The high-affinity IgE receptor, also known as FcεRI, or Fc epsilon RI, is the high-
affinity
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Commerce, finance and law
* Affinity (law), kinship by marriage
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* Affinity Credit Union, a Saskatchewan-based credit union
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receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
for the
Fc region
The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune s ...
of
immunoglobulin E
Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") 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 Π...
(IgE), an
antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
isotype involved in the
allergy
Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...
disorder and
parasites
Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson ha ...
immunity. FcεRI is a
tetramer
A tetramer () ('' tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula ...
ic receptor complex that binds Fc portion of the ε
heavy chain of
IgE
Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") 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 c ...
. It consists of one alpha (FcεRIα – antibody binding site), one beta (FcεRIβ – which amplifies the downstream signal), and two gamma chains (FcεRIγ – the site where the downstream signal initiates) connected by two disulfide bridges on
mast cells
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a ...
and
basophils
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
. It lacks the beta subunit on other cells. It is constitutively expressed on mast cells and basophils
and is inducible in
eosinophils
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
.
Tissue distribution
FcεRI is found on epidermal
Langerhans cell
A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...
s, eosinophils, mast cells, and basophils. As a result of its cellular distribution, this receptor plays a major role in controlling
allergic responses. FcεRI is also expressed on
antigen-presenting cells, and controls the production of important immune mediators (
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s,
interleukin
Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...
s,
leukotriene
Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase.
Leukotrienes ...
s, and
prostaglandins) that promote
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
. The most known mediator is
histamine
Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered ...
, which results in the five symptoms of inflammation: heat, swelling, pain, redness and loss of function.
FcεRI was demonstrated in bronchial/tracheal airway smooth muscle cells in normal and asthmatic patients. FcεRI cross-linking by IgE and anti-IgE antibodies led to Th2 (IL-4, -5, and -13) cytokines and CCL11/eotaxin-1 chemokine release; and (
a2+) mobilization, suggesting a likely IgE-FcεRI-ASM-mediated link to airway inflammation and AHR.
Mechanism of action
Crosslinking of the FcεRI via IgE-
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
complexes leads to degranulation of mast cells or basophils and release of
inflammatory mediators.
Under laboratory conditions,
degranulation of isolated basophils can also be induced with
antibodies to the FcεRIα, which crosslink the receptor. Such crosslinking and potentially pathogenic
autoantibodies to the FcεRIα have been isolated from human
cord blood
Cord blood (umbilical cord blood) is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders s ...
, which suggest that they occur naturally and are present already at birth. However, their
epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...
on FcεRIα was masked by IgE, and the affinity of the corresponding autoantibodies found in healthy adults appeared lowered.
See also
*
Omalizumab
Omalizumab, sold under the brand name Xolair, is a medication used to treat asthma, nasal polyps, and urticaria (hives).
Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody that specifically binds to free human immunoglo ...
References
External links
*
{{DEFAULTSORT:Fceri
Fc receptors
Proteins