Helm Ricki M, Ermel Richard W, Frick Oscar L
Department of Pediatrics, Division of Allergy/Immunology, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, USA.
Environ Health Perspect. 2003 Feb;111(2):239-44. doi: 10.1289/ehp.5705.
Food allergy can present as immediate hypersensitivity [manifestations mediated by immunoglobulin (Ig)E], delayed-type hypersensitivity (reactions associated with specific T lymphocytes), and inflammatory reactions caused by immune complexes. For reasons of ethics and efficacy, investigations in humans to determine sensitization and allergic responses of IgE production to innocuous food proteins are not feasible. Therefore, animal models are used a) to bypass the innate tendency to develop tolerance to food proteins and induce specific IgE antibody of sufficient avidity/affinity to cause sensitization and upon reexposure to induce an allergic response, b) to predict allergenicity of novel proteins using characteristics of known food allergens, and c) to treat food allergy by using immunotherapeutic strategies to alleviate life-threatening reactions. The predominant hypothesis for IgE-mediated food allergy is that there is an adverse reaction to exogenous food proteins or food protein fragments, which escape lumen hydrolysis, and in a polarized helper T cell subset 2 (Th2) environment, immunoglobulin class switching to allergen-specific IgE is generated in the immune system of the gastrointestinal-associated lymphoid tissues. Traditionally, the immunologic characterization and toxicologic studies of small laboratory animals have provided the basis for development of animal models of food allergy; however, the natural allergic response in large animals, which closely mimic allergic diseases in humans, can also be useful as models for investigations involving food allergy.
食物过敏可表现为速发型超敏反应(由免疫球蛋白IgE介导的表现)、迟发型超敏反应(与特定T淋巴细胞相关的反应)以及免疫复合物引起的炎症反应。出于伦理和有效性的原因,在人体中确定对无害食物蛋白产生IgE的致敏和过敏反应的研究并不可行。因此,动物模型被用于:a)绕过对食物蛋白产生耐受的固有倾向,诱导具有足够亲和力/亲合力的特异性IgE抗体以引起致敏,并在再次接触时诱导过敏反应;b)利用已知食物过敏原的特征预测新型蛋白的致敏性;c)通过免疫治疗策略治疗食物过敏以减轻危及生命的反应。IgE介导的食物过敏的主要假说是,对外源食物蛋白或食物蛋白片段存在不良反应,这些蛋白或片段逃脱了管腔水解作用,并且在极化的辅助性T细胞2(Th2)环境中,胃肠道相关淋巴组织的免疫系统中会发生免疫球蛋白类别转换为过敏原特异性IgE。传统上,小型实验动物的免疫学特征和毒理学研究为食物过敏动物模型的开发提供了基础;然而,大型动物的自然过敏反应与人类的过敏性疾病非常相似,也可作为涉及食物过敏研究的模型。