CELL BIOLOGY OF IMMUNE INTERACTIONS

这项研究计划的长期目标是挖掘新的见解 详细的分子和细胞事件， 识别外来抗原并产生适当的免疫 应答特别是，这些研究将旨在了解 特定细胞的分子和细胞机制：细胞相互作用，以及 这种相互作用如何导致β的激活和分化 辅助性T细胞（Th）细胞，以及胸腺中的T细胞选择。 这些研究将主要在单细胞水平进行， 双重和三重免疫荧光显微镜。这种细胞生物学 技术已经证明在体外形成特异性稳定的 Th：β-细胞结合物，并已确定了几个重要的早期 由这种T：B相互作用触发的细胞内和膜事件。 这些研究的结果将增加我们对 免疫系统细胞的保护机制 入侵微生物、病毒感染和某些恶性肿瘤。的 本研究的具体目的是：1.为了研究细胞内和 由克隆的Th（Th 1， Th 2）细胞与静息β细胞，其将是Ag/MHC特异性的， 非特异性或旁观者（存在特异性时为非特异性）β 细胞2.为了研究淋巴因子（例如， IL 2、IL 4）分泌。3. 为了研究静息β细胞的活化和分化， T; β缀合物，包括其中几个β缀合物的复合缀合物， 细胞同时与一个T细胞结合。4.继续研究 触发细胞内和细胞膜的信号传导机制 重排，这是以前在特定的T：β和 CTL：TC缀合物。5.为了研究定义的信号机制， 未成熟T细胞群。

The long term objective of this research proposal is to gin new insights into the detailed molecular and cellular events which are triggered by recognition of foreign antigens and which generate the appropriate immune responses. In particular, the studies will be aimed at understanding the molecular and cellular mechanisms of specific cell:cell interactions, and how such interactions cause the activation and differentiation of Beta cells by T-helper (Th) cells, as well as T cell selection in the thymus. These studies will be conducted primarily at the single cell level using double and triple immunofluorescence microscopy. Such cell biological techniques already demonstrated the in vitro formation of specific stable Th:Beta-cell conjugates, and have identified several important early intracellular and membrane events triggered by such T:B interactions. The results of these studies will increase our knowledge of the mechanisms by which cells of the immune system can protect against invading microorganisms, viral infections, and some malignancies. The specific aims of the proposed research are: 1. To study intracellular and membrane rearrangements induced by the interactions of cloned Th (Th1, Th2) cells with resting Beta cells which will be either Ag/MHC specific, non-specific or bystander (non-specific in the presence of specific) Beta cells. 2. To study the spatial and temporal induction of lymphokine (e.g. IL2, IL4) secretion in specific and mixed (bystander) T:B conjugates. 3. To study the activation and differentiation of resting Beta cells in T;Beta conjugates, including complex conjugates in which several Beta cells are simultaneously bound to one T cell. 4. To continue to study the signalling mechanisms that trigger the intracellular and membrane rearrangements, which were identified before in specific T: Beta and CTL:TC conjugates. 5. To study the signalling mechanisms in defined populations of immature T cells.