Administrative Core

行政核心

• 批准号: 10395996
• 负责人: Frances E. Lund
• 金额: $ 44.45万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10395996
• 关键词: Accounting; Adaptive Immune System; Antibodies; Antigens; Asthma; Autoimmunity; B-Lymphocytes; Blood; Budgets; CD4 Positive T Lymphocytes; Cardiovascular Diseases; Cell Fraction; Cell Lineage; Cell Transplantation; Cells; Cellular biology; Collaborations; Collection; Data; Diabetes Mellitus; Effector Cell; Elephants; Ensure; Event; Expenditure; Feedback; Financial Support; Fostering; Future; Goals; Graft Rejection; Grant; Guidelines; Health; Health Care Costs; Heterogeneity; Host Defense; Human; Human Resources; Immune; Immune system; Immunity; Immunology; Individual; Infection; Institution; Investigation; Investments; Mediating; Medicine; Memory; Memory B-Lymphocyte; Molecular; Monitor; Morbidity - disease rate; Mus; Organ; Participant; Pathologic; Plasma Cells; Play; Policies; Production; Progress Reports; Property; Regulation; Reporting; Research; Research Personnel; Research Project Grants; Research Support; Role; Schedule; Scientist; Services; Study models; Tail; Time; Tissues; Transplantation; Travel; United States National Institutes of Health; Universities; Visit; Work; arm; chemokine; chronic inflammatory disease; cytokine; human tissue; immune function; insight; interest; lecturer; meetings; member; mortality; mouse model; pathogenic bacteria; pathogenic virus; programs; response; success; symposium; tissue injury; tissue repair; tumor-immune system interactions

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.

核心A：行政核心 项目概要 免疫系统在保护我们免受感染以及解决或修复组织损伤方面发挥着至关重要的作用 感染或其他造成损害的环境侵害也是一个主要因素。 导致慢性炎症性疾病，从而增加医疗费用以及发病率和死亡率 美国，包括心血管疾病、糖尿病、自身免疫、哮喘、移植排斥等。 在过去的三十年里，我们已经了解了很多关于免疫细胞如何发育和成熟、免疫细胞如何 细胞被激活并分化为“效应”细胞，免疫细胞记忆如何启动和维持 以及免疫细胞如何以功能性方式促进免疫介导的保护和损伤。 计划中，我们对通过呈现有助于免疫功能的 B 谱系细胞特别感兴趣 抗原并激活 CD4 T 细胞，通过产生 细胞因子和趋化因子，最重要的是，通过分化为短寿命和长寿命的抗体 产生浆细胞 (ASC) 和长寿命记忆 B 细胞这些细胞负责体液臂。 适应性免疫系统的组成部分，是宿主防御大多数病毒和细菌病原体的关键。 然而，ASC 产生的抗体也是造成与 ASC 相关的大部分组织损伤的原因。 我们对自身免疫、哮喘和移植的许多见解。 B 淋巴细胞和 ASC 来自转基因小鼠模型研究，尽管这些 研究内容非常丰富，很明显小鼠和人类并不相同，因此有必要 为了更好地了解人类 B 细胞如何影响免疫（功能障碍），我们对人类 B 细胞进行了研究。 仍然相当初级——主要是因为研究仅限于容易获得的循环血液 这相当于我们研究大象的尾巴而没有看到整个大象。 当我们只检查一小部分细胞时，就会错过 B 细胞的大部分复杂性和异质性。 在这个 U19 中，我们计划超越大象尾巴，因为我们的目标是 全面检查人类 B 细胞的分子、细胞和功能特性 特别是在不易接近的人体组织和器官中，核心 A 的主要目标是提供 对整个计划以及各个项目和核心的监督和支持我们将实现这一目标。 通过：(i) 为所有项目和核心提供科学、行政、监管和财务监督；以及 (ii) 组织科学互动，包括该计划的每月研究进展会议 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 东南大学人类免疫学小组中心和人类免疫学主题会议 通过这些活动，核心 A 将确保该计划的整体成功。