MECHANISMS OF ORAL TOLERANCE

描述（改编自研究者摘要）：成功的关键 免疫系统是宿主维持对许多免疫系统的耐受性的能力。 “自身”抗原，同时仍保留对 "外国侵略者"。 免疫耐受的调节 边缘化一直是一个长期的争论，但仍然知之甚少。 一 外周耐受性的一个显著特征是， 当摄入或吸入外来抗原时， 全身免疫反应。 尽管作出了巨大努力， 建立无反应性仍然是有争议的，关键是 影响耐受诱导的变量仍然定义不清。 的 本申请的目的是通过利用 小鼠中T辅助细胞对细胞色素c的反应得到了充分表征， 最近开发的肽/MHC四聚体特异性染色方法， 研究T细胞调节全身免疫反应所带来的 通过口服给予抗原和 呈递或口服引入的抗原。 研究人员的目标是 理解（i）口服免疫耐受/免疫诱导机制 引入的抗原，和（ii）抗原呈递的特征 （抗原呈递细胞，抗原呈递量， 抗原呈递）及其对T细胞应答的影响。 实现 这些目标，研究人员将首先分析内源性和诱导 抗原喂养后T细胞对细胞色素c的反应，并使用 为探讨口服耐受/免疫机制提供依据 诱导 他们还将描述这种情况下的抗原呈递， 系统，并确定肠上皮细胞（IEC）的潜力， 抗原提呈细胞在粘膜免疫中的作用。 更好地理解 免疫细胞在粘膜系统中的作用以及 口服引入的抗原对全身免疫应答的机制是 开发治疗自身免疫性疾病的治疗方案的基础 疾病和过敏反应。 这些信息也可能是重要的， 粘膜疫苗的发展。

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.