醫(yī)學(xué)免疫學(xué)課件：第五章 補(bǔ)體系統(tǒng) Complement

UNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體系統(tǒng)ComplementJulesBordet(1870-1961),discovererofcomplement

UNIVERSITASAMOIENSISGAOFENGGUANG概述補(bǔ)體：complement是存在于正常人或脊椎動物血清與組織液中一組與免疫有關(guān)并具有酶活性的球蛋白，具有抗微生物、免疫調(diào)節(jié)和免疫損傷的作用,多種組織細(xì)胞以肝細(xì)胞和巨噬細(xì)胞為主可合成補(bǔ)體蛋白。UNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體系統(tǒng)的組成與命名補(bǔ)體固有成分：經(jīng)典途徑旁路途徑甘露聚糖結(jié)合凝集素（mannan-bindinglectin,MBL）激活途徑的MBL、絲氨酸蛋白酶(serineprotease)活化的共同組分補(bǔ)體調(diào)節(jié)蛋白：補(bǔ)體受體：UNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體成分的理化性質(zhì)在補(bǔ)體成分中，C3含量最高，C4、S蛋白、H因子次之，D因子最低。某些補(bǔ)體成分不穩(wěn)定，加熱56℃30分鐘滅活，許多理化因素可使補(bǔ)體失活。90%補(bǔ)體成分由肝臟合成UNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體的代謝補(bǔ)體的來源肝細(xì)胞、巨噬細(xì)胞、角質(zhì)形成細(xì)胞、內(nèi)皮細(xì)胞、腸道上皮細(xì)胞、腎小球細(xì)胞等補(bǔ)體生物合成的調(diào)節(jié)補(bǔ)體基因表達(dá)存在組織特異性生物合成受多種因素調(diào)節(jié)補(bǔ)體的分解代謝代謝較快，每天更新一半補(bǔ)體激活途徑UNIVERSITASAMOIENSISGAOFENGGUANG

補(bǔ)體的激活補(bǔ)體活化的經(jīng)典途徑補(bǔ)體活化的MBL途徑補(bǔ)體活化的旁路途徑UNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體活化的經(jīng)典途徑

classicalpathwayUNIVERSITASAMOIENSISGAOFENGGUANG激活物和激活條件抗原—抗體復(fù)合物：合適濃度的IgM、IgG1--3的免疫復(fù)合物激活經(jīng)典途徑，游離和可溶性抗體不能激活補(bǔ)體C反應(yīng)蛋白、LPS、髓鞘脂、某些病毒蛋白UNIVERSITASAMOIENSISGAOFENGGUANG固有成分及激活順序識別階段活化階段補(bǔ)體活化的共同末端效應(yīng)識別階段活化階段UNIVERSITASAMOIENSISGAOFENGGUANGUNIVERSITASAMOIENSISGAOFENGGUANGUNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體活化的MBL途徑

Lectinpathway$$$UNIVERSITASAMOIENSISGAOFENGGUANG激活物甘露聚糖結(jié)合凝集素(MBL):鈣依賴性糖結(jié)合蛋白，屬凝聚素家族，可與甘露糖殘基結(jié)合。激活順序Lectin-initiatedpathwayUNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體活化的旁路途徑

alternativepathway$$$UNIVERSITASAMOIENSISGAOFENGGUANG旁路途徑的激活原免疫因素聚合免疫球蛋白：聚合IgG1-3能激活經(jīng)典途徑和替代途徑，聚合IgA、IgE、IgG4只能激活替代途徑非免疫因素胰蛋白酶類：能激活經(jīng)典、替代途徑其他經(jīng)典途徑激活原：SPA、雙鏈DNA、RNA病毒。其他替代途徑激活原：酵母多糖、細(xì)菌脂多糖、眼鏡蛇毒激活過程補(bǔ)體激活的放大SpontaneousactivationofC3(C3tick-over)StabilizationofC3convertaseUNIVERSITASAMOIENSISGAOFENGGUANG替代途徑的激活特點可以識別自己和非己補(bǔ)體系統(tǒng)重要的放大機(jī)制UNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體活化的共同末端效應(yīng)$$$ThelyticpathwayUNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體激活UNIVERSITASAMOIENSISGAOFENGGUANG三條激活途徑的特點經(jīng)典途徑激活物C3-C5轉(zhuǎn)化酶依賴抗體，感染后期作用大旁路途徑激活物C3-C5轉(zhuǎn)化酶正反饋無需抗體，感染早期作用更大凝集素途徑激活物質(zhì)廣泛識別后的后續(xù)過程同經(jīng)典途徑對經(jīng)典途徑和旁路途徑的交叉促進(jìn)作用無需抗體，感染早期作用更大UNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體激活的調(diào)節(jié)（簡述）控制補(bǔ)體活化的啟動補(bǔ)體的自身調(diào)控補(bǔ)體調(diào)節(jié)蛋白的作用經(jīng)典途徑的調(diào)節(jié)旁路途徑的調(diào)節(jié)膜攻擊復(fù)合物形成的調(diào)節(jié)UNIVERSITASAMOIENSISGAOFENGGUANG經(jīng)典途徑的調(diào)節(jié)（簡述）C1抑制分子C1INH：抑制經(jīng)典途徑C3轉(zhuǎn)化酶的形成C4結(jié)合蛋白和補(bǔ)體受體1：與C4b結(jié)合I因子：裂解C4b膜輔助蛋白membranecofactorproteinMCP:促進(jìn)I因子的作用衰變加速因子decayacceleratingfactorDAF:與C2競爭結(jié)合C4b補(bǔ)體受體1UNIVERSITASAMOIENSISGAOFENGGUANG旁路途徑的調(diào)節(jié)抑制旁路途徑C3轉(zhuǎn)化酶的組裝：H因子與B因子競爭結(jié)合C3b抑制旁路途徑C3轉(zhuǎn)化酶的形成：I

C3b,H、CR1、MCP輔助促進(jìn)形成的C3轉(zhuǎn)化酶解離：CR1、DAF促進(jìn)Bp自轉(zhuǎn)化酶解離對旁路途徑的正性調(diào)節(jié)作用：備解素properdinRegulationofactivatedC3byCr1

RegulationofactivatedC3byDafRegulationofC1rs(C4convertase)byC1-INHUNIVERSITASAMOIENSISGAOFENGGUANG膜攻擊復(fù)合物形成的調(diào)節(jié)CD59：膜反應(yīng)性溶解抑制物MIRLMembraneinhibitorofreactivelysis阻止MAC組裝C8結(jié)合蛋白干擾C8與C9結(jié)合S蛋白：阻止C5b67與靶細(xì)胞膜結(jié)合群集素：抑制MAC組裝，促進(jìn)MAC自膜解離UNIVERSITASAMOIENSISGAOFENGGUANGUNIVERSITASAMOIENSISGAOFENGGUANGUNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體的生物學(xué)意義溶菌、溶解病毒和細(xì)胞的細(xì)胞毒作用調(diào)理作用免疫粘附：C3b炎癥介質(zhì)作用C3aC4aC5aUNIVERSITASAMOIENSISGAOFENGGUANG補(bǔ)體的病理生理學(xué)意義機(jī)體抗感染防御的