The evolution of IgE‐mediated type I hypersensitivity and its immunological value

Abstract

The allergic phenotype manifests itself in a spectrum of troublesome to life‐threatening diseases, from seasonal hay fever, through the food allergies, atopic eczema, asthma, to anaphylaxis. Allergy, that is an overreaction to allergen in hypersensitive individuals, results from the production of IgE, mast cell and basophil sensitisation and degranulation, requiring a range of medications to manage the conditions. Yet it is highly likely that allergy evolved for a purpose and that allergic diseases are accidental consequences of an insufficiently regulated immune response. This article presents a viewpoint from which to restore the immunological reputation of the allergic phenotype. We consider the evolutionary origins of potential allergens, toxins and parasites, and how they might have influenced early‐mammal species in existence when IgE first developed. We conclude that the allergic phenotype has likely saved the lives of many more mammals than have ever died from allergy, so justifying the positive role of IgE in our evolution.

Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

“…When the body’s first contact with allergens, antigen-presenting cells like monocytes-macrophages and dendritic cells (DCs) present antigen information to T helper lymphocytes, causing them to secrete cytokines. B lymphocytes then transform into plasma cells and secrete various allergen-specific IgE in response to the cytokines derived from T helper lymphocytes [ 32 ]. Specific IgE can bind to FcεRI on the surface of MCs.…”

“…In humans, FcεRI can be expressed as both αβγ2 and αγ2. In rodents, however, FcεRI is only expressed in the form of αβγ2 [ 32 , 33 ]. The extracellular domain of the α chain can bind to the Fc segment of IgE, which is a critical site for triggering allergic reactions.…”

“…The primary role of the β subunit is to enhance the tyrosine kinase activity and calcium influx and then to amplify the expression of FcεRI on the surface of MCs [ 17 ]. When the allergens enter again, FcεRI/IgE complexes are cross-linked with high-affinity antigens on the surface of sensitive MCs, the FcεRI receptor will be activated, causing signal transduction in MCs and promoting the degranulation of MCs and the subsequent release of inflammatory mediators, like histamine, serotonin and leukotriene, which are involved allergic reactions or inflammation [ 32 ].…”

Receptors of specialized pro-resolving mediators - a probable target of pharmacological restoration of homeostasis in allergic inflammation

“…Ранее было выдвинуто, обосновано и в последующем подкреплено новым фактическим материалом представление о том, что аллергия является эволюционно сформированной биологически целесообразной формой реактивности, направленной на распознавание низких концентраций аллергена, поступающего в определенном временном режиме в организм, и состоит в организации аллергического воспаления, предназначенного для элиминации чужеродного антигенного материала, не распознаваемого другими иммунологическими способами [1, 2]. Признание биологической целесообразности аллергической реактивности находится в согласии с недавно высказанным в доступной для широкой аудитории форме заключением о том, «что аллергический фенотип спас жизнь значительно большего числа млекопитающих, чем когда-либо погибших от аллергии, обосновывая тем самым положительную роль IgE в нашей эволюции» [3].…”

IgE Diseases

“…The elderly allergens of protozoa and helminths also date from the same times, in such a way that all the ingredients for the IgE-mediated allergic response existed with the appearance of mammals. Namely: mast cells and basophils, allergens, Ig-E, and its receptors, and possibly Th 2 cytokines [5].…”