Administrative Core

核心A：行政核心 项目摘要 免疫系统在保护我们免受感染和解决或修复组织损伤方面起着至关重要的作用。 在感染或其他造成损害的环境侮辱之后。免疫系统也是一个主要的 慢性炎症性疾病的推动者，这些疾病推高了医疗保健成本和发病率和死亡率 美国，包括心血管疾病、糖尿病、自身免疫、哮喘、移植排斥反应和许多其他疾病。 在过去的三十年里，我们学到了很多关于免疫细胞如何发育和成熟，如何免疫 细胞被激活并分化为“效应”细胞，免疫细胞记忆是如何启动和维持的 以及免疫细胞如何在功能上对免疫介导的保护和损害做出贡献。在这辆U19 计划中，我们对B系细胞特别感兴趣，它通过呈现 抗原和激活CD4T细胞，通过产生 细胞因子和趋化因子，最重要的是，通过分化为短期和长期抗体 产生浆细胞(ASCs)和长寿记忆B细胞。这些细胞负责体液臂 是适应性免疫系统的关键，是宿主抵御大多数病毒和细菌病原体的关键。 然而，ASCs产生的抗体也是与以下疾病相关的组织损伤的主要原因 自身免疫、哮喘和移植。我们对血管紧张素转换酶的保护和病理功能的许多见解 B淋巴细胞和ASCs来自转基因小鼠模型研究，尽管这些 研究提供了非常丰富的信息，很明显，老鼠和人类不是一模一样的，有必要 为了更好地了解人类B细胞如何对免疫(Dys)功能做出贡献。我们对人类B细胞的研究是 仍然是非常初级的--很大程度上是因为研究仅限于容易接触到的循环血液 车厢。这就相当于研究大象的尾巴而不看整头大象--我们 当我们只检查B细胞中的一小部分时，我们忽略了B细胞的大部分复杂性和异质性 都存在于人体内。在这款U19中，我们计划超越大象尾巴，因为我们的目标是 全面检测人类B细胞的分子、细胞和功能特性 尤其是在不易接触到的人体组织和器官中。核心A的主要目标是提供 监督和支持整个计划以及个别项目和核心。我们将实现这一目标 通过：(1)向所有项目和核心提供科学、行政、监管和财务监督；和(2) 组织科学互动，包括该计划的每月进行中的研究会议 科学家与科学顾问委员会的年度务虚会，与其他合作社的年度会议 东南部人类免疫学团体中心和人类免疫学主题会议 免疫学研讨会。通过这些活动，核心A将确保该计划的全面成功。

Core A: Administrative Core Project Summary The immune system plays a critical role in protecting us from infection and resolving or repairing tissue injury following infection or other environmental insults that cause damage. The immune system is also a major contributor to chronic inflammatory diseases that drive health care costs and morbidity and mortality in the U.S., including cardiovascular disease, diabetes, autoimmunity, asthma, transplant rejection and many others. Over the last three decades we have learned much about how immune cells develop and mature, how immune cells are activated and differentiate into “effector” cells, how immune cell memory is initiated and maintained and how immune cells contribute in a functional way to immune-mediated protection and damage. In this U19 Program, we are particularly interested in B lineage cells that contribute to immune function by presenting antigen and activating CD4 T cells, by altering the immune microenvironment through the production of cytokines and chemokines and, most importantly, by differentiating into short- and long-lived antibody producing plasma cells (ASCs) and long-lived memory B cells. These cells are responsible for the humoral arm of the adaptive immune system and are key to host defense against most viral and bacterial pathogens. However, antibodies produced by ASCs are also responsible for much of the tissue damage associated with autoimmunity, asthma and transplantation. Many of our insights into the protective and pathologic functions of B lymphocytes and ASCs have come from genetically modified mouse model studies and, although these studies have been very informative, it is clear that mice and humans are not identical and that there is a need to better understand how human B cells contribute to immune (dys)function. Our studies of human B cells are still quite rudimentary – largely because the studies have been limited to the easily accessible circulating blood compartment. This is the equivalent of studying the tail of the elephant without seeing the whole elephant – we miss most of the complexity and heterogeneity of B cells when we only examine a tiny fraction of the cells that are present in the body. In this U19, we plan to move beyond the elephant tail as our goal is to comprehensively examine the molecular, cellular and functional properties of human B cells that reside specifically in the less accessible human tissues and organs. The major objective of Core A is to provide oversight and support for the overall Program and the individual projects and cores. We will meet this objective by: (i) providing all projects and cores with scientific, administrative, regulatory and financial oversight; and (ii) organizing scientific interactions, including the monthly research in progress meetings for the Program scientists, the annual retreat with the scientific advisory board, the annual meeting with other Cooperative Centers on Human Immunology groups and the Human Immunology themed session at the Southeastern Immunology Symposium. Through these activities, Core A will ensure the overall success of the Program.