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介导的过敏性疾病如食物过敏、哮喘和花粉热的增加。仅在美国，食物过敏每年就导致30，000例过敏反应和200例死亡。过敏性疾病升级的原因尚不清楚。近几十年来，潜在的风险因素，如改善生活条件和使用铝（明矾）佐剂疫苗已被提出与过敏性疾病的患病率增加。我们的假设是，过敏风险因素的累积效应在宿主中产生了Th2偏向的免疫环境，使宿主易于发生过敏。本提案的目的是利用小鼠模型确定拟定过敏风险因素（包括低LPS环境和暴露于明矾佐剂疫苗）的存在是否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性致敏的发展。为了实现这一目标，将小鼠维持在标准小鼠饲养条件下或设计用于模拟经历了增加的过敏性疾病的现代工业化国家的条件下。“现代”条件将包括低内毒素、暴露于明矾佐剂免疫或低内毒素与明矾佐剂疫苗组合。所有小鼠将对花生抗原致敏。致敏完成后，用花生激发小鼠，并监测过敏反应的发生率和严重程度。本申请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，并提供一个模型来评估新疗法预防花生食物过敏诱导的能力。

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.