IMPORTANCE OF ANTIGEN SPECIFIC IGA RESPONSES IN CONTROLLING SIV/SHIV INFECTION

抗原特异性 IGA 反应在控制 SIV/SHIV 感染中的重要性

• 批准号: 8359778
• 负责人: Bapi Pahar
• 金额: $ 45.19万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359778
• 关键词: Acquired Immunodeficiency Syndrome; Antigens; Disease Progression; Dose; Funding; Grant; Immune; Immune response; Immune system; Immunity; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infection; Infectious Diseases Research; Intestines; Macaca; Memory B-Lymphocyte; Mucosal Immune Responses; National Center for Research Resources; Plasma; Principal Investigator; Research; Research Infrastructure; Resources; Role; Route; SIV; Sampling; Secretory Immunoglobulin A; Site; Source; Tissues; United States National Institutes of Health; Viremia; Virus; arm; cost; lymph nodes; peripheral blood; response; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A. SPECIFIC AIMS 1: To compare the role of antigen specific IgA, IgG and IgM immune responses in macaques with different levels of immunity to SIV/SHIV infection. We will compare antigen specific IgA & IgG responses in macaques intravenously, intravaginally, and intrarectally inoculated with SIVmac251 (a highly pathogenic virus that consistently results in persistent viremia and AIDS) to macaques mucosally inoculated with low doses of SHIVsf162p3 (which usually results in low to undetectable plasma viremia and lack of disease progression). Antigen specific immunoglobulin responses will also be assessed in SIVmac251 inoculated macaques, which are able to control their infection and become long-term nonprogressors (LNTP). 2: To quantify effector memory B cells in macaques infected with SIV by different inoculation routes. Since the mucosal immune system is "compartmentalized" into mucosal and systemic arms, we hypothesize that mucosal immune responses may differ depending on the route of inoculation. Thus, effector memory B cells will be evaluated and quantified in different tissues including peripheral blood, intestines, lymph nodes, and BAL samples of intravenously and mucosally inoculated macaques. We will also quantify secretory IgA and IgG from both systemic and mucosal immune sites. Using this approach, we predict that we will be able to correlate SIV specific mucosal immune responses with reduction of viremia and protection from disease progression in macaques infected with pathogenic viruses.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 A.具体目标 1：要比较抗原特异性IgA的作用，IgG和IgM免疫反应在猕猴中具有不同水平的SIV/SHIV感染的免疫力。我们将比较猕猴中的抗原特异性IgA和IgG反应，浸润和内部接种了SIVMAC251（一种高度致病的病毒，始终导致持久性病毒和辅助病毒）对猕猴接种了较低的shivsf1622 pup（通常会导致猕猴）接种痕迹（通常会导致猕猴）（通常是在斑疹中）。进展）。抗原特异性免疫球蛋白反应也将在SIVMAC251接种猕猴中进行评估，这些猕猴能够控制其感染并成为长期的非推测器（LNTP​​）。 2：用不同的接种途径在猕猴中定量猕猴中的效应子存储B细胞。由于粘膜免疫系统被“分隔”为粘膜和全身性臂，因此我们假设粘膜免疫反应可能取决于接种途径。因此，将在不同组织中评估和定量效应记忆B细胞，包括外周血，肠，淋巴结和固定性和粘膜接种猕猴的BAL样品。 我们还将从系统性和粘膜免疫部位量化分泌的IgA和IgG。使用这种方法，我们预测，我们将能够将SIV特异性粘膜免疫反应与病毒血症的降低和免受病原病毒感染猕猴的疾病进展的保护相关联。