IMMUNOREACTIVE MACROMOLECULES IN COCCIDIOIDES CELL TYPES

球孢子细胞类型中的免疫反应性大分子

基本信息

批准号：
3128552
负责人：
GARRY Thomas COLE
金额：
$ 14.27万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-09-01 至 1989-08-31
项目状态：
已结题

项目摘要

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.

粗球孢子菌 (Coccidioides immitis) 是一种致病真菌，是引起人类和其他动物的原发性呼吸道感染。它是地方性的美国西南部从加利福尼亚州到德克萨斯州及其自然栖息地是干旱的土壤。这种真菌的腐生阶段释放传染性繁殖体或节分孢子进入空气并被宿主吸入。每年约有10万人被感染。虽然不到一半这些感染会产生症状，这些症状确实造成了重大影响发病率和死亡率。后者仅限于个人感染发生肺外传播的人。这种生物体是独一无二的在真菌中，寄生阶段发生在重复的过程中形态发生循环涉及繁殖体转化为多核小球随后在内部分裂产生无数微小的内生孢子。后者在宿主体内传播转化为新一代小球。这些形态形式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有化脓反应。因此，C. immitis 是一个理想的模型检查宿主细胞响应的复杂机制对繁殖体和寄生周期的连续细胞类型的损害。这种宿主与病原体的相互作用在这一领域和其他领域知之甚少。真菌性疾病。有证据表明抗原成分 C.immitis 的细胞包膜在形态发生过程中发生改变。这样的变化可能与宿主反应的变化有关。还公布了数据表明与相关的临床显着的生物活性这种疾病，包括细胞介导的免疫反应、与免疫球蛋白抗体和针对挑战的免疫保护实验动物由细胞壁组分引发。本次活动的目的项目是鉴定抗原成分和生物活性分离的 C. immitis 细胞类型的可溶性壁成分，制备针对这些级分的多克隆和单克隆抗体并评估分数的同质性，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，并评估实验动物中该级分的免疫保护能力。这这些研究的结果将改善免疫诊断球孢子菌病的各种临床表现及其依据开发针对这种真菌疾病的人类疫苗。