3-肿瘤与免疫-抗肿瘤机制.pptxVIP

抗肿瘤免疫机制Mechanism of Immune Response to Tumor;Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. NATURE REVIEWS | CANCER VOLUME 14 | FEBRUARY 2014 ;细胞免疫抗肿瘤作用;;T细胞在抗肿瘤的特异性免疫中是主要效应细胞。;1. T细胞的分化、成熟和活化 2. T细胞抗肿瘤的效应机制;T细胞的分化、成熟和活化 T细胞在胸腺中分化、成熟 T细胞抗原受体和相关分子 抗原的识别和T细胞活化、增殖;Most of the immature thymocytes in the thymus die either because they make an unproductive TCR-gene rearrangement or because they fail positive or negative selection. Three mature T-cell populations(green, pink, blue) are produced and move to the peripheral lymphoid organs. Most T cells express the ??TCR and either CD4(blue) or CD8 (pink). A few T cells express the ?? TCR (green); most of these lack both CD4 and CD8. Note that the boundary between the early and the late phase of T-cell development is not sharp.;; Positive and negative selection of thymocytes in the thymus. Thymic selection involves thymic stromal cells (epithelial cells, dendritic cells, and macrophages), and results in mature T cells that are both self-MHC restricted and self-tolerant.;阳性选择（positive selection） 在胸腺皮质中，CD4+CD8+双阳性T细胞，其TCR能与胸腺基质细胞表面的MHCⅠ/Ⅱ类分子-抗原肽结合，且具适当（低）亲和力的DP细胞分化为单阳性（SP）T细胞，其中与Ⅰ类分子结合的DP细胞分化为CD8+T细胞（SP）；与Ⅱ类分子结合的DP细胞分化为CD4+T细胞（SP）；而不能与MHC-抗原肽结合或高亲和力的DP细胞则发生凋亡遭克隆清除。此过程也称为胸腺的阳性选择。生物学意义：赋予成熟的T细胞具有MHC限制性。;T细胞抗原受体和相关分子;;;; Homing of lymphocytes Examples of homing receptors and vascular addressins involved in selective trafficking of na?ve and effector T cells. (a) Na?ve T cell tend to home to secondary lymphoid tissue through their HEV regions. (b,c) Various subsets of effector T cells express high levels of particular homing receptors that allow them to home to endothelium in particular tertiary extralymphoid tissues.;;; Overview of TCR-mediated signaling. TCR engagement by peptide-MHC complexes initiates the assembly of a signaling complex. An early step is the Lck-mediated phosphorylation of ITAMs on the zeta chains of the TCR complex, creating docking