IMMUNOBIOLOGY OF THE OLFACTORY MUCOSA

本申请中描述的实验的长期目标 描绘出嗅觉细胞之间的局部相互作用 粘膜和免疫系统的细胞，这是居民在这个感觉 动物模型中的神经上皮;以表征 嗅觉免疫屏障对病原体入侵，特别是病毒， 通过嗅觉神经进入中枢神经系统;以及 将从这些实验中获得的见解应用于调查 人类嗅觉粘膜的免疫生物学。 具体目标是： 1)描述T淋巴细胞功能亚群的分布， 健康和病毒接种动物的嗅觉粘膜; 2） 鉴别并描述巨噬细胞，中性粒细胞， 嗜酸性粒细胞和肥大细胞，细胞介导的免疫剂，在 健康和病毒接种动物的嗅觉粘膜; 3） 表征炎症介质的作用， 病毒感染，鲍曼氏腺粘液分泌和粘膜 组织学; 4）表征鼻内病毒引起的变化 接种，在表达和分布的成分， 分泌免疫系统（即，分泌型伊加、J链和分泌型IgA 成分）; 5）比较免疫反应， 在具有充分表征的突变的动物中鼻内病毒接种 影响正常动物的免疫系统;以及6） 测定P物质/降钙素基因相关肽的作用 从外部粘膜的神经消耗]对病毒的神经支配。 诱导免疫应答，如前述实验所表征。 一种嗜神经病毒，单纯疱疹1型，将鼻内接种 健康的大鼠和小鼠。 粘膜免疫反应的发展 将使用细胞特异性抗体和免疫组织化学 技术，以确定类型，数量和分布的具体 免疫系统的细胞以不同的速度浸润嗅觉粘膜， 接种后间隔。 将使用计算机视频图像分析 为了量化和比较从健康和病毒接种的 动物 这项工作的结果将应用于分析的 免疫屏障的人类嗅觉粘膜，并可能有影响， 上呼吸道病毒感染的治疗 至于针对病原体的粘膜疫苗的设计和开发， 有机体

The long-term objectives of the experiments described in this application are to delineate the local interactions between the cells of the olfactory mucosa and the cells of the immune system that are resident in this sensory neuroepithelium in animal models; to characterize the response of the olfactory immune barrier to pathogen invasion, particularly by viruses that gain access to the central nervous system through the olfactory nerves; and to apply the insights gained from these experiments to the investigation of the immunobiology of the human olfactory mucosa. The specific aims are: 1) to describe the distribution of functional subsets of T lymphocytes in the olfactory mucosa of healthy and virus inoculated animals; 2) to identity and describe the distribution of macrophages, neutrophils, eosinophils and mast cells, agents of cell-mediated immunity, in the olfactory mucosa of healthy and virus-inoculated animals; 3) to characterize the effects of inflammatory mediators, released as a result of viral infections, on mucus secretion by Bowman's glands and on mucosal histology; 4) to characterize changes, resulting from intranasal virus inoculation, in the expression and distribution of constituents of the secretory immune system (i.e., secretory IgA, J. chain and secretory component) in the olfactory mucosa; 5) to compare the immune response to intranasal virus inoculation in animals with well-characterized mutations affecting the immune system with those of normal animals; and 6) to determine the effect of substance P/calcitonin gene-related peptide depletion from nerves of the extrinsic mucosa] innervation on virus-. Induced immune responses as characterized by the preceding experiments. A neurotropic virus, herpes simplex type 1, will be intranasally inoculated into healthy rats and mice. The development of the mucosal immune response will be analyzed using cell-specific antibodies and immunohistochemical techniques to identify the types, numbers, and distribution of specific cells of the immune system that infiltrate the olfactory mucosa at varying post-inoculation intervals. Computerized video image analysis will be used to quantify and compare the data obtained from healthy and virus-inoculated animals. The results of this work will be applied to an analysis of the immune barrier of the human olfactory mucosa and may have implications for the treatment of viral infections of the upper respiratory tract as well as for the design and development of mucosal vaccines against pathogenic organisms.