Modulation of Biodefense Responses to Microbial Pathogens

项目总结(见说明)： 本次更新的计划项目《对微生物病原体的生物防御反应的调节》由四个项目和三个核心组成，重点关注对B类和C类生物防御病原体及其产品的免疫反应。该计划的主题是定义针对病毒和细菌病原体及其产品的保护性免疫发展的参数。中心假设是，T细胞激活的早期事件决定了长期免疫是否被诱导为对 疫苗接种，或者是否对细菌毒素产生损害。每个项目都侧重于主题的一个独特方面，以加深我们对感染性病原体的免疫反应的理解。项目1(Lefrancois)建议研究单增李斯特菌减毒疫苗诱导CD8 T细胞免疫的机制。T细胞与DC的相互作用和CD4T细胞帮助的作用将使用 活体系统，包括原位显微镜和新型报告小鼠。项目2(McSorley)将研究不同形式的沙门氏菌感染和疫苗接种对CD4记忆T细胞的发展，并将确定对继发性伤寒的保护性免疫的关键要求。项目3(Vella)集中于了解肺部注射金黄色葡萄球菌肠毒素激活T细胞如何影响病理黏膜反应。项目4(考利)试图了解影响 关于肺部流感病毒感染后T细胞反应与抗体的相互作用。 所有四个项目的组成部分都旨在检查T细胞对粘膜和周围部位微生物制剂的诱导反应，并了解每种反应的细胞参与者之间的复杂相互作用。这些项目利用活体模型和深入的细胞免疫学技术，并得到三个核心的支持：行政管理、流式细胞术和荧光显微镜/免疫组织化学。 这些项目和核心相互协作，相互促进，以实现计划的目标。再加上强有力的机构支持，预计在对病原体及其副产品的免疫反应调控方面将继续获得重大的新见解。

PROJECT SUMMARY (See instructions): This renewal of the program project "Modulation of biodefense responses to microbial pathogens" is composed of four projects and three cores focused on the immune response to Category B and C Biodefense Pathogens and their products. The program theme is to define the parameters for development of protective immunity against viral and bacterial pathogens and their products. The central hypothesis is that early events in T cell activation determine whether or not long-term immunity is induced in response to vaccination, or whether damage is initiated in response to a bacterial toxin. Each project focuses on a unique aspect of the theme to deepen our understanding of the immune response to infectious agents. Project 1 (Lefrancois) proposes to investigate the mechanisms by which attenuated Listeria monocytogenes vaccines induce CD8 T cell immunity. T cell-DC interactions and the role of CD4 T cell help will be examined using in vivo systems including in situ microscopy and novel reporter mice. Project 2 (McSorley) will examine development of CD4 memory T cells in response to different forms of Salmonella infection and vaccination and will define the critical requirements for protective immunity to secondary typhoid. Project 3 (Vella) is centered on understanding how T cell activation by pulmonary administration of Staphylococcus aureus enterotoxin impacts the pathological mucosal response. Project 4 (Cauley) seeks to understand the impact on pulmonary influenza virus infection of the interaction between T cell responses and antibody. Components of all four projects are aimed at examining the induction of T cell responses to microbial agents in mucosal and peripheral sites and to understanding the complex interplay between the cellular participants of each response. The projects utilize in vivo models and in-depth cellular immunological techniques and are supported by 3 cores: administrative, flow cytometry and fluorescence microscopy/immunohistochemistry. The projects and cores synergistically interact and mutually reinforce one another to achieve the goals of the program. Coupled with strong institutional support, it is anticipated that significant new insights in immune response regulation to pathogens and their byproducts will continue to be obtained.