IN VITRO APPROACH TO PROBLEMS OF CLINICAL ALLERGY

这项补助金的目的是将实验室的发现转化为改进 在临床实践中。 第一个领域涉及昆虫超敏反应。 毒液免疫疗法具有高度保护性;最近的研究表明，它可能 因为它可以在五年后停止。 我们想确认 这一点，以确定保护的持续时间，并了解机制 发生这种情况。 另一个目标是了解 昆虫过敏 我们已经证明，4%的人口是昆虫 敏感的历史和25%有IgE抗体对昆虫 毒液 将对这些患者进行前瞻性研究，以确定 历史和免疫参数之间的关系， 将使我们能够前瞻性地识别出有严重蜇伤风险的患者。 最后，我们打算使用纯化的昆虫毒液来提高准确性 皮肤测试诊断。 第二个领域涉及免疫疗法， 吸入性过敏 在哮喘免疫治疗的背景下，我们将 将临床保护与可释放性参数的变化（即， 嗜碱性粒细胞释放各种促分泌素的变化）和 介质释放和细胞在急性和晚期反应。 过敏性鼻炎的免疫治疗导致对鼻粘膜的反应降低 急性期的抗原攻击;我们怀疑晚期的抗原攻击的减少， 阶段将更加戏剧化。 这两个阶段的反应将是 在免疫治疗之前和期间进行评估。 最后，我们将确定 吸入性过敏的免疫疗法是否可以在五年后终止 年 第三个研究领域利用了一种新的鼻过敏原系统， 激发和灌洗测量介质（组胺、PGD、激肽、驯服 酯酶，白三烯，趋化因子）和细胞（淋巴细胞， 嗜酸性粒细胞和嗜中性粒细胞）和巨噬细胞来源的组胺释放 在后期反应中发现的因子， 交联IgE。 我们将评估各种药理学激动剂， 系统 标准和新型试剂都将根据其 体外对嗜碱性粒细胞和肥大细胞介质释放的影响。 我们已经表明 寒冷干燥的空气挑战（运动诱发哮喘的模型）也 导致临床敏感人群释放介质，并将研究 药理学激动剂在该模型中。 在这种情况下，体外筛选 涉及高渗刺激的释放，我们假设这是 冷空气在体内诱导释放的机制。

The aim of this grant is to translate laboratory findings into improvements in clinical practice. A first area concerns insect hypersensitivity. Venom immunotherapy is highly protective; recent work suggests that it may be curative since it can be stopped after five years. We wish to confirm this, to define the duration of protection, and to understand the mechanism by which this occurs. Another goal is to understand the natural history of insect allergy. We have demonstrated that 4% of the population is insect sensitive by history and that 25% have IgE antibodies against insect venoms. These patients will be studied prospectively to establish the relationship between historical and immunologic parameters and hopefully will allow us to prospectively identify patients at serious risk of sting. Finally, we intend to use purified insect venoms to increase the accuracy of skin test diagnosis. A second area relates to immunotherapy for inhalant allergies. In the context of immunotherapy for asthma, we will relate clinical protection to changes in releasability parameters (i.e. changes in basophil release to a variety of secretagogues) and changes in mediator release and cells in acute and late phase reactions. Immunotherapy for allergic rhinitis leads to a decreased response to nasal antigen challenge in the acute phase; we suspect that decrement of the late phase will be even more dramatic. Both phases of this response will be assessed before and during immunotherapy. Finally, we will ascertain whether immunotherapy for inhalant allergy can be terminated after five years. The third area of study utilizes a novel system of nasal allergen challenge and lavage measuring mediators (histamine, PGD, kinins, TAME esterase, leukotrienes, chemotactic factors) and cells (lymphocytes, cosinophils and neutrophils) and a macrophage-derived histamine releasing factor which is found in late phase reactions and which acts by cross-linking IgE. We will assess various pharmacologic agonists in this system. Both standard and novel agents will be chosen based on their effects in vitro on basophil and mast cell mediator release. We have shown that cold, dry air challenge (a model of exercise-induced asthma) also causes mediator release from clinically sensitive persons and will study pharmacologic agonists in this model. In this instance the in vitro screen involves release by hyperosmolar stimuli, which we postulate is the mechanism of cold air induced release in vivo.