Aging and Immunity to Infections

描述(申请人提供)：衰老和对感染的免疫力。传染病，如流感，在老年人口中导致高发病率和高死亡率。此外，疫苗对老年人口的效力也大大降低，使他们更容易受到感染。虽然众所周知，对流感感染的获得性免疫反应和免疫随着年龄的增长而下降，但与年龄相关的特定T细胞功能变化的影响仍有待阐明。在人类群体中定义随着年龄增长的免疫反应的潜在缺陷是极其困难的。幸运的是，小鼠模型允许我们精确地检查免疫系统中与年龄相关的变化，并确定这些变化对特定病原体的反应的影响。因此，该计划的重点是评估与年龄相关的T细胞功能变化的发展，以及这些变化如何导致免疫力下降。该计划中的项目利用复杂的小鼠模型来识别适应性免疫中与年龄相关的缺陷，并分析这些缺陷的影响、这些缺陷涉及的机制以及它们是否可以克服。项目1“衰老对流感免疫的影响”将研究年龄对初始启动和随后生成的CD4T细胞的影响，以及这一影响是否可以增强。项目2“使用细胞因子增强老年CD4细胞同源功能”将重点研究与年龄相关的变化在CD4T细胞同源辅助功能中的作用，以及这如何影响疫苗接种后保护性抗体的产生。项目3“年龄对CDS T细胞对流感免疫的影响”将研究CDS T细胞记忆的生成和功能，随着年龄的增长，CDS T细胞的记忆能力显著减少，这可能是由于记忆T细胞亚群的动态平衡发生变化。项目4“衰老对T细胞库和对流感病毒的细胞免疫的影响”将研究与年龄相关的CD4和CDS T细胞库的变化，以及这些变化如何影响对流感感染的反应能力。所产生的知识将使今后制定战略以克服这些缺陷并提高老年人的疫苗效力。

DESCRIPTION (provided by applicant): Aging and immunity to infections. Infectious diseases, such as influenza, lead to high morbidity and mortality in elderly populations. In addition, the efficacy of vaccines is also significantly reduced for elderly populations, leaving them much more vulnerable to infection. While it is well known that the adaptive immune response to influenza infection and immunization declines with aging, the impact of specific age-related changes in T cell function remain to elucidated. Defining the underlying defects in the immune response with aging in human populations is extremely difficult. Fortunately, mouse models allow us to precisely examine age-related changes in the immune system and determine the effect of these changes on a response to a particular pathogen. Thus, the key focus of this program is to assess the development of age-related changes in T cell function and how these contribute to reduced immunity. The projects in this program take advantage of sophisticated mouse models to identify age-related defects in adaptive immunity and to analyze the impact of these defects, the mechanisms involved in these defects and whether they can be overcome. Project 1 "Impact of aging on CD4 immunity to flu" will examine the impact of age on the initial priming and subsequent generation of CD4 T cells and if this can be enhanced. Project 2 "Enhancing aged CD4 cognate function with cytokines" will focus on examining the role of age-related changes in CD4 T cell cognate helper function and how this impacts the production of protective antibodies following vaccination. Project 3 "Impact of age on CDS T cell immunity to influenza" will examine CDS T cell memory generation and function, which is dramatically reduced with aging possibly due to changes in homeostasis of memory T cell subsets. Project 4 "Impact of aging on the T cell repertoire and cellular immunity to influenza virus" will examine age-related changes in CD4 and CDS T cell repertoire and how these influence the ability to respond to influenza infection. The knowledge generated will allow the future development of strategies to overcome these defects and enhance vaccine efficacy for the elderly.