MUCOSAL AND SERUM IGA SYSTEMS IN AIDS

艾滋病中的粘膜和血清 IGA 系统

• 批准号: 2062397
• 负责人: SUSAN JACKSON
• 金额: $ 19.69万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2062397
• 关键词: AIDS; HIV infections; SCID mouse; antibody receptor; antigen antibody reaction; antiviral antibody; colostrums; cytokine; female; galactose; galactosyltransferases; human subject; immune complex; immunoglobulin A; intestinal mucosa; neutralizing antibody; secretory immune system; tissue /cell culture

The importance of the mucosal immune system in pathogenesis HIV infection and its potential significance in the production of protective vaccines has only recently been acknowledged. It is clear that infection with this virus profoundly affects the mucosal immune system. Particularly noteworthy is the effect on the gastrointestinal tract. The present application proposes to extend ongoing studies aimed at defining parameters of the human IgA system in HIV infection. This will be done by fully characterizing the functions of secretory IgA anti-HIV antibodies isolated from the colostrum of seropositive women, determining the role(s) of IgA antibodies in mediating infection of mucosal epithelial cells and by studying IgA function in vivo using severe combined immunodeficient (SCID) mice reconstituted with human cells and infected with HIV. The following specific aims are proposed: 1. Determination of the potential of IgA antibodies to enhance HIV infection of epithelial cells via either the polymeric immunoglobulin receptor (secretory compontent, SC) or by carbohydrate-mediated interactions (galactose of IgA molecules and cell surface galactosyltransferase), using the HT29 and T84 human cell lines of gastrointestinal origin known to express SC and galactosyltransferase; 2. Elucidation of the role of cytokines in enhancement of infection and uptake of HIV by gastrointestinal epithelial cell lines; 3. Characterization of the function(s) of secretory IgA anti-HIV antibodies isolated from the colostrum of HIV-positive mothers.

粘膜免疫系统在HIV感染发病机制中的重要性 及其在保护性疫苗生产中的潜在意义 直到最近才被承认。很明显，感染了这种病毒 病毒对粘膜免疫系统有深远的影响。尤其是 值得注意的是对胃肠道的影响。现在 应用程序建议扩展正在进行的研究，旨在定义 人类免疫球蛋白A系统在HIV感染中的参数这件事会做到的 通过充分研究分泌型IgA抗HIV的功能 从血清阳性妇女的初乳中分离的抗体，测定 免疫球蛋白A抗体在介导粘膜感染中的作用(S) 上皮细胞和免疫球蛋白A功能的体内研究 重组人细胞联合免疫缺陷(SCID)小鼠 感染了艾滋病毒。提出了以下具体目标：1. 免疫球蛋白A抗体增强HIV感染潜能的测定 通过聚合免疫球蛋白受体 (分泌成分，SC)或通过碳水化合物介导的相互作用 (IgA分子的半乳糖和细胞表面半乳糖基转移酶)， 利用已知的胃肠道来源的HT29和T84人类细胞系 表达SC和半乳糖基转移酶；2.阐明Sc和半乳糖基转移酶的作用 细胞因子在促进人类免疫缺陷病毒感染和吸收中的作用 胃肠上皮细胞系；3.人胃肠上皮细胞系的特性 人类免疫缺陷病毒分泌型抗HIV抗体的功能(S) 艾滋病毒阳性母亲的初乳。