Allergy, Anaphylaxis, and Nonallergic Hypersensitivity: IgE, Mast Cells, and Beyond

Abstract

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.

Bilateral swelling of the salivary glands and sicca symptoms: an unusual differential diagnosis—Kimura’s disease, a rare allergic condition with a high IgE serum level—a case report and review of the literature

“… 2 3 The physiological function of IgE is to provide protective immunity against helminth parasites, but it can also mediate type I hypersensitivity reactions that contribute to the pathogenesis of allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. However, despite IgE causing an abundance of human disease, it was not until 1967 that the molecule was discovered, 2 and this is in part due to its very low serum concentration relative to other antibody isotypes—over one hundred thousand-fold less than IgG in healthy individuals. 3 Despite the importance of IgE in immune biology and allergic pathogenesis, the cells and the pathways that produce and regulate IgE in detail are poorly understood.…”

“…The TH2 branch of the adaptive immune system favours CD4+TH2 cells, eosinophils, basophils, mast cells, type 2 innate lymphoid cells as well as the production of cytokines such as IL-4, IL-5, IL-9 and IL-13 and humoral antibody responses of the immunoglobulin antibody IgE isotype. 2 Monomers of this antibody which is found only in mammals are synthesised by plasma cells and they consist of two heavy and two light chains. IgE, discovered in 1967, 3 is thought to be important for the immune response against infections by certain parasitic worms.…”

“…This promotes the release of a large variety of inflammatory mediators including histamine which are responsible for the symptoms of immediate hypersensitivity. 2 Histamine is a neuro-immuno-endocrine system mediator, which influences a whole spectrum of physiologic functions of various tissues and cells, including immunity. The half-life of histamine in plasma is relatively short, a few minutes.…”

“…Indeed, it is now well established that IgE-dependent allergies are TH2 driven. The TH2 branch of the adaptive immune system favours CD4+TH2 cells, eosinophils, basophils, mast cells, type 2 innate lymphoid cells as well as the production of cytokines such as IL-4, IL-5, IL-9 and IL-13 and humoral antibody responses of the immunoglobulin antibody IgE isotype 2. Monomers of this antibody which is found only in mammals are synthesised by plasma cells and they consist of two heavy and two light chains.…”

Mast Cell Tryptase and Carboxypeptidase A3 in the Formation of Ovarian Endometrioid Cysts

“…At the same time, the co-cultivation of MCs with endometriotic epithelial cells and endometrial stromal cells leads to the increased production of pro-inflammatory and chemokinetic cytokines [ 14 ], which may explain the pathogenesis of the special properties of the integrative buffer metabolic environment. The special role of MCs is associated with the functional features of their integration into both the immune and stromal landscapes of the tissue microenvironment [ 15 , 16 , 17 , 18 , 19 ]. MCs were first identified by Paul Ehrlich and described in his doctoral dissertation in 1878 [ 20 , 21 ].…”