IMMUNOPATHOLOGY OF THE CENTRAL NERVOUS SYSTEM

该项目的目标是描述中央 神经系统（CNS）免疫应答，以开发特异性 免疫调节策略。 在今后一段时期，我们将重点关注 实验性血管炎动物模型的血管免疫学改变 过敏性脑脊髓炎（EAE）作为神经免疫学的原型 疾病 Ia的内皮细胞表达，Ia的基因产物之一， 主要组织相容性位点和纤连蛋白，一种血浆糖蛋白 沉积在炎症灶中，将在急性和 慢性EAE，使用免疫电子显微镜来阐明其原位 角色 诱导改变的内皮细胞Ia和纤连蛋白表达 被激活的T细胞及其可溶性产物淋巴因子， 在皮肤和中枢神经系统中进行检查，以确定 内皮细胞活化 将动物研究的发现与 在人类疾病过程中， 在人类脱髓鞘和炎症条件下进行的研究， 组织切片的免疫过氧化物酶染色。 慢性EAE诱导的精确原位和体内表征 将在豚鼠和家兔中使用髓鞘蛋白脂质致敏， 在组织切片和流式细胞仪中使用单克隆抗体染色 外周血细胞计数以确定这种髓磷脂的作用 在整个中枢神经系统组织的免疫反应的组成部分。 诱发EAE 豚鼠的整个组织的致敏作用将通过以下方式在体内调节： 用抗T细胞和抗Ia单克隆抗体治疗。 了解免疫学参数，特别是 内皮细胞改变和免疫调节机制， 可能与EAE的临床和组织学表现有关， 适用于了解发病机制和设计特异性 多发性硬化症的免疫治疗 效应器机制的知识 EAE可能对理解自身免疫性有更广泛的意义， CNS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.