Regulation of Humoral Immunity to Influenza Virus

流感病毒体液免疫的调节

基本信息

批准号：
8068104
负责人：
Nicole Baumgarth
金额：
$ 3.19万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2010-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8068104
关键词：
Affect Agonist Antibodies Antibody Formation Antigens Antiviral Agents Antiviral Response B Cell Proliferation B-Lymphocyte Subsets B-Lymphocytes Biology CD4 Positive T Lymphocytes Cells Chimera organism Collaborations Data Defect Development Enzyme-Linked Immunosorbent Assay Figs - dietary Flushing Funding Goals Grant Graph Humoral Immunities ITGAX gene Immune Immunity Immunization Immunoglobulin A In Vitro Individual Infection Influenza Interferon-beta Interferons Knockout Mice Knowledge Mediating Memory Methods Modeling Mus Nature Outcome Pathology Physiological Process Protocols documentation Published Comment Publishing Receptors, Antigen, B-Cell Regulation Reporting Research Respiratory System Respiratory tract structure Role Serum Shapes Signal Transduction Stimulus Structure of germinal center of lymph node T cell response T-Cell Receptor T-Lymphocyte TLR3 gene TLR7 gene Testing Text Tissues Toll-like receptors Transgenic Mice Virus Virus Diseases Voice Work Writing base human TLR3 protein in vivo influenzavirus irradiation lymph nodes novel vaccines programs response

项目摘要

in part by studies conducted during the initial funding period of this grant, suggests that immediate early exposure of B cells to infection-induced innate signals shape the responses of B cells. Little is known about the nature of these signals and the mechanisms by which they affect the B cell response. The working hypothesis to be tested here is that infection-induced local innate immune signals differentially regulate various B cell subsets involved in the induction of protective immunity to influenza virus infection. The long-term objective of the studies is to determine how respiratory tract immunity to viral infections is induced and regulated. The objective of this proposal is to determine the mechanisms by which innate immune signals, particularly type I IFN shape the quality and magnitude of antiviral B cell responses. This is based on studies during the last funding period which showed type I IFN as a major infection-induced B cell stimulus in regional lymph nodes within 2 days of infection. To achieve our objective three Specific Aims will be carried out. Specific Aim #1 will determine the mechanisms by which direct IFNR-signals received by B cells affect the magnitude and protective capacity of individual B cell response components to influenza: B-1 cells, extrafollicular foci and germinal center responses. Specific Aim #2 will determine the role of toll-like receptor (TLR) 3 and 7-mediated signals on antiviral B cell response regulation to influenza infection and their integration with stimuli provided by the B cell receptor and/or T cell help. In Specific Aim #3 the effects of IFNR-mediated B cell stimulation on local CD4 T cell responses to influenza virus infection and particular the affects on CD40-CD40L mediated help will be investigated. In vitro and in vivo tests are aided by the use of virus-specific T cell receptor transgenic mice. Completion of these studies will contribute to a better understanding of the processes that regulate the induction of protective antiviral B cell responses to influenza virus. Project Description Page 6

部分是通过在本项目初始资助期间进行的研究 grant，表明 B 细胞立即早期暴露于感染诱导的先天性信号塑造 B 细胞的反应。人们对这些物质的性质知之甚少信号及其影响 B 细胞反应的机制。工作中这里要检验的假设是感染诱导的局部先天免疫信号差异性调节参与保护性诱导的各种 B 细胞亚群对流感病毒感染具有免疫力。研究的长期目标是确定如何诱导和调节呼吸道对病毒感染的免疫力。这该提案的目的是确定先天免疫的机制信号，尤其是 I 型 IFN 决定抗病毒 B 细胞的质量和强度回应。这是基于上一个资助期间的研究，该研究表明类型 I IFN 作为感染后 2 天内区域淋巴结中主要感染诱导的 B 细胞刺激物感染。为了实现我们的目标，我们将实现三个具体目标。具体目标 #1 将确定 B 细胞直接接收 IFNR 信号的机制影响个体 B 细胞反应成分的强度和保护能力流感：B-1 细胞、滤泡外病灶和生发中心反应。具体目标#2 将确定 Toll 样受体 (TLR) 3 和 7 介导的信号对抗病毒 B 的作用细胞对流感感染的反应调节及其与所提供刺激的整合通过 B 细胞受体和/或 T 细胞的帮助。在具体目标#3 中，IFNR 介导的影响 B 细胞刺激局部 CD4 T 细胞对流感病毒感染的反应，特别是将研究对 CD40-CD40L 介导的帮助的影响。体外和体内测试借助病毒特异性 T 细胞受体转基因小鼠的帮助。完成这些研究将有助于更好地理解调节过程诱导针对流感病毒的保护性抗病毒 B 细胞反应。项目描述第6页