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1、获得性细胞免疫应答,9 Acquired Cellular Response,Peripheral lymphoid organs and immune recognition(外周淋巴器官与免疫识别),启动阶段 Ag processing and presentation T cell stimulation-activation增殖 T cell activation and proliferation效应阶段Effector T cells调节复原Immunoregulation,9-1 获得性免疫应答的基本过程,9-2 DC启动获得 性免疫应答,9-3 T 细胞的活化,9-3-1 T-
2、APC Interaction,T细胞与APC的附着,TCR扫描APC表面,9-3-2 ecognition of MHC/peptide complex by TCR,TCR抗原结合部位,抗原的特异性识别,TCR 识别 MHC/抗原肽 的分子解剖,MHC-a 螺旋,抗原肽,CDR1,CDR2,CDR3,CDR3,CDR2,CDR1,TCR-b 链,TCR-a 链,MHC-a 螺旋,9-3-3 T细胞活化的“双信号模型”,T细胞活化过程中的信号转导,9-4 抗原特异性淋巴细胞的克隆扩增与选择,9-5 Effector T Cells(效应T细胞),辅助性T细胞：Th1与Th2,Tc细胞,效应T
3、细胞的调节,再次免疫应答,CD4+,CD8+,CD4+25+,2 hrs Wash x 3,1 hrs Wash x 3,51Cr,4 hrs 37,BCL,Measure Specific 51Cr-Release,+Virus,Experimental procedure for testing antigen-specific CTL activity,T cells,Harvest supernatant,9-6 效应T细胞的MHC限制性,Rolf ZinkernaglePeter DohertyNobel Prize 1996,Ag Specificity,9-7 Adhesion
4、molecules and Immigration of lymphocytes,淋 巴 细 胞 循 环 途 径,9-8 Immunological memory,Memory T Cells:Resting stateLong lived(continuously renewal)Easily triggered(do not need co-stimulatory molecules)Responsible for maintaining immunological memory,9-8 获得性免疫应答的调节,神经内分泌系统对免疫系统的调节作用,抗原对免疫应答的调节作用,活化诱导的细胞死亡
5、（CTLA4）,调节性 T 细胞,转导负性信号的免疫细胞膜分子,CD4+CD25+Regulatory T cells,A unique lineage of regulatory T cells capable of maintaining self tolerance in vivo,T,CD8,CD4,CD4+25+,Th1,Tc2,Tc1,Th2,Th3,Tr1,Peripheral T lymphocyte,5-10%,30%,Th4?,60%,Thymus,CD4,Effectors,Regulators,Normal mouse,CD4+T-cell suspensions el
6、iminated of CD25+cells,T cell-deficient mouse,Autoimmune diseases thyroid stomach salivary gland Langerhans islets adrenal glands ovaries testes,CD4+CD25+Tr cells:Comprise 5-10%of peripheral CD4 T cells in human and miceProduced in thymus as an unique lineage of CD4 T cellsSecret IL-10 and/or TGF-b,
7、but little IL-2Anergic and suppressive,CD45RBlow,CTLA-4 high,Maintain immunological toleranceInhibit proliferation of CD4+CD25-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 exogenou
8、s IL-2,by using anti-CD28 mAb,Function of CD4+CD25+T cells,Anti-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 cells are the main targets of immunoregulation,Regulatory T cells Anti-idiotypic T cells Th1,Th2,Th3,Tr1 CD4+25+T cells CD8+gd-T-cells CD4CD8 Double negative Tr cells NKT cells Anergic T cells,
