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1、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-APC Interaction,T细胞与APC的附着,TCR扫
2、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细胞的调节,再次免疫应答,CD4+,CD8+,CD4+25+
3、,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 Zinkernagle Peter Doherty Nobel Prize 1996,Ag Specificity,9-7 Adhesion molecules and Immigration o
4、f lymphocytes,淋 巴 细 胞 循 环 途 径,9-8 Immunological memory,Memory T Cells: Resting state Long 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（CTLA4）,调节性 T 细胞,转导负性
5、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 eliminated of CD25+ c
6、ells,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 mice Produced in thymus as an unique lineage of CD4 T cells Secret IL-10 and/or TGF-b, but little I
7、L-2 Anergic and suppressive,CD45RBlow, CTLA-4 high,Maintain immunological tolerance Inhibit 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 exogenous IL-2
8、, by using anti-CD28 mAb,Function of CD4+CD25+ T cells,Anti-idiotypic network Surface 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,