BOVINE IGG AND HUMAN IMMUNOLOGIC RESPONSES & DISEASES

牛 IGG 和人类免疫反应

• 批准号: 3136690
• 负责人: ANTHONY KULCZYCKI
• 金额: $ 16.28万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3136690
• 关键词: antibody receptor; antiidiotype antibody; cell mediated cytotoxicity; colitis; cow; diet; human subject; immunoglobulin G; immunopathology; immunoregulation; laboratory mouse; leukocyte activation /transformation; milk; mitogens; plaque assay; rheumatoid factor; tissue /cell culture

Bovine milk IgG, the major xenogeneic immunoglobulin found in the human diet (often 500 mg/day), is sometimes significantly absorbed in humans and selectively found in human breast milk. Bovine milk IgG has an unusual specificity pattern for some human FcGamma receptors and has immunomodulatory properties in vitro. Our major aim is to test a hypothesis (consistent with epidemiologic data) that dietary bovine IgG, possibly in conjunction with human antibodies, may significantly influence human responses in vivo and may play a role in the pathogenesis of some human immunologic diseases. We plan: (1) To study mechanisms by which bovine milk IgG inhibits antibody secretion from pokeweed mitogen stimulated human peripheral blood mononuclear cells in vitro, and B cell maturation pathway sites of inhibition. Human mononuclear cells will be cultured with bovine IgG preparations to characterize the subclass region, and aggregate size of IgG and the cell types involved in the observed inhibition. To evaluate effects of bovine IgG on spontaneous antibody secretion, mitogenesis, MLR, and cytotoxicity. (2) To examine bovine milk IgG inhibition of mouse plaque-forming cell (PFC) responses in vitro with studies not possible in the human system. To evaluate effects of in vivo and in vitro exposure of mouse cells on LPS-induced and antigen-specific PFC responses, to compare inhibitory effects of bovine, human and mouse IgG subclasses, to examine mechanisms of inhibition and possible suppressor cells and/or factors. (3) To measure bovine IgG levels and molecular size of bovine IgG-containing fractions in human breast milk in mothers of normal infants and mothers of infants with colic. To study proteolysis, absorption, cellular association, transplacental and transmammary passage, and serum half-life of bovine IgG in humans and animal models. (4) To determine whether bovine IgG exposures, serum levels of bovine IgG, or antibodies to bovine IgG are related to the occurrence and severity of infantile colic, of eosinophilic gastroenteritis, and, in preliminary studies, of ulcerative colitis. These aims will further our long term objectives: (1) Studying regulation of immune responses by IgG via FcGammaR, esp. the effects of bovine IgG from dietary sources on human immune responses in vitro and in vivo. (2) Examine potential roles of bovine IgG and of human immune responses to it in the pathogenesis of infantile colic, eosinophilic gastroenteritis, and ulcerative colitis.

牛牛奶IgG，人类中发现的主要异构免疫球蛋白 饮食（通常为500毫克/天），有时会显着吸收 在人类母乳中有选择地发现。 牛牛奶IgG有不寻常的 某些人fcgamma受体的特异性模式，并且具有 体外免疫调节特性。 我们的主要目的是测试 假设（与流行病学数据一致），饮食中的牛IgG， 可能与人类抗体结合使用，可能会显着影响 人体反应在体内，可能在某些的发病机理中发挥作用 人类免疫疾病。 我们计划：（1）研究机制 牛牛奶IgG抑制pokeweed有丝分裂的抗体分泌 在体外刺激人类外周血单核细胞和B细胞 抑制的成熟途径。 人类的单核细胞将是 用牛IgG制剂培养以表征亚类区域， IgG的骨料大小以及所观察到的细胞类型 抑制。 评估牛IgG对自发抗体的影响 分泌，有丝分裂，MLR和细胞毒性。 （2）检查牛奶 IgG抑制小鼠形成细胞（PFC）反应在体外与 人类系统不可能进行研究。 评估体内的影响 小鼠细胞在LPS诱导的和抗原特异性上的体外暴露 PFC反应比较牛，人和小鼠IgG的抑制作用 子类，检查抑制和可能的抑制剂机制 细胞和/或因素。 （3）测量牛IgG水平和分子大小 母亲的母乳中含牛IgG的含量 绞痛婴儿的正常婴儿和母亲。 研究蛋白水解， 吸收，细胞缔合，移植和跨乳腺癌， 和人类和动物模型中牛IgG的血清半衰期。 （4）至 确定牛IgG暴露，牛IgG的血清水平还是 牛IgG的抗体与发生的发生和严重程度有关 婴儿绞痛，嗜酸性胃肠炎，初步 研究，溃疡性结肠炎。 这些目标将进一步我们的长期目标： （1）研究IgG通过FCGAMMAR研究免疫反应的调节，尤其是。这 饮食来源的牛IgG对人类免疫反应的影响 体内和体内。 （2）检查牛IgG和人类免疫反应的潜在作用 它在婴儿绞痛，嗜酸性胃肠炎的发病机理中， 和溃疡性结肠炎。