MOLECULAR IMMUNOPATHOGENESIS OF DEMYELINATING DISEASE

脱髓鞘疾病的分子免疫发病机制

• 批准号: 3100371
• 负责人: JOHN N WHITAKER
• 金额: $ 72.67万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3100371
• 关键词: immunopathology; myelinopathy

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.

该计划项目的核心目标是对关键的分析 与原位中枢神经系统有关的细胞和可溶性元素 （CNS）免疫反应。 具体重点已放在两个单元格上 类型，B细胞和星形胶质细胞以及它们的免疫功能 可能会发挥炎症性中枢神经系统脱髓鞘。 第1号项目 由星形胶质细胞产生细胞因子，尤其是免疫调节 细胞因子白介素6（LL-6）。研究将重点放在调查上 与星形胶质细胞LL-6基因有关的细胞和分子机制 表达并表征信号通路，顺式作用DNA LL-6诱导涉及的元素和星形胶质细胞核因子。 项目 2号还在检查由由免疫反应的介体产生的 星形胶质细胞，这是补体蛋白质。 项目2将定义 产生的补体蛋白的结构和功能特征 通过星形胶质细胞，分析补体基因的分子方面 响应细胞因子，干扰素 - γ（LFN-gamma）的表达。 项目3号将确定抗IDiotype（抗ID）在 改变对髓磷脂碱性蛋白（MBP）的体液和细胞免疫。 两个都 抗ID对T和B细胞的体外作用，以及体内影响 改变鼠实验性过敏性脑脊髓炎（EAE）将是 检查。 另外，可能与多发性硬化症（MS）的关系 将被研究。 项目4将确定分子特征 带有LD的单克隆抗体（MAB），T细胞受体（TCR）和MAB 他们反应的抗LDS。 重点将放在LD-Anti-LD上 涉及MBP肽的反应。 目的是确定 分子识别理论可以为 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 可溶性（细胞因子，补体蛋白，抗体）因子 原位中枢神经系统免疫反应以及这些反应的最终关系 炎症性中枢神经系统脱髓鞘疾病（例如MS和EAE）的成分。