URINARY TRACT INFECTIONS--IMMUNE BASIS OF SUSCEPTIBILITY

尿路感染——易感性的免疫基础

• 批准号: 2444061
• 负责人: WALTER J HOPKINS
• 金额: $ 21.25万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444061
• 关键词: B lymphocyte; Escherichia coli; MHC class II antigen; T cell receptor; T lymphocyte; adult human (21+); antibacterial antibody; bacterial antigens; bactericidal immunity; child (0-11); family genetics; female; genetic strain; human subject; immune tolerance /unresponsiveness; immunodeficiency; immunogenetics; immunopathology; laboratory mouse; relapse /recurrence; urinary bladder epithelium; urinary tract infection; virulence; western blottings

DESCRIPTION: (Adapted from the applicant's abstract) UTI remain a common and serious clinical problem that affect 10-15 percent of all women in their lifetime. Women seeking treatment for acute UTI account for over 5 million visits to physician's offices annually in the United States. Health care costs to treat only uncomplicated lower tract infections are nearly one billion dollars per year. The most accepted hypothesis for the pathophysiology of ascending UTI in susceptible women is that uropathogens carried in the fecal flora sequentially colonize the vaginal introitus, urethra, bladder, and finally the kidneys. E. coli strains are responsible for the majority of UTIs and have specific virulence factors such as adhesins for uroepithelial cell receptors, certain O and K antigens, and hemolysins. The reasons for increased susceptibility of female children and certain adult women are unknown but may be due to increased binding of E. coli to epithelial cells lining the vagina and bladder in conjunction with decreased levels of urinary antibody to infecting organisms. The roles of immune defects in UTI have not been comprehensively studied, although immunologic hyporesponsiveness in UTI may be a critical and heretofore undefined factor in explaining susceptibilities. The author's work with animal models of increased susceptibility to UTI has shown that: 1) severe T and B cell deficiencies decrease the ability of mice to resolve an infection; 2) induced hyporesponsiveness to E. coli in monkeys leads to poor resolution of an E. coli UTI; 3) increased levels of serum and urinary anti E. coli antibody correlate with early resolution of an E. coli UTI; 4) inbred mouse strains have variable susceptibility to an E. coli UTI; and 5) the specificities of anti E. coli antibodies produced in mice correlate with susceptibility to UTI. Studies of patients with recurrent UTI's have shown that they have different patterns of antibody responses to E. coli antigens than nonsusceptible women and different frequencies of some major histocompatibility antigens. The proposed research will focus on defining an immunogenetic basis of susceptibility to UTIs. It will: 1) define the nature and role of genetically determined immunodeficiency in murine UTI susceptibility; 2) determine the role of acquired immunologic hyporesponsiveness in development of UTIs; and 3) investigate the heritability of susceptibility to UTIs.

描述：（根据申请人的摘要进行了改编）UTI仍然是 常见和严重的临床问题影响了所有人的10-15％ 女性一生。寻求急性UTI帐户治疗的妇女 每年在曼联每年访问医师办公室的500万次访问 国家。医疗保健费用仅处理简单的下层 每年感染近十亿美元。最接受的 易感妇女升级UTI的病理生理学的假设 是在粪便植物群中携带的尿道疾病依次定植 阴道介绍，尿道，膀胱，最后是肾脏。 E. 大肠杆菌菌株对大多数UTI负责，并且具有特定 毒力因子，例如用于巨细胞受体的粘附素， 某些O和K抗原和血素蛋白。增加的原因 女子女和某些成年女性的敏感性未知 但可能是由于大肠杆菌与上皮细胞的结合增加所致 与水平降低的阴道和膀胱衬里 感染生物体的尿抗体。免疫缺陷的作用 尽管免疫学 UTI中的低回应可能是一个关键的，迄今为止未定义 解释敏感性的因素。作者与动物的合作 对UTI敏感性增加的模型表明：1）严重的T和 B细胞缺陷降低了小鼠解决A的能力 感染; 2）在猴子中引起大肠杆菌的诱发性不足导致 大肠杆菌UTI的分辨率不佳； 3）血清水平增加和 尿抗大肠杆菌抗体与E.早期分辨率相关。 大肠杆菌; 4）近交小鼠菌株对E具有可变的敏感性。 大肠杆菌; 5）产生的抗大肠杆菌抗体的特异性 在小鼠中，与对UTI的敏感性相关。患者的研究 复发性尿路表示表明它们具有不同的抗体模式 对大肠杆菌抗原的反应比不敏感的女性和不同 一些主要的组织相容性抗原的频率。提议 研究将着重定义易感性的免疫遗传基础 到乌蒂斯。它将：1）定义遗传学的性质和作用 在鼠UTI易感性中确定的免疫缺陷； 2）确定 获得的免疫学不足在发展中的作用 尿路3）调查对尿路感染易感性的遗传力。