IMMUNOGENETICS OF TRICHINELLA SPIRALIS IN THE MOUSE

小鼠旋毛虫的免疫遗传学

• 批准号: 3137351
• 负责人: DONALD WASSOM
• 金额: $ 17.01万
• 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/3137351
• 关键词: alleles; cell growth regulation; cell population study; cellular immunity; developmental genetics; gene complementation; gene expression; genetic mapping; genetic strain; growth /development; histocompatibility antigens; histocompatibility gene; host organism interaction; humoral immunity; immunogenetics; immunoregulation; 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 比不感染旋毛虫的小鼠更容易感染旋毛虫。二 其他H-2基因和4号染色体上的一个基因也是已知的 以影响抗旋毛虫的反应。实验是 建议比较表型表达的细胞和 体液抗寄生虫反应受各基因调控 确认身份。用于细胞和分子机制的研究 它强调了I-E表达和 易受感染，表达I-E Will的转基因小鼠 将Eα基因插入I-E阴性区构建 拥有Eβ功能基因的小鼠。H-2同源基因 品系的小鼠及其交配的精选后代 将对这些菌株进行研究，以确定某些I-E等位基因是否 与感染的易感性有关，而其他人则不是。在……里面 此外，FV-1同基因株小鼠及其杂交后代 将对它们之间的关系进行研究，以更准确地将基因映射到 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。最近开发的一种方法来计数寄生虫- 将使用特异性抗体分泌细胞，以及 克隆的旋毛虫特异性T细胞群体，以识别和 鉴定I-J阳性旋毛虫特异性抑制性T细胞， 并确定自身反应性T细胞是否具有调节功能 在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是 用敏感和耐药小鼠的血清来表征 从可溶性虫子提取物中沉淀抗原的菌株。 将单抗用于亲和纯化相关 这些制剂中的抗原。免疫调节 对保护性抗原的反应，纯化到均一，将是 在小鼠身上比较了敏感和耐药菌株。《长河》 这个项目的范围目标是确定免疫调节如何 寄主的敏感品系和抗性品系不同。