The high-affinity IgE receptor, also known as FcεRI, or Fc epsilon RI, is the high-
affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Pa ...
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
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 region allows antibodies to activate the immune sys ...
of
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 ...
(IgE), an
antibody
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
isotype involved in
allergy
Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...
disorders and
parasite
Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted str ...
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) " 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 ...
. 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. They are the largest type of granulocyte. They are responsible for inflammatory reactio ...
. 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 and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...
.
Tissue distribution
FcεRI is found on epidermal
Langerhans cell
A Langerhans cell (LC) is a tissue-resident macrophage of the skin once thought to be a resident dendritic cell. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in t ...
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 cell
An antigen-presenting cell (APC) or accessory cell is a Cell (biology), cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize the ...
s, 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 produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
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 inflammation, inflammatory mediators produced in leukocytes by the redox, oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxyg ...
s, and
prostaglandin
Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...
s) that promote
inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
. The most known mediator is
histamine
Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...
, 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
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal muscle, skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non-striated ...
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 (airway
smooth muscle cell
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called becau ...
)-mediated link to airway inflammation and
airway hyperresponsiveness
Bronchial hyperresponsiveness (or other combinations with airway or hyperreactivity, BH used as a general abbreviation) is a state characterised by easily triggered bronchospasm (contraction of the bronchioles or small airways).
Bronchial hyperres ...
.
Mechanism of action
Crosslinking of the FcεRI via IgE-
antigen
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
...
complexes leads to degranulation of mast cells or basophils and release of
inflammatory mediators.
Under laboratory conditions,
degranulation
Degranulation is a cellular process that releases antimicrobial, cytotoxic, or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including gran ...
of isolated basophils can also be induced with
antibodies
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
to the FcεRIα, which crosslink the receptor. Such crosslinking and potentially pathogenic
autoantibodies
An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies.
Pr ...
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 ...
, 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 part of an antibody that binds to the epitope is called a paratope. Although e ...
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 among others, is an injectable medication to treat severe persistent allergic forms of asthma, nasal polyps, urticaria (hives), and immunoglobulin E-mediated food allergy.
Omalizumab is a recombi ...
References
External links
*
{{DEFAULTSORT:Fceri
Fc receptors
Proteins