醫(yī)學(xué)免疫學(xué)09細(xì)胞免疫應(yīng)答PPT課件

1、peripheral lymphoid organs and immune recognitionperipheral lymphoid organs and immune recognition( (外周淋巴器官與免疫識(shí)別外周淋巴器官與免疫識(shí)別) )啟動(dòng)階段啟動(dòng)階段 ag processing and presentation t cell stimulation - activation增殖增殖 t cell activation and proliferation效應(yīng)階段效應(yīng)階段effector t cells調(diào)節(jié)復(fù)原調(diào)節(jié)復(fù)原immunoregulation9-1 9-1 獲得性免疫應(yīng)答

2、的基本過程獲得性免疫應(yīng)答的基本過程9-2 dc9-2 dc啟動(dòng)獲得啟動(dòng)獲得 性免疫應(yīng)答性免疫應(yīng)答被膜被膜輸出淋巴管輸出淋巴管外 來 抗 原 的 捕 獲 與 遞 呈 局局 部部 組組 織織引流淋巴管引流淋巴管樹突細(xì)胞樹突細(xì)胞異物抗原異物抗原輸入淋巴管輸入淋巴管皮質(zhì)皮質(zhì)淋淋 巴巴 結(jié)結(jié)9-3 t 9-3 t 細(xì)胞的活化細(xì)胞的活化 9-3-1 t-apc interactioncd4mhc-iitcr/cd31icam-1b7-1b7-2lfa-1lfa-1icam-3lfa-3b7-1cd28cd28lfa-1icam-3cd22參與參與 t 細(xì)胞活化的膜表面分子細(xì)胞活化的膜表面分子t t細(xì)胞細(xì)胞

3、apcctla-4t t細(xì)胞與細(xì)胞與apcapc的附著的附著tcrtcr掃描掃描apcapc表面表面9-3-2 ecognition of mhc/peptide complex by tcr 9-3-2 ecognition of mhc/peptide complex by tcr tcr 識(shí)別 mhc/抗原肽復(fù)合分子 tcr抗原肽mhct 細(xì)胞抗原遞呈細(xì)胞tcrtcr抗原抗原結(jié)合部位結(jié)合部位抗原的特異性識(shí)別抗原的特異性識(shí)別tcr 識(shí)別識(shí)別 mhc/抗原肽抗原肽 的分子解剖的分子解剖mhc-a a 螺旋螺旋抗原肽抗原肽cdr1cdr2cdr3cdr3cdr2cdr1tcr-b b 鏈鏈tc

4、r-a a 鏈鏈mhc-a a 螺旋螺旋apc th細(xì)胞細(xì)胞活性封閉活性封閉th細(xì)胞活化的雙信號(hào)模型細(xì)胞活化的雙信號(hào)模型il-2rapcth信號(hào)信號(hào)1信號(hào)信號(hào)2炎癥炎癥 lps 細(xì)菌細(xì)菌 化學(xué)趨化因子化學(xué)趨化因子 補(bǔ)體補(bǔ)體 tnf-a il-1 il-6il-2th信號(hào)信號(hào)1th細(xì)胞活細(xì)胞活化、增殖化、增殖9-3-3 t9-3-3 t細(xì)胞活化的細(xì)胞活化的“雙信號(hào)模型雙信號(hào)模型”ag recognition provides the first signal for t cell activationtc 細(xì)胞活化的雙信號(hào)模型細(xì)胞活化的雙信號(hào)模型fynplcca+zap-70激酶鏈的信號(hào)整合激酶

5、鏈的信號(hào)整合轉(zhuǎn)錄因子被活化轉(zhuǎn)錄因子被活化早期基因早期基因 il-2 il-2基因基因 il-2r il-2ra a基因基因t 細(xì)胞活化的信號(hào)轉(zhuǎn)導(dǎo)細(xì)胞活化的信號(hào)轉(zhuǎn)導(dǎo)cd4tcrlck pi-3kt t細(xì)胞活化過程細(xì)胞活化過程中的信號(hào)轉(zhuǎn)導(dǎo)中的信號(hào)轉(zhuǎn)導(dǎo)9-4 9-4 抗原特異性淋巴細(xì)胞的克隆擴(kuò)增與選抗原特異性淋巴細(xì)胞的克隆擴(kuò)增與選擇擇ctl(%)9-5 effector t cells (9-5 effector t cells (效應(yīng)效應(yīng)t t細(xì)胞細(xì)胞) )輔助性t細(xì)胞：th1與th2tc細(xì)胞效應(yīng)t細(xì)胞的調(diào)節(jié)再次免疫應(yīng)答ttcth0tc2tc1tregth?th2th1tregcd4+cd8+cd

6、4+25+ 2 hrs wash x 3 1 hrs wash x 3 51cr 4 hrs 37bclmeasure specific 51cr-release+ virusexperimental procedure for testing antigen-specific ctl activityt cells harvest supernatantctl 殺傷靶細(xì)胞的機(jī)制殺傷靶細(xì)胞的機(jī)制表表 9 9- -2 2 t tc c與與n nk k細(xì)細(xì)胞胞的的比比較較t tc cn nk ktcr+，cd8+，cd3+tcr-，cd8-，cd3-cd16-，cd56-cd16+，cd56+mh

7、c/抗原肽提供殺傷信號(hào)mhc分子提供殺傷抑制信號(hào)病毒感染后期清除被病毒感染的細(xì)胞病毒感染初期防止病毒擴(kuò)散9-6 9-6 效應(yīng)效應(yīng)t t細(xì)細(xì)胞的胞的mhcmhc限制性限制性rolf zinkernaglepeter dohertynobel prize 1996 ag specificity9-7 adhesion molecules and immigration of lymphocytes 脾 臟（5小時(shí)）血液循環(huán)（30分鐘）骨髓、上皮腹腔 淋巴結(jié)（12小時(shí)）粘摸下組織其它組織肝 、大腦輸出淋 巴管 輸 入 淋 巴 管45%42%10%活化淋巴細(xì)胞未活化淋巴細(xì)胞不參加再循環(huán)的細(xì)胞 （ ？）

8、10%52% 淋 巴 細(xì) 胞 循 環(huán) 途 徑免 疫 后 天 數(shù)外周血中抗原特異性t細(xì)胞的比率感應(yīng)階段初次免疫再次免疫1/100001/10001/1000 7 14 21 28 35 42 t 細(xì) 胞 免 疫 應(yīng) 答 的 一 般 規(guī) 律9-8 immunological memorymemory t cells:resting statelong lived (continuously renewal)easily triggered (do not need co-stimulatory molecules)responsible for maintaining immunological

9、memory 9-8 9-8 獲得性免疫應(yīng)答的調(diào)節(jié)獲得性免疫應(yīng)答的調(diào)節(jié)神經(jīng)內(nèi)分泌系統(tǒng)對(duì)免疫系統(tǒng)的調(diào)節(jié)作用抗原對(duì)免疫應(yīng)答的調(diào)節(jié)作用活化誘導(dǎo)的細(xì)胞死亡（ctla4）調(diào)節(jié)性 t 細(xì)胞轉(zhuǎn)導(dǎo)負(fù)性信號(hào)的免疫細(xì)胞膜分子中樞神經(jīng)系統(tǒng)松果體激素精神因素神經(jīng)肽免疫介質(zhì)內(nèi)分泌激素內(nèi)分泌系統(tǒng)免疫系統(tǒng)免疫介質(zhì)內(nèi)分泌激素神 經(jīng) 內(nèi) 分 泌 與 免 疫 系 統(tǒng) 的 相 互 調(diào) 節(jié)ctla-4cd28pppb7-2b7-1apc凋亡信號(hào)凋亡信號(hào)活化信號(hào)活化信號(hào)cd4+cd25+ regulatory t cellsa unique lineage of regulatory t cells capable of mainta

10、ining self tolerance in vivotcd8cd4cd4+25+th1tc2tc1th2th3tr1peripheral t lymphocyte5-10%30%th4?60%thymuscd4effectorsregulatorsnormal mousecd4+t-cell suspensions eliminated of cd25+ cells t cell-deficient mouseautoimmune diseases thyroid stomach salivary gland langerhans islets adrenal glands ovaries

11、 testes cd4+cd25+ tr cells: comprise 5-10% of peripheral cd4 t cells in human and mice produced in thymus as an unique lineage of cd4 t cells secret il-10 and/or tgf-b, but little il-2 anergic and suppressive cd45rblow, ctla-4 high maintain immunological tolerance inhibit proliferation of cd4+cd25-

12、t cells in vitro, need activation via tcr and cell-cell contact to function, but il-10 and tgf-b may also participate suppressive capacity could be reversed by adding exogenous il-2, by using anti-cd28 mab function of cd4+cd25+ t cellsanti-idiotypic networksurface molecules transducing inhibitory or apoptosis signals regulatory t cells ts cells anti-idiotypic t cells th1, th2, th3, tr1 cd4+25+ cd4+ t c