IMMUNOREACTIVE MACROMOLECULES IN COCCIDIOIDES CELL TYPES

粗球孢子菌（Coccidioides immitis）是一种致病真菌， 人和其他动物的主要呼吸道传染病。 它是一种地方病， 美国西南部从加州到得克萨斯的一个地区及其自然栖息地 是干旱的土壤。 这种真菌的腐殖期释放出传染性的 繁殖体或节孢子进入空气中，被宿主吸入。 每年约有10万人感染。 虽然不到一半的 这些感染会产生症状，这些症状确实会引起显著的 发病率和死亡率。 后者仅限于个人 感染扩散到肺外的人 这种生物是独一无二的 在真菌中，寄生阶段发生在重复的 包括繁殖体转变成 多核小球体，随后内部分裂产生一个 无数微小的内生孢子 后者在宿主体内传播， 转化成新一代的小球 这些形态是 与不同的组织反应相关;例如，小球是 主要与肉芽肿反应和释放的内生孢子有关 化脓性反应 因此，C. immitis是一种理想的模型， 研究宿主细胞对病毒应答的复杂机制， 寄生周期的繁殖体和连续细胞类型的损伤。 这种宿主-病原体相互作用在这方面和其他方面知之甚少。 肌肉疾病 已有证据表明， C.在形态发生过程中，免疫系统发生改变。 等 变化可能与宿主反应的变化有关。 公布的数据还 表明与以下相关的临床显著生物活性 这种疾病，包括细胞介导的免疫反应，与 免疫球蛋白抗体和免疫保护作用 通过细胞壁部分诱发实验动物。 其目的是 项目是确定抗原组成和生物活性 C.可溶性壁组分的分级。免疫细胞类型，制备 多克隆和单克隆抗体，以这些部分，并评估 组分的均匀性，确定位置和/或呈现 使用细胞表面探针检测细胞包膜上的抗原，并评估 在实验动物中的级分的免疫保护能力。 的 这些研究的结果将提供改进的免疫诊断， 球孢子菌病的各种临床表现以及基础 用于开发对抗这种真菌疾病的人类疫苗。

Coccidioides immitis is a pathogenic fungus which is the causative agent of a primary respiratory infection of man and other animals. It is endemic to southwestern United States from California to Texas and its natural habitat is arid soil. The saprobic phase of this fungus releases infectious propagules, or, arthroconidia, into the air which are inhaled by the host. About 100,000 people are infected each year. Although less than half of these infections produce symptoms, those that do account for a significant amount of morbidity and mortality. The latter is limited to individuals who suffer extrapulmonary spread of the infection. This organism is unique among fungi in that the parasitic stage occurs in a repetitive morphogenetic cycle involving conversion of the propagule into a multinucleate spherule which subsequently cleaves internally to produce a myriad of tiny endospores. The latter disseminate within the host and convert into a new generation of spherules. These morphological forms are associated with different tissue responses; e.g., the spherules are associated primarily with granulomatous response and the relased endospores with suppurative response. Thus, C. immitis is an ideal model for examining the intricate mechanisms by which the host cells respond to the insult of the propagule and successive cell types of the parasitic cycle. Such host-pathogen interactions are poorly understood in this and other mycotic diseases. Evidence has been presented that antigenic composition of the cell envelope of C. immitis is altered during morphogenesis. Such changes may be related to variations in host response. Published data also indicate that clinically significant biological activities associated with this disease, including cell-mediated immune responses, reactivity with immununoglobulin antibody and immunoprotection against challenge in experimental animals are elicited by cell wall fractions. The aims of this project are to identify the antigenic composition and biological activity of fractionated soluble wall components of C. immitis cell types, prepare polycolonal and monoclonal antibodies to these fractions and assess the homogeneity of the fractions, determine the location and/or presentation of antigens on the cell envelope using cell surface probes, and evaluate the immunoprotective capacity of the fractions in experimental animals. The results of these studies will provide for improved immunodiagnosis of the various clinical manifestations of coccidioidomycosis as well as the basis for developing a human vaccine against this fungal disease.