IGA OF SERUM GLOBULINS AND EXTERNAL SECRETIONS

血清球蛋白和体外分泌物的 IGA

• 批准号: 3156044
• 负责人: THOMAS B TOMASI
• 金额: $ 27.86万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3156044
• 关键词: B lymphocyte; T lymphocyte; cellular immunity; clone cells; complementary DNA; genetic regulation; immunoglobulin A; lymphatic tissue; molecular pathology; monoclonal antibody; mucosa; radioimmunoassay; serology /serodiagnosis

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.

这笔赠款支持了我们长期努力来描述 分泌性免疫系统。 我们试图阐明其本质 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持续进行 与潜在有害的环境因素发生冲突。 粘膜研究 免疫力具有广泛的医学意义。 例如，在 针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：派尔氏淋巴结 (PP) 中的 B 细胞如何变成 致力于IgA。 将使用反向噬菌斑来研究 Ig 类别转换， 放射免疫分析，并在分子水平上使用 cDNA 探针 各种CH基因。 将尝试促使从 CMu 转向 CAlpha 与 T 细胞因子、FcAlpha 片段和抗 Ig。 这 PP 中辅助细胞的特征将使用以下方法进行评估 针对巨噬细胞和树突状细胞的单克隆抗体，抗原特异性 T 细胞克隆和同种反应性 T 细胞系。 我们将探索 口服抗原导致同时发生的机制 诱导分泌抗体和全身抑制（口服 宽容）。 口服耐受的基因调控及其作用 IgG 的同种型特异性 T、IgA 的 TH 以及衍生自的可溶性因子 这些细胞将被研究。 小鼠 IgA 缺乏症模型（抗 IgA 体内）将用于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 将探讨是否口服肿瘤细胞免疫（有或没有） inter-leukin-2) 导致细胞毒性 T 细胞和肿瘤免疫。 研究 概述了新生儿和新生儿的 IgA 和分泌性免疫反应 CBA/N 小鼠。 新生小鼠将用各种细胞进行重组 制剂，包括富含辅助细胞的制剂，以确定 对 IgA 反应个体发育的影响。 最后，T细胞“归巢”至 肠道和远端粘膜部位（使用 126IUDR 标记的 T 细胞，来自 各种来源）将用于正常小鼠、辐射小鼠和裸鼠 确定 T 细胞是否影响 B 细胞的迁移模式。