Immunoglobulin G
Immunoglobulin G (IgG) is a
Function
Antibodies are major components of
It does this through several mechanisms:[citation needed]
- IgG-mediated binding of pathogens causes their immobilization and binding together via opsonization) allows their recognition and ingestion by phagocytic immune cellsleading to the elimination of the pathogen itself;
- IgG activates all the classical pathway of the complement system, a cascade of immune protein production that results in pathogen elimination;
- IgG also binds and neutralizes toxins;
- IgG also plays an important role in intracellular antibody-mediated proteolysis, in which it binds to TRIM21 (the receptor with greatest affinity to IgG in humans) in order to direct marked virions to the proteasome in the cytosol;[2]
- IgG is also associated with type II and type III hypersensitivity reactions.
IgG antibodies are generated following
IgG is secreted as a monomer that is small in size allowing it to easily
Therefore, in the first six months of life, the newborn has the same antibodies as the mother and the child can defend itself against all the pathogens that the mother encountered in her life (even if only through vaccination) until these antibodies are degraded. This repertoire of immunoglobulins is crucial for the newborns who are very sensitive to infections, especially within the respiratory and digestive systems.[citation needed]
IgG are also involved in the regulation of allergic reactions. According to Finkelman, there are two pathways of systemic
IgG antibodies can prevent IgE mediated anaphylaxis by intercepting a specific antigen before it binds to mast cell–associated IgE. Consequently, IgG antibodies block systemic anaphylaxis induced by small quantities of antigen but can mediate systemic anaphylaxis induced by larger quantities.[4]
Structure
IgG antibodies are large globular proteins made of four peptide chains;
The Fc regions of IgGs bear a highly conserved N-glycosylation site at asparagine 297 in the constant region of the heavy chain.[8] The N-glycans attached to this site are predominantly core-fucosylated biantennary structures of the complex type.[9] In addition, small amounts of these N-glycans also bear bisecting GlcNAc and α-2,6-linked sialic acid residues.[10] The N-glycan composition in IgG has been linked to several autoimmune, infectious and metabolic diseases.[11]
Subclasses
There are four IgG subclasses (IgG1, 2, 3, and 4) in humans, named in order of their abundance in serum (IgG1 being the most abundant).[12]
Name | Percentage | Crosses placenta easily | Complement activator | Binds to Fc receptor on phagocytic cells | Half life[13] |
IgG1 | 66% | yes (1.47)* | second-highest | high affinity | 21 days |
IgG2 | 23% | no (0.8)* | third-highest | extremely low affinity | 21 days |
IgG3 | 7% | yes (1.17)* | highest | high affinity | 7 days |
IgG4 | 4% | yes (1.15)* | no | intermediate affinity | 21 days |
* Quota cord/maternity concentrations blood. Based on data from a Japanese study on 228 mothers.[14] |
Note: IgG affinity to Fc receptors on phagocytic cells is specific to individual species from which the antibody comes as well as the class. The structure of the hinge regions (region 6 in the diagram) contributes to the unique biological properties of each of the four IgG classes. Even though there is about 95% similarity between their Fc regions, the structure of the hinge regions is relatively different.[citation needed]
Given the opposing properties of the IgG subclasses (fixing and failing to fix complement; binding and failing to bind FcR), and the fact that the immune response to most antigens includes a mix of all four subclasses, it has been difficult to understand how IgG subclasses can work together to provide protective immunity. In 2013, the Temporal Model of human IgE and IgG function was proposed.[15] This model suggests that IgG3 (and IgE) appear early in a response. The IgG3, though of relatively low affinity, allows IgG-mediated defences to join IgM-mediated defences in clearing foreign antigens. Subsequently, higher affinity IgG1 and IgG2 are produced. The relative balance of these subclasses, in any immune complexes that form, helps determine the strength of the inflammatory processes that follow. Finally, if antigen persists, high affinity IgG4 is produced, which dampens down inflammation by helping to curtail FcR-mediated processes.[citation needed]
The relative ability of different IgG subclasses to fix complement may explain why some anti-donor antibody responses do harm a graft after organ transplantation.[16]
In a mouse model of autoantibody mediated anemia using IgG isotype switch variants of an anti erythrocytes autoantibody, it was found that mouse IgG2a was superior to IgG1 in activating complement. Moreover, it was found that the IgG2a isotype was able to interact very efficiently with FcgammaR. As a result, 20 times higher doses of IgG1, in relationship to IgG2a autoantibodies, were required to induce autoantibody mediated pathology.[17] Since mouse IgG1 and human IgG1 are not entirely similar in function, and the inference of human antibody function from mouse studies must be done with great care. However, both human and mouse antibodies have different abilities to fix complement and to bind to Fc receptors.[citation needed]
Role in diagnosis
The measurement of immunoglobulin G can be a diagnostic tool for certain conditions, such as autoimmune hepatitis, if indicated by certain symptoms.[18] Clinically, measured IgG antibody levels are generally considered to be indicative of an individual's immune status to particular pathogens. A common example of this practice are titers drawn to demonstrate serologic immunity to measles, mumps, and rubella (MMR), hepatitis B virus, and varicella (chickenpox), among others.[19]
Testing of IgG is not indicated for diagnosis of allergy, and there is no evidence that it has any relationship to food intolerances.[20][21][22]
See also
References
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- ^ Janeway CA Jr; Travers P; Walport M; et al. (2001). "Ch3 Antigen Recognition by B-Cell and T-cell Receptors". Immunobiology: The Immune System in Health and Disease (5th ed.). New York: Garland Science.
- ^ "Antibody Basics". Sigma-Aldrich. Retrieved 2014-12-10.
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