第十三章B淋巴細(xì)胞介導(dǎo)的體液免疫應(yīng)答Section13humoralimmuneresponse

mediatedbyBlymphocyte第一節(jié)B細(xì)胞對(duì)TD抗原的免疫應(yīng)答Chapter1BcellresponsetoTcell-dependentantigenAntigenrecognitionofBcellsBcellrecognizesandbindsanantigeninitsfree,unprocessedformthroughBCR.NoMHCrestriction.DoublesignalsforBcellsactivationAntigensignal:recognitionofantigenbytheBCRIgα/Igβ(CD79a/CD79b):transmitantigenstimulussignalCo-receptors:CD19/CD21/CD81accessorysignalCD40CD40L二、B細(xì)胞活化需要的信號(hào)B細(xì)胞活化的第一信號(hào)：BCR特異性結(jié)合抗原啟動(dòng)第一信號(hào)，經(jīng)由Igα/Igβ傳導(dǎo)入胞內(nèi)，B細(xì)胞共受體(CD19/CD21/CD81)加強(qiáng)信號(hào)的傳導(dǎo)；B細(xì)胞活化的第二信號(hào)（協(xié)同刺激信號(hào)）

CD40/CD40L（活化的Th細(xì)胞）B細(xì)胞活化的信號(hào)轉(zhuǎn)導(dǎo)途徑BCR交聯(lián)PLC-γ活化途徑MAP激酶活化途徑轉(zhuǎn)錄因子活化相關(guān)基因轉(zhuǎn)錄SyK被募集并活化Igα/Igβ胞質(zhì)區(qū)ITAM磷酸化活化酪氨酸激酶（Blk、Fyn或Lyn）InteractionbetweenTHandBcellsTHcellsprovideaccessorysignal

（CD40/CD40L）andcytokines

(Th1IL-2、IFN-γ、Th2IL-4、5、6)forBcellsactivationanddifferentiation.Bcellsprovideantigensignal

（peptide-MHCⅡcomplex）andcostimulatorysignal

（B7/CD28）

forTHcellsactivation.ProliferationandterminaldifferentiationofBcells

ActivatedCD4+ThsecretecytokineswhichactonBcellsTh1:IL-2IFN-γTh2:IL-4IL-5IL-6三、B細(xì)胞的增殖和終末分化細(xì)胞因子信號(hào)Th1:IL-2IFN-γTh2:IL-4IL-5IL-6活化的CD4+Th細(xì)胞分泌細(xì)胞因子，作用于B細(xì)胞。

專職APC（DC）捕捉、加工抗原遷移至局部淋巴結(jié)的T細(xì)胞區(qū)APC捕捉TCR結(jié)合抗原肽-MHC分子T細(xì)胞被激活(Th)表達(dá)該抗原特異性BCR的B細(xì)胞B細(xì)胞被激活進(jìn)入淋巴濾泡表達(dá)該抗原特異性TCR的T細(xì)胞增殖形成生發(fā)中心DevelopmentanddifferentiationofBcellsingerminalcentersTheeventsassociatedwiththedevelopmentanddifferentiationinvolvessomatichypermutation,affinitymaturation,Igheavy-chainclassswitchandmemoryBcellformation.SomatichypermutationFullyassembledV/JandV/D/JexonsinBcellsundergopointmutationatanunusuallyhighrateduringthecourseofanimmuneresponse,thisphenomenonistermedsomatichypermutation.IndividualcellsthatundergohighaffinitymutantsandexpresshigheraffinityAbareselected.FormtheBCRdiversity.AffinitymaturationTheantibodiesproducedlaterinanimmuneresponsetendtohavehigheraffinityforthetargetantigenthanthoseproducedearlier,thisphenomenonistermedaffinitymaturation.Especiallytheantibodyproducedinsecondaryresponsetendstobehigheraffinitythanthatinprimaryresponse.Somatichypermutationandantigenselectionarethoughttoaccountforthisphenomenon.（一）體細(xì)胞高頻突變和Ig親和力成熟生發(fā)中心母細(xì)胞的輕鏈和重鏈V基因可發(fā)生高頻率的點(diǎn)突變，稱為體細(xì)胞高頻突變；在每次細(xì)胞分裂中，IgV區(qū)基因中大約每1000個(gè)bp中就有一對(duì)發(fā)生突變；體細(xì)胞高頻突變?cè)诳乖T導(dǎo)下發(fā)生；再次免疫應(yīng)答時(shí)抗原會(huì)優(yōu)先結(jié)合高親和力的BCR，產(chǎn)生高親和力的抗體，稱為抗體親和力成熟；導(dǎo)致BCR多樣性及體液免疫應(yīng)答中抗體的多樣性。（二）Ig的類別轉(zhuǎn)換在免疫應(yīng)答中首先分泌IgM，隨后可表達(dá)IgG、IgA或IgE，而其IgV區(qū)不發(fā)生改變，這種可變區(qū)相同而Ig類別發(fā)生變化的過(guò)程稱為Ig的類別轉(zhuǎn)換或同種型轉(zhuǎn)換；類別轉(zhuǎn)換的遺傳學(xué)基礎(chǔ)是同一V區(qū)基因與不同重鏈C基因的重排；Ig的類別轉(zhuǎn)換在抗原誘導(dǎo)下發(fā)生，接受Th細(xì)胞分泌的多種細(xì)胞因子的調(diào)節(jié)。（三）漿細(xì)胞的形成又稱抗體形成細(xì)胞，能合成和分泌特異性抗體；大部分遷入骨髓，在較長(zhǎng)時(shí)間內(nèi)持續(xù)產(chǎn)生抗體；表面不再表達(dá)BCR和MHCⅡ類分子，不能再與抗原起反應(yīng)，也失去了與Th相互作用的能力；MemoryBlymphocyteResideinlymphoidfolliclesorcirculateintheblood,surviveforyears.Haveahigheraffinityreceptorandmorereadilyactivatedtoproliferateandsecreteantibodybyantigenstimulationinsecondaryresponse.（四）記憶性B細(xì)胞的產(chǎn)生生發(fā)中心中存活下來(lái)的B細(xì)胞，或分化發(fā)育成漿細(xì)胞，或成為記憶性細(xì)胞離開(kāi)生發(fā)中心進(jìn)入血液參與再循環(huán)；記憶性B細(xì)胞不產(chǎn)生Ig，但再次與同一抗原相遇時(shí)可迅速活化，產(chǎn)生大量抗原特異的Ig。Antibody:neutralization,opsonization,complementactivationandADCC.MemoryBcellsEffector

五、B細(xì)胞的效應(yīng)

抗體的效應(yīng)記憶性B細(xì)胞的效應(yīng)第二節(jié)B細(xì)胞對(duì)TI抗原的免疫應(yīng)答Chapter2Bcellresponseto

Tcell-independentantigenTIantigenTI-1antigenTI-2antigenAthighconcentrationsTI-1antigenactswithBcellsasamitogen.AtlowconcentrationsTI-1antigenelicitsanantigen-specificantibodyresponse.

BcellresponsetoTI-1antigensTI-1抗原又被稱為B細(xì)胞絲裂原，如LPS，成熟或不成熟的B細(xì)胞均可被激活。高濃度時(shí)經(jīng)絲裂原受體與B細(xì)胞結(jié)合誘導(dǎo)多克隆B細(xì)胞增殖和分化；低濃度時(shí)激活抗原特異性B細(xì)胞。激活初始B細(xì)胞無(wú)需Th細(xì)胞輔助，誘導(dǎo)產(chǎn)生低親和力的IgM，單獨(dú)不足以誘導(dǎo)Ig類別轉(zhuǎn)換、抗體親和力成熟及記憶性B細(xì)胞形成。TI-2antigensaregenerallyhighlyrepetitivepolymericantigens.TI-2antigensactivateBcellsthroughcross-linkingofBCRmolecules.BcellresponsetoTI-2antigensTI-2抗原誘導(dǎo)B細(xì)胞的激活

多為細(xì)菌胞壁與莢膜多糖，具有高度重復(fù)的結(jié)構(gòu)，僅能激活成熟的B細(xì)胞，應(yīng)答的主要是B-1細(xì)胞。通過(guò)其高度重復(fù)的抗原表位使B細(xì)胞的mIg廣泛交聯(lián)而被激活，但過(guò)度交聯(lián)會(huì)使成熟B細(xì)胞出現(xiàn)耐受。TI-2抗原Don’trequirethepresenceofTHcells.GenerateprimarilyIgMantibodiesoflowaffinity.Nosomatichypermutation,noaffinitymaturation,noIgheavy-chainclassswitchandnomemoryBcellsformation.CharacteristicsofBcellresponsetoTIantigen無(wú)Ig親和力成熟無(wú)Ig類別轉(zhuǎn)換，只能產(chǎn)生IgM無(wú)需Th細(xì)胞和巨噬細(xì)胞的參與無(wú)記憶性B細(xì)胞形成,不能引起免疫記憶B細(xì)胞對(duì)TI-Ag的應(yīng)答特點(diǎn)第三節(jié)體液免疫應(yīng)答抗體產(chǎn)生的一般規(guī)律Chapter3Rulesofantibodyproduction（一）初次應(yīng)答潛伏期(lagphase)：抗原刺激后至血清中能測(cè)到特異抗體前的階段；對(duì)數(shù)期(logphase)

：抗體量呈指數(shù)增長(zhǎng)；平臺(tái)期(plateauphase)：血清中抗體濃度基本維持在一個(gè)相當(dāng)穩(wěn)定的較高水平；下降期(declinephase)：血清中抗體濃度慢慢下降。PrimaryresponseMostoftheantigenisprocessedbydentriticcells.Developin4-5daysafterantigenintroduction,5-10daysrequiredtoreachpeakserumantibodyconcentration.Achievelowantibodyconcentration.Durationisshort.TheantibodiesinitiallyproducedarepredominantlyIgMwithlowantigenaffinities.SecondaryresponseMeromyBcellsserveastheprincipalAPCs.Activatedatverylowconcentrationsofantigen.Shorterlagperoid.Achievehighaffinityandhighconcentrationofantibody.Durationislong.IgGtendstopredominate.（二）再次應(yīng)答①潛伏期短；②誘發(fā)再次應(yīng)答所需抗原劑量?。虎劭贵w濃度增加快，快速到達(dá)平臺(tái)期，平臺(tái)高；④抗體維持時(shí)間長(zhǎng)；⑤再次應(yīng)答主要產(chǎn)生