上海交通大學(xué)機(jī)體防御與免疫-5補(bǔ)體系統(tǒng)ppt課件

1、第四講 補(bǔ)體The complement system補(bǔ)體補(bǔ)體complementcomplement，C C）：）： 一組一組 蛋白質(zhì)蛋白質(zhì) 激活后具有活性激活后具有活性Complement is a group of proteins that form Complement is a group of proteins that form the principal effector arm of humoral immune the principal effector arm of humoral immune system. By a series of specific acti

2、vation system. By a series of specific activation steps, complement proteins mediate a set of steps, complement proteins mediate a set of activities ranging from the initiation of activities ranging from the initiation of inflammation, neutralization of pathogens, inflammation, neutralization of pat

3、hogens, clearance of immune complexes, disruption of clearance of immune complexes, disruption of cell membranes, and regulation of the immune cell membranes, and regulation of the immune response. response. 抗微生物防御反應(yīng)抗微生物防御反應(yīng) 免疫調(diào)節(jié)免疫調(diào)節(jié) 免疫病理?yè)p傷免疫病理?yè)p傷一一. 補(bǔ)體系統(tǒng)的組成補(bǔ)體系統(tǒng)的組成補(bǔ)體的固有成分：補(bǔ)體激活級(jí)聯(lián)反應(yīng)的補(bǔ)體成分補(bǔ)體的固有成分：補(bǔ)體激活級(jí)聯(lián)反

4、應(yīng)的補(bǔ)體成分經(jīng)典途徑經(jīng)典途徑MBL途徑途徑旁路途徑旁路途徑共同末端成分共同末端成分C1q、C1r、C1s、C4、C2、C3MBL、絲氨酸蛋白酶、絲氨酸蛋白酶B因子、因子、D因子因子C5、C6、C7、C8、C9補(bǔ)體調(diào)節(jié)蛋白：包括備解素、補(bǔ)體調(diào)節(jié)蛋白：包括備解素、I因子、因子、C1抑制物等抑制物等補(bǔ)體受體：包括補(bǔ)體受體：包括CR1CR5、C3aR等等共包含共包含 30 余種余種命名原則命名原則 nomenclatureC：靜止?fàn)顟B(tài)如：靜止?fàn)顟B(tài)如 C1 C9）C：激活狀態(tài)如：激活狀態(tài)如 C4b2b） iC：滅活狀態(tài)如：滅活狀態(tài)如 iC3b） inactivateda：某成分裂解后產(chǎn)生的小片段如：某成

5、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：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 fragment designated “b”. But C2 is an exception.二二. 補(bǔ)體的激活補(bǔ)體的激活識(shí)別階段識(shí)別階段 recognize

6、 and initiate 活化階段活化階段 cascade of activation效應(yīng)階段效應(yīng)階段 effect三條途徑、三個(gè)階段、三個(gè)酶、一個(gè)三條途徑、三個(gè)階段、三個(gè)酶、一個(gè)MACMAC3 pathways, 3 steps, 3 enzymes, a membrane 3 pathways, 3 steps, 3 enzymes, a membrane attack complex attack complex （一經(jīng)典途徑（一經(jīng)典途徑 (classical (classical pathway)pathway)1.1.激活物及激活條件激活物及激活條件 AbAgAbAg復(fù)合物復(fù)合物I

7、CIC）（IgMIgM、IgG1IgG1、2 2、3 3）構(gòu)象改變構(gòu)象改變 暴露暴露 補(bǔ)體結(jié)合部位補(bǔ)體結(jié)合部位2 2個(gè)以上補(bǔ)體結(jié)合位點(diǎn)個(gè)以上補(bǔ)體結(jié)合位點(diǎn)與與C1qC1q球型頭部結(jié)合球型頭部結(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.

8、 2. 激活順序激活順序 (complement activation cascade)(complement activation cascade)C1C1AbAgAbAgC1C1(C1(C1脂酶脂酶) )C4C4C4a C4a C4bC4bC2C2C2a C2a C2bC2bC4b2aC4b2a （C3C3轉(zhuǎn)化酶）轉(zhuǎn)化酶） C3 C3 convertaseconvertase( (與細(xì)胞膜或與細(xì)胞膜或AbAgAbAg結(jié)合結(jié)合) )C3C3C3bC3bC3aC3aC4b2a3bC4b2a3bC5 convertase (C5轉(zhuǎn)化酶轉(zhuǎn)化酶)C5C5C5aC5aC5bC5bC6C6、C7C7C5

9、b67C5b67C8C8C5b678C5b678多個(gè)多個(gè)C9C9C5b6789C5b6789n n( (攻膜復(fù)合體攻膜復(fù)合體) ) MAC MACMembrane attack complex經(jīng)典激活途徑之識(shí)別、活化階段經(jīng)典激活途徑之識(shí)別、活化階段關(guān)鍵酶：關(guān)鍵酶：C4b2b 和和 C4b2b3b補(bǔ)體激活的共同末端效應(yīng)階段補(bǔ)體激活的共同末端效應(yīng)階段（二）（二） MBLMBL途徑途徑 (MBL pathway)(MBL pathway)病原體病原體急性期反應(yīng)急性期反應(yīng)機(jī)體機(jī)體MBLMBL（甘露聚糖結(jié)合凝集素）（甘露聚糖結(jié)合凝集素）Mannose binding lectinMannose bind

10、ing lectin甘露糖殘基甘露糖殘基 MASP MASP(MBL(MBL相關(guān)的絲氨酸蛋白酶相關(guān)的絲氨酸蛋白酶) )MBL associated serine MBL associated serine proteinaseproteinaseMASP + MBL C1MASP + MBL C1以后過(guò)程同經(jīng)典途徑以后過(guò)程同經(jīng)典途徑MASPMASP（三旁路途徑（三旁路途徑 (alternative pathway)自發(fā)產(chǎn)生自發(fā)產(chǎn)生C3C3b滅活滅活B因子因子C3bBD因子因子BaC3bBb(C3轉(zhuǎn)化酶轉(zhuǎn)化酶)降解降解細(xì)菌、內(nèi)毒素、酵母多糖、細(xì)菌、內(nèi)毒素、酵母多糖、葡聚糖、凝聚的葡聚糖、凝聚的I

11、gAIgG4、結(jié)合在結(jié)合在外表外表C3bnBb(C5轉(zhuǎn)化酶轉(zhuǎn)化酶)以后同經(jīng)典以后同經(jīng)典補(bǔ)體激活的共同末端效應(yīng)階段補(bǔ)體激活的共同末端效應(yīng)階段三三. 補(bǔ)體的生物學(xué)作用補(bǔ)體的生物學(xué)作用（一裂解靶細(xì)胞（一裂解靶細(xì)胞 (cell lysis)MAC在細(xì)胞膜上形成小孔在細(xì)胞膜上形成小孔溶菌、細(xì)胞毒溶菌、細(xì)胞毒（二補(bǔ)體活性片段介導(dǎo)的生物學(xué)效應(yīng)（二補(bǔ)體活性片段介導(dǎo)的生物學(xué)效應(yīng)1. 調(diào)理作用調(diào)理作用(opsonization)：2. 清除免疫復(fù)合物清除免疫復(fù)合物(clearance of immune complex)：C3b、C4b以及以及 iC3b氨基端與抗原結(jié)合，氨基端與抗原結(jié)合， 羧基端與吞噬細(xì)胞的羧基

12、端與吞噬細(xì)胞的CR結(jié)合結(jié)合C3b與與Ig及血細(xì)胞表面及血細(xì)胞表面CR結(jié)合可促進(jìn)結(jié)合可促進(jìn)IC清除清除3. 引起炎癥反應(yīng)引起炎癥反應(yīng) (inflammation)C3a、C4a、C5a過(guò)敏毒素過(guò)敏毒素趨化作用趨化作用 (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 formatio