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{{technical|date=December 2021}}
{{short description|Antibody isotype}}
[[File:Antibody IgG1 surface.png|thumb|The water-accessible surface area of an IgG antibody]]
'''Immunoglobulin G''' ('''Ig GIgG''') is a [[Antibody#Classes|type]] of [[antibody]]. Representing approximately 75% of [[blood plasma|serum]] [[immunoglobulins|antibodies]] in humans, IgG is the most common type of antibody found in [[Circulatory system|blood circulation]].<ref>{{Cite journal|last1=Vidarsson|first1=Gestur|last2=Dekkers|first2=Gillian|last3=Rispens|first3=Theo|date=2014|title=IgG subclasses and allotypes: from structure to effector functions|journal=Frontiers in Immunology|volume=5|pages=520|doi=10.3389/fimmu.2014.00520|issn=1664-3224|pmc=4202688|pmid=25368619|doi-access=free}}</ref> IgG molecules are created and released by [[plasma B cell]]s. Each IgG antibody has two [[paratope]]s.
 
== Function ==
 
Antibodies are major components of [[humoral immunity]]. IgG is the main type of antibody found in [[blood]] and [[extracellular fluid]], allowing it to control infection of body [[Tissue (biology)|tissue]]s. By binding many kinds of [[pathogen]]s such as [[virus]]es, [[bacteria]], and [[fungi]], IgG protects the body from infection.{{cn|date=January 2023}}
 
It does this through several mechanisms:{{cn|date=January 2023}}
* IgG-mediated binding of pathogens causes their immobilization and binding together via [[agglutination (biology)|agglutination]]; IgG coating of pathogen surfaces (known as [[opsonization]]) allows their recognition and ingestion by [[phagocytosis|phagocytic immune cells]] leading to the elimination of the pathogen itself;
* IgG activates all the [[classical complement pathway|classical pathway]] of the [[complement system]], a cascade of immune [[protein]] production that results in pathogen elimination;
* IgG also binds and [[neutralisation (immunology)|neutralizes]] [[toxin]]s;
* IgG also plays an important role in [[antibody-dependent cell-mediated cytotoxicity]] (ADCC) and [[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;<ref name="pmid21045130">{{cite journal |vauthors=Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC |title=Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21) |journal=Proceedings of the National Academy of Sciences, USA |volume=107 |issue=46 |pages=19985–19990 |year=2010 |pmid=21045130 |doi=10.1073/pnas.1014074107 |pmc=2993423|bibcode=2010PNAS..10719985M |doi-access=free }}</ref>
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IgG antibodies are generated following [[class switching]] and maturation of the antibody response, thus they participate predominantly in the [[Memory B cell|secondary immune response]]. <ref>{{Cite journal|last1=Vidarsson|first1=Gestur|last2=Dekkers|first2=Gillian|last3=Rispens|first3=Theo|date=2014|title=IgG subclasses and allotypes: from structure to effector functions|journal=Frontiers in Immunology|volume=5|pages=520|doi=10.3389/fimmu.2014.00520|issn=1664-3224|pmc=4202688|pmid=25368619|doi-access=free}}</ref>
 
IgG is secreted as a monomer that is small in size allowing it to easily [[PerfusionDiffusion|perfusediffuse]] into tissues. It is the only [[Antibody#Isotypes|antibody isotype]] that has [[Neonatal Fc receptor|receptors]] to facilitate passage through the human [[placenta]], thereby providing protection to the [[fetus]] ''[[Uterus|in utero]]''. Along with [[IgA]] secreted in the [[breast milk]], residual IgG absorbed through the placenta provides the [[neonate]] with humoral immunity before its own [[immune 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.{{cn|date=January 2023}}
 
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.{{cn|date=January 2023}}
 
IgG are also involved in the regulation of allergic reactions. According to Finkelman, there are two pathways of systemic [[anaphylaxis]]:<ref name="anaphylaxis mouse" /><ref>{{cite journal |title=Identification of markers that distinguish IgE-from IgG mediated anaphylaxis |journal=Proceedings of the National Academy of Sciences, USA |year=2011 |volume=108 |issue=30 | pages=12413–12418 | vauthors=Khondoun MV, Strait R, Armstrong L, Yanase N, Finkelman FD|doi=10.1073/pnas.1105695108|pmid=21746933 |pmc=3145724|bibcode=2011PNAS..10812413K |doi-access=free }}</ref> antigens can cause systemic anaphylaxis in mice through classic pathway by cross-linking [[IgE]] bound to the [[mast cell]] receptor FcεRI, stimulating the release of both [[histamine]] and [[platelet activating factor]] (PAF). In the alternative pathway antigens form complexes with IgG, which then cross-link [[macrophage]] receptor FcγRIII and stimulates only PAF release.<ref name="anaphylaxis mouse">{{cite journal|last1=Finkelman|first1=Fred D.|title=Anaphylaxis: Lessons from mouse models|journal=Journal of Allergy and Clinical Immunology|date=September 2007|volume=120|issue=3|pages=506–515|doi=10.1016/j.jaci.2007.07.033|pmid=17765751}}</ref>
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== Structure ==
[[File:Anatomy of an IgG.png|thumb|left|The various regions and domains of a typical IgG]]▼
IgG antibodies are large globular proteins made of four peptide chains<ref>{{cite book |author1=Janeway CA Jr |author2=Travers P |author3=Walport M | title=Immunobiology: The Immune System in Health and Disease | publisher=Garland Science | year=2001 | location=New York | edition=5th | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK27144/ | chapter=Ch3 Antigen Recognition by B-Cell and T-cell Receptors|display-authors=etal}}</ref>; two identical γ (gamma) heavy chains of about 50&nbsp;kDa and two identical light chains of about 25&nbsp;kDa. The resulting tetrameric quaternary structure, therefore, has a total molecular weight of about 150&nbsp;[[kDa]].<ref>{{cite web|title=Antibody Basics|publisher=[[Sigma-Aldrich]]| access-date=2014-12-10 | url=http://www.sigmaaldrich.com/life-science/cell-biology/antibodies/learning-center/antibody-explorer/technical-support/antibody-basics.html}}</ref> The two heavy chains are linked to each other and to a light chain each by [[disulfide bonds]]. The resulting tetramer has two identical halves, which together form a Y-like shape. Each end of the fork contains an identical [[antigen]] binding site. The various regions and domains of a typical IgG are depicted in the figure to the left. The Fc regions of IgGs bear a highly conserved [[N-linked glycosylation|N-glycosylation]] site at asparagine 297 in the constant region of the heavy chain.<ref>{{Cite journal|last=Cobb|first=Brian A.|date=2019-08-27|title=The History of IgG Glycosylation and Where We Are Now|journal=Glycobiology|volume=30|issue=4|pages=202–213|doi=10.1093/glycob/cwz065|issn=1460-2423|pmid=31504525|pmc=7109348|doi-access=free}}</ref> The N-glycans attached to this site are predominantly core-fucosylated biantennary structures of the complex type.<ref>{{Cite journal|last1=Parekh|first1=R. B.|last2=Dwek|first2=R. A.|last3=Sutton|first3=B. J.|last4=Fernandes|first4=D. L.|last5=Leung|first5=A.|last6=Stanworth|first6=D.|last7=Rademacher|first7=T. W.|last8=Mizuochi|first8=T.|last9=Taniguchi|first9=T.|last10=Matsuta|first10=K.|date=1–7 August 1985|title=Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG|journal=Nature|volume=316|issue=6027|pages=452–457|doi=10.1038/316452a0|issn=0028-0836|pmid=3927174|bibcode=1985Natur.316..452P|doi-access=free}}</ref> In addition, small amounts of these N-glycans also bear bisecting GlcNAc and α-2,6-linked sialic acid residues.<ref>{{cite journal |year=2008 |title=Analysis of immunoglobulin glycosylation by LC-ESI-MS of glycopeptides and oligosaccharides |journal=Proteomics |volume=8 |issue=14 |pages=2858–2871 |pmid=18655055 |doi=10.1002/pmic.200700968 |vauthors=Stadlmann J, Pabst M, Kolarich D, Kunert R, Altmann F |s2cid=22821543 }}</ref> The N-glycan composition in IgG has been linked to several autoimmune, infectious and metabolic diseases.<ref>{{Cite journal|last1=de Haan|first1=Noortje|last2=Falck|first2=David|last3=Wuhrer|first3=Manfred|date=2019-07-08|title=Monitoring of Immunoglobulin N- and O-glycosylation in Health and Disease|journal=Glycobiology|volume=30|issue=4|pages=226–240|doi=10.1093/glycob/cwz048|issn=1460-2423|pmid=31281930|pmc=7225405|doi-access=free}}</ref>▼
IgG antibodies are large globular proteins made of four peptide chains;<ref>{{cite book |author1=Janeway CA Jr |author2=Travers P |author3=Walport M | title=Immunobiology: The Immune System in Health and Disease | publisher=Garland Science | year=2001 | location=New York | edition=5th | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK27144/ | chapter=Ch3 Antigen Recognition by B-Cell and T-cell Receptors|display-authors=etal}}</ref> two identical γ (gamma) heavy chains of about 50&nbsp;kDa and two identical light chains of about 25&nbsp;kDa. The resulting tetrameric quaternary structure, therefore, has a total molecular weight of about 150&nbsp;[[kDa]].<ref>{{cite web|title=Antibody Basics|publisher=[[Sigma-Aldrich]]| access-date=2014-12-10 | url=https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/protein-biology/western-blotting/antibody-basics}}</ref> The two heavy chains are linked to each other and to a light chain each by [[disulfide bonds]]. The resulting tetramer has two identical halves, which together form a Y-like shape. Each end of the fork contains an identical [[antigen]] binding site. The various regions and domains of a typical IgG are depicted in the figure "Anatomy of an IgG".
▲[[File:Anatomy of an IgG.png|thumb|left|The various regions and domains of a typical IgG]]
 
▲IgG antibodies are large globular proteins made of four peptide chains<ref>{{cite book |author1=Janeway CA Jr |author2=Travers P |author3=Walport M | title=Immunobiology: The Immune System in Health and Disease | publisher=Garland Science | year=2001 | location=New York | edition=5th | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK27144/ | chapter=Ch3 Antigen Recognition by B-Cell and T-cell Receptors|display-authors=etal}}</ref>; two identical γ (gamma) heavy chains of about 50&nbsp;kDa and two identical light chains of about 25&nbsp;kDa. The resulting tetrameric quaternary structure, therefore, has a total molecular weight of about 150&nbsp;[[kDa]].<ref>{{cite web|title=Antibody Basics|publisher=[[Sigma-Aldrich]]| access-date=2014-12-10 | url=http://www.sigmaaldrich.com/life-science/cell-biology/antibodies/learning-center/antibody-explorer/technical-support/antibody-basics.html}}</ref> The two heavy chains are linked to each other and to a light chain each by [[disulfide bonds]]. The resulting tetramer has two identical halves, which together form a Y-like shape. Each end of the fork contains an identical [[antigen]] binding site. The various regions and domains of a typical IgG are depicted in the figure to the left. The Fc regions of IgGs bear a highly conserved [[N-linked glycosylation|N-glycosylation]] site at asparagine 297 in the constant region of the heavy chain.<ref>{{Cite journal|last=Cobb|first=Brian A.|date=2019-08-27|title=The History of IgG Glycosylation and Where We Are Now|journal=Glycobiology|volume=30|issue=4|pages=202–213|doi=10.1093/glycob/cwz065|issn=1460-2423|pmid=31504525|pmc=7109348|doi-access=free}}</ref> The N-glycans attached to this site are predominantly core-fucosylated biantennary structures of the complex type.<ref>{{Cite journal|last1=Parekh|first1=R. B.|last2=Dwek|first2=R. A.|last3=Sutton|first3=B. J.|last4=Fernandes|first4=D. L.|last5=Leung|first5=A.|last6=Stanworth|first6=D.|last7=Rademacher|first7=T. W.|last8=Mizuochi|first8=T.|last9=Taniguchi|first9=T.|last10=Matsuta|first10=K.|date=1–7 August 1985|title=Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG|journal=Nature|volume=316|issue=6027|pages=452–457|doi=10.1038/316452a0|issn=0028-0836|pmid=3927174|bibcode=1985Natur.316..452P|doi-access=free}}</ref> In addition, small amounts of these N-glycans also bear bisecting GlcNAc and α-2,6-linked sialic acid residues.<ref>{{cite journal |year=2008 |title=Analysis of immunoglobulin glycosylation by LC-ESI-MS of glycopeptides and oligosaccharides |journal=Proteomics |volume=8 |issue=14 |pages=2858–2871 |pmid=18655055 |doi=10.1002/pmic.200700968 |vauthors=Stadlmann J, Pabst M, Kolarich D, Kunert R, Altmann F |s2cid=22821543 }}</ref> The N-glycan composition in IgG has been linked to several autoimmune, infectious and metabolic diseases.<ref>{{Cite journal|last1=de Haan|first1=Noortje|last2=Falck|first2=David|last3=Wuhrer|first3=Manfred|date=2019-07-08|title=Monitoring of Immunoglobulin N- and O-glycosylation in Health and Disease|journal=Glycobiology|volume=30|issue=4|pages=226–240|doi=10.1093/glycob/cwz048|issn=1460-2423|pmid=31281930|pmc=7225405|doi-access=free}}</ref>
 
== 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). <ref>{{Cite journal|last1=Vidarsson|first1=Gestur|last2=Dekkers|first2=Gillian|last3=Rispens|first3=Theo|date=2014|title=IgG subclasses and allotypes: from structure to effector functions|journal=Frontiers in Immunology|volume=5|pages=520|doi=10.3389/fimmu.2014.00520|issn=1664-3224|pmc=4202688|pmid=25368619|doi-access=free}}</ref>
 
{| class="wikitable"
|! '''Name''' || '''Percentage''' || '''Crosses [[placenta]] easily''' || '''Complement activator''' || '''Binds to [[Fc receptor]] on phagocytic cells''' || '''Half life'''<ref>Bonilla FA Immuno Allergy Clin N Am 2008; 803–819</ref>
|-
| [[IGHG1|IgG1]] || 66% || yes (1.47)* || second-highest || high affinity || 21 days
|-
| [[IGHG2|IgG2]] || 23% || no (0.8)* || third-highest || extremely low affinity || 21 days
|-
| [[IGHG3|IgG3]] || 7% || yes (1.17)* || highest || high affinity || 7 days
|-
| [[IGHG4|IgG4]] || 4% || yes (1.15)* || no || intermediate affinity || 21 days
|-
| colspan="56"| ''* Quota cord/maternity concentrations blood. Based on data from a Japanese study on 228 mothers.''<ref>{{cite journal |vauthors=Hashira S, Okitsu-Negishi S, Yoshino K |title=Placental transfer of IgG subclasses in a Japanese population |journal=Pediatrics International |volume=42 |issue=4 |pages=337–342 |date=August 2000 |pmid=10986861 |doi=10.1046/j.1442-200x.2000.01245.x |s2cid=24750352 }}</ref>
|}
 
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== Role in diagnosis ==
[[File:Autoinjector with Amgevita by Amgen (Adalimumab)-6390.jpg|thumb|[[Adalimumab]] is an IgG antibody.]]
 
The measurement of immunoglobulin G can be a diagnostic tool for certain conditions, such as [[autoimmune hepatitis]], if indicated by certain symptoms.<ref name="abstracts">{{cite journal |vauthors=Lakos G, Soós L, Fekete A, Szabó Z, Zeher M, Horváth IF, Dankó K, Kapitány A, Gyetvai A, Szegedi G, Szekanecz Z |date=Mar–Apr 2008 |title=Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis: association with disease duration, rheumatoid factor production and the presence of shared epitope |journal=Clinical and Experimental Rheumatology |volume=26 |issue=2 |pages=253–260 |pmid=18565246 |url=http://www.clinexprheumatol.org/pubmed/find-pii.asp?pii=18565246 |access-date=2014-02-26 |archive-url=https://web.archive.org/web/20141211141601/http://www.clinexprheumatol.org/pubmed/find-pii.asp?pii=18565246 |archive-date=2014-12-11 |url-status=dead }}</ref> 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.<ref name="Shors2011">{{cite book|author=Teri Shors|title=Understanding Viruses|chapter-url=https://books.google.com/books?id=Uk8xP5LRHr4C&pg=103|edition=2nd|date=August 2011|publisher=Jones & Bartlett Publishers|isbn=978-0-7637-8553-6|pages=[https://archive.org/details/understandingvir0000shor/page/103 103–104]|chapter=Ch5 Laboratory Diagnosis of Viral Diseases and Working with Viruses in the Research Laboratory|url=https://archive.org/details/understandingvir0000shor/page/103}}</ref>
 
Testing of IgG is not indicated for diagnosis of allergy, and there is no evidence that it has any relationship to food intolerances.<ref name="AAAAIfive">{{Cite web|vauthors=((American Academy of Allergy, Asthma, and Immunology)), ((American Academy of Allergy, Asthma, and Immunology)) |title=Five Things Physicians and Patients Should Question |publisher=[[American Academy of Allergy, Asthma, and Immunology]] |work=Choosing Wisely: an initiative of the [[ABIM Foundation]] |url=http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_AAAAI.pdf |access-date=August 14, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20121103151124/http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_AAAAI.pdf |archive-date=November 3, 2012 }}</ref><ref name="pmid19119701">{{cite journal |vauthors=Cox L, Williams B, Sicherer S, Oppenheimer J, Sher L, Hamilton R, Golden D |title=Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force |journal=Annals of Allergy, Asthma & Immunology |volume=101 |issue=6 |pages=580–592 |year=2008 |pmid=19119701 |doi= 10.1016/s1081-1206(10)60220-7}}</ref><ref>{{Cite journal|last1=Stapel|first1=Steven O.|last2=Asero|first2=R.|last3=Ballmer-Weber|first3=B. K.|last4=Knol|first4=E. F.|last5=Strobel|first5=S.|last6=Vieths|first6=S.|last7=Kleine-Tebbe|first7=J.|last8=EAACI Task Force|date=July 2008|title=Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report|url=https://pubmed.ncbi.nlm.nih.gov/18489614/|journal=Allergy|volume=63|issue=7|pages=793–796|doi=10.1111/j.1398-9995.2008.01705.x|issn=1398-9995|pmid=18489614|s2cid=14061223}}</ref>
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== External links ==
* [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=IgG&rid=imm.section.323#325 Janeway Immunobiology – The structure of a typical antibody (IgG)]
* [httphttps://wwwednieuw.home.xs4all.nl/~ednieuw/IgGsubclasses/subkl.htm A booklet with everything you wanted to know about IgG subclasses]
 
{{immune_system}}
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