MECHANISM OF ANTIBODY PROTECTION TO C NEOFORMANS

描述(改编自申请人的摘要)：隐球菌 新生杆菌是一种引起致命的脑膜脑脊髓炎的真菌。 免疫抑制的个体。因为单靠抗真菌药物并不能 清除感染后，小鼠的单抗(MAb)已经 产生到真菌的荚膜多糖。在课程中 研究这些单抗的大型库的保护潜力 在体内，在免疫功能和免疫功能不全的小鼠中，我们有 确定保护性、非保护性和增强抗体。我们有 表明抗体调节感染的能力 取决于效应器的同种类型、表位特异性和状态 细胞。特别是，IgG3单抗不能延长动物的寿命， 在某些情况下会增强感染，而IgGi、IgG2b 而这些单抗的IgG2a同型开关变异体可以延长小鼠的寿命 这只动物。 这表明效应器细胞上的FCR也在发挥作用。 以确定这些抗体在体内的效力。此外， CD_4~+、CD_8~+T细胞和干扰素-γ在T细胞免疫功能中的作用 被动注射抗体以调节感染。初步 实验表明，IgG3和IgGI的不同作用也可以 用原代巨噬细胞进行体外观察。我们建议在这里做 遗传缺陷小鼠的体内外实验学习 为什么不同同型抗体对小鼠感染有调节作用 新生葡萄球菌以不同的方式。希望这些研究能够 为抗体的作用机制提供了新的见解 预防和治疗新生杆菌感染，也许还有其他 被包裹的有机体。

DESCRIPTION (Adapted from the applicant's abstract): Cryptococcus neoformans is a fungus that causes a lethal meningoencephalomyelitis in immunosuppressed individuals. Since anti-fungal agents alone do not clear the infection, mouse monoclonal antibodies (mabs) have been generated to the capsular polysaccharide of the fungus. In the course of studying the protective potential of a large library of these mabs in vivo in both immunocompetent and immunoincompetent mice, we have identified protective, non-protective and enhancing antibodies. We have shown that the ability of the antibodies to modulate the infection depends upon the isotype, epitope specificity and state of the effector cells. In particular, IgG3 mabs do not prolong the life of the animals, and in certain situations can enhance the infection, while IGGI, IgG2b and IgG2a isotype switch variants of these mab can prolong the life of the animal. This suggests that the FcRs on effector cells are also playing a role. In determining the efficacy of these antibodies in vivo. Furthermore, CD4+ and CD8+ T cells and interferon-y play a role in the ability of the passively administered antibodies to modulate infection. Preliminary experiments reveal that the different effects of IgG3 and IGGI can also be observed in vitro with primary macrophages. We propose here to do in vitro and in vivo experiments with genetically defective mice to learn why antibodies of different isotypes modulate the infection of mice with C neoformans in different ways. It is hoped that these studies will provide new insights into the mechanism of action of antibodies in preventing and treating infection with C neoformans, and perhaps other encapsulated organisms.