Evaluation of Antigen-Specific Immune Interactions with Commensal Bacteria in Neonates

项目摘要/摘要 定植于新生儿胃肠道的共生细菌可能会对 免疫系统，因为新生儿微生物区系的变化已与发展相关。 晚年疾病，如哮喘、过敏或炎症性肠病。然而，人们对此知之甚少 针对新生儿共生菌的抗原特异性免疫反应。因此，这笔赠款的前提是 确定抗原特异性T细胞和B细胞对共生菌的初始反应是 了解新生儿共生细菌如何对免疫系统产生长期影响。这里, 我们将利用我们在TCR谱系和成年小鼠的共生细菌反应方面的经验来 新生儿T细胞反应的特征(目标1)。我们还将研究母体免疫球蛋白A的作用以及它是如何 影响早期T和B细胞反应(目标2)。最后，我们会问，这些早期的适应性反应是否 被产前抗生素或新生儿感染扰乱，可能为异常粘膜奠定基础 免疫动态平衡(目标3)。因此，这些数据将产生对抗原特异性的更深层次的理解 新生儿免疫反应及其在免疫系统个体发育中的独特作用。

Project Summary/Abstract The commensal bacteria that colonize the neonatal gastrointestinal tract may exert long lasting effects on the immune system, as alterations in the neonatal microbiota have been associated with the development of diseases later in life such as asthma, allergy, or inflammatory bowel disease. However, little is known about the antigen-specific immune response to neonatal commensal bacteria. The premise of this grant, therefore, is that determining the initial antigen-specific T and B cell response to commensal bacteria is fundamental to understanding how neonatal commensal bacteria may exert long-lasting effects on the immune system. Here, we will leverage our experience with TCR repertoires and commensal bacterial reactivity in adult mice to characterize to T cell response in neonates (Aim 1). We will also examine the role of maternal IgA and how it affects the early T and B cell response (Aim 2). Finally, we will ask whether these early adaptive responses are disrupted by ante-partum antibiotics or neonatal infections, potentially setting the stage for abnormal mucosal immune homeostasis (Aim 3). Thus, these data will generate a deeper understanding of the antigen-specific neonatal immune response and its unique role in the ontogeny of the immune system.