MECHANISMS OF ORAL TOLERANCE

描述(改编自调查者摘要)：成功的关键 免疫系统是指宿主对多种疾病保持耐受的能力 “自身”抗原，同时仍保留强烈反应的能力 “外国侵略者”。耐受性和免疫力的调节 外围国家一直是一个争论不休的问题，但人们对此仍知之甚少。一 外周耐受性的显著特征是，某些类别的 外来抗原，当摄入或吸入时，可下调或阻止 全身免疫反应。尽管付出了巨大的努力，但 建立无响应性仍然是有争议的，关键 影响耐受诱导的变量仍然没有明确的定义。这个 本应用程序的目标是通过使用 小鼠和小鼠T辅助细胞对细胞色素c的反应 新近发展起来的多肽/MHC四聚体染色技术 研究T细胞对全身免疫反应的调节作用 通过口服抗原的方式和特点 提出或口头介绍抗原。调查人员的目标是 了解(一)口服诱导耐受/免疫的机制 引入的抗原，以及(Ii)抗原呈递的特征 (抗原呈递细胞、抗原呈递的量、时间 抗原提呈)以及它们对T细胞反应的影响。要实现 在这些目标中，调查人员首先会分析内生和诱因 T细胞在抗原喂养后对细胞色素c的反应，并使用 以信息为基础探讨口服耐受/免疫机制 归纳法。他们还将在这一点上描述抗原呈现的特征 系统，并测定肠上皮细胞(IEC)作为 粘膜免疫中的抗原提呈细胞。更好地理解 免疫细胞在粘膜系统中的作用及其影响和 口服抗原对全身免疫反应的作用机制是 开发治疗自身免疫的治疗方案的基础 疾病和过敏反应。这些信息也可能对 粘膜疫苗的开发。

DESCRIPTION (Adapted from Investigator's abstract): The key to a successful immune system is the ability of the host to maintain tolerance to many "self" antigens while still preserving the ability to react strongly to "foreign invaders". The regulation of tolerance and immunity in the periphery has been a long debated, yet remains poorly understood. One remarkable feature of peripheral tolerance is the fact that some classes of foreign antigens, when ingested or inhaled, can downregulate or prevent systemic immune reactions. Despite intense efforts, the mechanism of establishing non-responsiveness is still controversial, and the critical variables that influence tolerance induction remain poorly defined. The objective of this application is to clarify these issues by making use of the well characterized T helper cell responses to cytochrome c in mice and the recently developed peptide/MHC tetramer method of staining specific T-cells to study the regulation of systemic immune responses brought about by the oral administration of antigens and the characteristics of presentation or orally introduced antigens. The investigators goals are to understand (i) the mechanism of tolerance/immunity induction by orally introduced antigen, and (ii) the characteristics of the antigen presentation (antigen presenting cells, amount of antigen presented, the timing of antigen presentation) and their impact on the T-cell responses. To achieve these goals, the investigators will first analyze the endogenous and induced T-cell response to cytochrome c after antigen feeding, and use the information as a basis to probe the mechanism of oral tolerance/immunity induction. They will also characterize the antigen presentation in this system and determine the potential of intestinal epithelial cells (IEC) as antigen presenting cells in mucosal immunity. A better understanding of the role of immune cells in the mucosal system as well as the impact and the mechanism of orally introduced antigen on systemic immune responses is fundamental for developing therapeutic protocols for treating autoimmune diseases and allergic reactions. The information may also be important for mucosal vaccine development.