MOLECULAR IMMUNOPATHOGENESIS OF DEMYELINATING DISEASE

该计划项目的中心目标是分析关键的 细胞和可溶性成分与原位中枢神经系统的关系 (中枢神经系统)免疫反应。特别强调了两个单元格 类型，B细胞和星形胶质细胞，以及它们所具有的免疫功能 可能在炎症性中枢神经系统脱髓鞘中发挥作用。关于第一号项目 星形胶质细胞产生细胞因子，特别是免疫调节 细胞因子白介素6(IL-6)。研究的重点将是调查 星形胶质细胞IL-6基因的细胞分子机制 表达，并鉴定信号通路，顺式作用DNA 参与IL-6诱导的因素和星形胶质细胞核因子。项目 2号还在检查一种免疫反应的介体，这种免疫反应由 星形胶质细胞，这是补充蛋白。第2号项目将定义 产生的补体蛋白的结构和功能特征 并对补体基因的分子方面进行了分析 细胞因子干扰素-伽马(LFN-伽马)的表达。 项目3将确定抗独特型(抗id)在 改变对髓鞘碱性蛋白(MBP)的体液和细胞免疫。两者都有 抗id对T、B细胞的体外作用及体内效应 改变小鼠实验性变态反应性脑脊髓炎(EAE) 检查过了。此外，与多发性硬化症(MS)的可能关系 将会被研究。4号项目将确定分子特征 携带LD的单抗、T细胞受体和单抗 抗LDS，它们对此做出反应。重点将放在LD-反LD上 涉及MBP多肽的反应。我们的目标是确定 分子识别理论可以提供一个结构上的解释 Jerne提出的免疫网络的反应。 统一的主题是研究细胞(T细胞、B细胞、星形胶质细胞)和 涉及的可溶性(细胞因子、补体蛋白、抗体)因子 中枢神经系统原位免疫反应及其终极关系 炎症性中枢神经系统脱髓鞘疾病的成分，如MS和EAE。

The central goal of this program project is the analysis of crucial cellular and soluble elements involved with in situ central nervous system (CNS) immune responses. Specific emphasis has been placed on two cell types, the B-cell and the astrocyte, and the immune functions which they may play in inflammatory CNS demyelination. Project No. 1 is concerned with cytokine production by astrocytes, particularly the immunomodulatory cytokine interleukin-6 (lL-6). Studies will focus on the investigation of the cellular and molecular mechanisms involved in astrocyte lL-6 gene expression, and characterize the signaling pathways, cis-acting DNA elements and astrocyte nuclear factors involved in lL-6 induction. Project No. 2 is also examining a mediator of immune responses produced by astrocytes, this being complement proteins. Project No. 2 will define the structural and functional characteristics of complement proteins produced by astrocytes, and analyze the molecular aspects of complement gene expression in response to the cytokine, interferon-gamma (lFN-gamma). Project No. 3 will determine the effects of anti-idiotype (anti-id) in altering humoral and cellular immunity to myelin basic protein (MBP). Both in vitro effects of anti-id on T and B-cells, and in vivo effects in altering murine experimental allergic encephalomyelitis (EAE) will be examined. In addition, possible relationships with multiple sclerosis (MS) will be studied. Project No. 4 will determine the molecular features of ld-bearing monoclonal antibody (MAb), the T-cell receptor (TCR) and MAb anti-lds with which they react. The emphasis will be on ld-anti-ld reactions involving MBP peptides. The objective is to determine is the molecular recognition theory can provide a structural explanation for the reactions of the immune network proposed by Jerne. The unifying theme is to study cellular (T-cells, B-cells, astrocytes) and soluble (cytokines, complement proteins, antibodies) factors involved with in situ CNS immune responses, and the ultimate relationship of these components to inflammatory CNS demyelinating diseases such as MS and EAE.