NATURAL HISTORY STUDIES: GBS AND PNEUMOCOCCAL INFECTION

此更新计划的目标是进一步探讨 肺炎链球菌感染的自然病史， B组链球菌(GBS)、b型流感嗜血杆菌。 这三种病原体是细菌感染最严重的原因。 在婴儿和儿童身上，并且仍然是主要的疾病原因 在其他方面健康的年轻女性(GBS产后感染)和 老年成人(肺炎球菌)。它们有许多共同的生物学和 免疫学特征，以及他们的疾病潜在性 尽管在抗生素治疗和开发方面取得了进展，但仍处于高位 疫苗的数量。令人满意的预防模式还有待于 意识到了。本节目将重点关注主持人的关键方面- 寄生虫之间的关系可能有助于解释 并提出预防疾病的新方法 核心项目为整个项目提供临床支持。 同时继续提供重要的流行病学信息 通过新的和正在进行的临床研究，它提供了必要的 患者材料、细菌分离株和流行病学数据 从定义明确的患者群体中。血清流行病学 调查项目1将利用这些材料来更多地 准确定义免疫学术语中的“保护”。它的研究 将从以下方面评估功能性(吞噬细胞)抗体 到测量的属性，批判性地检查亲和力的作用 并被特定的IgA抗体阻断。抗体的研究 除操作外的其他功能将集中在激活上 在体外和急性疾病中对血小板和中性粒细胞的影响。 GBS多糖的免疫化学将在#年进行研究 项目2.GBS抗原和GBS之间的相似性 人类宿主的糖偶联物将被检查与 殖民和疾病。这些的分子基础 将使用现代核磁共振技术、单克隆技术来研究相似性 抗体和化学修饰的GBS抗原：概念 “毒性”将从生物特性方面进行检查。 细菌和它们的多糖胶囊。 项目3将研究沙门氏菌表面蛋白抗原 肺炎球菌开发一种蛋白质分型系统并评估 表面蛋白作为候选疫苗的可能应用。 表面蛋白的流行病学--将进行相关研究 人类对肺炎球菌定植的抗体反应和 疾病。

The objective of this renewal program is to further explore the natural history of infections caused by Streptococcus pneumoniae, group B streptococcus (GBS), and Hemophilus influenzae type b. These three pathogens account for most serious bacterial infection in infants and children and remain significant causes of disease in otherwise healthy young women (GBS puerpural infections) and in aging adults (the pneumococcus). They share many biological and immunological features, and their disease potential has continued to be high, despite advances in antibiotic therapy and development of vaccines. Satisfactory modes of prevention have yet to be realized. This program will focus upon key aspects of host- parasite relationships that may help explain the development of disease and suggest new approaches to its prevention The Core Project provides clinical support for the entire program. While continuing to yield important epidemiologic information through new and ongoing clinical studies, it provides essential patient materials, bacterial isolates, and epidemiological data from well defined patient populations. Seroepidmeiological investigations Project 1 will make use of these materials to more precisely define "protection" in immunological terms. Its studies will evaluate functional (opsonophagocytic) antibody with respect to measured properties, critically examining the roles of avidity and blocking by specific IgA antibodies. Studies of antibody functions other than opsonization will focus upon the activation of platelets and neutrophils in vitro and in acute disease. The immunochemistry of GBS polysaccharides will be studied in Project 2. The similarities between GBS antigens and glycoconjugates of the human host will be examined in relation to colonization and disease. The molecular basis for these similarities will be studied with modern NMR techniques, monoclonal antibodies, and chemically modified GBS antigens: The concept of "virulence" will be examined with respect to biological properties of the bacteria and their polysaccharide capsules. Project 3 will study the surface protein antigens of the pneumococci to develop a protein typing system and to evaluate the possible application of surface proteins as candidate vaccines. The epidemiology of surface protein--will be studied in correlation with the human antibody response to pneumococcal colonization and disease.