第15章 T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答課件

第15章適應(yīng)性免疫應(yīng)答:

T細(xì)胞對(duì)抗原的識(shí)別及免疫應(yīng)答Theadaptiveimmunity:----TherecognitiontoantigenofTCellandimmuneresponsemediatedbyit第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答免疫應(yīng)答的概述**一.授課要點(diǎn)§2.T細(xì)胞的活化過(guò)程§1.T細(xì)胞對(duì)抗原的識(shí)別§3.效應(yīng)T細(xì)胞的應(yīng)答效應(yīng)第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答二、免疫應(yīng)答概述

（immuneresponse）1.概念免疫細(xì)胞識(shí)別抗原后活化、增殖、分化為效應(yīng)Ｔ細(xì)胞及產(chǎn)生特異性抗體，從而將抗原清除的一系列生理學(xué)過(guò)程。第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答2.特點(diǎn)（1）特異性（specificity）（2）記憶性（memory）

(3)識(shí)別性:“自己”“非己”第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答

3.免疫應(yīng)答類(lèi)型正常應(yīng)答異常應(yīng)答正應(yīng)答體液免疫細(xì)胞免疫自身免疫病超敏反應(yīng)負(fù)應(yīng)答自身耐受免疫缺陷病第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答§1.T細(xì)胞對(duì)抗原的識(shí)別RecognitiontoantigenofTcell第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答§1.T細(xì)胞對(duì)抗原的識(shí)別一.APC向T細(xì)胞提呈抗原過(guò)程二.APC與T細(xì)胞的相互作用三.進(jìn)行抗原識(shí)別的部位第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答1.外源性抗原局部組織APCTh淋巴組織APC抗原清除效應(yīng)T應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答CTL２.內(nèi)源性抗原（腫瘤，病毒感染細(xì)胞）APC凋亡細(xì)胞APC第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答TCR掃描抗原第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答免疫突觸（Tcellsynapse）APCT第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答免疫突觸（Tcellsynapse）TcellMHC－ⅡAPCCD4CD80/86LFA-3特異性TCRCD28CD2LFA-2ICAM-1非特異第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答TCR識(shí)別MHC/抗原肽的分子解剖MHC-Ⅱ抗原肽CDR3CDR3CDR1CDR2TCR-bCDR2CDR1TCR-aAPCTＨ第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答TcellTCRMHC－ⅡAPCCD4第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答APC啟動(dòng)免疫應(yīng)答外來(lái)抗原的捕獲與遞呈淋巴結(jié)輸出淋巴管輸入淋巴管皮質(zhì)

局部組織引流淋巴管樹(shù)突細(xì)胞異物抗原第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答T細(xì)胞與APC的黏附TCR“掃描”APC表面TCR識(shí)別MHC-抗原肽二、抗原識(shí)別總結(jié)第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答§2.T細(xì)胞活化的過(guò)程一.活化信號(hào)產(chǎn)生三.活化涉及的靶基因二.活化信號(hào)轉(zhuǎn)導(dǎo)途徑四.抗原特異性T細(xì)胞克隆及分化第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答(一)T細(xì)胞的活化劑1.APC提呈的抗原肽2.抗T細(xì)胞表面分子mAb3.超抗原（sAg)4.絲裂原(mitogens)第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答(二)T細(xì)胞活化需雙信號(hào)刺激1.TCR與MHC+Ag的結(jié)合2.協(xié)同信號(hào)分子之間的粘附3.CK促進(jìn)T細(xì)胞充分活化１２第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答-S-S-zhz-S-S-zITAM-S-S-VaCaVbCb

TCR-ab-S-S-zhz-S-S-z-S-S-VaCaVbCbAPC第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答12IL-1,2,6,123第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答APC表達(dá)協(xié)同信號(hào)分子的意義（1）保證T細(xì)胞應(yīng)答在時(shí)間和地點(diǎn)上的準(zhǔn)確性（2）增強(qiáng)T、B和Mφ之間相互作用（3）靜止的APC不表達(dá)協(xié)同信號(hào)分子，保護(hù)自身抗原抗原。第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答CD28ActivatedTcellCD28crosslinkedbyB7（４）CostimulatorymoleculesalsoassociatewithinhibitoryreceptorsCTLA-4bindsCD28withahigheraffinitythanB7molecules/CTLA-4B7CD28TcellB722Signal1+Co-stimulationinducesCTLA-4Thelackofsignal2totheTcellshutsdowntheTcellresponse.Cross-linkingofCTLA-4byB7inhibitsco-stimulationandinhibitsTcellactivation-----第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答正常組織感染組織第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答二.T細(xì)胞活化信號(hào)的轉(zhuǎn)導(dǎo)過(guò)程(一)TCR識(shí)別抗原表位，產(chǎn)生信號(hào)(二)PTK（蛋白酪氨酸激酶）活化(三)TCR活化信號(hào)胞內(nèi)轉(zhuǎn)導(dǎo)途徑第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答CD4LCKTCR+CD3FynCD3各鏈ITAM磷酸化ZAP-70磷酸化G蛋白NF-κBDAGPLC-γ分解PIP2IP3MAP激酶AP-1NFAT第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答三.活化涉及的靶基因1.增加表達(dá)CKs和CKR2.增加表達(dá)黏附分子第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答TH細(xì)胞克隆增殖旁/自分泌第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答克隆增殖，增加了效應(yīng)細(xì)胞的數(shù)量第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答THp識(shí)別活化增殖分化MφTH1BTH2效應(yīng)TH0TH3TGF-βTr1IL-10THm再次應(yīng)答TH細(xì)胞分化過(guò)程第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答Tcp識(shí)別活化增殖分化效應(yīng)TcTcm再次應(yīng)答Tc細(xì)胞分化過(guò)程Tc1Tc1殺傷調(diào)節(jié)Tc第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答§3.效應(yīng)T細(xì)胞的應(yīng)答效應(yīng)一.TH細(xì)胞--DTH二.CD8+T細(xì)胞(CTL/Tc):

直接特異性殺傷第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答外來(lái)抗原的捕獲與遞呈淋巴結(jié)輸出淋巴管輸入淋巴管皮質(zhì)

局部組織引流淋巴管樹(shù)突細(xì)胞異物抗原DC效應(yīng)T細(xì)胞免疫應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答TCD45ROLFA-1VLA-4ICAM-1VCAM-1效應(yīng)T細(xì)胞炎癥部位血管的作用血管第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答ChronicInflammation(lung)

Cotranetal.*

=inflammatorycellsreplacementbyconnectivetissuedestructionofparenchyma第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答特點(diǎn)1.輔助Mφ殺傷2.MHC-Ⅱ類(lèi)分子限制3.引起單個(gè)核細(xì)胞浸潤(rùn)的炎癥反應(yīng)抗細(xì)胞內(nèi)寄生物抗病毒免疫移植排斥反應(yīng)第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答§3.效應(yīng)T細(xì)胞的應(yīng)答效應(yīng)二、CD8+細(xì)胞毒性T細(xì)胞1.直接特異性殺傷靶細(xì)胞2.細(xì)胞裂解和凋亡（apoptosis）第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答靶細(xì)胞Tc1活化增殖分化Tc2CTL２.Tc細(xì)胞介導(dǎo)的免疫應(yīng)答效應(yīng)識(shí)別調(diào)節(jié)CD8+TTm第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答病毒感染細(xì)胞Tc細(xì)胞對(duì)病毒抗原的識(shí)別第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答CTL殺傷機(jī)制滲透溶解穿孔素少殺傷穿孔素顆粒酶主要途徑誘導(dǎo)凋亡Fas-FasL主要途徑第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答ppppCTL/TC細(xì)胞PPppppp

FasLFasperforingranulysinapoptosisdead第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答特點(diǎn)1.直接特異性殺傷作用2.殺傷作用受MHC-I類(lèi)分子限制3.效應(yīng)性細(xì)胞Tc可連續(xù)殺傷靶細(xì)胞抗病毒免疫抗腫瘤免疫移植排斥反應(yīng)第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答CTL殺傷靶細(xì)胞的電鏡結(jié)果第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答Tc細(xì)胞的免疫調(diào)節(jié)1.CD8+T：

Tc1：

Tc2：2.CD4+T：Th1與Th2的相互抑制IL-2,IFN-γIL-4,5，6，10第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答三.免疫記憶

（Immunologicalmemory）第15章T細(xì)胞對(duì)抗原的識(shí)別和應(yīng)答免疫后天數(shù)外周血中抗原特異性T細(xì)胞的比率初次免疫再次免疫1/100001/10001/100071421283542

T細(xì)胞免疫應(yīng)答的一般規(guī)律第15章T細(xì)胞對(duì)抗原的識(shí)別和