IMMUNE RESPONSES IN VIVO TO EGG ANTIGENS OF S MANSONI

对曼氏曼氏菌卵抗原的体内免疫反应

• 批准号: 3141662
• 负责人: Donald A Harn
• 金额: $ 20.33万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1993-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3141662
• 关键词: Schistosoma mansoni; affinity chromatography; carbohydrate structure; egg proteins; electrofocusing; glycosylation; granuloma; helminthic antigen; high performance liquid chromatography; host organism interaction; immunological substance; immunopathology; laboratory mouse; lectin; lymphocyte proliferation; medical complication; microorganism classification; oligosaccharides; parasitic liver disorder; peptide structure; protein purification; protozoal vaccine; radionuclides; schistosomiasis

Schistosomiasis is a widespread helminthic disease of humans. The egg granuloma is the primary cause of pathology and morbidity. The immune response to the parasite eggs is normally modulated, down-regulated. Those persons who do not modulate the immune response to the eggs develop, in the case of mansoni and japonica, serious hepatosplenic disease. There is now mounting evidence that modulation in patients may be due to neonatal or in utero exposure to egg antigens or specific anti-idiotypic antibodies. This proposal describes experiments aimed at defining schistosome egg antigens which elicit granuloma formation. We propose to do this by separating saline soluble and urea soluble egg antigens into distinct pI fractions via agarose-isoelectricfocusing. The pI fractions will be covalently coupled to beads and tested in the bead granuloma assay. Granuloma-eliciting pI fractions would then be characterized, including testing for the presence of carbohydrate residues. We will determine the involvement of carbohydrate residues in the granulomatous response. The specific aims of this proposal are: 1) to test via the bead granuloma assay, the granuloma-eliciting properties of pI fractions of egg antigens; 2) to determine if granuloma-eliciting pI fractions contain carbohydrates, and if so, are these properties altered by de-glycosylation; 3) to test native or de-glycosylated KLH, or Lacto-N-fucopentaose III in the bead granuloma assay; 4) to investigate the cellular involvement in the putative granuloma response to carbohydrate epitopes; 5) to partially characterize the granuloma-eliciting antigens; 6) to isolate individual antigens, peptides, glycans or oligosaccharides and then retest these in the granuloma assay; 7) to test if isolated antigens, peptides, glycans or oligosaccharides sensitize naive mice for hepatic granuloma formation. The proposed research will identify egg antigen(s) which elicit granuloma formation in vivo. Identification of relevant antigen(s) will lead to studies on modulation of the granulomatous response due to in utero or neonatal exposure to these antigens. These experiments could lead to the development of an antipathology vaccine. Additionally, patients responsiveness to candidate egg antigens may allow us to predict which patients are likely to develop serious hepatosplenic disease, and therefore be more aggressive with drug intervention.

血吸虫病是一种广泛的人类蠕虫病。 鸡蛋 肉芽瘤是病理和发病率的主要原因。 免疫 通常调节对寄生虫卵的反应。 那些 不调节对鸡蛋的免疫反应的人 Mansoni和Japonica病例，严重的肝肾病。 现在有 越来越多的证据表明，患者的调节可能是由于新生儿或 子宫暴露于鸡蛋抗原或特定的抗IDiotypic抗体。 该建议描述了旨在定义黑素卵的实验 引起肉芽肿的抗原。 我们建议这样做 将盐水可溶性和尿素可溶性鸡蛋抗原分离成不同的PI 通过琼脂糖 - 以等分线的分数。 PI分数将是 共价耦合到珠子并在珠颗粒瘤测定中进行测试。 然后将颗粒状瘤PI分数进行表征，包括 测试碳水化合物残基的存在。 我们将确定 碳水化合物残基参与肉芽肿反应。 该提案的具体目的是：1）通过珠颗粒测试 测定，卵子抗原的PI级分的肉芽肿特性； 2）确定颗粒瘤pi级分是否包含碳水化合物， 如果是这样，这些特性是否会因去糖基化而改变。 3）测试 珠子中的天然或去糖基化的KLH，或珠子中的乳酸-N-渗透体III 肉芽肿测定； 4）研究推定的细胞参与 肉芽肿对碳水化合物表位的反应； 5）部分描述 颗粒瘤抗原； 6）分离单个抗原， 肽，聚糖或寡糖，然后在 肉芽肿测定； 7）测试是孤立的抗原，肽，聚糖还是 寡糖使天真小鼠对肝肉芽肿的形成敏感。 拟议的研究将确定引起肉芽肿的卵抗原 体内形成。 相关抗原的识别将导致 研究因子宫或子宫或 新生儿暴露于这些抗原。 这些实验可能导致 开发抗病理疫苗。 此外，患者 对候选蛋抗原的反应能力可能使我们能够预测 患者可能会出现严重的肝plenic疾病，因此 通过药物干预更具积极性。