Protective role of cross-reactive anti-enteric antibody

描述（由申请方提供）：我们假设，土著植物群引发了适应性免疫应答，这些适应性免疫应答可在与病原体（与宿主具有共同或相似的细胞表面抗原）初次感染期间招募。我们使用啮齿类柠檬酸杆菌，小鼠的粘膜病原体，研究这些反应的性质和招聘。我们小组先前的研究已经确定，早期T细胞依赖性血清抗体应答对于在感染的急性期存活至关重要，而预先存在的分泌型伊加似乎会影响定植的早期事件，从而影响随后的感染严重程度。该提案概述了一系列实验，以确定来自正常植物群的抗原，这些抗原引起针对啮齿柠檬酸杆菌的免疫球蛋白应答，啮齿柠檬酸杆菌是一种与EPEC和其他B类生物恐怖主义制剂相似的附着和消失病原体。我们将确定血清和粘膜抗体对这些共同抗原的作用，目的如下：（1）确定C。啮齿类和啮齿类物种，初次感染的小鼠对其产生抗体应答，（2）产生针对这些抗原的单克隆粘膜（伊加）和血清（IgG或IgM）抗体，并评估施用的免疫球蛋白影响定殖和症状性感染的发展的能力，（3）确定通过使用交叉反应性抗原的系统性疫苗接种策略在野生型和免疫缺陷小鼠中赋予的保护。这些实验的结果将为理解土著植物群的免疫保护功能提供分子基础，并有助于开发更好的疫苗和治疗方法，以提供对许多人类和兽医重要的肠道病原体的广泛保护。

DESCRIPTION (provided by applicant): We hypothesize that the indigenous flora primes adaptive immune responses that can be recruited during primary infection with pathogens that share common or similar cell surface antigens with commensals. We use Citrobacter rodentium, a mucosal pathogen of mice, to study the nature and recruitment of these responses. Prior studies by our group have identified that an early T cell-dependent serum antibody response is critical for surviving the acute phase of infection while pre-existing secretory IgA appears to impact early events in colonization, which influence the subsequent severity of infection. This proposal outlines a series of experiments to define antigens from normal flora that elicit immunoglobulin responses against Citrobacter rodentium, an attaching and effacing pathogen similar to the EPEC and other class B bioterrorism agents. We will determine the role of serum and mucosal antibody against these shared antigens with the following aims:(1) identify antigens shared between C. rodentium and commensal species to which mice naive to infection generate an antibody response, (2) develop monoclonal mucosal (IgA) and serum (IgG or IgM) antibodies against these antigens and assess the ability of administered immunoglobulin to impact colonization and the development of symptomatic infection (3) ascertain protection conferred in wild-type and immunodeficient mice by systemic vaccination strategies using cross-reactive antigens. The results from these experiments will provide a molecular basis for understanding the immunoprotective functions of the indigenous flora, and can assist in the development of better vaccines and therapeutics to provide broad protection against many enteric pathogens of human and veterinary importance.