MECHANISMS OF HYPERSENSITIVITY STATES

豚鼠是一个很好的模型，在其中研究的机制， 速发型和迟发型超敏反应 在我们的实验室里， 初步证据表明，我们可以使潜在的重要 观察亲同型细胞抗体、肥大细胞和 嗜碱性粒细胞在豚鼠超敏状态中的作用。 迄今为止，我们的数据表明IgG 1和IgE都可以介导 豚鼠的睾丸收缩，它们似乎是通过 分离组织受体。 此外，我们已经能够分离肺 组织肥大细胞，并有能力研究的生物化学 这些抗体直接作用于细胞， 在即时反应中发挥重要作用。 我们也有能力 分离纯的血液嗜碱性粒细胞群体（85-100%纯度）。 根据这些观察，我们建议详细研究 IgG 1和IgE肺受体的独特性质。 我们计划做 这是通过悬浮从IgG 1或IgE致敏的肺组织获得的 动物在灌流室，同时测量收缩， 在用特异性抗原刺激时释放的介质。 我们还将 我想用亲同型细胞抗体将这些组织研究扩展到 分离的肺肥大细胞，通过研究该细胞的IgG 1和IgE 受体和检测介质从这些分离的细胞释放时， 用IgG 1或IgE抗体致敏。 我们建议的第二个独立但相关的部分是审查 离体颗粒的豚鼠皮肤炎症激发电位 从纯化的血液嗜碱性粒细胞（90-100%纯度）获得。 有了这个， 我们希望能够明确嗜碱性粒细胞参与迟发性 含有嗜碱性粒细胞的皮肤反应。 豚鼠与人类在主要介质方面的相似性 肥大细胞和嗜碱性粒细胞释放的激素使得这些研究 在理解类似事件的即时和延迟 人类的超敏状态。

The guinea pig is an excellent model in which to study mechanisms of immediate and delayed hypersensitivity. In our laboratory, we have preliminary evidence suggestive that we can make potentially important observations as to the role of homocytotropic antibody, mast cells, and basophils in guinea pig hypersensitivity states. Our data to date has demonstrated that both IgG1 and IgE can mediate polmonary contraction in the guinea pig and they seem to do so through separate tissue receptors. Furthermore, we have been able to isolate lung tissue mast cells and have the capability to study the biochemistry of these antibodies directly on this cell which has been shown to play an important role in immediate reactions. We also have the capability of isolating pure populations of blood basophilis (85-100% purity). Based upon these observations, we propose to study in detail the distinctive nature of the IgG1 and IgE pulmonary receptors. We plan to do this by suspending pulmonary tissue obtained from IgG1 or IgE sensitized animals in a superfusion chamber and simultaneously measure contraction and mediators released upon stimulation with specific antigen. We also would like to extend these tissue studies with homocytotropic antibody to the isolated pulmonary mast cell by studying this cell for IgG1 and IgE receptors and examining mediator release from these isolated cells when sensitized with IgG1 or IgE antibodies. A second separate but yet related part of our proposal is to examine the inflammatory provoking potential in guinea pig skin of isolated granules obtained from purified blood baseophils (90-100% purity). With this we hope to define some of the mechanisms of basophil involvement in delayed cutaneous reactions containing basophils. The similarity of the guinea pig to humans as far as primary mediators released by mast cells and basophils makes these studies of potential importance in understanding similar events in immediate and delayed hypersensitivity states in humans.