MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们对长期存在的关于生理学和 T细胞依赖区域的淋巴结构型，并进化了很多 结合免疫组织学、体内示踪剂更丰富的认识 研究和细胞培养。首先，在T细胞依赖区，T细胞 在一组高度有序的走廊中迁徙。它们的拓扑结构 走廊针对高效电池接触进行了优化：a)狭窄的水溶液 由富含细胞外基质的基质细胞排列的通道适合 用于为细胞迁移提供牵引力，以及c)通过抗原提呈 交叉性树突状细胞(IDC) 抗原。第二，存在有效的网状内皮细胞屏障。 将这个隔室与淋巴/鼻窦隔开。第三， 可溶性示踪剂从淋巴向T细胞依赖区的移动 通过沿史无前例的管道系统运输而发生，该管道系统由 构成迷宫内壁的基质细胞。第四， 基质细胞似乎通过以下方式调节淋巴结的环境 产生自己的可溶性因子，如TGFb，和趋化因子，如 IL-8和MCP-1。了解这些特征对于治疗 免疫反应不足的疾病(如癌症)或 夸张(如关节炎和糖尿病。 我们正在研究形态和生化过程， 淋巴细胞黏附和迁移。T淋巴细胞的调节性变化 细胞骨架对T细胞的迁移和识别是必不可少的，在 无论是在国内还是其他地方。我们正在研究形态和生化 这些过程中涉及的变化。我们发现，这些变化 细胞内钙离子调节细胞骨架和细胞形态 这些进程中的多个步骤，包括：a)诱导 微绒毛，我们认为它在监测过程中至关重要 在LN走廊中；b)T细胞的信号有效相互作用 受体；以及c)诱导急性肌动蛋白聚合。此外，我们 正在研究一种高度特异的复杂分子的组装 CD3包被的T细胞黏附/相互作用部位的复合体 珠子，作为一种简化的模型，在其中详细了解什么 当T细胞遇到抗原阳性细胞时就会发生。

We have questioned longstanding dogmas regarding the physiology and architecture of T-cell dependent area of lymph nodes, and evolved a much richer understanding by a combination of immunohistology, in vivo tracer studies, and cell culture. First, in the T-cell-dependent area T cells migrate in a highly organized set of corridors. The topology of those corridors is optimized for efficient cell contact: a) narrow aqueous channels lined b) by stromal cells rich in extracellular matrix suitable for providing traction for cell migration and c) by antigen-presenting interdigitating dendritic cells (IDC) specialized for presenting antigen. Second, there is an effective reticulo-endothelial cell barrier which isolates this compartment from the lymph/sinuses. Third, the movement of soluble tracers from lymph into the T cell dependent areas occurs by transport along an unprecedented conduit system ensheathed by the very stromal cells that form the walls of the labyrinth. Fourth, the stromal cells appear to condition the environment of the lymph node by producing their own soluble factors such as TGFb, and chemokines such as IL-8 and MCP-1. Understanding these features is important to treating diseases where immune responses are deficient (such as cancers) or exaggerated (such as arthritis and diabetes. We are investigating the morphological and biochemical processes whereby lymphocytes adhere and migrate. Regulated changes in T lymphocyte cytoskeleton are essential to T cell migration and recognition, both in LN and elsewhere. We are investigating morphological and biochemical changes involved in these processes. We find that changes in intracellular calcium regulate both cytoskeleton and morphology at multiple steps in these processes, including: a) induction of microvilli, which we believe are critical in the process of surveillance in the LN corridors; b) signaling effective interaction by the T cell receptor; and c) inducing acute actin polymerization. Furthermore, we are investigating the assembly of a highly specific complex molecular complex at the site of adhesion/interaction of T cells with CD3-coated beads, as a simplified model in which to understand in detail what happens when T cells encounter antigen-positive cells.