Environmental conditions and their impact on host immunity

描述（由申请人提供）：工业化国家经历了th2依赖性、IgE介导的过敏性疾病的增加，如食物过敏、哮喘和花粉热。仅在美国，食物过敏每年就会导致3万例过敏反应和200例死亡。过敏性疾病增加的原因尚不清楚。近几十年来，生活条件的改善和铝（明矾）佐剂疫苗的使用等潜在风险因素被认为与过敏性疾病的患病率增加有关。我们的假设是，过敏风险因素的累积效应在宿主体内创造了一个th2偏倚的免疫环境，使宿主容易发生过敏。本研究的目的是利用小鼠模型来确定包括低脂多糖环境和暴露于铝佐剂疫苗在内的过敏风险因素是否会影响宿主全身和粘膜免疫系统的表型。此外，我们将确定这些过敏风险因素的存在是否会影响花生过敏敏化的发展。为了实现这一目标，将把小鼠饲养在标准的小鼠住房条件下，或在模拟现代工业化国家的条件下饲养，这些国家的过敏性疾病正在增加。“现代”条件将包括低内毒素，暴露于铝佐剂免疫或低内毒素结合铝佐剂疫苗。所有的老鼠都会对花生抗原敏感。致敏试验完成后，将用花生刺激小鼠，并监测过敏反应的发生率和严重程度。本应用程序中提出的实验将为未来的机制研究提供基础，以确定导致食物过敏患病率增加的环境因素，并为评估新疗法预防诱导花生食物过敏的能力提供模型。

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.