IMMUNOGENETICS OF TRICHINELLA SPIRALIS

旋毛虫的免疫遗传学

• 批准号: 3137353
• 负责人: DONALD WASSOM
• 金额: $ 16.52万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3137353
• 关键词: Trichinella; alleles; cell growth regulation; cell population study; cellular immunity; developmental genetics; gene complementation; gene expression; genetic mapping; genetic strain; genetically modified animals; growth /development; histocompatibility antigens; histocompatibility gene; host organism interaction; humoral immunity; immunogenetics; immunoregulation; laboratory mouse; microorganism antigen; microorganism immunology; microscopy; plaque assay; trichinosis

Mice which express H-2 encoded I-E molecules are more susceptible to T. spiralis infection than mice which do not. Two additional H-2 genes and a gene on chromosome 4 are also known to influence the anti-Trichinella response. Experiments are proposed to compare the phenotypically expressed cellular and humoral anti-parasite responses regulated by each of the genes identified. For studies on the cellular and molecular mechanisms which underly the association between I-E expression and susceptibility to infection, transgenic mice which express I-E will be constructed by inserting the E alpha gene into I-E-negative mice which possess a functional gene at E beta. H-2 congenic strains of mice and selected offspring from matings between these strains will be studied to determine if certain I-E alleles are associated with susceptibility to infection while others are not. In addition, Fv-1 congenic strains of mice and offspring from crosses between them will be studied to more precisely map the gene on chromosome 4 which influences the anti-Trichinella responses, and to determine if the gene controlling I-J expression cosegregates with the gene controlling susceptibility to T. spiralis infection. A recently developed assay to enumerate parasite- specific antibody secreting cells will be used, along with populations of cloned, T. spiralis-specific T cells, to identify and characterize I-J positive, Trichinella-specific suppressor T cells, and to determine if autoreactive T cells with regulatory functions arise during the course of a T. spiralis infection. Functional antigens from different development stages of the parasite will be characterized using serum from susceptible and resistant mouse strains to precipitate antigens from soluble worm extracts. Monoclonal antibodies will be used to affinity purify relevant antigens from these preparations. Regulation of the immune response to protective antigens, purified to homogeneity, will be compared in susceptible and resistant strains in mice. The long range goal of this project is to determine how immune regulation differs in susceptible and resistant strains of hosts.

表达 H-2 编码的 I-E 分子的小鼠更 比不感染旋毛虫的小鼠更容易感染螺旋毛虫。 二 另外的 H-2 基因和 4 号染色体上的基因也是已知的 影响抗旋毛虫反应。 实验是 建议比较表型表达的细胞和 每个基因调节的体液抗寄生虫反应 确定。 用于细胞和分子机制的研究 这是 I-E 表达与 表达 I-E 的转基因小鼠对感染的易感性 通过将Eα基因插入I-E阴性构建 拥有E beta功能基因的小鼠。 H-2同源 小鼠品系和从它们之间交配中选出的后代 将研究这些菌株以确定某些 I-E 等位基因是否 与感染易感性相关，而其他则不然。 在 此外，Fv-1同系小鼠品系和杂交后代 将研究它们之间的关系，以更精确地绘制基因图谱 影响抗旋毛虫反应的 4 号染色体， 并确定控制 I-J 表达的基因是否 与控制旋毛虫易感性的基因共分离 感染。 最近开发的一种检测寄生虫的方法 将使用特异性抗体分泌细胞，以及 克隆的螺旋毛虫特异性 T 细胞群，以识别和 表征 I-J 阳性、旋毛虫特异性抑制 T 细胞， 并确定自身反应性T细胞是否具有调节功能 在螺旋毛虫感染过程中出现。 功能性 来自寄生虫不同发育阶段的抗原将被 使用来自易感和耐药小鼠的血清进行表征 菌株从可溶性蠕虫提取物中沉淀抗原。 单克隆抗体将用于亲和纯化相关 来自这些制剂的抗原。 免疫调节 对保护性抗原的反应，纯化至同质性，将是 比较小鼠的敏感菌株和耐药菌株。 长的 该项目的目标是确定免疫调节如何 宿主的敏感菌株和耐药菌株有所不同。