PNEUMOCOCCAL SERUM OPSONIZATION IN SICKLE CELL DISEASE

镰状细胞病中肺炎球菌血清的调理作用

• 批准号: 3348668
• 负责人: ANN B BJORNSON
• 金额: $ 9.3万
• 依托单位: JAMES N. GAMBLE INSTITUTE OF MEDICAL RES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3348668
• 关键词: Streptococcus pneumoniae; bactericidal immunity; blood chemistry; child (0-11); complement; complement pathway; human subject; human tissue; immunoglobulin G; opsonin; radiotracer; scintillation counter; serology /serodiagnosis; serotyping; sickle cell anemia

The concentration dependence, kinetics, and mechanism of the restorative effect of normal human immunoglobulin (Ig)G on deficient serum opsonization for serotype 10 Streptococcus pneumoniae in children and adolescents with sickle cell disease will be investigated. Labeled bacteria will be incubated with unsupplemented patients' sera or patients' sera supplemented with increasing concentrations of purified normal human IgG. The bacteria will be washed, incubated with normal human polymorphonuclear leukocytes (PMNs), and the kinetics of uptake and intracellular killing will be determined. Results will be compared to those obtained with bacteria opsonized with age-matched control sera. Subsequent experiments will be performed to determine if the restorative effect of IgG is due to enhancement of alternative or classical complement pathway C3 convertase formation with resultant cleavage and surface deposition of trace-labeled C3 or augmentation of uptake by the leukocytes. Binding of labeled F(ab')2 fragments, Fc fragments, and whole IgG to the pneumococci will be compared, and the restorative effect of the fragments on the deficient opsonization will be determined. Relationships between opsonization for multiple pneumococcal serotypes and opsonization and alternative complement pathway activation by the homologous serotype will also be investigated. Uptake by human PMNs of labeled serotypes 7, 10, 15, and 24 after opsonization with patients' or control sero will be measured. Alternative pathway-mediated reduction in the B antigenic determinant of human C3 will be quantitated in the sera after incubation with the bacteria. Data from the patients and controls from each measurement will be compared, and specifide correlations on the patient's data will be determined. The knowledge derived from this investigation will increase understanding of the cause of deficient pneumococcal serum opsonization in the sickle cell disease and of one mechanism by which this abnormality can be corrected.

本研究旨在探讨该修复剂的浓度依赖性、动力学和机制。 正常人免疫球蛋白（IG）G对缺陷型血清调理作用影响 血清型10肺炎链球菌在儿童和青少年 将对镰状细胞病进行研究。 标记的细菌将 用未补充的患者血清或补充的患者血清孵育 用浓度增加的纯化的正常人IgG。 细菌 将被洗涤，与正常人多形核白细胞一起孵育 （PMNs），并且摄取和细胞内杀伤的动力学将是 测定 结果将与细菌获得的结果进行比较 用年龄匹配的对照血清调理。 后续实验将在 以确定IgG的恢复作用是否是由于 替代或经典补体途径C3转化酶的增强 形成伴随着所产生的分裂和表面沉积的痕量标记的 C3或增加白细胞的摄取。 标记的F（ab '）2的结合 将比较肺炎球菌的Fc片段、Fc片段和完整IgG， 以及碎片对调理作用不足的恢复作用 将被确定。 调理作用与多种 肺炎球菌血清型与调理作用和补体旁路途径 还将研究同源血清型的激活。 吸收 用调理素处理后标记的血清型7、10、15和24的人PMN 将测量患者或对照血清。 替代途径介导 人C3的B抗原决定簇的减少将在 与细菌孵育后的血清。 来自患者的数据， 将比较每个测量的对照， 患者的数据将被确定。 从这方面获得的知识 调查将增加对缺乏的原因的了解 肺炎球菌血清调理素在镰状细胞病和一个 这是一种可以纠正这种异常的机制。