CELL BIOLOGY OF IMMUNE INTERACTIONS

这项研究计划的长期目标是获得新的见解。 详细的分子和细胞事件，这些事件由 识别外来抗原，并产生适当的免疫 回应。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Beta的激活和分化 通过T辅助(Th)细胞，以及胸腺中T细胞的选择。 这些研究将主要在单细胞水平上进行，使用 双重和三重免疫荧光显微镜。这种细胞生物学 技术已经证明了在体外形成特定的稳定 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 免疫系统的细胞可以通过哪些机制来防御 入侵的微生物、病毒感染和一些恶性肿瘤。这个 拟议研究的具体目标是：1.研究细胞内和 克隆的Th(Th1， Th2)具有静止的Beta细胞的细胞，其将是Ag/MHC特异性的， 非特定或旁观者(在特定的情况下为非特定的)Beta 细胞。2.研究淋巴因子在时间和空间上的诱导作用。 IL_2、IL_4)特异性和混合型(旁观者)T：B结合物分泌。3. 大鼠静息状态下β细胞的活化与分化研究 T；Beta共轭，包括其中几个Beta 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机制 重排，以前在特定的T：β和 CTL：TC结合物。5.研究定义的信令机制 成群的未成熟T细胞。

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.