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1、第15章B淋巴細(xì)胞活化 與抗體的產(chǎn)生BLymphocyteActivation&AntibodyProductionContentsB細(xì)胞免疫應(yīng)答抗體產(chǎn)生的一般規(guī)律B1細(xì)胞對TI抗原的免疫應(yīng)答T、B細(xì)胞活化信號的轉(zhuǎn)導(dǎo)第一節(jié)B細(xì)胞免疫應(yīng)答抗原識別階段活化、增殖和分化階段效應(yīng)階段RecirculatingBcellsnormallypassthroughlymphoidorgansBcellsinbloodEfferentlymphTcellareaBcellareaAntigenentersnodeinafferent
2、lymphaticYYYYYYYYYYYYYYYYYYBcellsleaveblood& enterlymphnodeviahighendothelialvenulesBcellsproliferaterapidlyGERMINALCENTRETransientstructureofIntenseproliferationGerminalcentrereleasesBcellsthatdifferentiateintoplasmacellsRecirculatingBcellsaretrappedbyforeigna
3、ntigensinlymphoidorgans一、抗原識別BCR特異性識別天然抗原的抗原決定簇直接識別，無需APC加工處理無MHC限制性二、活化、增殖分化階段活化增殖分化1、活化外周淋巴組織T、B細(xì)胞交界處的T細(xì)胞區(qū)內(nèi)雙信號雙信號----第一信號第一信號（抗原特異性信號）BCR結(jié)合特異性抗原表位，啟動第一信號由Igα/Igβ傳入胞內(nèi)協(xié)同受體CD19/CD21/CD81輔助第一信號的傳遞內(nèi)吞抗原—加工處理—肽-MHCП類—供T識別雙信號----第二信號第二信號（協(xié)同刺激信號）CD40/CD40L等？？Th2細(xì)胞輔助Th
4、細(xì)胞的輔助初次應(yīng)答中DC激活未致敏Th2細(xì)胞再次應(yīng)答中B細(xì)胞激活記憶Th2細(xì)胞活化的Th2細(xì)胞識別B細(xì)胞表面的肽-MHCП類復(fù)合物提供第二信號：表達(dá)CD40L，CD40L-CD40分泌細(xì)胞因子：IL-4，5，6等BB2.InternalizationviaBCRinducestheexpressionofCD403.Antigendegradationbyexogenousantigenprocessingpathway4.Agpeptide-MHCcomplexesareexpressedatthecellsurf
5、aceFateofAntigensInternalisedbyBcells1.uptakeofantigenbyspecificBCRYYYTcellhelptoBcellsBSignal1 Ag&BCRTh1.TCR2.CD43.CD40LThSignal2–CD40/CD40LYYYBThSignal2Signal1Signal1&2thusallowtheBcelltosurviveTcellsregulatethesurvivalofBcellsandthuscontroltheclonalselection
6、ofBcellsCytokinesCytokinesIL-4 IL-5IL-6 IFN-gTGF-bTcellhelptoBcellsSynaptictetheringofaBcell(red)toaTcell(green)Tcell(incentre)surroundedbyBcellswithcytoskeletonstainedgreen2、增殖分化部位——生發(fā)中心（初級、次級）活化B細(xì)胞在Th2細(xì)胞分泌的多種細(xì)胞因子作用下增殖、分化為即漿細(xì)胞并發(fā)生抗體轉(zhuǎn)類ThSignal2YYYBSignal1Cytokin
7、esIL-4 IL-5IL-6 IFN-gTGF-bIgMIgG3IgG1IgG2bIgG2aIgEIgAIL4inhibitsinhibitsinducesinhibitsinducesIL-5augmentsIFN-ginhibitsinducesinhibitsinducesinhibitsTGF-binhibitsinhibitsinducesinducesPCBBBBBBBBBBBBBBProliferation&DifferentiationIg轉(zhuǎn)類淋巴細(xì)胞的分化途徑分泌IgM的漿細(xì)胞轉(zhuǎn)類成其它漿母細(xì)胞，
8、入髓質(zhì)成漿細(xì)胞體細(xì)胞高頻突變，親和力成熟分化為記憶性B細(xì)胞，部分Th2也分化為記憶性細(xì)胞somatichypermutation&AffinityMaturationFiveBCR:allspecificfordifferentaffinitiesBBBBBOnlythiscell,thathasahighaffinity,isrescuedf
