9免疫细胞

DepartmentofImmunology,MedicalCollegeofNanchangUniversity第九章免疫细胞Chapter9immunocytes/immunecells第一节造血干细胞第二节淋巴细胞第三节抗原提呈细胞第四节固有免疫细胞DepartmentofImmunology,MedicalCollegeofNanchangUniversity第一节造血干细胞Part1hematopoieticstemcells(HSC)HSC的概述自我更新（self-renewing）能力多向分化（multilineagedifferentiation）潜能主要表面分子：CD34和CD117(c-kit)并表现为谱系阴性（Lin-）DepartmentofImmunology,MedicalCollegeofNanchangUniversityDepartmentofImmunology,MedicalCollegeofNanchangUniversityPart1hematopoieticstemcells(HSC)图示：HSC的分化途径DepartmentofImmunology,MedicalCollegeofNanchangUniversity第九章免疫细胞Chapter9immunocytes/immunecells第一节造血干细胞第二节淋巴细胞第三节抗原提呈细胞第四节固有免疫细胞DepartmentofImmunology,MedicalCollegeofNanchangUniversity第二节淋巴细胞Part2lymphocyte淋巴细胞的概述免疫系统的主要细胞分类：T细胞、B细胞和NK细胞DepartmentofImmunology,MedicalCollegeofNanchangUniversity淋巴细胞(lymphocytes)未活化淋巴细胞直径6~7微米，浆/核比例很小（左，普通光镜）。透射电镜显示未活化淋巴细胞胞核致密，胞浆中细胞器很少（右）。DepartmentofImmunology,MedicalCollegeofNanchangUniversityLymphocytesDepartmentofImmunology,MedicalCollegeofNanchangUniversityTLymphocyte来源于骨髓，在胸腺中发育成熟成熟T细胞位于外周淋巴组织的T细胞区外周血中占总淋巴细胞的60-80%表面有多种分化抗原参与细胞免疫BLymphocyte在骨髓中发育成熟成熟B细胞位于外周淋巴组织的B细胞区外周血中占总淋巴细胞的10-15%表面有多种分化抗原参与体液免疫DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞的概述胸腺依赖性淋巴细胞（thymus-dependentlymphocyte）外周血中占淋巴细胞总数的60%-80%DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocytesDepartmentofImmunology,MedicalCollegeofNanchangUniversityT淋巴细胞的分化发育一、T细胞在胸腺中的发育1.T细胞在胸腺中的分化阶段2.T细胞在胸腺内的阴性选择和阳性选择二、T细胞在外周免疫器官中的发育初始T细胞效应T细胞记忆性T细胞AgDepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyte图示：T细胞的分化发育DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞的分化发育过程DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞发育的阳性选择（positiveselection，PS）双阳性细胞单阳性细胞（CD4+/CD8+SP细胞）具有识别、结合MHC分子的能力及MHCⅡ/Ⅰ类分子限制性DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞发育的阴性选择（negativeselection，NS）能识别并结合自身抗原的SP细胞被清除获得中枢自身免疫耐受Aire驱使组织限制性抗原在胸腺上皮细胞表达DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyte阴性选择CD4+CD8+成熟的CD4+/CD8+T细胞巨噬细胞树突状细胞双阳细胞TCRCD4CD8CD3MHCI/IITCR与MHC分子结合TCR不与MHC分子结合上皮细胞高亲和力受体与自身MHC分子或自身MHC分子+抗原肽相结合凋亡凋亡阳性选择DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞的分化发育过程DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞的表面分子鉴定、分离T细胞的重要依据识别和结合抗原、与其它细胞相互作用的物质基础功能分类：1.TCR复合物2.T细胞共受体3.T细胞协同刺激分子4.T细胞丝裂原结合分子及其它表面分子DepartmentofImmunology,MedicalCollegeofNanchangUniversityDepartmentofImmunology,MedicalCollegeofNanchangUniversityTwoSignalofTCellActivation：T细胞APCTCR抗原肽-MHC分子复合物产生Signal①CD3转导Signal①CD4MHCⅡ类分子/增强Signal①CD8分子MHCI类分子CD28B7CD2LFA-3产生Signal②LFA-1ICAM-1DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞抗原受体（Tcellantigenreceptor，TCR）T细胞特征性表面标志及特异性识别抗原的受体功能：特异性识别抗原，产生抗原识别信号分类：1.TCRαβ：占90%-95%2.TCRγδ：占5%-10%TCRDepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteTCR结构示意图DepartmentofImmunology,MedicalCollegeofNanchangUniversityα链β链TCRAntigensRecognizedbyTCRDepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteCD3分子六聚体，形成TCR复合物特点：1.胞浆区较长2.含免疫受体酪氨酸活化基序（immunoreceptortyrosine-basedactivationmotif，ITAM）功能：转导抗原识别信号DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞共受体（Tcellco-receptor）CD4+T细胞：CD4与MHCⅡ类分子结合CD8+T细胞：CD8与MHCⅠ类分子结合功能：辅助TCR识别抗原DepartmentofImmunology,MedicalCollegeofNanchangUniversityDepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteCD8/CD4辅助TCR识别抗原肽-MHC分子复合物示意图TCRMHCII抗原肽TCR抗原提呈细胞CD8CD4抗原肽MHCICD8+T细胞CD4+T细胞抗原提呈细胞DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞协同刺激分子（Tcellco-stimulator）CD28：配体B7（CD80/CD86）CD2/E受体：配体CD58（LFA-3）LFA-1：配体ICAM-1功能：产生T细胞活化的第二信号即协同刺激信号DepartmentofImmunology,MedicalCollegeofNanchangUniversityCD28分子：T细胞活化中非常重要的一种共刺激分子配体：B7(B7-1、B7-2）静止和活化的T细胞上均表达通过ITAM结构传递活化信号CTLA-4:与CD28分子高度同源，参与T细胞的自身调节配体：B7(B7-1、B7-2）但与B7亲和力高于CD28只表达于活化T细胞表面通过ITIM结构传递抑制信号自限作用Co-stimulatorymoleculesDepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteB7DepartmentofImmunology,MedicalCollegeofNanchangUniversityCD40L：•主要表达于活化的CD4+T细胞表面•配体：CD40•促进抗原提呈细胞活化促进T细胞的活化Co-stimulatorymoleculesDepartmentofImmunology,MedicalCollegeofNanchangUniversityCD2:又称LFA-2(lymphocytefunctionassociatedantigen2)/E受体•主要表达在成熟T细胞、胸腺细胞和NK细胞表面•配体：LFA-3（CD58）CD59CD48•SRBC受体：花环试验用于分离T细胞Co-stimulatorymoleculesDepartmentofImmunology,MedicalCollegeofNanchangUniversityDepartmentofImmunology,MedicalCollegeofNanchangUniversityDepartmentofImmunology,MedicalCollegeofNanchangUniversityLFA-1和ICAM-1Co-stimulatorymoleculesDepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyte与T细胞识别抗原、活化相关的主要表面分子示意图DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞其它表面分子T细胞丝裂原受体：与相应的丝裂原PHA/ConA/PWM结合，可检测T细胞增殖水平细胞因子受体：与不同的细胞因子结合，发挥不同作用DepartmentofImmunology,MedicalCollegeofNanchangUniversityTlymphocyteT细胞亚群及其功能活化阶段不同：初始/效应/记忆性T细胞TCR不同：αβT细胞和γδT细胞表面分子不同：CD4+T细胞和CD8+T细胞功能不同：辅助性/细胞毒性/调节性T细胞DepartmentofImmunology,MedicalCollegeofNanchangUniversityT细胞亚群---据所处活