PNEUMOCOCCAL SERUM OPSONIZATION IN SICKLE CELL DISEASE

恢复剂的浓度依赖性、动力学及作用机制 正常人免疫球蛋白G对缺乏性血清调理作用的影响 儿童和青少年肺炎链球菌10型的检测 将对镰状细胞病进行调查。被标记的细菌将被 与未添加的患者血清或已添加的患者血清孵育 随着纯化的正常人免疫球蛋白浓度的增加。细菌 将被洗涤，与正常的人多形核白细胞孵育 (PMN)，摄取和细胞内杀伤的动力学将是 下定决心。实验结果将与细菌实验结果进行比较。 用年龄匹配的对照血清进行调理。随后的实验将是 以确定免疫球蛋白的修复作用是否源于 替代或经典补体途径C3转换酶的增强 生成的痕量标记的解理和表面沉积 C3或白细胞摄取增加。标记F(ab‘)_2的结合 将比较肺炎球菌的片段、Fc片段和完整的Ig G， 以及碎片对缺损性视光的恢复作用 将会被确定。多重态光学电离之间的关系 肺炎链球菌的血清型和调理作用及替代补体途径 同源血清型的激活也将被调查。吸纳 标记血清型7、10、15和24的人中性粒细胞与 将测量患者或对照的血清。替代途径介导的 人类C3 B抗原决定簇的减少将在#年定量 与细菌孵育后的血清。来自患者的数据和 将比较来自每一次测量的对照，并指定相关 病人的数据将会被确定。由此衍生出的知识 调查将增加对缺陷原因的了解 镰状细胞病和1例肺炎球菌血清调理 纠正这种反常现象的机制。

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.