Unique aspects of respiratory immunity

呼吸道免疫的独特之处

• 批准号: 6441192
• 负责人: Troy D Randall
• 金额: $ 43.25万
• 依托单位: TRUDEAU INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6441192
• 关键词: cellular immunity; gene targeting; genetically modified animals; immunoregulation; laboratory mouse; mucosal immunity; respiratory function; secretory immune system

DESCRIPTION (provided by applicant): The respiratory tract faces unique immunologic demands. Since excessive immune or inflammatory responses can be as damaging to the lung as uncontrolled infection, it is thought that the respiratory tract has developed mechanisms that keep the pulmonary immune system and the associated inflammatory response in check, yet prepared to respond quickly to potentially deadly or disease-causing materials. Understanding these mechanisms is important for developing knowledge-based approaches to intervene in many pulmonary diseases. In order to separate those aspects of respiratory immunity that are determined locally from those that are determined at systemic sites, we examined respiratory immune responses in mice that lacked all encapsulated lymph nodes (LNs), Peyer?s patches and spleen, but retained the nasal associated lymphoid tissue (NALT), as well as the interstitial lymphoid areas of the lung. Using these mice, we demonstrated that the respiratory tract can perform many immune functions in the complete absence of conventional lymphoid organs. Furthermore, we showed that the NALT and the lymphoid areas of the lung are formed by mechanisms that bypass the lymphotoxin-a signaling pathway, which is required for the development of all encapsulated lymphoid organs. In light of our preliminary data, we hypothesize that respiratory immune responses can be initiated directly in the respiratory tract by novel mechanisms and that these mechanisms regulate respiratory immunity and accommodate the special needs of the respiratory system. To test this hypothesis, we propose to define in Aim 1 whether immune responses generated directly in the NALT and/or lung result in effective immunity to primary or secondary challenge, to determine in Aim 2 whether cellular immune responses generated in the NALT and/or lung differ in the absence of conventional lymphoid tissues, to determine in Aim 3 how humoral immune responses in the respiratory tract differ in the absence of conventional lymphoid tissues, and to determine in Aim 4 the molecular mechanisms that control the recruitment and organization of naive lymphocytes in the lung. Together, these experiments will clarify the immune functions of NALT as well as the interstitial lymphoid areas in the lung, and will identify those aspects of respiratory immunity that are specific to these tissues. The knowledge gained by these experiments will facilitate the rational design of protective or therapeutic strategies targeted to these tissues to control pulmonary diseases.

描述(由申请人提供)： 呼吸道面临着独特的免疫需求。由于过度 免疫或炎症反应对肺的损害与 不受控制的感染，人们认为呼吸道已经发育 保持肺免疫系统和相关的 炎症反应受控，但准备对潜在的 致命的或致病的物质。了解这些机制是 对于开发以知识为基础的方法来干预许多 肺部疾病。为了将呼吸道的这些方面分离出来 在当地确定的豁免权与在 系统站点，我们检查了缺乏的小鼠的呼吸免疫反应 所有包膜淋巴结(LN)、Peyer、S补片和脾，但保留 鼻相关淋巴组织(NALT)以及间质 肺的淋巴样区。使用这些小鼠，我们证明了 呼吸道可以在完全没有肺炎的情况下执行许多免疫功能。 常规的淋巴器官。此外，我们还证明了NALT和 肺的淋巴样区是由绕过 淋巴毒素--ALL发育所必需的信号通路 包裹的淋巴器官。根据我们的初步数据，我们 假设呼吸道免疫反应可以直接在 呼吸道通过新的机制和这些机制调节 呼吸系统免疫和适应呼吸道的特殊需要 系统。为了检验这一假设，我们建议在目标1中定义免疫 直接在NALT和/或肺中产生的反应导致有效的 对第一次或第二次挑战的免疫力，以确定目标2中是否 NALT和/或肺中产生的细胞免疫反应不同于 没有常规淋巴组织，以确定目标3如何体液 呼吸道中的免疫反应不同于缺乏 常规淋巴组织，并在目标4中测定分子 控制幼稚淋巴细胞招募和组织的机制 在肺里。总之，这些实验将阐明人的免疫功能 NALT以及肺的间质淋巴样区域，并将识别 呼吸道免疫的这些方面是这些组织所特有的。这个 通过这些实验所获得的知识将有助于合理地设计 针对这些组织的保护性或治疗性策略以控制 肺部疾病。