IGA OF SERUM GLOBULINS AND EXTERNAL SECRETIONS

这笔赠款支持了我们的长期努力， 分泌免疫系统 我们试图阐明 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。 粘膜研究 免疫具有广泛医学意义。 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 研究以下内容：派尔集合淋巴结（PP）中的B细胞如何成为 致力于伊加。 IG类切换将使用反向斑块进行研究， 放射免疫分析，并在分子水平上与cDNA探针的 各种CH基因。 将尝试诱导从CMU切换到 C α与T细胞因子、Fc α片段和抗Ig。 的 PP中辅助细胞的特征将使用 抗巨噬细胞和树突细胞的单克隆抗体，抗原特异性 T细胞克隆和同种异体反应性T细胞系。 我们将探讨 口服给予抗原导致同时发生 分泌性抗体的诱导和全身抑制（口服 公差）。 口服耐受性的遗传调控及 IgG的同种型特异性Ts，伊加的TH和来源于 将对这些细胞进行研究。 小鼠伊加缺乏模型（抗IgA 体内）将被用来研究分泌系统的作用， 口服耐受性和调节摄入抗原的吸收。 我们 将探讨是否口服免疫肿瘤细胞（有和没有 白细胞介素-2）导致细胞毒性T细胞和肿瘤免疫。 研究 概述了新生儿的伊加和分泌性免疫反应， CBA/N小鼠。 新生小鼠将用各种细胞 包括那些富含辅助细胞的制剂，以确定 对伊加反应的个体发育的影响。 最后，T细胞“归巢”到 肠和远端粘膜部位（使用来自 各种来源）将用于正常、辐射和裸/裸小鼠 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.