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Introduction Activation of Complement Regulation of the Complement Activation

Chapter 4. Complement System. 补体系统. Introduction Activation of Complement Regulation of the Complement Activation Biological function of the Complement. Ⅰ.Introduction. 1.Discovery of the complement 2.Definition, components and nomencleature of the complement system.

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Introduction Activation of Complement Regulation of the Complement Activation

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  1. Chapter 4 Complement System 补体系统 Introduction Activation of Complement Regulation of the Complement Activation Biological function of the Complement

  2. Ⅰ.Introduction 1.Discovery of the complement 2.Definition, components and nomencleature of the complement system

  3. 1.Discovery of the complement bacteria (细菌) immune serumagglutination andbacteriolysis inactivated serum agglutination but no bacteriolysis fresh serum bacteriolysis Ab 37℃ (Charles Bordet, 1894) (免疫血清) (凝集) ( 溶菌) 56 ℃,30min (灭活血清) ? bacteria Conclusion: 新鲜血清中有两种成分参与溶菌 : 一种是耐热的抗体, 另一种是不耐热、能辅助和补充抗体溶菌作用的成分, 称为补体(complement) Immune hemolysis

  4. 2.Definition , components and nomenclature of the complement system A.Definition 补体是存在正常人和脊椎动物血清中一组经活化后具有酶活性、可辅助和补充特异性抗体介导溶菌溶血作用的蛋白质, 包括30多种可溶性蛋白和膜结合蛋白,故称为补体系统 B.Components and nomenclature

  5. B.Components and nomenclature Inherent components of the complement Regulatory proteins Complement receptors classical pathway:C1 (q、r、s) 、 C4 、C2  MBL pathway: MBL、serine protease  alternative pathway:B factor、D factor…  terminal pathway: C3、C5~C9 (甘露聚糖结合凝集素, 丝氨酸蛋白酶) properdin、H factor、I factor 、 C4bp … (备解素) CR1~CR5、C2aR、C4aR… Other C3a、C3b; C3bBb and iC3b…

  6. Ⅱ.Activation of the Complement 补体的激活是指补体的各个成分在激活物作用下，以连锁的酶促反应依次被激活(也称为补体级联反应),最终导致溶细胞效应的过程 1.Three pathways of complement activation Classical pathwayMBL pathwayAlternative pathway 2.The common terminal pathway

  7.  Classical pathway  activator condition Ag-Ab complex(IgG1,2,3 or IgM) *every C1q must bind to at least of two Ig-Fc fragments of IC *free or soluble antibody can’t activate the complement CH3 of IgM/ CH2 of IgG 1 IgM molecule or 2 IgG molecules  initiation activation of classical pathway C1(C1q) binds to Ig-Fc fragment of IC identification stage activation stage membrane attacking stage (terminal pathway)

  8. •identification stage ---C1 identified the IgFc of the IC and formation of C1 esterase Ca2+ (IC) 暴露Fc段补体结合点 (C1酯酶) 与IgFc段结合部位 C1s C1s Mg++ C1q---identification C1r,C1s---catalysis •activation stage ---formation of the C3 convertase and the C5 convertase. •membrane attacking stage

  9. MBL Pathway  activator  initiation MBL(mannan binding lectin) MBL combine with the pathogen-mannose residue and serine protease activation of MBL pathway (similar to Classical pathway) MBL ＋ ＋

  10. Alternative Pathway  activator Initiation ---LPS,polysaccharide, condense IgA and IgG4 ---activator directly activate alternative pathway 具蛋白酶活性

  11. 2.Common Terminal Pathway (Membrane attacking stage) ---C5 convertase can split C5→→→→the membrane attack complex(MAC) was form and cause the target cell lysis. C5 convertase classical pathway ---C4b2b3b alternative pathway -- ---C3bnBb MBL pathway ---C4b2b3b C5转化酶 C5a C5

  12. p40图4-6 共同的末端途径 细胞溶解 (从激活物质、参与成分、 C3/C5转化酶及生物学作用做比较)

  13. Ⅲ.Regulation of the Complement Activation 1.Self regulation of the complement 2.The regulator factor: limit or enhance the the process of the activation ---decay of C3 convertase, C5 convertase, C4b, C3b, C5b…… ---C1 inhibitor,I factor,MCP,H factor,CR1, DAF,C4 binding protein,CD59,C8bp……

  14.  Regulation of classical pathway C1抑制分子 与C1rC1s结合 DAF 同C2竞争与C4b结合 结合 裂解 失活 C4bp CR1 + I因子 + MCP (membrane cofactor protein)

  15.  Regulation of alternative pathway 竞争结合C3b 裂解 I因子 抑制B因子与C3b结合 H因子 + 解离 CR1,DAF H因子,CR1 和MCP DAF:衰变加速因子)

  16.  Regulation of the forming of the membrane attack complex CD59 阻碍C7C8与C5b~6结合 干扰C9与C8结合 C8bp

  17. Ⅳ.Biological Function of the Complement System 1.Mediate cytolysis 2.Biological effects mediated by activated complement fragments Opsonization(调理作用) Cause inflammation Clear the immune complex Regulate the immune response

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