IMMUNOREACTIVE MACROMOLECULES OF COCCIDIOIDES CELL TYPES

球孢子虫是一种人类呼吸道真菌病原体， 谷热(球孢子菌病)的病原体。暴露于 空气传播的感染细胞(节孢子)可导致一系列 临床疾病来自良性、自限性的感染细胞 (节孢子虫)可导致一系列临床疾病，从良性的， 对严重的、进行性的、通常是致命的真菌病的自限性感染 涉及肺和肺外组织。免疫学 危害健康的疾病，虽然会出现在一些患者身上，但并不是 免疫球虫感染的先决条件。存在一个一致的和 可预测的免疫模式在不同阶段的患者中的应用 球孢子菌病，这可能与最初接触 节分生孢子，然后反复接触可溶性抗原 寄生循环期间主要起源于壁的部分(即， 球体-内孢子阶段)。我们的假设是节孢子， 球体和内孢子引起不同的寄主反应 由于抗原性和/或数量上的差异 寄主最初接触的细胞壁的组成。 已有可能将可溶性的、抗原性的络合物从 在体外生长的节孢子和球体上的细胞被膜， 在体液和细胞免疫分析中表征它们的免疫反应性， 并使用各种分离技术获得纯化的组分。在……里面 拟议的调查我们将描述这些提纯的 根据它们的化学成分、抗原性 在标准化的免疫电泳法和免疫扩散法中， 患者抗体检测中的相对免疫反应性 吸附和T细胞对均一组分的反应。我们还将 重点检查这些纯化成分的生物学功能 它们可能的酶活性及其对真菌形态发生的影响 和宿主入侵。我们最近开发的一个cdna表达文库 以及金龟子的基因组文库的可用性 重组DNA技术在我们进一步鉴定中的应用 这些纯化的、与壁相关的组分。首先，我们将筛选 使用精选免疫探针和寡核苷酸探针的文库 对应于那些具有已建立重要性的所选分数 在宿主抗体反应、组织入侵或免疫球虫形态发生过程中， 并从同源融合中克隆调控生产的基因 多肽。最终，我们将确定这些基因在 节孢子体-球体-内孢子的体外发育。我们相信 这种研究免疫球虫抗原的综合方法将导致 为了更好地理解人类免疫应答的模式 宿主和促成致病性的因素，以及识别 潜在的诊断DNA探针和分子靶点的开发 新型抗真菌化合物。

Coccidioides immitis is a fungal respiratory pathogen of humans and causative agent of valley fever (coccidioidomycosis). Exposure to the airborne, infectious cells (arthroconidia) can lead to a range of clinical disease from a benign, self-limited infectious cells (arthroconidia) can lead to a range of clinical disease from a benign, self-limited infection to a severe, progressive and often fatal mycosis involving pulmonary and extrapulmonary tissues. Immunologically compromising illnesses, although present in some patients, are not prerequisite to infection by C. immitis. There exists a consistent and predictable immunological pattern in patients at various stages of coccidioidomycosis, which may be related to initial exposure to the arthroconidia, followed by repeated exposure to soluble antigenic fractions of primarily wall origin during the parasitic cycle (i.e., spherule-endospore phase). Our hypothesis is that arthroconidia, spherules, and endospores of C. immitis elicit different host responses because of qualitative and/or quantitative differences in the antigenic composition of their cell wall to which the host is originally exposed. It has been possible to isolate soluble, antigenic complexes from the cell envelopes off arthroconidia and spherules grown in vitro, characterize their immunoreactivity in humoral and cellular immunoassays, and obtain purified components using various separation techniques. In the proposed investigations we will characterize these purified components on the basis of their chemical composition, antigenic identity in standardized immunoelectrophoresis and immunodiffusion tests, and relative immunoreactivity in assays which measure patient antibody adsorption and T-cell response to the homogeneous fractions. We will also examine the biological function of these purified components, with focus on their possible enzymatic activity and impact on fungal morphogenesis and host invasion. Our recent development of a cDNA expression library and the availability of a genomic library for C. immitis permits application of recombinant DNA technology in our further characterization of these purified, wall-associated fractions. Initially, we will screen the libraries using selected immunoprobes and oligonucleotide probes corresponding to those selected fractions with established significance in host antibody response, tissue invasion, or C. immitis morphogenesis, and clone the genes which regulate production off the homologous fusion peptides. Ultimately, we will determine expression of these genes during arthroconidium-spherule-endospore development in vitro. We believe that this comprehensive approach to the study of C. immitis antigens will lead to a better understanding of the pattern of immunological response by the host and factors which contribute to pathogenicity, as well as identify potential diagnostic DNA probes and molecular targets for development of novel antifungal compounds.