IMMUNOPATHOLOGY OF THE CENTRAL NERVOUS SYSTEM

该项目的目标是描述中央 神经系统(CNS)免疫反应以发展特异性为目的 免疫调节策略。在接下来的一段时间里，我们将重点关注 实验性动物模型血管的免疫学改变 变态反应性脑脊髓炎(EAE)作为神经免疫学的原型 疾病。血管内皮生长因子基因产物Ia的内皮细胞表达 主要组织相容性基因座和血浆糖蛋白纤维连接蛋白 它沉积在炎症性病灶中，将在急性和 慢性EAE的免疫电子显微镜原位分析 角色。诱导内皮细胞Ia和纤维连接蛋白表达改变 由活化的T细胞及其可溶性产物淋巴因子 在皮肤和中枢神经系统进行检查，以确定细胞和分子基础 内皮细胞激活。将动物研究的结果联系起来 随着人类疾病的进程，内皮细胞的变化将是 在人类脱髓鞘和炎症条件下进行的研究 组织切片免疫过氧化物酶染色。 慢性EAE的精确原位和活体特征 髓鞘蛋白脂对豚鼠和兔的致敏作用 在组织切片和血流中使用单抗染色进行 外周血细胞计数以确定这种髓鞘的作用 对整个中枢神经系统组织的免疫反应中的组成部分。诱发EAE的原因是 豚鼠的整体组织致敏作用将在体内通过 用抗T细胞和抗Ia单抗治疗。 了解免疫学参数，特别是 内皮细胞改变和免疫调节机制，其中 可能与EAE的临床和组织学表达有关 适用于了解发病机制和设计特异的 多发性硬化的免疫治疗。关于执行器机构的知识 可能对理解自身免疫性和 中枢神经系统外的炎症。

The goal of this project is to characterize the components of the central nervous system (CNS) immune response for the purpose of developing specific strategies of immunomodulation. In the forthcoming period we will focus on the immunological alterations of vessels in the animal model experimental allergic encephalomyelitis (EAE) as an archetype of neuroimmunological disease. Endothelial cell expression of Ia, one of the gene products of the major histocompatibility locus, and fibronectin, a plasma glycoprotein which is deposited in inflammatory foci, will be studied in acute and chronic EAE using immunoelectron microscopy to elucidate their in situ roles. Induction of altered endothelial cell Ia and fibronectin expression by activated T cells and their soluble products, lymphokines, will be examined in the skin and CNS to define the cellular and molecular basis of endothelial cell activation. To correlate findings from animal studies with human disease processes, alterations of endothelial cells will be studied in human demyelinating and inflammatory conditions using immunoperoxidase staining of tissue sections. Precise in situ and in vivo characterization of chronic EAE induced by sensitization with myelin proteolipid in guinea pigs and rabbits will be performed using monoclonal antibody staining in tissue sections and in flow cytometry of peripheral blood to determine the role of this myelin component in the immune response to whole CNS tissue. EAE induced by sensitization with whole tissue in guinea pigs will be modulated in vivo by treatment with an anti-T cell and anti-Ia monoclonal antibodies. An understanding of the immunologic parameters, particularly the endothelial cell alterations and immunoregulatory mechanisms, which contribute to the clinical and histological expression of EAE may be applicable to understanding the pathogenesis and designing specific immunotherapy of multiple sclerosis. Knowledge of the effector mechanisms of EAE may have broader implications to understanding autoimmunity and inflammation outside of the CNS.