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

项目总结/摘要 定植在新生儿胃肠道的肠道细菌可能对新生儿的胃肠道产生长期的影响。 免疫系统，因为新生儿微生物群的改变与 在以后的生活中的疾病，如哮喘，过敏或炎症性肠病。然而，人们对此知之甚少。 抗原特异性免疫反应的新生儿肠道细菌。因此，这笔赠款的前提是， 确定初始抗原特异性T细胞和B细胞对细菌的应答是 了解新生儿肠道细菌如何对免疫系统产生长期影响。在这里， 我们将利用我们在成年小鼠中TCR库和肠道细菌反应性方面的经验， 表征新生儿中的T细胞应答（目的1）。我们还将研究母体伊加的作用，以及它是如何 影响早期T和B细胞应答（目的2）。最后，我们会问，这些早期适应性反应是否 被产前抗生素或新生儿感染破坏，可能为异常粘膜 免疫稳态（目标3）。因此，这些数据将产生对抗原特异性的更深入的理解。 新生儿免疫应答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.