Environmental conditions and their impact on host immunity

环境条件及其对宿主免疫力的影响

基本信息

批准号：
8588929
负责人：
Herman F Staats
金额：
$ 7.51万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8588929
关键词：
Adjuvant Allergic Allergic Disease Allergic Reaction Aluminum Anaphylaxis Antibiotics Antigens Area Asthma Bacterial Infections Basophils CD4 Positive T Lymphocytes Cessation of life Child Developed Countries Developing Countries Development Disease Eczema Elements Endotoxins Environment Environmental Risk Factor Epidemiology Equilibrium Exposure to Farming environment Food Hypersensitivity Foundations Future Goals Hay fever Helper-Inducer T-Lymphocyte Hospitalization House mice Human Hygiene Hypersensitivity IgE Immune Immune system Immunity Immunization Incidence Infection Interferons Interleukin-12 Interleukin-4 Life Measures Mediating Modeling Monitor Mus Peanuts - dietary Phenotype Predisposition Prevalence Prevention Production Reaction Research Risk Risk Factors Severities Signal Transduction Sodium Chloride United States Vaccinated Vaccination Vaccine Adjuvant Vaccines Virus Diseases cytokine design environmental allergy experience improved mast cell mouse model novel prevent public health relevance research study response toll-like receptor 4

项目摘要

DESCRIPTION (provided by applicant): Industrialized countries have experienced an increase in Th2-dependent, IgE- mediated allergic diseases such as food allergy, asthma, and hay fever. Food allergy causes 30,000 cases of anaphylaxis and 200 deaths annually in the United States alone. The cause for the escalation in allergic disease remains unknown. In recent decades, potential risk factors such as improved living conditions and the use of aluminum (alum)-adjuvanted vaccines have been proposed as being associated with the increased prevalence of allergic disease. It is our hypothesis that the cumulative effect of the allergy risk factors creates a Th2-biased immune environment in the host that predisposes the host to the development of allergy. The goal of this proposal is to utilize a mouse model to determine if the presence of proposed allergy risk factors including low LPS environment and exposure to alum-adjuvanted vaccines influences the phenotype of the host systemic and mucosal immune system. Additionally, we will determine if the presence of these allergy risk factors influences the development of allergic sensitization to peanut. To achieve this goal, mice will be maintained in standard mouse housing conditions or in conditions designed to mimic modern, industrialized countries that have experienced increased allergic diseases. The "modern" conditions will include low endotoxin, exposure to alum-adjuvanted immunizations or low endotoxin combined with alum-adjuvanted vaccines. All mice will be sensitized to peanut antigens. Upon completion of sensitization mice will be challenged with peanut and monitored for the incidence and severity of an allergic reaction. The experiments proposed in this application will provide the foundation for future mechanistic studies to define environmental factors that contribute to the increased prevalence of food allergy and provide a model to evaluate novel therapies for their ability to prevent the induction of peanut food allergy.

描述（由申请人提供）：工业化国家的Th2依赖性，IgE介导的过敏性疾病（例如食物过敏，哮喘和花粉症）的增加。仅在美国，食物过敏就会每年在每年发生30,000例过敏反应和200例死亡。过敏性疾病升级的原因仍然未知。近几十年来，已经提出了潜在的危险因素，例如改善的生活条件和使用铝（校友）的疫苗（铝）疫苗与过敏性疾病的患病率的增加有关。我们的假设是，过敏危险因素的累积效应在宿主中产生了32个偏见的免疫环境，使宿主易过过敏。该提案的目的是利用小鼠模型来确定提出的过敏风险因素的存在是否存在，包括低LPS环境和暴露于明矾辅助疫苗会影响宿主系统性和粘膜免疫系统的表型。此外，我们将确定这些过敏危险因素的存在是否会影响对花生的过敏敏化的发展。为了实现这一目标，小鼠将保持在标准的小鼠住房条件下或旨在模仿现代，工业化国家的条件，这些国家经历了增加过敏性疾病。 “现代”条件将包括低内毒素，暴露于明矾辅助免疫接种或低内毒素与明矾辅助疫苗结合使用。所有小鼠将对花生抗原敏感。敏化后，花生将受到挑战，并监测过敏反应的发病率和严重程度。本应用程序中提出的实验将为未来的机械研究提供基础，以定义有助于食品过敏的患病率增加的环境因素，并提供了一种模型，以评估新型疗法以防止诱导花生食物过敏的能力。