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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(duì)TI抗原的免疫應(yīng)答T、B細(xì)胞活化信號(hào)的轉(zhuǎn)導(dǎo)第一節(jié)B細(xì)胞免疫應(yīng)答抗原識(shí)別階段活化、增殖和分化階段效應(yīng)階段RecirculatingBcellsnormallypassthroughlymphoidorgansBcellsinbloodEfferentlymphTcellareaBcellareaAntigenentersnodei
2、nafferentlymphaticYYYYYYYYYYYYYYYYYYBcellsleaveblood& enterlymphnodeviahighendothelialvenulesBcellsproliferaterapidlyGERMINALCENTRETransientstructureofIntenseproliferationGerminalcentrereleasesBcellsthatdifferentiateintoplasmacellsRecirculatingBcellsar
3、etrappedbyforeignantigensinlymphoidorgans一、抗原識(shí)別BCR特異性識(shí)別天然抗原的抗原決定簇直接識(shí)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(hào)雙信號(hào)----第一信號(hào)第一信號(hào)（抗原特異性信號(hào)）BCR結(jié)合特異性抗原表位，啟動(dòng)第一信號(hào)由Igα/Igβ傳入胞內(nèi)協(xié)同受體CD19/CD21/CD81輔助第一信號(hào)的傳遞內(nèi)吞抗原—加工處理—肽-MHCП類—供T識(shí)別雙信號(hào)----第二信號(hào)第二信號(hào)（協(xié)同
4、刺激信號(hào)）CD40/CD40L等？？Th2細(xì)胞輔助Th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(shí)別B細(xì)胞表面的肽-MHCП類復(fù)合物提供第二信號(hào)：表達(dá)CD40L，CD40L-CD40分泌細(xì)胞因子：IL-4，5，6等BB2.InternalizationviaBCRinducestheexpressionofCD403.Antigendegradationbyexogenousantigenprocessingpathway4.Agpeptide-M
5、HCcomplexesareexpressedatthecellsurfaceFateofAntigensInternalisedbyBcells1.uptakeofantigenbyspecificBCRYYYTcellhelptoBcellsBSignal1 Ag&BCRTh1.TCR2.CD43.CD40LThSignal2–CD40/CD40LYYYBThSignal2Signal1Signal1&2thusallowtheBcelltosurviveTcellsregulatethesur
6、vivalofBcellsandthuscontroltheclonalselectionofBcellsCytokinesCytokinesIL-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(jí)、次級(jí)）活化B細(xì)胞在Th2細(xì)胞分泌
7、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ThSignal2YYYBSignal1CytokinesIL-4 IL-5IL-6 IFN-gTGF-bIgMIgG3IgG1IgG2bIgG2aIgEIgAIL4inhibitsinhibitsinducesinhibitsinducesIL-5augmentsIFN-ginhibitsinducesinhibitsinducesinhibitsTGF-binhibitsinhibitsinducesinducesPCBBBBBBBBBBBB
8、BBProliferation&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，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
