獲得性細(xì)胞免疫應(yīng)答

1、獲得性細(xì)胞免疫應(yīng)答,9 Acquired Cellular Response,Peripheral lymphoid organs and immune recognition(外周淋巴器官與免疫識(shí)別),,啟動(dòng)階段 Ag processing and presentation T cell stimulation --- activation增殖 T cell activatio

2、n and proliferation效應(yīng)階段Effector T cells調(diào)節(jié)復(fù)原Immunoregulation,9-1 獲得性免疫應(yīng)答的基本過程,9-2 DC啟動(dòng)獲得 性免疫應(yīng)答,9-3 T 細(xì)胞的活化,9-3-1 T-APC Interaction,T細(xì)胞與APC的附著,TCR掃描APC表面,,,9-3-2 ecognition of MHC/peptide complex by TCR,TCR

3、抗原結(jié)合部位,抗原的特異性識(shí)別,,TCR 識(shí)別 MHC/抗原肽 的分子解剖,,MHC-a 螺旋,抗原肽,CDR1,CDR2,CDR3,CDR3,CDR2,CDR1,TCR-b 鏈,,,,,,,,,,,,,,,,,,,TCR-a 鏈,MHC-a 螺旋,,,,,,,9-3-3 T細(xì)胞活化的“雙信號(hào)模型”,T細(xì)胞活化過程中的信號(hào)轉(zhuǎn)導(dǎo),9-4 抗原特異性淋巴細(xì)胞的克隆擴(kuò)增與選擇,9-5 Effector T Cells (效應(yīng)T細(xì)胞),輔助

4、性T細(xì)胞：Th1與Th2,Tc細(xì)胞,效應(yīng)T細(xì)胞的調(diào)節(jié),再次免疫應(yīng)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

5、antigen-specific CTL activity,T cells,,,,Harvest supernatant,9-6 效應(yīng)T細(xì)胞的MHC限制性,Rolf ZinkernaglePeter DohertyNobel Prize 1996,Ag Specificity,9-7 Adhesion molecules and Immigration of lymphocytes,淋 巴 細(xì) 胞 循 環(huán) 途 徑,9-8

6、 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 獲得性免疫應(yīng)答的調(diào)節(jié),神經(jīng)內(nèi)分泌系統(tǒng)

7、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,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,Th

8、3,Tr1,,,,,,,,,Peripheral T lymphocyte,,,5-10%,30%,Th4?,,,,60%,Thymus,,CD4,,,,,Effectors,Regulators,,,Normal mouse,,CD4+T-cell suspensions eliminated of CD25+ cells,,T cell-deficient mouse,Autoimmune diseases

9、 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

10、CD4 T cellsSecret IL-10 and/or TGF-b, 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 cel

11、l-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 cells,Anti-idiotypic networkSurface mo

12、lecules 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 c