Anaphylaxis is a life-threatening
IgE-dependent type 1
hypersensitivity reaction in which multiple organ systems are involved. The existence of
allergen exposure and specific
IgE are the major contributors to this systemic reaction. The decision of the immune system to respond to
allergens is highly dependent on factors including the type and load of
allergen, behavior and type of antigen-presenting cells, innate immune response stimulating substances in the same micromilieu, the tissue of exposure, interactions between T and B lymphocytes, costimulators, and genetic propensity known as atopy. Antigen-presenting cells introduce processed
allergens to T-helper lymphocytes, where a decision of developing different types of T-cell immunity is given under the influence of several
cytokines,
chemokines, costimulatory signals and regulatory T cells. Among Th2-type
cytokines,
interleukin (IL)-4 and
IL-13 are responsible for class switching in B cells, which results in production of
allergen-specific
IgE antibodies that bind to specific receptors on mast cells and basophils. After re-exposure to the sensitized
allergen, this phase is followed by activation of
IgE Fc receptors on mast cells and basophils resulting in biogenic mediator releases responsible for the symptoms and signs of
anaphylaxis. Since the discovery of regulatory T cells, the concepts of immune regulation have substantially changed during the last decade. Peripheral T-cell tolerance is a key immunologic mechanism in healthy immune response to
self antigens and non-infectious non-
self antigens. Both naturally occurring CD4+CD25+ regulatory T (Treg) cells and inducible populations of
allergen-specific, IL-10-secreting Treg type 1 cells inhibit
allergen-specific effector cells and have been shown to play a central role in the maintenance of peripheral homeostasis and the establishment of controlled immune responses. On the other hand, Th17 cells are characterized by their
IL-17 (or IL-17A),
IL-17F,
IL-6,
tumor necrosis factor-alpha, and
IL-22 expressions, which coordinate local tissue
inflammation through upregulation of proinflammatory
cytokines and
chemokines. This chapter is mainly focused on antigen presentation pathways and
allergen-specific T-cell responses.