FUNGAL ANTIGENS AND ANTIFUNGAL RESPONSE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 常见的霉菌，烟曲霉，是一种条件致病菌和侵袭性曲霉病的最常见的病原体。 这种疾病通常由免疫功能低下的宿主感染，包括癌症患者，据报道死亡率> 80%。 我们的长期目标是开发一种疫苗，并为曲霉病的早期诊断和监测提供更好的手段。 我们的具体假设是：1）某些曲霉菌抗原具有免疫保护作用，和2）某些抗原可作为曲霉菌感染早期阶段的指示物。 我们的假设基于以下观察。 首先，用粗真菌蛋白提取物或活分生孢子接种的小鼠在免疫抑制后感染后存活（例如，用皮质类固醇治疗）。其次，真菌在其生命周期的不同阶段积极分泌各种特定的蛋白质和肽。已经描述了超过60种曲霉属的抗原和过敏原（1-4）。然而，只有其中之一，多糖半乳甘露聚糖，是常规检测诊断曲霉感染。基于这些观察，我们的实验重点是A的鉴定、结构和免疫学特征。烟曲霉抗原我们计划利用和改进新的质谱技术，以检测和鉴定复杂的混合物，如培养上清液，支气管肺泡灌洗液（BAL），血液和尿液中的真菌来源的蛋白质和肽。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The common mold, Aspergillus fumigatus, is an opportunistic pathogen and the most frequently isolated causative agent of invasive aspergillosis. The disease is often contracted by immunocompromised hosts, including cancer patients, with reported mortality rates > 80%. Our long-term goals are to develop a vaccine and to provide better means for the early diagnosis and monitoring of aspergillosis. Our specific hypotheses are: 1) certain aspergillus antigens have an immunoprotective effect, and 2) some antigens may serve as indicators of early stages of aspergillus infections. We base our hypotheses on the following observations. First, mice vaccinated with crude fungal protein extracts or viable conidia survive infection following immunosuppression (e.g., with corticosteroid treatment). Second, the fungus actively secretes a variety of specific proteins and peptides at different stages of its lifecycle. More than 60 antigens and allergens of Aspergillus have been described (1-4). However, only one of them, the polysaccharide galactomannan, is routinely assayed to diagnose Aspergillus infections. Based on these observations, our experimental focus is on the identification and structural and immunological characterization of A. fumigatus antigens. We plan to utilize and improve novel mass spectrometric techniques to detect and identify proteins and peptides of fungal origin from complex mixtures such as culture supernatants, bronchoalveolar lavage (BAL) fluid, blood and urine.