Control of immediate hypersensitivity responses in parasitic and other diseases

控制寄生虫病和其他疾病的速发型超敏反应

• 批准号: 7964399
• 负责人: Thomas Nutman
• 金额: $ 16.16万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7964399
• 关键词: Allergens; Allergic; Antibodies; Antigens; Basophils; CD4 Positive T Lymphocytes; Chronic; Coupled; Disease; Epidemiology; Event; Genetic Transcription; Helminths; IgE; IgG4; Immediate hypersensitivity; Immune System Diseases; Immunoglobulin G; Immunoglobulin Switch Recombination; Infection; Inflammation; Interleukin-10; Measurement; Measures; Methods; Molecular; Parasites; Parasitic infection; Patients; Physiological; Recruitment Activity; Regulation; Site; Source; Syndrome; Variant; airborne allergen; eosinophil; monocyte; novel marker; response; tool

Hypereosinophilic conditions have been studied extensively, and we have identified new markers that distinguish among several important variants of this syndrome. The interaction between helminth infeciton and allergic disease has been studied using epidemiological tools coupled with physiological measurements of allergic disease and immunological assessments. We have demonstrated that chronic helminth infection protects against allergic diseases. Studies done to date have demonstrated the CD4+ cells (and neither the monocytes nor the basophils) are the overwhelmingly major source of IL-10 in chronic filarial infection. We have developed quantitative methods for examination of germline transcription for each of the antibody isotypes and have begun to use these methods to examine the molecular events that occur when antigens induce specific switch recombination events. Also baseline IgE and IgG4 germline transcription profiles have been measured in patients with allergic and parasitic infections and associated elevations of IgE and IgG4. An exhaustive search for parasite allergens that may cross-react with aeroallergens has been performed. We have identified a number of parasite antigens and the allergens orthologues and have studied the IgE and IgG responses to these. We have demonstrated unequivocally that parasite infections induced both parasite-specific IgE and IgE that interacts with enviromental allergens to which the parasite antigens are closely related.

嗜酸性粒细胞增多症已经被广泛研究，我们已经确定了新的标志物，区分这种综合征的几个重要变种。 蠕虫感染和过敏性疾病之间的相互作用已经研究了流行病学的工具，加上过敏性疾病的生理测量和免疫学评估。我们已经证明，慢性蠕虫感染可以预防过敏性疾病。迄今为止所做的研究已经证明，在慢性丝虫感染中，CD 4+细胞（而不是单核细胞或嗜碱性粒细胞）是IL-10的压倒性主要来源。 我们已经开发了用于检查每个抗体同种型的生殖系转录的定量方法，并且已经开始使用这些方法来检查当抗原诱导特异性开关重组事件时发生的分子事件。 此外，在过敏性和寄生虫感染以及IgE和IgG 4相关升高的患者中测量了基线IgE和IgG 4种系转录谱。 已经对可能与空气过敏原发生交叉反应的寄生虫过敏原进行了详尽的搜索。 我们已经确定了一些寄生虫抗原和过敏原直系同源物，并研究了IgE和IgG对这些抗原的反应。 我们已经明确表明，寄生虫感染诱导寄生虫特异性IgE和IgE与环境过敏原，寄生虫抗原密切相关的相互作用。