NEW MURINE MODELS OF PNEUMOCYSTIS CARINII INFECTION

卡氏肺囊虫感染的新鼠模型

• 批准号: 3139340
• 负责人: CHARLES L SIDMAN
• 金额: $ 21.78万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-15 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3139340
• 关键词: AIDS; B lymphocyte; Pneumocystis; Pneumocystis pneumonia; T lymphocyte; alleles; antibody dependent killer cell; antibody specificity; autoimmune disorder; biological polymorphism; bone marrow transplantation; cellular immunity; clone cells; disease /disorder model; enzyme linked immunosorbent assay; flow cytometry; gene expression; gene mutation; genetic manipulation; helper T lymphocyte; histochemistry /cytochemistry; histocompatibility antigens; immunochemistry; immunofluorescence technique; immunogenetics; laboratory mouse; lipopolysaccharides; lysosomes; major histocompatibility complex; model design /development; monoclonal antibody; opportunistic infections; protozoal antigen; radiation genetics; scanning electron microscopy; suppressor T lymphocyte; tissue /cell culture; tissue mosaicism

Pneumocystis carinii (Pc) is a poorly understood but significant current health problem in immunocompromised individuals, including those with Acquired Immunodeficiency Syndrome. To gain more information concerning the basic biology and opportunities for intervention with this organism, this project will develop and exploit two new models of Pc infection in the mouse to study the immunological mechanisms and genetic determinants of variation in the mammalian response to Pc. The following three specific aims will be addressed. 1. Development of two new murine models of Pc infection. These are: a. The single gene mutation "severe combined immunodeficiency" (gene symbol scid). Homozygotes for this mutation have essentially no antigen-specific immunity at any time in their lives, and develop and die from severe Pc infection. b. Irradiated normal recipients of bone marrow from mice bearing the "lymphoproliferation" (symbol lpr) mutation. Unlike recipients of normal marrow, recipients of lpr marrow develop an apparent autoimmune syndrome that leads ultimately to profound cellular depletion of the lymphoid system, (presumed) severe immunodeficiency, and clinically evident Pc infection. 2. What are the important immunological mechanisms in resistance to and pathogenesis from Pc? The roles of a. B lymphocytes and antibodies, b. T lymphocytes, and c. non-antigen- specific accessory cells will be evaluated. 3. What are the genetic determinants of variation in the host's immunological and pathological responses to Pc? While exposing various animals to a common source of Pc, we will examine the effects of different alleles at a. the Major Histocompatibility complex (MHC), since this has major consequences for many forms of immunological reactivity, and b. non-MHC loci. (If such differences are found, the number and location of the non-MHC genes responsible will be sought.) The methodologies to be employed in these studies include histological and ultrastructural tissue examination at the light and electron microscopic levels, ELISA assays, cellular immunofluorescence and FACS analysis, tissue immunohistochemistry in vitro generation and in vivo utilization of monoclonal antibodies and T cell lines and clones, and classical genetic crosses using inbred and congenic mouse strains.

肺囊藻carinii（PC）是一个鲜为人知的，但很重要 免疫功能低下的个体中的当前健康问题， 包括患有免疫缺陷综合征的患者。 到 获取有关基本生物学的更多信息和 干预该生物的机会，该项目将 开发和利用鼠标中PC感染的两种新模型 研究免疫机制和遗传决定因素 哺乳动物对PC的反应的变化。 下列 将解决三个具体目标。 1。开发了两种新的PC感染鼠模型。 这些都是： 一个。 单基因突变“严重的合并 免疫缺陷”（基因符号SCID）。纯合子 该突变本质上没有抗原特异性免疫力 在他们生活中的任何时候，并因严重而发展和死亡 PC感染。 b。 辐照小鼠骨髓的正常接受者 带有“淋巴增生”（符号LPR）突变。 与正常骨髓的接受者不同，LPR的接受者 骨髓发展出明显的自身免疫性综合症 最终导致细胞的深刻耗竭 淋巴系统（假定）严重免疫缺陷，并且 临床上明显的PC感染。 2。什么是重要的免疫机制 PC的抵抗力和发病机理？ 一个。 b 淋巴细胞和抗体，b。 T淋巴细胞和c。非抗原 将评估特定的附件单元。 3。宿主变异的遗传决定因素是什么 免疫和病理对PC的反应？ 在暴露时 各种动物是PC的常见来源，我们将检查 不同等位基因的影响。 主要的组织相容性 复杂（MHC），因为这对许多人产生了重大影响 免疫反应的形式，b。非MHC基因座。 （如果是这样 发现差异，非MHC的数量和位置 将寻求负责的基因。） 这些研究中要采用的方法包括 组织学和超微结构组织检查 电子显微镜水平，ELISA分析，细胞 免疫荧光和FACS分析，组织 免疫组织化学体外产生和体内利用率 单克隆抗体，T细胞系和克隆的含量以及经典 遗传十字架使用近交和先天小鼠菌株。