IMMUNE REGULATION IN CYSTICERCOSIS

囊尾蚴病的免疫调节

• 批准号: 2672316
• 负责人: Raymond E. Kuhn
• 金额: $ 18.22万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672316
• 关键词: Cestoda; T cell receptor; cellular immunity; cellular pathology; cytokine; enzyme linked immunosorbent assay; flow cytometry; gene expression; genetically modified animals; glycoproteins; helper T lymphocyte; host organism interaction; immunoregulation; immunosuppression; intracellular parasitism; laboratory mouse; molecular cloning; monoclonal antibody; neutralizing antibody; nucleic acid sequence; nucleotides; parasitic diseases; protein structure function

Larvae of cestode parasites cause disease in man and domestic animals. In man the larvae of Taenia solium often invade the central nervous system and cause a disease known as neurocysticercosis which has numerous neurological complications including blindness, dementia, convulsions and, not infrequently, death. The infection is characterized by an inefficient and inconsistent cellular immune response but often an intense humoral immune response. It has been shown in several taeniid parasite-host relationships that immune responses are suppressed. In recent experiments we have demonstrated that larvae of Taenia crassiceps in BALB/c mice induce immunosuppression of Th1-like responses, which one would expect to be involved in anti-larval cellular responses; Th2 responses are relatively unaffected. It was also determined that these larvae secrete a glycoprotein of 175 Kd (gp175), consisting of peptide subunits of 68 and 55/52 kDa, which selectively downregulates Th1 responses. Earlier we described similar secreted molecules by larvae of T. solium in patients with neurocysticercosis but did not determine their biological effects. Recent experiments have shown that gpl75 suppresses the ability of human peripheral blood lymphocytes to respond to stimulation with phytohemagglutinin. In the present proposal we are requesting support to continue the studies on the biological role of gpl75 by determining its activities in downregulating both the induction and expression of immune responses, the effects of neutralizing gpl75 on growth and development of larvae in vivo, and to clone the genes and produce recombinant subunit peptides in order to more readily determine the immunoregulatory activity of this parasite- derived immunosuppressive molecule.

寄生虫幼虫会引起人和家畜的疾病。在……里面 猪带绦虫幼虫常侵袭中枢神经系统 并导致一种称为脑囊虫病的疾病，这种疾病有许多 神经系统并发症包括失明、痴呆症、抽搐和， 死亡并不少见。这种感染的特点是效率低下。 和不稳定的细胞免疫反应，但通常是强烈的体液 免疫反应。它已经在几种带绦虫寄生虫宿主中显示出来 免疫反应被抑制的关系。在最近的实验中 我们已经证明粗带绦虫幼虫在BALB/c小鼠体内 诱导Th1样反应的免疫抑制，这是人们预期的 参与抗幼虫细胞反应；Th2反应是 相对不受影响。还确定这些幼虫分泌一种 175kD的糖蛋白(Gp175)，由68和 55/52 kDa，选择性下调Th1反应。早些时候我们 在患者中描述了类似的索氏毛滴虫幼虫分泌的分子 患有脑囊虫病，但没有确定它们的生物学效应。 最近的实验表明，gpl75可以抑制人类的能力。 外周血淋巴细胞对刺激的反应 植物血凝素。 在本提案中，我们请求支持继续进行研究。 通过测定gpl75在细胞内的活性探讨其生物学作用 下调免疫反应的诱导和表达， 中和gpl75对幼虫体内生长发育的影响 克隆基因并按顺序生产重组亚单位多肽 为了更容易地确定这种寄生虫的免疫调节活性- 衍生免疫抑制分子。