第十六章 體液免疫應(yīng)答：B淋巴細(xì)胞對抗原的識別及免疫應(yīng)答.doc

第十六章 適應(yīng)性免疫：B淋巴細(xì)胞對抗原的識別及免疫應(yīng)答教學(xué)內(nèi)容與要求：1掌握特異性體液免疫的應(yīng)答(對TI抗原的應(yīng)答特點, 對TD抗原的應(yīng)答過程中細(xì)胞間, 細(xì)胞因子與細(xì)胞間的相互作用特點);2掌握抗體產(chǎn)生的一般規(guī)律(初次與再次應(yīng)答的比較)教學(xué)時數(shù)：2學(xué)時教學(xué)對象： 教學(xué)手段：多媒體課件時間安排：第一節(jié) B細(xì)胞對TD抗原的免疫應(yīng)答（1.5學(xué)時）第二節(jié) B細(xì)胞對TD抗原的免疫應(yīng)答（0.3學(xué)時）第三節(jié) 體液免疫應(yīng)答的一般規(guī)律（0.2學(xué)時） 特異性體液免疫應(yīng)答主要由B細(xì)胞介導(dǎo)。B細(xì)胞BCR特異性識別及結(jié)合抗原，啟動B細(xì)胞活化，導(dǎo)致B細(xì)胞增殖并分化成抗體分泌細(xì)胞或記憶細(xì)胞。B細(xì)胞識別的抗原主要是TD抗原，還有TI抗原。B細(xì)胞對TD抗原的應(yīng)答需要Th細(xì)胞輔助。第一節(jié)B細(xì)胞對TD抗原的免疫應(yīng)答（response to TD-Ag of B cell） 一 B細(xì)胞對TD抗原的識別 二 Th細(xì)胞B細(xì)胞免疫應(yīng)答中的作用 三 B細(xì)胞的激活、增殖和終末分化 四 B細(xì)胞在生發(fā)中心的分化成熟一、 B細(xì)胞對TD抗原的特異性識別 （一）B細(xì)胞經(jīng)由BCR識別抗原 BCR可變區(qū)與抗原特異性結(jié)合，產(chǎn)生第一活化信號。（二）第一信號經(jīng)由Iga/Igb傳入胞內(nèi) 活化PTK，使Iga/Igb胞內(nèi)區(qū)ITAM磷酸化，繼而激活syk，引起PLCg活化，通過磷脂酰肌醇途徑產(chǎn)生IP3和DG，再分別激活PKC和使胞內(nèi)Ca2+濃度升高，參與B細(xì)胞激活、增殖。(三) B細(xì)胞活化輔助受體的作用 B細(xì)胞表面CD19/CD21/CD81/Leu13形成B細(xì)胞活化的共受體(。CD19是酪氨酸激酶的底物；CD21胞外區(qū)可與附著抗原的補體片段結(jié)合。（四）BCR交聯(lián)介導(dǎo)的信號轉(zhuǎn)導(dǎo)途徑。二、Th細(xì)胞在B細(xì)胞免疫應(yīng)答中的作用（一） Th細(xì)胞對B細(xì)胞應(yīng)答的輔助作用 ( help to B cell from Th cell )Th細(xì)胞提供B細(xì)胞第二活化信號 活化T細(xì)胞表達的CD40L與B細(xì)胞表面CD40分子結(jié)合產(chǎn)生第二活化信號。Th細(xì)胞產(chǎn)生細(xì)胞因子的作用 激活的Th細(xì)胞 ( 主要是Th2 ) 產(chǎn)生多種細(xì)胞因子( 如IL-4、IL-5、IL-6、IL-10、IL-13等 )，可輔助B細(xì)胞活化、增殖與分化。 （二） T細(xì)胞的輔助作用發(fā)生于T細(xì)胞區(qū)和生發(fā)中心ThThThBcytokinesThBm The process of humoral immune response induced by TD antigen三、B細(xì)胞的激活、增殖和終末分化 靜系息的B淋巴細(xì)胞在抗原的誘導(dǎo)下分化成為分泌抗體的漿細(xì)胞。四、B細(xì)胞在生發(fā)中心的分化成熟第二節(jié) B細(xì)胞對TI抗原的免疫應(yīng)答 TI抗原(如某些細(xì)菌多糖、多聚蛋白質(zhì)、及脂多糖等)可直接激活未致敏B細(xì)胞，而無需抗原特異性T細(xì)胞輔助。TI抗原可分成兩類，即TI-1和TI-2，它們通過不同機制激活B細(xì)胞。1. TI-1抗原誘導(dǎo)的B細(xì)胞應(yīng)答 ( B cell response induced by TI-Ag ) TI-1抗原常被稱為B細(xì)胞絲裂原。B細(xì)胞對TI-1抗原的應(yīng)答在機體抵御某些胞外病原體感染中發(fā)揮重要作用，因其無需Th細(xì)胞預(yù)先致敏和克隆擴增，故應(yīng)答發(fā)生早。但TI-1抗原單獨不足以誘導(dǎo)Ig類別轉(zhuǎn)換、抗原親和力成熟及記憶B細(xì)胞形成。2. TI-2抗原誘導(dǎo)的B細(xì)胞應(yīng)答（response to TI-Ag of B cell） TI-2抗原多屬細(xì)菌胞壁與莢膜多糖成份，具有高度重復(fù)結(jié)構(gòu)。TI-2抗原只能激活成熟B細(xì)胞，主要是B-1細(xì)胞。TI-2抗原可使B細(xì)胞mIg發(fā)生廣泛交聯(lián)。第三節(jié) 體液免疫應(yīng)答的一般規(guī)律一、初次應(yīng)答所需抗原量多、抗體潛伏期長、抗體濃度低、維持時間短、親和力低、以IgM為主。二、 再次應(yīng)答其特點為：潛伏期短，約為初次應(yīng)答潛伏期的一半；抗體合成快速到達平臺期，平臺高持續(xù)時間長；下降期持久(機體長時間合成抗體)：誘發(fā)再次應(yīng)答所需抗原劑量?。恢饕a(chǎn)生IgG，其親和力高，較均一。Table Features of primary and secondary antibody responsesFeature Primary response secondary responsetime lag after immunization usually 5-10 days usually 1-3 dayspeak response smaller largerantibody isotype usually IgMIgG relative increase in IgG, and IgAantibody affinity lower average affinity, high average affinitymore variable (affinity maturation)induced by all immunogens only protein antigensrequired immunization relatively high doses of antigens, low doses of antigens. Fig 11-2 Kinetics of primary and secondary humoral immune response Summary1. Humoral immunity is mediated by antibodies and is the effecror arm of the adaptive immune system responsible for defense against extracellular microbes and microbial toxins. The antibodies that provide protection against infection may be produced by long-lived antibody-secreting cells generated by the first exposure to microbial antigen or by reactivation of memory B cells by the antigen.2. The effector functions of antibodies include neutralization of antigens, Fc receptor-dependent phagocytosis of opsonized particles, and activation of the complement system.3. Antibodies block, or neutralize, the infectivity of microbes by binding to the microbes and sterically hindering interactions of the microbes with cellular receptors. Antibodies similarly block the pathologic actions of toxins by preventing binding of the toxins to host cells.4. Antibody-coated (opsonized) particles are phagocytosed by binding of the Fc portions of the antibodies to phagocyte Fc receptors. There are several types of Fc receptors specific for different subclasses of IgG and IgA and IgE antibodies, and different Fc receptors bind the antibodies with varying affinities. Attachment of antigen-complexed Ig to phagocyte F c receptors also delivers signals that stimulate the microbicidal activities of phagocytes.復(fù)習(xí)思考題：1. 獲得性免疫應(yīng)答與天然免疫相比具有那些特點？2. 請解釋在抗感染免疫應(yīng)答的過程中，獲得性免疫應(yīng)答與天然免疫是如何進行協(xié)作的？3. 如何理解免疫功能具有雙重性？4. 效應(yīng)性T細(xì)胞、記憶T細(xì)胞、未T活化細(xì)胞在本質(zhì)上有何不同？5. T細(xì)胞識別抗原有何特點？6. 效應(yīng)性T細(xì)胞是如何發(fā)揮作用的？7. 比較B細(xì)胞對TD、TI