AN IN VITRO APPROACH TO PROBLEMS OF CLINICAL ALLERGY

这笔赠款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的过敏性。 毒液免疫疗法具有很强的保护性；最近的研究表明，它可能 要治愈，因为它可以在五年后停止。我们想确认一下 这是为了定义保护的期限，并了解其机制 这是通过它发生的。另一个目标是了解地球的自然历史 昆虫过敏。我们已经证明了4%的种群是昆虫 25%的人有抗昆虫的IgE抗体 毒液。将对这些患者进行前瞻性研究，以确定 病史和免疫学参数之间的关系 将使我们能够前瞻性地识别被叮咬的严重风险的患者。 最后，我们打算使用提纯的昆虫毒液来提高准确率 皮试诊断的结果。第二个领域与免疫疗法有关 吸入性过敏。在哮喘的免疫治疗方面，我们将 将临床保护与释放性参数(即 嗜碱性细胞释放到各种促分泌剂的变化)和 急性期和晚期反应中的介质释放和细胞。 变应性鼻炎的免疫治疗导致对鼻腔的反应降低 急性期的抗原挑战；我们怀疑晚期的减少 这一阶段将更加戏剧化。此响应的两个阶段都将是 在免疫治疗前和治疗期间进行评估。最后，我们将确定 吸入性过敏的免疫治疗能否在五点后终止 好几年了。第三个研究领域利用了一种新的鼻部过敏原系统 挑战和灌洗测量介质(组胺、前列腺素D、激动素、驯服 酯酶、白三烯、趋化因子)和细胞(淋巴细胞、 嗜酸性粒细胞和中性粒细胞)和巨噬细胞衍生的组胺释放 在后期反应中发现的一种因子，其作用方式为 交联型IgE。我们将在这方面评估各种药物激动剂 系统。标准和新型代理的选择将基于他们的 体外对嗜碱性粒细胞和肥大细胞介质释放的影响。我们已经展示了 寒冷干燥的空气挑战(运动性哮喘的一种模型)也 导致临床敏感患者的介质释放，并将进行研究 该模型中的药物激动剂。在这种情况下，体外筛选 包括通过高渗透压刺激释放，我们假设这是 冷空气诱导体内释放的机制。

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.