Mouse models of allergic inflammation: from allergic sensitization to immunotherapy

Allergic diseases are the result of an aberrant immune response by T helper type 2 cells to allergens. Allergic sensitization is considered to be a multifactorial process that involves among others, environmental factors, genetics and characteristics of allergens. In normal conditions, exposure to non-infectious protein antigens induces a state of tolerance, which is essential to maintain homeostasis under constant exposure to environmental antigens. A failure in the mechanisms of tolerance, leads to activation of pro-inflammatory pathways and the development of allergen specific T cell responses. The development of animal models of various allergies has been beneficial in allowing extensive investigations into mechanisms involved in the allergic pathways. These animal models can be used to predict potential risk factors as well as to test novel treatments and immunotherapy. The risk of anaphylaxis in humans is a limiting factor for the development of allergen-based immunotherapy. In this context, animal models can play an essential role in providing a platform for refining therapeutic treatments and ensuring safety, prior to application in humans. In this thesis we use animal models to address essential questions such as what makes an individual respond to allergens. We have studied this question from different perspectives and have identified a role for the capacity to cope with allergen induced oxidative stress; the role of epithelial contact with HDM allergens in the development of an IgE response; the immunological interplay between allergic immune responses directed against unrelated allergens in different compartments of the body and; the immunological interplay between cross-reactive allergens