- Immunoglobulin E
biology, Immunoglobulin E (IgE) is a class of antibody(or immunoglobulin" isotype") that has only been found in mammals. It plays an important role in allergy, and is especially associated with type 1 hypersensitivity. [cite journal |author=Gould H et al. |title=The biology of IGE and the basis of allergic disease |journal=Annu Rev Immunol |volume=21 |issue= |pages=579–628 |year= 2003|pmid=12500981 |doi=10.1146/annurev.immunol.21.120601.141103] IgE has also been implicated in immune systemresponses to most parasitic worms [cite journal |author=Erb KJ |title=Helminths, allergic disorders and IgE-mediated immune responses: where do we stand?|journal=Eur J Immunol |volume=37 |issue=5 |pages=1170–1173 |year=2007 | pmid=17447233 |doi=10.1002/eji.200737314] like " Schistosoma mansoni", " Trichinella spiralis", and " Fasciola hepatica", [cite journal |author=Fitzsimmons C, McBeath R, Joseph S, Jones F, Walter K, Hoffmann K, Kariuki H, Mwatha J, Kimani G, Kabatereine N, Vennervald B, Ouma J, Dunne D |title=Factors affecting human IgE and IgG responses to allergen-like Schistosoma mansoni antigens: Molecular structure and patterns of in vivo exposure |journal=Int. Arch. Allergy Immunol. |volume=142 |issue=1 |pages=40–50 |year=2007 |pmid=17019080 |doi=10.1159/000095997] [cite journal |author=Watanabe N, Bruschi F, Korenaga M |title=IgE: a question of protective immunity in Trichinella spiralis infection |journal=Trends Parasitol. |volume=21 |issue=4 |pages=175–8 |year=2005 |pmid=15780839 |doi=10.1016/j.pt.2005.02.010] [cite journal |author=Pfister K, Turner K, Currie A, Hall E, Jarrett EE |title=IgE production in rat fascioliasis |journal=Parasite Immunol |volume=5 |issue=6 |pages=587–593 |year=1983| pmid=6657297 |doi=10.1111/j.1365-3024.1983.tb00775.x] and may be important during immune defense against certain protozoan parasites such as " Plasmodium falciparum".cite journal |author=Duarte J, Deshpande P, Guiyedi V, Mécheri S, Fesel C, Cazenave P, Mishra G, Kombila M, Pied S |title=Total and functional parasite specific IgE responses in Plasmodium falciparum-infected patients exhibiting different clinical status |journal=Malar. J. |volume=6 |issue= |pages=1 |year=2007 |pmid=17204149 |doi=10.1186/1475-2875-6-1]
Although IgE is typically the least abundant isotype -
blood serumIgE levels in a normal ("non- atopic") individual are ~75 ng/ml,Fact|date=August 2008 compared to 10 mg/ml for the IgGs (the isotypes responsible for most of the classical adaptive immune response) - it is capable of triggering the most powerful immune reactions.
IgE was discovered in
1966by the Japanese scientist Kimishige Ishizaka. [cite journal |author=Ishizaka K, Ishizaka T, Hornbrook MM |title=Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity |journal=J. Immunol. |volume=97 |issue=1 |pages=75–85 |year=1966 |pmid=4162440 |doi=]
IgE elicits an immune response by binding to
Fc receptors found on the surface of mast cells and basophils, and are also found on eosinophils, monocytes, macrophages and platelets in humans. It has two main receptors:
FcεRI, the high-affinity IgE receptor
FcεRII, also known as CD23, is the low-affinity IgE receptor
IgE can upregulate the expression of both Fcε receptors. FcεRI is expressed only on mast cells and/or basophils in both mice and humans. Aggregation of
antigens and binding of IgE to the FcεRI on mast cells causes degranulationand the release of mediators from the cells, while basophils cross-linked with IgE release type 2 cytokines like interleukin-4(IL-4) and interleukin-13(IL-13) and other inflammatory mediators. The low affinity receptor (FcεRII) is always expressed on B cells, but its expression can be induced on the surfaces of macrophages, eosinophils, platelets and some T cells by IL-4.
There is much speculation into what physiological benefits IgE contributes, and so far, circumstantial evidence in animal models and statistical population trends have hinted that IgE may be beneficial in fighting gut
parasitessuch as " Schistosoma mansoni", but this has not been conclusively proven in humans.
Although it is not yet well understood, IgE may play an important role in the immune system’s recognition of
cancer[cite journal |author=Karagiannis S et al |title=Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells |journal=Eur J Immunol |volume=33 |issue=4 |pages=1030–40 |year=2003 |pmid=12672069 |doi=10.1002/eji.200323185] , in which the stimulation of a strong cytotoxic response against cells displaying only small amounts of early cancer markers would be beneficial. Of course, if this were the case, anti-IgE treatments such as omalizumabmight have some undesirable side effects.
Role in disease
Atopicindividuals can have up to 10 times the normal level of IgE in their blood (as do sufferers of hyper-IgE syndrome). However, this may not be a requirement for symptoms to occur as has been seen in asthmatics with normal IgE levels in their blood - recent research has shown that IgE production can occur locally in the nasal mucosa, without the involvement of lymphoid tissue [cite journal |author=Takhar P et al. |title=Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis |journal=J Immunol |volume=174 |issue=8 |pages=5024–32 |year=2005 |pmid=15814733] .
IgE that can specifically recognise an "allergen" (typically this is a protein, such as
dust miteDerP1, cat FelD1, grass or ragweedpollen, etc.) has a unique long-lived interaction with its high affinity receptor, FcεRI, so that basophilsand mast cells, capable of mediating inflammatory reactions, become "primed", ready to release chemicals like histamine, leukotrienes and certain interleukins, which cause many of the symptoms we associate with allergy, such as airway constriction in asthma, local inflammation in eczema, increased mucussecretion in allergic rhinitisand increased vascular permeability, ostensibly to allow other immune cells to gain access to tissues, but which can lead to a potentially fatal drop in blood pressure as in anaphylaxis. Although the mechanisms of each response are fairly well understood, why some allergics develop such drastic sensitivities when others merely get a runny nose is still one of science's hot topics. Regulation of IgE levels through control of B cell differentiation to antibody-secreting plasma cellsis thought to involve the "low affinity" receptor, FcεRII or CD23Fact|date=August 2008. CD23may also allow facilitated antigen presentation, an IgE-dependent mechanism whereby B cellsexpressing CD23are able to present allergen to (and stimulate) specific T helper cells, causing the perpetuation of a Th2 response, one of the hallmarks of which is the production of more antibodies.
IgE may be an important target in treatments for allergy and asthma.
Currently, severe allergy and asthma is usually treated with drugs (like anti-histamines) that damp down the late stages of inflammation and relax airway smooth muscle. Unfortunately, these treatments are fairly broad in their action, and so many have unpleasant side effects; they may also inhibit important protective responses. Fact|date=September 2008
In 2002, researchers at The
Randall Division of Cell and Molecular Biophysicsdetermined the structure of IgE [cite journal |author=Wan T et al. |title=The crystal structure of IgE Fc reveals an asymmetrically bent conformation |journal=Nat Immunol |volume=3 |issue=7 |pages=681–6 |year=2002 |pmid=12068291 |doi=10.1038/ni811] . Understanding of this structure (which is atypical of other isotypes in that it is highly bent and asymmetric), and of the interaction of IgE with receptor FcεRI will enable development of a new generation of allergy drugs that seek to interfere with the IgE-receptor interaction. A new treatment, omalizumab, a monoclonal antibody, recognises IgE not bound to its receptor and is used to neutralise or mop-up existing IgE and prevent it from binding to cells. It may be possible to design treatments cheaper than monoclonal antibodies (for instance, small molecule drugs) that use a similar approach to inhibit IgE binding to its receptor.
In 1975 Robert N. Hamburger, M.D. published "Peptide Inhibition of the P-K Reaction" based on blocking up to 89% of the IgE receptors on mast cells by the pentapeptide representing amino acids 320 to 324 on the epsilon chain of IgE. [cite journal |author=Hamburger R |title=Peptide inhibition of the Prausnitz-Küstner reaction |journal=Science |volume=189 |issue=4200 |pages=389–90 |year=1975 |pmid=1145208 |doi=10.1126/science.1145208]
IgM, IgA, IgD, IgG
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immunoglobulin — im mu*no*glob ulin ([i^]m m[ u]*n[ o]*gl[o^]b [ u]*l[i^]n) n. (1953) any one of a class of globular proteins which are antibodies and are produced by the immune system in animals. Note: The immunoglobulins form a series of related proteins which… … The Collaborative International Dictionary of English
immunoglobulin A — immunoglobulin im mu*no*glob ulin ([i^]m m[ u]*n[ o]*gl[o^]b [ u]*l[i^]n) n. (1953) any one of a class of globular proteins which are antibodies and are produced by the immune system in animals. Note: The immunoglobulins form a series of related… … The Collaborative International Dictionary of English
immunoglobulin D — immunoglobulin im mu*no*glob ulin ([i^]m m[ u]*n[ o]*gl[o^]b [ u]*l[i^]n) n. (1953) any one of a class of globular proteins which are antibodies and are produced by the immune system in animals. Note: The immunoglobulins form a series of related… … The Collaborative International Dictionary of English
immunoglobulin G — immunoglobulin im mu*no*glob ulin ([i^]m m[ u]*n[ o]*gl[o^]b [ u]*l[i^]n) n. (1953) any one of a class of globular proteins which are antibodies and are produced by the immune system in animals. Note: The immunoglobulins form a series of related… … The Collaborative International Dictionary of English
immunoglobulin M — immunoglobulin im mu*no*glob ulin ([i^]m m[ u]*n[ o]*gl[o^]b [ u]*l[i^]n) n. (1953) any one of a class of globular proteins which are antibodies and are produced by the immune system in animals. Note: The immunoglobulins form a series of related… … The Collaborative International Dictionary of English
Immunoglobulin M — Immunoglobulin M, or IgM for short, is a basic antibody that is present on B cells. It is the primary antibody against A and B antigens on red blood cells. IgM is by far the physically largest antibody in the human circulatory system. tructure… … Wikipedia
Immunoglobulin G — (IgG) is a monomeric immunoglobulin, built of two heavy chains γ and two light chains. Each IgG has two antigen binding sites. It is the most abundant immunoglobulin and is approximately equally distributed in blood and in tissue liquids,… … Wikipedia
Immunoglobulin D — (IgD) is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B lymphocytes where it is usually coexpressed with another cell surface antibody called IgM. IgD is also produced in a secreted form that is found … Wikipedia
immunoglobulin — immunoglobulin. См. иммуноглобулин. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) … Молекулярная биология и генетика. Толковый словарь.
immunoglobulin D — n IGD … Medical dictionary