User:Anthony Davis/Sandbox1 IgE
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IgE Receptor FcϵRIIgE Receptor FcϵRI
Antibodies are also known as immunoglobulins (Igs). They are part of the Adaptive immune system. When a pathogen invades the body antibodies bind to the pathogen in order to neutralize it and mark it for destruction. The antibodies are grouped into five types IgA, IgD, IgM, IgG, and IgE. They each have specific functions for example IgE binds to allergens and triggers the release of histamine from mast cells and basophils. The alpha subunit of the FcϵRI receptor found on mast cells for example, shown below is responsible for the binding of IgE.
FunctionFunction
The function of the FcϵRI receptor on the surface of mast cells and basophils is to bind to the IgE-antigen complex. [1]This elicits an immune response which induces these cells to release histamine and initiate an inflammatory response. This is seen in people who suffer from allergies such as Hay fever. Hay fever is an allergic reaction to pollen and some of the symptoms are a runny nose, sneezing, teary eyes. More serious allergic reactions could result in anaphylaxis in which there is restriction of the respiratory pathways and possible cardiac arrest which could result in death. An illustration of of the steps in an allergic reaction is shown in the following link[2]
The best way to deal with allergens is to avoid them. Some allergens such as pollen however are not easily avoided. The next best thing therefore is to treat the symptoms. This is accomplished by using antihistamines, topical nasal steroids, cromolyn sodium or decongestants.
CausesCauses
There are two main factors that contribute to the development of IgE mediated allergies and these are genetic and environmental. There are several genes that may make people susceptible to allergic reactions one such gene is located on chromosome 11q12-13 and is associated with asthma. There are four main environmental factors which are allergen levels, environmental pollution, dietary changes and changes and exposure to infectious diseases in early childhood.
StructureStructure
The FcεRI receptor is a tetrameric receptor complex consisting of one alpha, one beta, and two disulfide bridge connected gamma chains.[3]. The alpha subunit is the one dedicated to the binding of IgE. The structure of the FcϵRI alpha subunit is made up of two (Ig)domains . The domains form a convex shape at the top of the receptor that is directly involved in binding IgE. Another feature of the FcϵRI alpha subunit is the which forms part of the binding site for IgE. The FcεRI residues that have been implicated in IgE binding include residues numbers , and in the D2 C strand , in the C′-E loop , the F strand, in the FG loop, and in the G strand. In addition, residues 87 at the D1D2 interface and 128 in the C′-E loop are likely to be part of the IgE interaction site, since mutation of these residues influences receptor binding to IgE.
Some of these residues specifically are all exposed amino acids at the FcεRI surface and they form an area extending from the back side of the D2 domain to the top region near the D1D2 interface.
In proximity to to this binding site are a number of surface-accessible aromatic residues, including four prominent tryptophans at the top of the FcR molecule, residues The four tryptophans form a flat, hydrophobic ridge that neighbors the D2 FG loop. This unusual arrangement of four exposed tryptophans probably forms a contact surface for a complementary interaction with the IgE.
ResearchResearch
Current research involves allergy drugs that will disrupt or interfere with the interaction between IgE and its Fc receptor. The drug Omalizumab (trade name Xolair) is one such drug that is in use today to help people with allergic asthma. It works by binding to IgE thus interfering with its ability to bind to its receptor and induce an immune response. A recent study has shown an antibody (XmAb7195) to have five times more affinity to IgE than Omalizumab. Research pertaining to IgE and its FcϵRI receptor will continue to be important in regards to the treatment of allergic reactions and asthma.
ReferencesReferences
Chu S., Horton H., Pong E., Leung I., Chen H., Nguyen D., Bautista C., Muchhal U., Bernett M., Moore G., Szymkowski D., Desjarlais J. "Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcγRIIb with Fc-engineered antibody", The Journal of allergy and clinical immunology 1 April 2012 volume 129, issue 4, pp. 1102-1115.
Garman, S., Kinet, J., Theodore S."Crystal Structure of the Human High-Affinity IgE Receptor" Cell, volume 95 issue 7 pp.951 - 961.
Kelly,J., Allergic Reactions. Retrieved May 8,2012 from the National Institutes of Health website at http://www.niaid.nih.gov/topics/immuneSystem/Pages/disordersImages.aspx#allergicreaction.
Murphy,K., Travers, P., Walport M. (2008). Janeway's Immunobiology. New York, NY: Garland Science.
Scheinfeld N. (2005). Omalizumab: A recombinant humanized monoclonal IgE blocking antibody. Dermatology Online Journal. 11(1)2. Retrieved from http://dermatology.cdlib.org/111/reviews/omalizub/scheinfeld.html