MECHANISMS OF CELLULAR IMMUNE REACTIONS IN THE CNS

中枢神经系统细胞免疫反应的机制

• 批准号: 2266089
• 负责人: RAYMOND A SOBEL
• 金额: $ 19万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2266089
• 关键词: T cell receptor; antigen presentation; cellular immunity; central nervous system; experimental allergic encephalomyelitis; fibronectins; histopathology; human tissue; immunocytochemistry; immunoelectron microscopy; inflammation; integrins; laboratory mouse; laboratory rat; laminin; monoclonal antibody; multiple sclerosis; myelin proteolipid; myelinopathy; neuroimmunomodulation; receptor expression; stress proteins; vitronectin

The long range goal of this project is to understand mechanisms of cellular immune reactions in the central nervous system (CNS). The overall hypothesis is that surface expression of specific molecules on inflammatory and CNS resident cells play critical roles in immune- mediated injury. CNS tissue samples from animals with experimental allergic encephalomyelitis (EAE), a model of multiple sclerosis (MS), and from patients with CNS diseases are studied using routine histology and immunohistochemistry at the light microscopic and ultrastructural levels to visualize directly the locations of cell surface molecules that are effectors and targets in CNS immune reactions. The studies to be performed in the proposed grant period will determine: 1. (A) The regions of myelin proteolipid protein (PLP) that are localized on the external surface (intermediate dense line) and those epitopes that are localized on the cytoplasmic face (major dense line) in compact CNS myelin and (B) whether antibodies with specificities to epitopes on the external surface induce more demyelination than antibodies to epitopes on the cytoplasmic face in vivo in an acute EAE model. 2. Whether cell-surface integrin receptors of vitronectin and laminin are expressed on inflammatory cells in lesions of EAE and MS and whether this expression and colocalization with vitronectin and laminin correlate with the degree of inflammation and demyelination. 3. Whether the temporal dynamics, extent of infiltration of T cell receptor V tau delta+ cells and their target heat shock proteins correlate with clinical manifestations and type and degree of histologic injury in a mouse model of chronic EAE. This research addresses both the normal molecular structure of CNS myelin and mechanisms of demyelination in MS and other demyelinating diseases. Because integrins are both used by neoplastic cells for tissue invasion and by microorganisms as receptors, the results will also have implications for the pathogenesis of CNS metastatic tumors and infections.

本项目的长期目标是了解 中枢神经系统（CNS）的细胞免疫反应。 的 总的假设是，表面表达的特定分子， 炎症和CNS驻留细胞在免疫中起关键作用， 介导的损伤。 来自具有实验性的动物的CNS组织样品 过敏性脑脊髓炎（EAE），多发性硬化（MS）模型，和 使用常规组织学研究CNS疾病患者的组织学， 免疫组化在光镜和超微结构水平 直接观察细胞表面分子的位置， CNS免疫反应中的效应子和靶点。 这些研究将 在拟议的赠款期间进行的将决定： 1. (A)髓鞘蛋白脂质蛋白（PLP）的区域， 位于外表面（中间密集线）和那些 定位于细胞质表面的表位（主致密线） （B）抗体是否对 外表面上的表位诱导的脱髓鞘比 急性EAE细胞质表面抗原决定簇的抗体 模型 2. 玻连蛋白和层粘连蛋白的细胞表面整合素受体 在EAE和MS病变的炎性细胞上表达， 这种表达和与玻连蛋白和层粘连蛋白的共定位与 与炎症和脱髓鞘的程度有关 3. T细胞浸润的时间动态、程度 受体V tau δ +细胞及其靶向热休克蛋白 与临床表现、组织学类型和程度相关 慢性EAE小鼠模型中的损伤。 这项研究涉及中枢神经系统髓鞘的正常分子结构， 以及MS和其他脱髓鞘疾病的脱髓鞘机制。 因为整联蛋白都被肿瘤细胞用于组织侵袭 和微生物作为受体，结果也会有 中枢神经系统转移性肿瘤发病机制的影响， 感染.