Immunoglobulin G (IgG) is atype ofantibody. Representing approximately 75% ofserum antibodies in humans, IgG is the most common type of antibody found inblood circulation.[1] IgG molecules are created and released byplasma B cells. Each IgG antibody has twoparatopes.
Antibodies are major components ofhumoral immunity. IgG is the main type of antibody found inblood andextracellular fluid, allowing it to control infection of bodytissues. By binding many kinds ofpathogens such asviruses,bacteria, andfungi, IgG protects the body from infection.[citation needed]
It does this through several mechanisms:[citation needed]
IgG antibodies are generated followingclass switching and maturation of the antibody response, thus they participate predominantly in thesecondary immune response.[3]
IgG is secreted as a monomer that is small in size allowing it to easilydiffuse into tissues. It is the onlyantibody isotype that hasreceptors to facilitate passage through the humanplacenta, thereby providing protection to thefetusin utero. Along withIgA secreted in thebreast milk, residual IgG absorbed through the placenta provides theneonate with humoral immunity before its ownimmune system develops.Colostrum contains a high percentage of IgG, especially bovine colostrum. In individuals with prior immunity to a pathogen, IgG appears about 24–48 hours after antigenic stimulation.[citation needed]
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 systemicanaphylaxis:[4][5] antigens can cause systemic anaphylaxis in mice through classic pathway by cross-linkingIgE bound to themast cell receptorFcεRI, stimulating the release of bothhistamine andplatelet activating factor (PAF). In the alternative pathway, antigens form complexes with IgG, which then cross-linkmacrophage receptorFcγRIII and stimulates only PAF release.[4]
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 ofantigen but can mediate systemic anaphylaxis induced by larger quantities.[4]
IgG antibodies are large globular proteins made of four peptide chains;[6] two identical γ (gamma)heavy chains of about 50 kDa and two identicallight chains of about 25 kDa. The resulting tetramericquaternary structure, therefore, has a total molecular weight of about 150 kDa.[7] The two heavy chains are linked to each other and to a light chain each bydisulfide bonds. The resultingtetramer has two identical halves, which together form a Y-like shape. Each end of the fork contains an identicalantigen binding site. The various regions and domains of a typical IgG are depicted in the figure "Anatomy of an IgG."
The Fc regions of IgGs bear a highly conservedN-glycosylation site atasparagine 297 in the constant region of the heavy chain.[8] The N-glycans attached to this site are predominantlycore-fucosylated biantennary structures of the complex type.[9] In addition, small amounts of these N-glycans also bear bisectingGlcNAc and α-2,6-linkedsialic acid residues.[10] The N-glycan composition in IgG has been linked to several autoimmune, infectious and metabolic diseases.[11]
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 | Crossesplacenta easily | Complement activator | Binds toFc 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 toFc receptors.[citation needed]
Repeatedly administeringCOVID-19 vaccines causes an increase in the proportion of IgG4 antibodies and IgG4-switched B cells, which can lead to impairedcellular phagocytosis andcomplement decomposition function, given that IgG2 and IgG4 play a role of in mediating non-inflammatory or anti-inflammatory functions. After the second vaccine dose, IgG4 accounted for 0.04% of the total IgG response, but after the third vaccine dose, it increased to 19.27%. Also, a significant increase was observed in the proportion of IgG4-producing B cells within thememory B cell pool that bound to the spike protein after the third vaccination.[18]
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The measurement of immunoglobulin G can be a diagnostic tool for certain conditions, such asautoimmune hepatitis, if indicated by certain symptoms.[19] 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.[20]
Testing of IgG is not indicated for diagnosis of allergy, and there is no evidence that it has any relationship to food intolerances.[21][22][23]