1、第四講 補(bǔ)體 The complement system,補(bǔ)體（complement，C）： 一組 蛋白質(zhì) 激活后具有活性 Complement is a group of proteins that form the principal effector arm of humoral immune system. By a series of specific activation steps, complement proteins mediate a set of activities ranging from the initiation of inflammation, neutra

2、lization of pathogens, clearance of immune complexes, disruption of cell membranes, and regulation of the immune response.,抗微生物防御反應(yīng) 免疫調(diào)節(jié) 免疫病理損傷,一. 補(bǔ)體系統(tǒng)的組成,補(bǔ)體的固有成分：補(bǔ)體激活級聯(lián)反應(yīng)的補(bǔ)體成分,經(jīng)典途徑 MBL途徑 旁路途徑 共同末端成分,C1q、C1r、C1s、C4、C2、C3,MBL、絲氨酸蛋白酶,B因子、D因子,C5、C6、C7、C8、C9,補(bǔ)體調(diào)節(jié)蛋白：包括備解素、I因子、C1抑制物等,補(bǔ)體受體：包括CR1CR5、C3aR等,共

3、包含 30 余種,命名原則 nomenclature,C：靜止?fàn)顟B(tài)（如 C1 C9） C：激活狀態(tài)（如 C4b2b） iC：滅活狀態(tài)（如 iC3b） inactivated a：某成分裂解后產(chǎn)生的小片段（如3a） b：某成分裂解后產(chǎn)生的大片段（如3b） A bar placed over the symbol of the component to indicate active enzymatic activity. The smaller fragment resulting from cleavage of a component is designated “a” and larger

4、 fragment designated “b”. But C2 is an exception.,二. 補(bǔ)體的激活,識別階段 recognize and initiate 活化階段 cascade of activation 效應(yīng)階段 effect,三條途徑、三個階段、三個酶、一個MAC 3 pathways, 3 steps, 3 enzymes, a membrane attack complex,（一）經(jīng)典途徑 (classical pathway),1.激活物及激活條件 AbAg復(fù)合物（IC）,（IgM、IgG1、2、3）,構(gòu)象改變 暴露 補(bǔ)體結(jié)合部位,2個以上補(bǔ)體結(jié)合位點,與C1q

5、球型頭部結(jié)合,The classical pathway is initiated by binding of antibody to an antigen. Binding of C1q to Fc portion of antibody results in activation of the proteolytic enzyme activities of C1r and, subsequently C1s.,2. 激活順序 (complement activation cascade),C1,AbAg,C1,(C1脂酶),C4,C4a C4b,C2,C2a C2b,C4b2a,（C3轉(zhuǎn)

6、化酶） C3 convertase,(與細(xì)胞膜或AbAg結(jié)合),C3,C3bC3a,C4b2a3b,C5 convertase (C5轉(zhuǎn)化酶),C5,C5aC5b,C6、C7,C5b67,C8,C5b678,多個C9,C5b6789n,(攻膜復(fù)合體) MAC,Membrane attack complex,經(jīng)典激活途徑之識別、活化階段,補(bǔ)體激活的共同末端效應(yīng)階段,（二） MBL途徑 (MBL pathway),病原體,急性期反應(yīng),機(jī)體,MBL,（甘露聚糖結(jié)合凝集素） Mannose binding lectin,甘露糖殘基,MASP,(MBL相關(guān)的絲氨酸蛋白酶) MBL associated

7、serine proteinase,MASP + MBL C1 以后過程同經(jīng)典途徑,MASP,（三）旁路途徑 (alternative pathway),自發(fā)產(chǎn)生,C3,C3b,滅活,B因子,C3bB,D因子,Ba,C3bBb,(C3轉(zhuǎn)化酶),降解,細(xì)菌、內(nèi)毒素、酵母多糖、葡聚糖、凝聚的IgAIgG4、,結(jié)合在,表面,C3bnBb,(C5轉(zhuǎn)化酶),以后同經(jīng)典,補(bǔ)體激活的共同末端效應(yīng)階段,三條激活途徑的主要不同點,三. 補(bǔ)體的生物學(xué)作用,（一）裂解靶細(xì)胞 (cell lysis),MAC在細(xì)胞膜上形成小孔,溶菌、細(xì)胞毒,（二）補(bǔ)體活性片段介導(dǎo)的生物學(xué)效應(yīng),1. 調(diào)理作用(opsonization

8、)：,2. 清除免疫復(fù)合物(clearance of immune complex)：,C3b、C4b以及 iC3b,氨基端與抗原結(jié)合，,羧基端與吞噬細(xì)胞的CR結(jié)合,C3b與Ig及血細(xì)胞表面CR結(jié)合可促進(jìn)IC清除,3. 引起炎癥反應(yīng) (inflammation),C3a、C4a、C5a,過敏毒素 趨化作用,(a) Photomicrograph of poly-C9 complex formed by in vitro polymerization of C9. (b) Photomicrograph of complementinduced lesions on the membrane of a red blood cell. These lesions result from formation of membrane-attack complexes.,Scanning electron microgra