BOVINE IGG AND HUMAN IMMUNOLOGIC RESPONSES & DISEASES

牛乳免疫球蛋白，人类体内发现的主要异种免疫球蛋白 饮食(通常是每天500毫克)，有时在人体内被大量吸收， 选择性地存在于人类母乳中。牛乳免疫球蛋白有一种不同寻常的 某些人FcGamma受体和Has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)饮食中的牛免疫球蛋白， 可能与人类抗体结合，可能会显著影响 人体在体内的反应，可能在某些疾病的发病机制中发挥作用 人类免疫性疾病。我们计划：(1)研究通过什么机制 牛乳免疫球蛋白抑制商陆有丝分裂原抗体的分泌 体外刺激人外周血单个核细胞和B细胞 成熟途径的抑制部位。人类单个核细胞将成为 用牛免疫球蛋白制剂培养以鉴定亚类区域， 以及免疫球蛋白的聚集大小和所观察到的细胞类型 抑制力。评价牛免疫球蛋白对自发抗体的影响 分泌、有丝分裂、MLR和细胞毒性。(2)检测牛乳 环磷酰胺对小鼠空斑形成细胞免疫球蛋白的体外抑制作用 研究在人类系统中是不可能的。为了评价体内试验的效果 体外暴露小鼠细胞对内毒素诱导和抗原特异性的影响 PFC反应，比较牛、人和鼠免疫球蛋白的抑制效果 子类，以研究抑制机制和可能的抑制子 细胞和/或因子。(3)测定牛免疫球蛋白水平和分子大小 婴儿母亲母乳中含牛免疫球蛋白组分的检测 正常婴儿和绞痛婴儿的母亲。为了研究蛋白质分解， 吸收，细胞联合，经胎盘和跨乳房通道， 牛免疫球蛋白在人和动物模型中的血清半衰期。(4)至 确定牛免疫球蛋白暴露、血清牛免疫球蛋白水平或 抗牛免疫球蛋白抗体与猪瘟的发生和严重程度有关 婴儿绞痛，嗜酸性胃肠炎，初步 溃疡性结肠炎的研究。 这些目标将会推动我们的长远目标： (1)研究免疫球蛋白通过FcGammaR等途径对免疫应答的调节作用。这个 日粮牛免疫球蛋白对人免疫功能的影响 体外和体内。 (2)检测牛免疫球蛋白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制中起重要作用。 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.