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1、ComplementsystemWeilinChen,Ph.DInstituteofimmunology,ZJULecture4IntroductionActivationoftheComplementSystemRegulationofcomplementactivationBiologicfunctionsofcomplementsystemJulesBodet(1870-1961),1894，DiscovererofComplementEhrlich（Complement）IntroductionComplement(C)
2、Agroupofserumproteinsinvolvedinthecontrolofinflammation,theactivationofphagocytesandthelyticattackoncellmembranes.Thisactivityisdestroyed(inactivated)byheatingserumat56degreesCfor30minutes.ComplementSystem-consistsofalargenumberofproteinswhichbecomeenzymesafterbeinga
3、ctivated.IntroductionProteinsoftheComplementSystem1.Innateproteins2.RegulatoryProteins3.ComplementreceptorIntroductionProteinsoftheComplementSystem1.innateproteinsclassicalpathway:C1q,C1r,C1s,C4,C2MBLpathway:MBL,MASPalternativepathway:B,Dterminalpathway:C3,C5,C6,C7,C
4、8,C9IntroductionProteinsoftheComplementSystem2.RegulatoryproteinsC1-INH,C4-BP,factorI,factorH,Sprotein,Sp40/40,decay-acceleratingfactor(DAF)3.complementreceptor:CR1—CR5,C3aR,C2aR,C4aR,etc.IntroductionComplementproducedcellsLivercellsMacrophagesIntroductionNotation:C-
5、----complementC1,C2,C3,C4a-----smallfragmentC4a,C3a,C5ab-----largefragmentC4b,C3b,C5b,C2a¯-----activated(enzyme)C1i-----inactivatediC3bActivationoftheComplementSystemPathwaysofcomplementactivation:1.Classicalpathway2.MBLpathwayMBL:mannan-bindinglectin3.Alternativepat
6、hwayClassicalpathwayasuitableAbboundtoantigen(Ag),Ag-Abcomplex(IC)C1,C4,C2andC3Ca++andMg++cations1.C1activation2.C4andC2activation(generationofC3convertase)3.C3activation(generationofC5convertase)4.GenerationofC5convertasemarkstheendoftheclassicalpathwayActivators:Ac
7、tivationofthispathwaymayoccurviaAg-Abcomplex(immunecomplex,IC).IgG(IgG1～3)andIgMaremostefficientinreactingwithcomplement.(C1---CH3ofIgM;CH2ofIgG)OnlyonemoleculeofIgMisrequired,whereasatleasttwomoleculesofIgGareneeded.solubleantibodycan’tactivatecomplementClassicalpat
8、hwayThreesteps：1.Recognition(C1activation)Thecomponentsinvolved：C1q,C1r,C1sAg+Ab→IC→bindC1q→C1r→C1s→C12.ActivationThecomponentsinvo
