IGA OF SERUM GLOBULINS AND EXTERNAL SECRETIONS

这笔赠款支持了我们长期的努力，以确定 分泌型免疫系统。我们曾试图阐明 所涉及的细胞和分子以及它们的详细机制 粘膜水平的相互作用使宿主能够继续 与潜在的有害环境因素发生冲突。关于粘膜的研究 免疫力具有广泛的医学意义。例如，在 对传染病和过敏性疾病的抵抗力和免疫预防； 其中许多主要影响粘膜。具体来说，我们将 研究如下：Peyer‘s Patches(PP)中的B细胞是如何变成 致力于免疫球蛋白A。将使用反向斑块来研究IG类切换， 放射免疫分析，并在分子水平上用cDNAs探针检测 不同的CH基因。将尝试促使从CMU切换到 有T细胞因子的CAlpha、FcAlpha片段和抗Ig。这个 PP中的辅助细胞特性将使用以下方法进行评估 抗巨噬细胞和树突状细胞的单抗，抗原特异性 T细胞克隆和同种异体反应性T细胞系。我们将探索 口服抗原导致并发的机制 分泌型抗体的诱导和全身抑制(口服 容忍度)。口服耐受性的遗传调控及其作用 免疫球蛋白同型特异性T_s、免疫球蛋白A同型特异性T_H和来源于 这些细胞将被研究。一种小鼠免疫球蛋白A缺乏模型(抗-IgA 体内)将被用来研究分泌系统在 口服耐受性和调节摄入抗原的吸收。我们 将探索口服肿瘤细胞免疫(有和没有) IL-2)可诱导细胞毒性T细胞和肿瘤免疫。研究 概述了新生儿和新生儿的免疫球蛋白A和分泌性免疫反应 CBA/N小鼠。新生的小鼠将被重组为各种细胞 包括那些富含辅助细胞的制剂，以确定 对免疫球蛋白A应答个体发育的影响。最后，T细胞“归巢”到 肠道和远端粘膜部位(使用126IUDR标记的T细胞 各种来源)将用于正常、照射和裸鼠 以确定T细胞是否影响B细胞的迁移模式。

This grant has supported our long-term efforts to characterize the secretory immune system. We have attempted to elucidate the nature of the cells and molecules involved and the detailed mechanisms by which their interactions at the mucosal level equip the host for its continuing conflict with potentially harmful environmental agents. Studies on mucosal immunity have a wide range of medical implications. For example, in resistance and immunoprophylaxis against infectious and allergic diseases, many of which primarily affect mucous membranes. Specifically, we will investigate the following: How B cells in Peyer's patches (PP) become committed to IgA. Ig class switching will be studied using reverse plaque, radioimmunoassay, and at the molecular level with cDNA probes for the various CH genes. Attempts will be made to induce switching from CMu to CAlpha with T cell factors, FcAlpha Fragments and anti-Ig. The characteristics of accessory cells in the PP will be assessed using monoclonal antibodies to macrophages and dendritic cells, antigen specific T cell clones and alloreactive T cell lines. We will explore the mechanisms by which orally administered antigens result in the concurrent induction of secretory antibodies and systemic suppression (oral tolerance). The genetic regulation of oral tolerance and the role of isotype specific Ts for IgG, TH for IgA and soluble factors derived from these cells will be studied. A model for IgA deficiency in mice (anti-IgA in vivo) will be used to investigate the role of the secretory system in oral tolerance and in regulating the absorption of ingested antigens. We will explore whether oral immunization with tumor cells (with and without inter-leukin-2) leads to cytotoxic T cells and tumor immunity. Studies are outlined on the IgA and secretory immune responses in the neonate and CBA/N mice. Neonatal mice will be reconstituted with various cell preparations including those enriched in accessory cells to determine the effect on the ontogeny of the IgA response. Finally, T cell "homing" to the gut and distal mucosal sites (using 126IUDR labeled T cells from various sources) will be employoed in normal, irradiated and nude/nude mice to determine if T cells influence the migration patterns of B cells.