《医学免疫学教学讲义》cellularimmunity.ppt

专业词汇 Immune response,Ir T cell mediated cellular immune response Recognition phase Activation phase Effector phase T cell synapse or immunological synapse Antigen recognition signal Costimulatory signal 下一讲 体液免疫应答 B细胞对TD-Ag的应答过程 B细胞对TI-Ag的应答过程 1.讲解目的是认识共受体和协同刺激分子在T细胞活化中的作用; 2.共受体: TCR识别MHCII类分子提呈的抗原同时,发生受体交联?CD4分子与MHCII类分子结合,引起CD4分子在空间上与TCR靠近?CD4分子胞内段连接的酪氨酸磷酸激酶Lck可使CD3分子链上酪氨酸磷酸化?导致ZAP70与fyn在膜受体附近募集,并被Lck激活?他们进而活化PLC ? 通过DAG和IP3途径分别活化转录因子NF-kB与NF-AT ? 他们转入细胞核内,作用于相关基因序列?相关基因的转录和合成. 3.协同刺激分子:B7与CD28的结合可激活PI-3K ?该信号与第一信号的信号分子(ZAP70,fyn)一起激活Ras-MAPK途径?fos/jun基因表达?二者形成二聚体,即转录因子AP-1 ?AP-1与NF-AT相互作用?IL-2基因的转录.因此,缺乏协同刺激信号,IL-2的合成受阻?T细胞无能. The binding of CD28 on T cell to B7 on APC cell delivers a co-stimulatory signal (left panel), thereby driving the activation and division of T cells that encounter specific antigen presented by an antigen-presenting cell. Once T cells are fully activated, then they express increased levels of CTLA-4. CTLA-4 has a higher affinity for B7 molecules than CD28 and thus binds most or all of the B7 molecules, effectively shutting down the proliferative phase of the response by inhibition of T cell growth factor IL-2 production and T cells no longer receive an activation signal. A naive T cell recognizes antigen on the surface of APC and receives the required two signals. It becomes activated, secretes IL-2 and responds to IL-2. IL-2 driven clonal expansion is followed by the differentiation of the T cells to armed effector cells. Once the cells have differentiated into effector T cells, any encounter with specific antigen triggers their effector actions without the need for co-stimulation. As shown here, the cytotoxic T cell can kill targets that express only the peptide/MHC complex without co-stimulatory signals. Tc胞浆中颗粒物质荧光着色。 CD4+T的活化 CD4+T细胞的活化 抗原识别信号（第一信号） 协同刺激信号（第二信号） 细胞因子信号（第三信号） T细胞活化信号转导 2、CD4+T cell proliferation and differentiation IL-2+IL-2R 活化的CD4+T细胞 表达多种细胞因子及受体 T细胞克隆增殖 分化为Th0 分化成Th1