IGA FC RECEPTORS ON MYCOPLASMAS & IMPACT ON DISEASE

拟议研究的长期目标是确定角色，如果 细菌表面的IgA Fc受体在 呼吸系统疾病的发病机制。Ig G Fc受体，最值得注意的 蛋白A，已经得到了广泛的表征和研究。IGA FC 受体的特征不是很好，到目前为止已经在 A组和B组链球菌。我们已经鉴定了几种支原体 它能结合人免疫球蛋白Fc片段。所有的支原体物种 结合的IgA Fc片段与呼吸道疾病相关 自然宿主。一个主要的威慑因素是确定 IgA Fc受体在疾病中一直缺乏一个模型系统来 充分评价Fc受体对微生物的影响 致病性。一种与IgA结合的支原体，支原体 肺支原体是小鼠呼吸道支原体病(MRM)的病原体。 是一种很好的传染性呼吸道疾病实验模型。 我们将对肺支原体上的IgA Fc受体(S)进行鉴定，以确定其与 不同宿主免疫球蛋白类别和亚类的特异性 物种。我们将确定人类来源的支原体是否也表达IgA Fc受体。我们将分离纯化M。IgA Fc受体(S)。 并测定其生化和免疫化学性质。 纯化的Fc受体(S)。免疫球蛋白A Fc受体(S)在慢性粒细胞白血病中的意义 呼吸道疾病将根据M。 不同毒力的肺原虫传代后Fc受体的表达 在自然宿主中，以及气雾剂后对肺清除的影响 暴露在IgA包被的肺支原体中。势Iga的性质和性质 IgA2 Fc受体可作为一种潜在的有用工具用于阐明 IgA Fc介导的效应器功能。最后，Ig A Fc的存在 肺分枝杆菌表面受体与特定参数的偶联 用于生产和量化小鼠系统中的呼吸系统疾病 使这成为一个特别有吸引力的模型来确定 呼吸道疾病中细菌IgA Fc受体的研究。

The long term goal of the proposed research is to determine the role, if any, that IgA Fc receptors on the surface of bacteria play in the pathogenesis of respiratory disease. IgG Fc receptors, most notably Protein A, have been characterized and studied extensively. IgA Fc receptors are less well characterized, and to date have been described in Group A and B streptococci. We have identified several mycoplasmal species which bind human IGA Fc fragments. All of the mycoplasmal species which bound IgA Fc fragments were associated with respiratory disease in their natural host. A major deterrent to determination of the significance of IgA Fc receptors in disease has been the lack of a model system to adequately evaluate the impact of the Fc receptors on microbial pathogenicity. One of the IgA-binding mycoplasma species, Mycoplasma pulmonis, is the etiologic agent of murine respiratory mycoplasmosis (MRM), and is an excellent experimental model for infectious respiratory disease. We will characterize the IgA Fc receptors(s) on M. pulmonis with respect to specificity for immunoglobulin classes and subclasses from different host species. We will determine if mycoplasmas of human origin also express IgA Fc receptors. We will isolate and purify the IgA Fc receptors(s) on M. pulmonis, and determine the biochemical and immunochemical properties of the purified Fc receptor(s). The significance of IgA Fc receptor(s) in respiratory disease will be determined based on expression by strains on M. pulmonis which differ in virulence, expression of Fc receptor after passage in the natural host, and effects on pulmonary clearance after aerosol exposure to IgA-coated M. pulmonis. The character of potential IgAl and IgA2 Fc receptors could represent a potentially useful tool in elucidation of IgA Fc mediated effector functions. Finally, the presence of IgA Fc receptors on the surface of M. pulmonis coupled with the defined parameters for production and quantitation of respiratory disease in the mouse system make this a particularly attractive model to determine the impact of bacterial IgA Fc receptors on respiratory disease.