Th1andTh2分析.ppt

小鼠Th1/Th2体外分化培养体系 Immunological Reviews 2013 Vol. 252: 12–23 * * 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. * Activation of naive T cells by the recognition of a peptide: MHC complex accompanied by co-stimulation induces expression and secretion of IL-2 and the expression of high-affinity IL-2 receptors. IL-2 binds to the high-affinity IL-2 receptors to promote T-cell growth in an autocrine fashion.The T cells are driven expansion and differentiation to memory and effector T cells. * * 影响Th1和Th2分化的因素： 1. 抗原: 寄生虫引起Th1;可溶性抗原Th2; 2. APC：巨噬细胞诱导Th1，B细胞诱导Th2 3. 微环境中的CK * 病理条件下，如胞内病原体感染Th1占优势，主要介导细胞免疫抵抗感染； 而对蠕虫感染和环境变应原的应答中Th2占优势。 如AIDS病Th1占优势好转，Th2占优势病情恶化。变态反应Th2占优势。 * Figure 1. Summary of the 4 CD4 T helper cell fates: their functions, their unique products, their characteristic transcription factors, and cytokines critical for their fate determination. * Figure 1. Cytokines play critical roles in differentiation and effector functions of Th1, Th2, and Th17 cells. Upon TCR activation triggered by antigen-presenting cells, naive CD4 T cells differentiate into distinct Th lineages in the context of combinations of cytokines. The differentiation processes involve upregulation of master transcriptional regulators and activation of STAT proteins (185). Each lineage expresses unique cytokine receptors, which can respond to cytokines produced by accessory cells. At later stages of Th cell differentiation, different Th cells preferentially express an IL-1 family receptor. Together with a STAT activator, an IL-1 family cytokine is capable of inducing effector cytokine production from Th cells in a TCR-independent manner (46–49). * Figu