Immunoglobulin E

Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) "isoform") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (ε chain) and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.

IgE also has an essential role in type I hypersensitivity, which manifests in various allergic diseases, such as allergic asthma, most types of sinusitis, allergic rhinitis, food allergies, and specific types of chronic urticaria and atopic dermatitis. IgE also plays a pivotal role in responses to allergens, such as anaphylactic reactions to drugs, bee stings, and antigen preparations used in desensitization immunotherapy.

IgE is typically the least abundant isotype: blood serum IgE levels in a non-atopic individual are less than 0.0001% of the total Ig concentration, compared to 75% for the IgGs at 10 mg/ml. Despite this, it is capable of triggering anaphylaxis, one of the most rapid and severe immunological reactions.

IgE was simultaneously discovered in 1966 and 1967 by two independent groups: by Teruko Ishizaka and her husband Kimishige Ishizaka at the Children's Asthma Research Institute and Hospital in Denver, Colorado, and by Gunnar Johansson and Hans Bennich [sv] in Uppsala, Sweden. Their joint paper was published in April 1969.

IgE primes the IgE-mediated allergic response by binding to Fc receptors found on the surface of mast cells and basophils. Fc receptors are also found on eosinophils, monocytes, macrophages and platelets in humans. There are two types of Fcε receptors:^{[citation needed]}

IgE can upregulate the expression of both types of Fcε receptors. FcεRI is expressed on mast cells, basophils, and the antigen-presenting dendritic cells in both mice and humans. Binding of antigens to IgE already bound by the FcεRI on mast cells causes cross-linking of the bound IgE and the aggregation of the underlying FcεRI, leading to degranulation (the release of mediators) and the secretion of several types of type 2 cytokines like interleukin (IL)-3 and stem cell factor (SCF), which both help the mast cells survive and accumulate in tissue, and IL-4, IL-5, IL-13, and IL-33, which in turn activate group 2-innate lymphoid cells (ILC2 or natural helper cells). Basophils share a common haemopoietic progenitor with mast cells; upon the cross-linking of their surface bound IgE by antigens, also release type 2 cytokines, including IL-4 and IL-13, and other inflammatory mediators. The low-affinity receptor (FcεRII) is always expressed on B cells; but IL-4 can induce its expression on the surfaces of macrophages, eosinophils, platelets, and some T cells.

The IgE isotype has co-evolved with basophils and mast cells in the defence against parasites like helminths (like Schistosoma) but may be also effective in bacterial infections. Epidemiological research shows that IgE level is increased when infected by Schistosoma mansoni, Necator americanus, and nematodes in humans. It is most likely beneficial in removal of hookworms from the lung.^{[citation needed]}

In 1981 Margie Profet suggested that allergic reactions have evolved as a last line of defense to protect against venoms. Although controversial at the time, new work supports some of Profet's thoughts on the adaptive role of allergies as a defense against noxious toxins.