肿瘤与免疫-抗肿瘤机制

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。
抗原的识别和T细胞活化、增殖
膜表面分子 相互作用
信号转导
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 sites to which the protein kinase ZAP-70 attaches and becomes activated by phosphorylation. A series of ZAP-70-catalyzed protein phosphorylations enable the generation of a variety of signals.
T细胞经三个发育阶段及胸腺选择后成为成熟T细胞，迁出胸腺进 入外周T细胞库。
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 naïve and effector T cells. (a) Naïve 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.
细胞免疫抗肿瘤作用
一、T细胞 二、NK细胞 三、NKT细胞 四、巨噬细胞(M)
T细胞在抗肿瘤的特异性 免疫中是主要效应细胞。
一、T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
T细胞在胸腺中分化、成熟
Most of the immature thymocytes in the thymus die either because they make an unproductive TCRgene 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 CD4wk.baidu.comblue) 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.
阴性选择（negative selection）
经历阳性选择的SP细胞在胸腺的皮髓质交界处及髓质区还须经历 阴性选择：凡是能识别自身抗原-MHC复合物、且具有高亲和力的 SP细胞发生凋亡遭克隆清除，其实质是清除自身反应性T细胞，即阴 性选择。生物学意义：赋予成熟的T细胞具有自身免疫耐受（中枢） 的特性。
抗肿瘤免疫机制
Mechanism of Immune Response to Tumor
细胞免疫抗肿瘤作用 体液免疫抗肿瘤作用 细胞因子抗肿瘤的作用
Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. NATURE REVIEWS | CANCER VOLUME 14 | FEBRUARY 2014
Positive and negative selection of thymocytes in the thymus
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.