REGULATION OF ANTIBODY RESPONSES OF INFANTS BY NK CELLS

NK 细胞对婴儿抗体反应的调节

• 批准号: 3322712
• 负责人: JOSEPH KAPLAN
• 金额: $ 7.08万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3322712
• 关键词: B lymphocyte; Haemophilus influenzae; Haemophilus influenzae vaccines; Streptococcus pneumoniae; Streptococcus vaccine; active immunization; acute phase protein; antibacterial antibody; antibody formation; bacterial antigens; bacterial polysaccharides; cell cell interaction; enzyme linked immunosorbent assay; genetic strain; helper T lymphocyte; immunoconjugates; immunosuppression; immunosuppressive; infant human (0-1 year); laboratory mouse; lymphocyte; mature animal; phosphorylcholine; sex linked trait; suppressor T lymphocyte; tissue /cell culture; weanling animal

The inability of infants and young children to mount adequate antibody responses to certain bacterial polysaccharide antigens including capsular polysaccharides of Strep. pneumoniae and H. Flu. type b has limited the effectiveness of vaccines in protecting this highly susceptible age group against infection with these organisms. The immunological basis for the infant's deficient antibody responses to bacterial polysaccharides has been unclear. In studies of mice, we have obtained evidence that NK cells physiologically down-regulate antibody responses to pneumococcal polysaccharides, and that this down-regulatory effect is the primary factor responsible for the inadequate response of infants to these antigens. This project is designed to confirm and extend these findings with the goal of elucidating how NK cells exert this inhibitory effect, why these antibody responses are more inhibited in infants than in adults, and whether the enhanced immunogenicity of protein-conjugates of bacterial polysaccharides is related to the ability to bypass NK cell down- regulation. The effect of NK cell depletion or supplementation on in vivo and in vitro anti-pneumococcal antibody responses of weanling and adult mice will be tested in terms of the temporal relationship to depletion or supplementation, the kinetics and Ig subclass distribution of antibody responses, and specificity. The in vitro anti-phophorylcholine response in various strains of mice will be used as a model system to investigate the mechanism of NK down-regulation. The role of NK cells in regulating the weak response of infants to H. Flu type b polysaccharide will be examined.

婴儿和幼儿无法满足 对某些细菌多糖抗原的抗体反应 包括链球菌的囊囊多糖。肺炎和H. 流感。类型B限制了疫苗保护的有效性 这个高度易感的年龄组反对感染这些 有机体。 婴儿缺乏的免疫学基础 对细菌多糖的抗体反应尚不清楚。 在对小鼠的研究中，我们获得了NK细胞的证据 生理上对肺炎球菌的抗体反应 多糖，这种下调作用是 负责婴儿反应不足的主要因素 这些抗原。 该项目旨在确认和扩展 这些发现的目的是阐明NK细胞如何发挥作用 抑制作用，为什么这些抗体反应更受抑制 在婴儿中比成年人，以及增强 细菌蛋白偶联物的免疫原性 多糖与绕过NK细胞向下的能力有关 规定。 NK细胞耗竭或补充对 体内和体外抗炎球菌抗体反应 断奶和成年小鼠将根据时间进行测试 与耗尽或补充，动力学和IG的关系 抗体反应的亚类分布和特异性。 这 各种小鼠菌株中体外抗噬胆碱反应 将用作研究模型系统来研究 NK下调。 NK细胞在调节弱的 婴儿对H.流感B型多糖的反应将是 检查。