MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们已经质疑了长期以来关于生理学的教条， 淋巴结的T细胞依赖区的结构，并进化了很多 通过结合免疫组织学、体内示踪剂 研究和细胞培养。首先，在T细胞依赖区， 在一系列高度有序的走廊中迁徙这些的拓扑结构 走廊被优化用于有效的细胞接触：a）狭窄的水通道， 衬有B）富含细胞外基质的基质细胞的通道 用于为细胞迁移提供牵引，和c）通过抗原呈递 指状突树突状细胞（IDC）专门用于呈递 抗原的第二，有一个有效的网状内皮细胞屏障 其将该隔室与淋巴/鼻窦隔离。三是 可溶性示踪剂从淋巴进入T细胞依赖性区域 通过运输沿着一个前所未有的管道系统发生， 形成迷路壁的基质细胞四是 基质细胞似乎通过以下方式调节淋巴结的环境： 产生它们自己的可溶性因子，如TGF β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 夸大（如关节炎和糖尿病。 我们正在研究形态学和生物化学过程， 淋巴细胞粘附并迁移。T淋巴细胞的调节变化 细胞骨架对T细胞迁移和识别至关重要， LN和其他地方。我们正在研究形态学和生物化学 这些过程中的变化。我们发现， 细胞内钙调节细胞骨架和形态， 在这些过程中的多个步骤，包括： 微绒毛，我们认为这在监控过程中至关重要 在LN通道中; B）通过T细胞的信号传导有效的相互作用 受体;和c）诱导急性肌动蛋白聚合。而且我们 正在研究一种高度特异性的复杂分子 在T细胞与CD 3-包被的 珠子，作为一个简化的模型，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.