MOLECULAR IMMUNOPATHOGENESIS OF DEMYELINATING DISEASE

脱髓鞘疾病的分子免疫发病机制

• 批准号: 2267846
• 负责人: JOHN N WHITAKER
• 金额: $ 79.32万
• 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/2267846
• 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.

该项目的核心目标是分析关键的 参与原位中枢神经系统的细胞和可溶性成分 (CNS)免疫反应。 特别强调了两个细胞 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CNS脱髓鞘中起作用。 1号项目关注 与星形胶质细胞产生细胞因子有关，特别是免疫调节 细胞因子白细胞介素-6（IL-6）。研究将侧重于调查 星形胶质细胞IL-6基因表达的细胞分子机制 表达，并表征信号通路，顺式作用DNA 元件和星形胶质细胞核因子参与IL-6诱导。 项目 号2也在研究由免疫系统产生的免疫反应的介质， 星形胶质细胞，这是补体蛋白。 项目2将定义 产生的补体蛋白的结构和功能特征 并分析补体基因的分子方面 在一些实施方案中，细胞因子IFN-γ（IFN-γ）的表达是响应于细胞因子IFN-γ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 抗id抗体对T和B细胞的体外作用，以及 改变小鼠实验性变态反应性脑脊髓炎（EAE）将是 考察 此外，与多发性硬化症（MS）的可能关系 将被研究。 4号项目将确定 携带Id的单克隆抗体（MAb）、T细胞受体（TCR）和MAb 抗爱滋病毒抗体 重点将放在LD-抗LD上 涉及MBP肽的反应。 目标是确定 分子识别理论可以提供一个结构解释， Jerne提出的免疫网络。 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）因子参与 原位CNS免疫反应，以及这些免疫反应之间的最终关系。 这些成分对炎性CNS脱髓鞘疾病如MS和EAE的作用。