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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 A.具体目标 1.比较不同免疫水平SIV/SIV感染猕猴的抗原特异性IgA、Ig G和Ig M免疫应答的作用。我们将比较静脉、阴道和直肠内接种SIVmac251(一种持续导致持续性病毒血症和艾滋病的高致病性病毒)的猕猴和粘膜接种低剂量SHIVsf162p3(通常会导致低或无法检测到的血浆病毒血症和疾病进展)的猕猴的抗原特异性IgA和IgG反应。还将评估接种SIVmac251的猕猴的抗原特异性免疫球蛋白反应，这些猕猴能够控制它们的感染并成为长期无进展(LNTP)。 2.定量检测不同接种途径感染SIV猕猴的效应记忆B细胞。由于黏膜免疫系统被“划分”为黏膜和全身免疫系统，我们推测黏膜免疫反应可能因接种途径的不同而不同。因此，效应记忆B细胞将在不同的组织中进行评估和量化，包括外周血、肠、淋巴结和静脉和粘膜接种的猕猴的BAL样本。我们还将对全身和粘膜免疫部位的分泌型免疫球蛋白A和抗体进行定量。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减少病毒症和保护感染病原病毒的猕猴的疾病进展联系起来。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.