ASPECTS OF INNER EAR IMMUNOLOGY

临床证据表明，有一种形式的感觉神经 通过免疫调节并有可能治愈的耳聋 如果及早发现的话。这一领域的进展一直受到以下因素的阻碍 人类内耳的不可及之处以及缺乏 自身免疫性耳聋的特异性诊断试验。实验 研究表明，内耳的防御机制 涉及对抗原和/或病原体的免疫应答 内淋巴囊是传入神经的重要组成部分。 内耳的肢体免疫。此外，动物模型显示 这些反应可以起到保护内耳的作用，或者 在其他情况下导致其功能障碍。可能会发生损坏 通过针对内耳组织的不适当活动 抗原或作为旁观者伤害的结果 炎症过程本身。 拟议的研究将确定潜在的基本机制 表征淋巴细胞亚群的内耳免疫 以及参与这些反应的调节性淋巴因子，以及 确定局部聚集的淋巴细胞的来源。这个 免疫介导性听力损失的幅度和持久性 以及药物干预是否可以改变 结果。因为我们有组织学证据表明免疫调节 听力损失与血管闭塞有关，实验表明 用于检测内耳免疫期间的耳蜗血流量 回应。对这种损伤机制的记录将形成 治疗这种疾病的新的治疗方式的基础 精神错乱。自身免疫动物模型的建立 感音神经性耳聋(ASNHL)是目前研究的焦点。 研究。这些动物的听力损失与一种 针对内耳组织的抗体，我们也已经 能够在疑似ASNHL患者的血清中进行识别。 这项提议将检查这种抗原的性质，以及 患者和实验动物具有共同的自身抗体反应性 用二维凝胶测定常见的抗原表位 电泳法。这一发现将是 开发一种人类ASNHL诊断测试。

Clinical evidence suggest that there is a form of sensorineural deafness that is immunologically mediated and potentially treatable if recognized early. Progress in this field has been hampered by the inaccessibility of the human inner ear and the lack of a specific diagnostic test for autoimmune deafness. Experimental studies have shown that the defense mechanisms of the inner ear involve immunological responsiveness to antigens and/or pathogens and that the endolymphatic sac is an important part of the afferent limb of inner ear immunity. Furthermore, animal models have shown that these responses can serve either to protect the inner ear, or under other conditions lead to its dysfunction. Damage may occur through inappropriate activity directed toward inner ear tissue antigens or as the result of bystander injury resulting from the inflammatory process itself. The proposed research will define the basic mechanisms underlying inner ear immunity by characterizing the lymphocyte subpopulations and the regulatory lymphokines involved in these responses, and determine the source of lymphocytes that accumulate locally. The magnitude and permanence of the immune-mediated hearing loss will be addressed, as well as whether drug intervention can alter the outcome. Since we have histological evidence that immune-mediated hearing loss is associated with vascular occlusion, experiments are designed to examine cochlear blood flow during inner ear immune responses. Documentation of this mechanism of injury would form the basis of new therapeutic modalities for treating such disorders. Development of an animal model of autoimmune sensorineural hearing loss (ASNHL) is the focus of ongoing research. Hearing loss in these animals is associated with an antibody directed against inner ear tissue that we have also been able to identify in the sera of patients with suspected ASNHL. This proposal will examine the nature of this antigen and whether patients and the experimental animals share autoantibody reactivity to common antigenic epitopes as determined by 2-dimensional gel electrophoresis. This finding would be an important step in developing a diagnostic test for ASNHL in humans.