淋巴細(xì)胞及T細(xì)胞免疫應(yīng)答總結(jié)

1、T淋巴細(xì)胞淋巴細(xì)胞 一、一、T淋巴細(xì)胞的表面分子及其作用淋巴細(xì)胞的表面分子及其作用 二、二、T淋巴細(xì)胞亞群淋巴細(xì)胞亞群 三、三、T淋巴細(xì)胞功能淋巴細(xì)胞功能 T細(xì)胞是由一群功能不同的異質(zhì)性淋巴細(xì)胞組成，細(xì)胞是由一群功能不同的異質(zhì)性淋巴細(xì)胞組成， 由于它在胸腺內(nèi)分化成熟故稱為由于它在胸腺內(nèi)分化成熟故稱為T細(xì)胞。細(xì)胞。 成熟成熟T細(xì)胞由胸腺遷出，移居于周圍淋巴組織中細(xì)胞由胸腺遷出，移居于周圍淋巴組織中 淋巴節(jié)的副皮質(zhì)區(qū)和脾白髓小動脈的周圍。淋巴節(jié)的副皮質(zhì)區(qū)和脾白髓小動脈的周圍。 T細(xì)胞執(zhí)行特異性細(xì)胞免疫應(yīng)答細(xì)胞執(zhí)行特異性細(xì)胞免疫應(yīng)答 并在并在TD-Ag誘導(dǎo)的體液免疫應(yīng)答中發(fā)揮重要作用誘導(dǎo)的體液免疫應(yīng)

2、答中發(fā)揮重要作用 一、一、T淋巴細(xì)胞表面分子淋巴細(xì)胞表面分子 1. TCRCD3復(fù)合物復(fù)合物 TCR可分為TCR和TCR兩種類型 結(jié)構(gòu)相似 兩條異源二聚體肽鏈藉二硫鍵組成的跨膜分子 每條肽鏈含V、C區(qū)，類似Ig結(jié)構(gòu) TCR-CD3復(fù)合物 是T細(xì)胞抗原受體與一組 CD3（Gamma DeltaEpsilon Zeta Eta ） 分子以非共價(jià)鍵結(jié)合而形 成的復(fù)合物，是T細(xì)胞識別 抗原和轉(zhuǎn)導(dǎo)信號的主要單 位。TCR特異識別由MHC 分子提呈的抗原肽，CD3 分子轉(zhuǎn)導(dǎo)T細(xì)胞活化的第一 信號 CD4 主要分布于成熟主要分布于成熟Th細(xì)胞、巨噬細(xì)胞、細(xì)胞、巨噬細(xì)胞、DC細(xì)胞等表面；細(xì)胞等表面； 是是HI

3、V受體，與受體，與APC表面表面MHC-II分子非多態(tài)區(qū)結(jié)合分子非多態(tài)區(qū)結(jié)合 CD8 主要分布于成熟主要分布于成熟Tc細(xì)胞表面，與細(xì)胞表面，與APC表面表面MHC-I分子分子 非多態(tài)區(qū)結(jié)合非多態(tài)區(qū)結(jié)合 既能加強(qiáng)既能加強(qiáng)T細(xì)胞與細(xì)胞與APC或靶細(xì)胞的相互作用，又能參與抗原或靶細(xì)胞的相互作用，又能參與抗原 刺激刺激TCR-CD3分子信號轉(zhuǎn)導(dǎo)分子信號轉(zhuǎn)導(dǎo) 2. CD4和和CD8分子分子 加強(qiáng)T細(xì)胞與APC或靶細(xì)胞 的相互作用 通過胞漿區(qū)的CxCP基序與 p56lck(Src family tyrosine kinase LCK) 酪氨酸激酶相連，參與T細(xì) 胞活化和增殖信號轉(zhuǎn)導(dǎo) CD4和和CD8 T細(xì)

4、胞輔助受體 3. 協(xié)同（輔助）信號分子協(xié)同（輔助）信號分子 協(xié)同信號分子 TCR-CD3復(fù)合分子可提供第1信號 協(xié)同刺激信號(costimulatouy signal)或第2 信號 參與T細(xì)胞活化的協(xié)同刺激信號主要是 CD28-CD80/86，CTLA4-CD80/86給予 已活化T細(xì)胞抑制信號。 CD40L TAPC CD28 CD80/86 CTLA4 CD40 LFA1ICAM1 LFA2LFA3 1、CD28和和CTLA-4 (intercellular adhesion molecule-1) T細(xì)胞與APC細(xì)胞間的主要輔助分子 2、ICOS 3、CD40L 4、CD2 5、LFA-

5、1和和ICAM-1 4. 其它一些受體其它一些受體 絲裂原受體 細(xì)胞因子受體 病毒受體 二、二、T細(xì)胞分化發(fā)育細(xì)胞分化發(fā)育 thymic corpuscle 胸腺微環(huán)境胸腺微環(huán)境是誘導(dǎo)并調(diào)控是誘導(dǎo)并調(diào)控T細(xì)細(xì) 胞分化發(fā)育的關(guān)鍵因素胞分化發(fā)育的關(guān)鍵因素 胸腺基質(zhì)細(xì)胞（胸腺基質(zhì)細(xì)胞（TSC） 細(xì)胞因子細(xì)胞因子 胸腺激素胸腺激素 雙陰性期（雙陰性期（DN） 原原T細(xì)胞（細(xì)胞（pro-T）、前）、前T細(xì)胞（細(xì)胞（pre-T） TCR 、 、CD3 、 、CD4 、 、CD8 雙陽性期（雙陽性期（DP） TCR 、 、CD3low、CD4 、 、CD8 單陽性期（單陽性期（SP） TCR 、 、CD3

6、、 、CD4 TCR 、 、CD3 、 、CD8 成熟成熟T細(xì)胞，具有識別抗原、介導(dǎo)細(xì)胞，具有識別抗原、介導(dǎo) 免疫應(yīng)答及參與免疫調(diào)節(jié)的功能免疫應(yīng)答及參與免疫調(diào)節(jié)的功能 1. T細(xì)胞發(fā)育的細(xì)胞發(fā)育的陽性選擇陽性選擇（positive selection） CD4+CD8+T細(xì)胞胸腺基質(zhì)細(xì)胞（表面MHC分子） 如果與MHC-I 結(jié)合，最終分 化為CD8+T細(xì)胞 如果與MHC-II結(jié) 合則最終分化為 CD4+T細(xì)胞 如果與MHC分子不 結(jié)合則在胸腺皮質(zhì) 中凋亡 胸腺細(xì)胞經(jīng)陽性選擇賦予成熟胸腺細(xì)胞經(jīng)陽性選擇賦予成熟T細(xì)胞在識細(xì)胞在識 別抗原時具有別抗原時具有MHC限制性限制性 2. T細(xì)胞發(fā)育的細(xì)胞發(fā)

7、育的陰性選擇陰性選擇（negative selection） 其TCR識別胸腺基質(zhì)細(xì)胞表面高親和力 的MHC或MHC-自身抗原肽的T細(xì)胞克 隆將發(fā)生凋亡 經(jīng)陰性選擇可清除自身反應(yīng)性經(jīng)陰性選擇可清除自身反應(yīng)性T細(xì)胞克隆細(xì)胞克隆 獲中樞耐受獲中樞耐受 DP或經(jīng)陽性選擇的SP的T細(xì)胞 T細(xì)胞在胸腺中的陽性選擇和陰性選擇 三、三、T細(xì)胞亞群細(xì)胞亞群 1）根據(jù)）根據(jù)TCR種類種類 T、T細(xì)胞細(xì)胞 在末梢血主要為在末梢血主要為T細(xì)胞可占細(xì)胞可占95%，而，而T細(xì)胞細(xì)胞 只占只占1%10%。T細(xì)胞為主要參予免疫應(yīng)答細(xì)胞為主要參予免疫應(yīng)答 的的T細(xì)胞，兩者特性和功能均不相同。細(xì)胞，兩者特性和功能均不相同。 T

8、CRT和和TCRT細(xì)胞細(xì)胞 TCR 分布分布 表型表型 識別抗原識別抗原 MHC限制限制 功能功能 TCRT TCRT 極大多樣性極大多樣性 60-70,外周淋巴組織外周淋巴組織 成熟成熟CD2CD3CD4/CD8 817aa 經(jīng)典經(jīng)典MHC Th、Tc 較少多樣性較少多樣性 5-15,粘膜上皮粘膜上皮 成熟大多數(shù)成熟大多數(shù)CD2CD3 簡單多肽、簡單多肽、 HSP、脂類、多糖、脂類、多糖 MHC樣分子樣分子 Tc 2）根據(jù)）根據(jù)T細(xì)胞是否表達(dá)細(xì)胞是否表達(dá)CD4或或CD8分類分類 CD4+ T細(xì)胞或細(xì)胞或CD8+ T細(xì)胞細(xì)胞 TCRTCD4+細(xì)胞：細(xì)胞：CD2+、CD3+、CD4+、CD8-

9、TCR識別抗原是識別抗原是MHC類分子限制性類分子限制性 TH0、Th1和和Th2、行使、行使Tc、Ts功能功能 TCRTCD8+細(xì)胞：細(xì)胞：CD2+、CD3+、CD4-、CD8+ TCR識別抗原是識別抗原是MHCI類分子限制性類分子限制性 行使行使Tc、Ts功能功能 Th細(xì)胞細(xì)胞 根據(jù)所分泌的細(xì)胞因子不同，根據(jù)所分泌的細(xì)胞因子不同， 將其分為將其分為Th0、Th1和和Th2亞型。亞型。 Tc細(xì)胞細(xì)胞 殺傷、分泌殺傷、分泌IFN、IL-4、IL-5 和和IL-10 Ts細(xì)胞細(xì)胞 TDTH 主要為主要為CD4 + Th1 3）功能性亞群：）功能性亞群：Th、Tc、TDTH、Ts 4）初始初始T細(xì)

10、胞和記憶性細(xì)胞和記憶性T細(xì)胞細(xì)胞 記憶性T細(xì)胞表達(dá)CD45RO，而初始T細(xì)胞 表達(dá)CD45RA 5）NK1.1 T細(xì)胞細(xì)胞 其TCR識別的抗原是由CD1分子提呈的脂類 和糖脂類抗原 Leukocyte Common antigen 1）免疫調(diào)節(jié)功能（Th1、 Th2 、 Th3、Ts 、 Treg） 2）特異性殺傷功能（CTL、Th1、T） 3）介導(dǎo)超敏反應(yīng)（TDTH） 4) 新型效應(yīng)細(xì)胞：Th17 四、四、T細(xì)胞功能細(xì)胞功能 Naturally occurring CD4+CD25+ Treg cells (56%) GITR and Foxp3 a cellcell contact mec

11、hanism Antigen-induced Tr1 and Th3 cells (IL-10) and/or (TGF-b) ck-dependent mechanism no specific marker has been identified. Adaptively induced CD4+ Treg cells GITR and Foxp3 a cell contact dependent or soluble factor-dependent (other than IL-10and/or TGF-b) mechanism glucocorticoid-induced TNFR f

12、amily related gene (GITR) CD8+ Treg cells NKT regulatory T cells Multiple subsets of Treg cells Naturally occurring CD4+CD25+Foxp3+ Tregs Development and function of naturally occurring CD4+CD25+ FoxP3+ regulatory T cells (nTregs). Development:bone marrow-derived CD4+ T cell precursors develop natur

13、ally into nTregs upon beneficial TCR engagement by self-peptideMHC complexes and Foxp3 induction in the thymus. Upon instruction in the thymus, nTregs emigrate into the periphery as functionally fully competent cells. Mode of action: upon TCR cross-linking, peripheral nTregs suppress the proliferati

14、on and IL-2 production by responder CD25CD4+ or CD8+ T cells in a contact-dependent manner either (a) directly or (b) indirectly via the APC. In addition: nTregs may (c) condition DC to become tolerogenic and turn down the response of conventional T cells on her part Extrathymic induction and functi

15、on of adaptive regulatory T cells. Adaptive regulatory T cells (aTregs) differentiate from naive conventional CD4+ T cells either as a result of suboptimal antigenic stimulation by resting/immature DC, the influence of suppressive cytokines like IL-10, TGF-b or cell contact-dependent interaction wit

16、h activated nTregs (infectious tolerance). Their mode of action involves both cell contactdependent (Tr1 cells) and contact-independent suppressive activities (Th3 cells). Through the production of IL-10 and TGF-b they convert immature DC into tolerizing APC Fig. 3 Role of Tregs in early and late st

17、ages of microbial infections. In the stages of an immune response against a microbial infection Tregs behave differently. A Throughout the early phase of the response the suppressive activity of Tregs is turned down by effector T cell-derived IL-2 and microbial components such as TLR-ligands. Tregs

18、respond to the stimulation by mature DC and proliferate. b At the late stage of the response, when the invading organism is cleared from the host, Tregs regain their suppressive function and participate in the silencing of the T cell response by acting on effector T cells and DC. Possibly, this late

19、 activity is also for the proper development of memory T cells Treg-based immune intervention strategies. Selective manipulation of Treg function is an emerging target for immune intervention strategies to either boost responses in cancer and microbial diseases or suppress those unwanted in autoimmu

20、nity, allergy, transplantation and pregnancy disorders. The transient depletion of Tregs as well as their modulation by microbial agents may allow a transient reduction of Treg activity and enforce anti-tumor responses and immunity against viral infections. On the other hand their selective activati

21、on could diminish chronic pathological immune responses Generation and conversion of Treg cells in the tumor microenvironment Tumor cells not only provide antigenic stimulation for T cell activation but also interact with tumor-infiltrating innate immune cells to secrete crucial cytokines for T-cell

22、 differentiation. Nave CD4+ T cells can be differentiated into different subsets of CD4+ T cells, including Th1, Th2, Treg and IL-17-producing T cells (Th17), depending upon the strength of antigen stimulation and cytokine milieu. It is known that combination of suboptimal antigen stimulation with T

23、GF-b favors the conversion of naive T cells into Treg cells but blocks the generation of Th1 or Th2 cells. However, TGF-b plus IL-6 facilitate the conversion of naive T cells into Th17 cells. Alternatively, naturally occurring CD4+CD25+ Treg cells directly derived from the thymus can cross- react wi

24、th some antigens expressed by cancer cells, thus promoting their expansion and accumulation in the tumor microenvironment. T-helper-cell differentiation Human IL-17 and IL-17R key features a Two isoforms (long and short). Therapeutic targets for autoimmune inflammatory diseases are associated prefer

25、entially with the IL-23/Th17 pathway The pathogenic role for IL-23, not IL-12, in mouse models of autoimmunity Studies by Cua and co-workers have demonstrated that disease development requires IL-23, but not IL-12, in EAE and CIA. Compared with wild-type susceptible mice, mice deficient for IL-23 (I

26、l23p19/) and both IL-23 and IL-12 (Il12p40/) failed to develop disease after antigenic challenge, whereas mice deficient for IL-12 (Il12p35/) developed more severe disease. Model of Th1 versus Th17 lineage development from naive CD4 T cell precursors (Tn) This model emphasizes the distinct lineages

27、leading to mature Th1 and Th17 effector cells (see main body of text for details). Question marks denote speculative or unknown aspects of Th17 differentiation that are yet to be defined. Antagonistic cytokine networks control CD4 effector T-cell differentiation Recent studies have established that

28、Th1 and Th2 effector cytokines, IFNg and IL-4, respectively, potently inhibit Th17 development. Furthermore, TGF-b, a cytokine previously implicated in Treg development and function, appears to be required for Th17 development, both through indirect effects (blockade of IFNg and IL-4 production by c

29、ells of the innate immune system) and through direct effects on naive CD4 T-cell precursors (Tn). CD4+T細(xì)胞分化和免疫調(diào)節(jié)細(xì)胞因子網(wǎng)絡(luò)模式簡圖 Although functional CD4 T cell development has been dominated by the Th1-Th2 paradigm for nearly two decades, the number of defined lineages has now increased. The cytokines ass

30、ociated with arrows indicate dominant cytokines involved in specification of each of the indicated lineages. The cytokines listed below each cell type indicate key effector or regulatory cytokines produced by differentiated cells of that lineage or, in the case of nTreg, a contact- dependent mechani

31、sm of suppression. Tn: naive, postthymic CD4 T cell precursors; Tp: thymic precursors.Dotted lines represent less well-defined lineage relationships. Diversification of CD4 T Cell Lineages Model of Branching Th17 and Adaptive Treg Lineage Development This model emphasizes distinct pathways leading t

32、o mature Th17 effector cells or Foxp3+ adaptive Tregs (aTreg), induced by a common requirement for TGF-b but differential effects of IL-6 and IL-23. Naive CD4 T cells (Tn) activated by antigen presented on immature DCs that do not produce IL-6 production are induced by TGF-b to express Foxp3 and dev

33、elop into aTregs (top panel). Tns activated bymature,TLR-activatedDCsthat produceIL-6 are induced by TGF-b to upregulate IL-23R and become competent for IL-17 production and IL-23 signaling. IL-23 signaling induces responsiveness to IL-18 and IL-1, which can act synergistically with IL-23 to induce

34、Th17 cytokineproduction independently ofTCRstimulation.Alternatively, TCR stimulation by antigen can induce Th17 cytokine production directly, without a requirement for IL-23, IL-1, or IL-18.Dotted lines indicate possible positive feedback loops by which cytokine products of Th17 (IL-6) or aTreg cel

35、ls (TGF-b1) may reinforce lineage development. 1. CD4輔助性T細(xì)胞 2. CD8殺傷性T細(xì)胞 細(xì)胞因子對Th1和Th2細(xì)胞的調(diào)節(jié)作用 3. 抑制性T細(xì)胞 4. 遲發(fā)型超敏反應(yīng)性T細(xì)胞 （TDTH） 5. NK1.1T細(xì)胞 掌握掌握TCR分型與結(jié)構(gòu)分型與結(jié)構(gòu) 掌握掌握T細(xì)胞分群及不同亞群的生物學(xué)特性細(xì)胞分群及不同亞群的生物學(xué)特性 掌握掌握T細(xì)胞發(fā)育過程細(xì)胞發(fā)育過程 熟悉熟悉T細(xì)胞表面主要膜分子及其作用細(xì)胞表面主要膜分子及其作用 了解了解TCRT細(xì)胞和細(xì)胞和TCRT細(xì)胞的異同點(diǎn)細(xì)胞的異同點(diǎn) T淋巴細(xì)胞對抗原的識別及免疫應(yīng)答淋巴細(xì)胞對抗原的識別及免

36、疫應(yīng)答 一、一、T細(xì)胞對抗原的識別細(xì)胞對抗原的識別 二、二、T細(xì)胞活化的過程細(xì)胞活化的過程 三、三、效應(yīng)性效應(yīng)性T細(xì)胞的應(yīng)答效應(yīng)細(xì)胞的應(yīng)答效應(yīng) 免疫應(yīng)答的基本過程免疫應(yīng)答的基本過程 抗原識別 抗原受體與抗原的特異性結(jié)合 免疫應(yīng)答 抗原識別、反應(yīng)、效應(yīng)的全過程 免疫反應(yīng) 免疫效應(yīng)物質(zhì)與抗原結(jié)合的過程 一、一、T細(xì)胞對抗原的識別細(xì)胞對抗原的識別 T 細(xì)胞抗原受體及其識別抗原的特點(diǎn)細(xì)胞抗原受體及其識別抗原的特點(diǎn) l 只識別表達(dá)于只識別表達(dá)于APC表面并與表面并與MHC分子結(jié)合分子結(jié)合 成復(fù)合物的多肽成復(fù)合物的多肽 l 只識別氨基酸一級序列的多肽線性決定簇只識別氨基酸一級序列的多肽線性決定簇 l TC

37、R識別抗原受到識別抗原受到MHC的限制的限制 CD4+T只識別與只識別與MHC-II分子結(jié)合的肽段分子結(jié)合的肽段 CD8+T只識別與只識別與MHC-I分子結(jié)合的肽段分子結(jié)合的肽段 T細(xì)胞與APC間的相互作用 （一）（一）T細(xì)胞與細(xì)胞與APC的非特異性結(jié)合的非特異性結(jié)合 T細(xì)胞與APC的非特異性結(jié)合 （二）（二）T細(xì)胞與細(xì)胞與APC的特異性結(jié)合的特異性結(jié)合 TCR與APC的特異性穩(wěn)定結(jié)合 （三）（三）T細(xì)胞和細(xì)胞和APC表面共刺激分子的結(jié)合表面共刺激分子的結(jié)合 CD28/B7、LFA-1/ICAM-1、CD2/CD58等等 （四）免疫突觸（四）免疫突觸（immunological synapse

38、） 中心是中心是TCR和抗原肽和抗原肽-MHC復(fù)合物復(fù)合物 周圍是細(xì)胞黏附分子對周圍是細(xì)胞黏附分子對 “筏筏”狀結(jié)構(gòu)，相互靠攏成簇狀結(jié)構(gòu)，相互靠攏成簇 （一）（一）T細(xì)胞活化的第一信號細(xì)胞活化的第一信號 二、二、T細(xì)胞活化的信號要求細(xì)胞活化的信號要求 CD4+T細(xì)胞的雙識別 （二）（二）T細(xì)胞激活的第二信號細(xì)胞激活的第二信號 CD28/B7 LFA-1/ICAM-1或或ICAM-2 CD2/LFA-3 CD40/CD40L等等 T細(xì)胞活化的雙信號 CD28/B7促進(jìn)促進(jìn)IL-2基因轉(zhuǎn)錄、合成基因轉(zhuǎn)錄、合成 缺乏時，缺乏時，T細(xì)胞細(xì)胞失能（失能（anergy） CTLA4與與CD28高同源性，與

39、高同源性，與B7親和力比親和力比CD28 高高20倍，結(jié)合后啟動抑制信號，有效制約特異性倍，結(jié)合后啟動抑制信號，有效制約特異性 T細(xì)胞克隆的過度增殖細(xì)胞克隆的過度增殖 （三）細(xì)胞因子促進(jìn)（三）細(xì)胞因子促進(jìn)T細(xì)胞充分活化細(xì)胞充分活化 IL-1、IL-2、IL-6、IL-12等細(xì)胞因子等細(xì)胞因子 三、三、T淋巴細(xì)胞活化信號的轉(zhuǎn)導(dǎo)過程淋巴細(xì)胞活化信號的轉(zhuǎn)導(dǎo)過程 抗原作用下跨膜分子及信號轉(zhuǎn)導(dǎo)成分的多聚化抗原作用下跨膜分子及信號轉(zhuǎn)導(dǎo)成分的多聚化 多聚作用多聚作用（multimerization）: TCR/CD3、輔助受體、輔助受體CD4或或CD8、CD45 等相互靠攏成簇（等相互靠攏成簇（cluste

40、ring） 免疫受體酪氨酸激活基序免疫受體酪氨酸激活基序 （immunoreceptor tyrosine-based activation motif, ITAM） D/Exx YxxL/V x(711) YxxL/V Y：酪氨酸：酪氨酸L：亮氨酸：亮氨酸 V：纈氨酸：纈氨酸D：天冬氨酸：天冬氨酸 E：谷氨酸：谷氨酸 T T 細(xì)細(xì) 胞胞 活活 化化 的的 信信 號號 傳傳 導(dǎo)導(dǎo) 四、轉(zhuǎn)錄因子活化及基因表達(dá)四、轉(zhuǎn)錄因子活化及基因表達(dá) （一）轉(zhuǎn)錄因子活化（一）轉(zhuǎn)錄因子活化 AP-1 (Fos、Jun) NF-B Oct-1 NFAT (nuclear factor of activated T

41、cell ) （二）（二）T細(xì)胞基因表達(dá)細(xì)胞基因表達(dá) n細(xì)胞因子基因細(xì)胞因子基因 n細(xì)胞因子受體基因細(xì)胞因子受體基因 n黏附分子基因黏附分子基因 nMHC （三）（三）T細(xì)胞克隆性增殖和分化細(xì)胞克隆性增殖和分化 nCD4 T細(xì)胞的增殖分化 細(xì)胞的增殖分化 nCD8 T細(xì)胞的增殖分化 細(xì)胞的增殖分化 五、效應(yīng)五、效應(yīng)T細(xì)胞的作用細(xì)胞的作用 Th0細(xì)胞細(xì)胞 Th2細(xì)胞介導(dǎo)細(xì)胞介導(dǎo)體液免疫體液免疫 Th1細(xì)胞介導(dǎo)細(xì)胞介導(dǎo)細(xì)胞免疫細(xì)胞免疫IL-12 IL-4 誘導(dǎo)遲發(fā)型超敏反應(yīng)，活化招募M在炎癥局部浸潤 活化增強(qiáng)APC表達(dá)MHC分子或其他粘附分子表達(dá) 活化CD8T、NK細(xì)胞，增強(qiáng)殺傷活性 1. Th1

42、型型CD4 T細(xì)胞的作用 細(xì)胞的作用 TH1細(xì)胞免疫應(yīng)答的效應(yīng)階段細(xì)胞免疫應(yīng)答的效應(yīng)階段 TH1 IL-2 IFN- TNF- GM-CSF IL-3等等 巨噬細(xì)胞、中性粒巨噬細(xì)胞、中性粒 細(xì)胞等活化、聚集、細(xì)胞等活化、聚集、 局部浸潤局部浸潤 遲發(fā)型遲發(fā)型 超敏反應(yīng)超敏反應(yīng) 巨噬細(xì)胞活化增強(qiáng)巨噬細(xì)胞活化增強(qiáng) MHC-II和粘附分子和粘附分子 表達(dá)表達(dá) 更有效的更有效的APC 形成形成 激活激活巨噬細(xì)胞巨噬細(xì)胞 NK細(xì)胞細(xì)胞 Tc細(xì)胞細(xì)胞 TH細(xì)胞細(xì)胞 更有效的發(fā)揮更有效的發(fā)揮 細(xì)胞免疫功能細(xì)胞免疫功能 記憶記憶 性性TH Th1細(xì)胞激活巨噬細(xì)胞的機(jī)制 Th1細(xì)胞所產(chǎn)生的細(xì)胞因子及其生物學(xué)作用

43、 調(diào)節(jié)調(diào)節(jié)M（招募、抑制：招募、抑制：IL-10/FasL/TGF- ） 活化活化B細(xì)胞，誘導(dǎo)細(xì)胞，誘導(dǎo)Ig類型轉(zhuǎn)換類型轉(zhuǎn)換 2. Th2型型CD4 T細(xì)胞的作用 細(xì)胞的作用 Th2型CD4+ T細(xì)胞與B細(xì)胞 壞死、凋亡、非溶解性途徑 Activation Induced Cell Death 3. CD8 細(xì)胞 細(xì)胞毒性毒性T細(xì)胞的作用細(xì)胞的作用 CD8+CTL胞毒效應(yīng)示意圖 CD8+T細(xì)胞免疫應(yīng)答的效應(yīng)階段細(xì)胞免疫應(yīng)答的效應(yīng)階段 穿孔素-顆粒酶系統(tǒng)的胞毒作用 T細(xì)胞介導(dǎo)免疫應(yīng)答及其免疫學(xué)細(xì)胞介導(dǎo)免疫應(yīng)答及其免疫學(xué) 效應(yīng)效應(yīng) IL-3 IL-2 IL2 IFN- TNF IL-2 IFN-

44、TNF IL-2 IFN- TNF IL-2 IL-4 IL-5 IL-10 效應(yīng)T細(xì)胞的作用 六、活化六、活化T細(xì)胞的轉(zhuǎn)歸細(xì)胞的轉(zhuǎn)歸 （一）活化（一）活化T細(xì)胞轉(zhuǎn)變?yōu)榧?xì)胞轉(zhuǎn)變?yōu)橛洃浶杂洃浶訲細(xì)胞細(xì)胞，參與再次免疫應(yīng)答，參與再次免疫應(yīng)答 （二）活化（二）活化T細(xì)胞發(fā)生細(xì)胞發(fā)生凋亡凋亡，及時終止免疫應(yīng)答，及時終止免疫應(yīng)答 1. 活化誘導(dǎo)的細(xì)胞死亡（活化誘導(dǎo)的細(xì)胞死亡（activation induced cell death, AICD） 2. 被動細(xì)胞死亡（被動細(xì)胞死亡（passive cell death, PCD） 淋巴細(xì)胞凋亡的兩種機(jī)制 掌握掌握T細(xì)胞對抗原的識別以及識別抗原的特點(diǎn)細(xì)胞對抗原的識別以及識別抗原的特點(diǎn) 掌握掌握T細(xì)胞活化的條件細(xì)胞活化的條件 掌握效應(yīng)性掌握效應(yīng)性CD4+T細(xì)胞和細(xì)胞和CD8+T的功能的功能 了解了解T細(xì)胞活化信號轉(zhuǎn)導(dǎo)過程細(xì)胞活化信號轉(zhuǎn)導(dǎo)過程 T淋巴細(xì)胞淋巴細(xì)胞 一、一、T淋巴細(xì)胞的表面分子及其作用淋巴細(xì)胞的表面分子及其作用 二、二、T淋巴細(xì)胞亞群淋巴細(xì)胞亞群 三、三、T淋巴細(xì)胞功能淋巴細(xì)胞功能 T細(xì)胞在胸腺中的陽性選擇和陰性選擇 三、三、T細(xì)胞亞群細(xì)胞亞群 1）根據(jù)）根據(jù)TCR種類種類 T、T細(xì)胞細(xì)胞 在末梢血主要為在末梢血主要為T細(xì)胞可占細(xì)胞可占95%，而，而T細(xì)胞細(xì)胞 只占只占1%10%。T細(xì)胞為主要參予免