Allergy, Anaphylaxis and Non-Allergic Hypersensitivity: IgE, Mast Cells and Beyond.

IgE-mediated type I hypersensitivity reactions have many reported beneficial functions in the immune defense against parasites, venoms, toxins etc. However, they are best-known for their role in allergy affecting nowadays almost one third of the population worldwide. IgE-mediated allergic diseases result from a maladaptive type 2 immune response that promotes the synthesis of IgE antibodies directed to a special class of antigens called allergens. IgE antibodies bind to type I high affinity IgE receptors (FcepsilonRI) on mast cells and basophils licensing them to get triggered in a subsequent encounter with the cognate allergen. This promotes the release of a whole set of inflammatory mediators including histamine responsible for the symptoms of immediate hypersensitivity. The development of type 2 driven allergies are dependent on a complex interplay of genetic and environmental factors at barrier surfaces including the host microbiome that builds up during early life. While without doubt IgE-mediated immediate hypersensitivity reactions are at the origin of the majority of allergies it has become clear that similar responses and symptoms can be triggered by other types of adaptive immune responses mediated via IgG or complement involving other immune cells and mediators. Likewise, various innate triggers via receptors expressed on mast cells have been found either to directly launch an allergic reaction and/or to amplify existing IgE-mediated responses. This review summarizes recent findings on both IgE-dependent and IgE-independent mechanisms in the development of allergies and provides an update on allergy diagnosis.