Puberty, Immunity and Malnutrition in S. Japonicum

描述：这项提案的总体目标是前瞻性地 研究青春期、保护性免疫反应、 菲律宾血吸虫青少年居民的营养状况 确定日本血吸虫病流行区的免疫学和发育预测因子 自然暴露的人类的抵抗力是 正在努力开发日本血吸虫病疫苗。 人类对其他血吸虫保护性免疫反应的研究进展 发生在流行社区的青春期。最近的一项假说指出 青春期的激素变化，如脱氢表雄酮的增加 (DHEA)，而不是累积暴露，启动和促进 对血吸虫病的保护性免疫反应 与营养不良有因果关系，导致了慢性营养不良的假设 感染会导致年龄增长减慢，并可能推迟青春期 发展。慢性寄生虫血症的动物模型已发现肿瘤坏死因子-α和 IL-6作为营养不良和恶病质的介体。这个调解人的制作是 随着脱氢表雄酮水平的增加而显著减弱。这些相互关系 提示脱氢表雄酮调节的感染周期、青春期延迟和 营养不良可能是导致儿童营养不良的原因。 感染血吸虫的青少年。 这项研究将采用纵向的治疗-再感染设计 自然暴露的人类来确定抗药性的免疫学预测因素 再感染及其与青春期的相互关系。此外， 营养状况与循环炎症介质的关系 还会检查青春期荷尔蒙。这些研究提供的资料 将影响日本血吸虫疫苗开发的所有阶段，包括 合适的抗原、保护性同工型和细胞因子的鉴定 寄主对青春期和营养的反应及其调控作用 这些反应的发展。

DESCRIPTION: The overall objective of this proposal is to prospectively investigate the interrelationships among puberty, protective immune responses, and nutritional status in adolescent Philippine residents of Schistosoma japonicum endemic areas Determining immunologic and developmental predictors of resistance in naturally exposed humans is a fundamental component of the ongoing effort to develop vaccines against schistosomiasis japonicum. Development of protective human immune responses to other schistosomes appears to occur during puberty in endemic communities. A recent hypothesis states that the hormonal changes of puberty, e.g., increasing dehydroepiandrosterone (DHEA), not cumulative exposure, initiate and promote the development of protective immune responses to schistosome infections Schistosomiasis is causally linked to malnutrition leading to the hypothesis that chronic infection results in attenuate growth for age and possibly delayed pubertal development. Animal models of chronic parasitemia have identified TNF-alpha and IL-6 as mediators of malnutrition and cachexia. Production of this mediator is significantly attenuated by increasing DHEA levels. These interrelationships suggest that a DHEA-modulated cycle of infection, pubertal delay, and malnutrition may be responsible for the marginal nutritional status of schistosome infected adolescents. This study will employ a longitudinal, treatment-reinfection design of naturally exposed humans to determine the immunologic predictors of resistance to reinfection and their interrelationships with puberty. In addition, the relationships among nutritional status, circulating mediators of inflammation and pubertal hormones will be examined. Information provided by these studies will influence all phases of vaccine development for S. japonicum including the identification of appropriate antigens, protective isotype and cytokine responses and the modulating effects of host pubertal and nutritional development on these responses.