BOVINE IGG AND HUMAN IMMUNOLOGIC RESPONSES & DISEASES

牛乳IgG，在人体中发现的主要异种免疫球蛋白 饮食（通常为500毫克/天），有时被人体显著吸收， 选择性地存在于人类母乳中。 牛奶IgG具有不寻常的 对某些人Fc γ受体的特异性模式， 体外免疫调节特性。 我们的主要目标是测试一个 假设（与流行病学数据一致）， 可能与人类抗体结合， 在人体内的反应，并可能发挥作用的发病机制，一些 人类免疫性疾病 我们计划：（1）研究机制， 牛乳IgG抑制美洲商陆有丝分裂原的抗体分泌 体外刺激人外周血单个核细胞和B细胞 成熟途径抑制位点。 人类单核细胞将 与牛IgG制品一起培养以表征亚类区域， 和IgG的聚集体大小以及所观察到的 抑制作用 评价牛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 体外IgG对小鼠空斑形成细胞（PFC）应答的抑制作用 在人类系统中无法进行的研究。 评价体内作用 以及小鼠细胞在LPS诱导的和抗原特异性的 PFC反应，比较牛、人和小鼠IgG的抑制作用 亚类，以检查抑制机制和可能的抑制因子 细胞和/或因子。 (3)测量牛IgG水平和分子大小 的母亲母乳中含牛IgG组分的含量 正常婴儿和患有绞痛的婴儿的母亲。 为了研究蛋白水解， 吸收、细胞结合、经胎盘和经乳房通过， 和牛IgG在人和动物模型中的血清半衰期。 (4)到 确定牛IgG暴露、牛IgG血清水平或 牛IgG抗体与下列疾病的发生和严重程度有关： 婴儿绞痛，嗜酸性胃肠炎，并在初步 溃疡性结肠炎的研究。 这些目标将促进我们的长期目标： (1)研究IgG通过Fc γ R调节免疫应答，特别是 饮食来源的牛IgG对人免疫应答的影响 体外和体内。 (2)检查牛IgG和人类免疫应答的潜在作用 它在婴儿绞痛，嗜酸性胃肠炎， 和溃疡性结肠炎

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.