ASPECTS OF INNER EAR IMMUNOLOGY

最近，人们越来越感兴趣的是，一些人 各种形式的进行性感音神经性耳聋可能具有免疫性 基础和实际可能会改进后的制度 免疫抑制剂。与这些观察结果相结合， 内耳已经被实验证明是通过 内耳内体液免疫反应的特征 抗原攻击的结果。这项拨款提案的主要目标是 是为了更好地了解内耳内的免疫反应 这些反应的来源，它们对耳蜗的影响 功能及其与人类状况的可能关系。 具体地说，这个项目将调查内耳抗原的命运。 挑战，抗原处理和抗体产生的场所， 在内耳内进化的抗体类别，其作用 内淋巴囊在内耳免疫反应中的时间效应 免疫对耳蜗功能的影响--免疫的机制 介导的内耳损伤，补体在这些反应中的作用， 自身免疫性感音神经性耳聋动物模型能否 以及梅尼埃病患者是否可以被证明有一个 他们的疾病的免疫学基础。这些研究将涉及油井 内耳免疫的特征性动物模型 反应可以通过一种敏感的酶免疫分析来测量，淋巴细胞 成纤维细胞生成试验、免疫组织化学定位研究、采用 迁移研究、电生理监测与耳蜗代谢 和血液流动分析。此外，梅尼埃病患者 将在体外进行淋巴细胞转化试验，以评估 细胞免疫机制是否在这种疾病中起作用。血清 也将对这些患者的内耳抗体进行筛查 通过酶免疫分析系统。这些研究应该澄清 内耳与宿主和局部免疫反应的关系 确定这种相互作用是保护还是可能有害于 正常的生理功能，从而导致疾病状态。

Recently there has been a growing interest in the possibility that some forms of progressive sensorineural hearing loss may have immunological bases and may actually be improved following the institution of immunosuppressive agents. In conjunction with these observations, the inner ear has been shown experimentally to be immunoresponsive through the characterization of humoral immune responses within the inner ear as a result of antigen challenge. The major objectives in this grant proposal are to better understand how immunological responses within the inner ear are generated, the origin of these responses, their effect on cochlear function and their possible relationship to human conditions. Specifically, this project will investigate the fate of inner ear antigen challenge, the site of antigen processing and antibody production, the antibody classes evolving within the inner ear, the role of the endolymphatic sac in inner ear immune responses, the temporal effects of immunity on cochlear function, the mechanisms responsible for immune mediated inner ear injury, the role of complement in these responses, whether an animal model of autoimmune sensorineural hearing loss can be created and whether patients with Meniere's disease can be shown to have an immunological basis to their disease. These studies will involve well characterized animal models of inner ear immunity in which inner ear immune responses can be measured by a sensitive enzyme immunoassay, lymphocyte blastogenesis assays, immunohistochemical localization studies, adoptive transfer studies, electrophysiological monitoring and cochlear metabolism and blood flow analyses. Additionally, patients with Meniere's disease will undergo in vitro assays of lymphocyte blastogenesis in order to assess whether cellular immune mechanisms are at play in this disorder. Serum from these patients will also be screened for antibodies to the inner ear by an enzyme immunoassay system. These studies should clarify the relationship of the inner ear to host and local immune responses and determine whether this interaction is protective or possibly deleterious to normal physiological function and thereby result in disease states.