MACs等） Terminal Pathway a 链 b 链 C3 分子组成及其各种结合位 -S-S- -S-S- CR1 CR3 CR2 N- N- C- C- P C3是由一条120 kDa的 a 链和一条70 kDa的 b 链共价组成的异二聚体型 b 球蛋白。深黑线段代表C3b与CR1，CR2和CR3等补体受体的结合位点。 C3 is the most abundant protein of the complement system (~1.3 mg/ml). Because of its abundance and its ability to activate itself, it greatly magnifies the response. 3-2 补体活化的替代途径 There is a spontaneous conversion of C3 to C3b. Ordinarily the C3b is quickly inactivated: the C3b binds to inhibitory proteins and sialic acid present on the surface of bodys own cells, and the process is aborted. The Alternative Pathway B D 因子 C3 的 自 动 裂 解 C3 C3a C3b C3bBb 的 产 生 C3b Bb C3b B D因子 C3b B B C3b 补 体 活 化 表 面 C3bBbP —— C3转化酶（C3 convertase） C3bnBb —— C5转化酶（C5 convertase） C3b C3bB C3 C3 与 C3