Administrative Core

行政核心

基本信息

批准号：
10592409
负责人：
Frances E. Lund
金额：
$ 9.93万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10592409
关键词：
Accounting Adaptive Immune System Antibodies Antigen Presentation Asthma Authorization documentation Autoimmunity B-Lymphocytes Blood Budgets CD4 Positive T Lymphocytes Cardiovascular Diseases Cell Fraction Cell Lineage Cell Transplantation Cells Cellular biology Collaborations Collection Communication Data Dedications 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 Learning 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 Rotation Schedule Scientist Services Study models Tail Time Tissues Transplantation Travel United States National Institutes of Health Universities Visit Work arm authority chemokine chronic inflammatory disease cytokine human tissue immune function insight interest lecturer meetings member mortality mouse model pathogenic bacteria pathogenic virus programs response scientific organization success symposium tissue injury tissue repair tumor-immune system interactions

项目摘要

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感染或其他造成损害的环境伤害。免疫系统也是主要的导致慢性炎症性疾病的贡献者，促进医疗保健成本，发病率和死亡率美国，包括心血管疾病，糖尿病，自身免疫性，哮喘，移植排斥等。在过去的三十年中细胞被激活并分化为“效应器”细胞，如何启动和维持免疫细胞记忆以及免疫电池如何以一种功能性的方式贡献免疫介导的保护和损害。在这个U19中程序，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和激活CD4 T细胞，通过生产改变免疫微环境细胞因子和趋化因子，最重要的是，通过区分短寿命和长寿命抗体产生浆细胞（ASC）和长寿命的记忆B细胞。这些细胞是造成体液臂的原因自适应免疫系统的关键是对大多数病毒和细菌病原体的防御的关键。但是，ASC生产的抗体也负责与自身免疫性，哮喘和移植。我们对受保护和病理功能的许多见解 B淋巴细胞和ASC来自转基因的小鼠模型研究，尽管这些研究研究非常有用，很明显，小鼠和人类并不相同，并且有必要为了更好地了解人B细胞如何促进免疫（DYS）功能。我们对人类B细胞的研究是仍然很基本 - 主要是因为研究仅限于易于获得的循环血液车厢。这相当于研究大象的尾巴而不看到整个大象 - 我们当我们仅检查一小部分细胞时，会错过B细胞的大部分复杂性和异质性存在于体内。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太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。我们将满足这个目标作者：（i）为所有项目和核心提供科学，行政，监管和财务监督；（ii）组织科学互动，包括该计划进行的每月研究科学家，科学顾问委员会的年度务虚会，与其他合作社的年度会议在东南部的人类免疫学组和人类免疫学主题课程的中心免疫学研讨会。通过这些活动，核心A将确保该计划的整体成功。