Rebecca Martin/Sandbox1
From Proteopedia
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== Introduction to IgA == | == Introduction to IgA == | ||
| - | IgA is the most abundant antibody in the body 10064707 | ||
| - | In fact, the body produces more IgA daily than than any other antibody 19079336 | ||
| - | IgA is also unique, in that it exists in multiple oligomeric states. | ||
| - | Two isotypes: IgA1 and IgA2 10064707 | ||
| - | Unique- multi oligomeric forms 19079336 | ||
| - | 3 forms: monomer, dimer, (sometimes 3 or 4) secretory 10064707 | ||
| - | Receptors: FcalphaR; pIgR, transferrin R (IgA1- recognizes O-glycosylation sites 15111057 ) | ||
| - | IgA | ||
| - | Participates in mucosal responses in the gut (IgA1~IgA2) and peripheral immune responses in the serum (90% monomeric IgA1) 10064707 | ||
| - | Secretory IgA – primary immune defense 15111057 | ||
| - | Neutralizes; immune exclusion commensals 19079336 | ||
| - | Serum iga – second line of defense after m/o invade 15111057 | ||
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{{STRUCTURE_1iga | PDB=1iga | SCENE= }} | {{STRUCTURE_1iga | PDB=1iga | SCENE= }} | ||
| + | The most extensive surface in contact with the external environment is not our skin, but the epithelial lining of our gastrointestinal, respiratory, and urogenital tracts <ref name="17428798">PMID:17428798</ref>. As a first line of defense in maintainance the integrity our mucosa, the immune system manufatures and secretes dimeric IgA to neutralize pathogenic organisms <ref name="15111057">PMID:15111057</ref> and exclude the entry of commensals at the mucosal border <ref name="19079336">PMID:19079336</ref>. In the serum, IgA functions as a second line of defense against pathogens that may breech the epithelial boundary <ref name="15111057"></ref>. The body produces more IgA than any other antibody isotype <ref name="19079336"></ref>. In fact, IgA is the most abundant antibody in the body, further illustrating IgA's critical role in immunity <ref name="10064707">PMID:10064707</ref>. Exploring IgA's structure and protein interactions illuminates the unique and critical function IgA plays in humoral immunity. | ||
| + | Unlike other antibody isotypes, IgA exists in mutiple oligomeric states, the a monomeric, a dimeric, and secretory forms being most common <ref name="10064707"></ref>, <ref name="19079336"></ref>. At least two isotypes exist, termed IgA1 and IgA2. IgA2 can further be categorized into 2 allotypes: IgA2 m(1) and IgA2 m(2). The receptors for IgA include the Fcα Receptor (FcαRI; CD89) and the polyimmunologlobulin receptor (pIgRI). When binding to FcαRI results in the dimerization, the consequent signaling results in effector functions, including respiratory burst, phaocytosis, and eosinophil degranulation. Binding to the pIgR results in transoocytosis and IgA secretion <ref name="15111057"></ref>. At the mucosal surface, an approximately equal ratio of secretory IgA1 (sIgA1) to secretory IgA2 (sIgA2) reside at the mucosal surface, with the exception of the colon, where the majority is sIgA2 <ref name="19109255"></ref>. In the serum, about 90% of the IgA is monomeric IgA1 <ref name ="10064707"></ref>. | ||
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== References == | == References == | ||
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| + | <references /> | ||
Revision as of 03:59, 23 April 2009
Contents |
Introduction to IgA
Template:STRUCTURE 1iga
The most extensive surface in contact with the external environment is not our skin, but the epithelial lining of our gastrointestinal, respiratory, and urogenital tracts Cite error: Invalid <ref> tag;
name cannot be a simple integer. Use a descriptive title. As a first line of defense in maintainance the integrity our mucosa, the immune system manufatures and secretes dimeric IgA to neutralize pathogenic organisms Cite error: Invalid <ref> tag;
name cannot be a simple integer. Use a descriptive title and exclude the entry of commensals at the mucosal border Cite error: Invalid <ref> tag;
name cannot be a simple integer. Use a descriptive title. In the serum, IgA functions as a second line of defense against pathogens that may breech the epithelial boundary Cite error: Invalid <ref> tag;
refs with no name must have content. The body produces more IgA than any other antibody isotype Cite error: Invalid <ref> tag;
refs with no name must have content. In fact, IgA is the most abundant antibody in the body, further illustrating IgA's critical role in immunity Cite error: Invalid <ref> tag;
name cannot be a simple integer. Use a descriptive title. Exploring IgA's structure and protein interactions illuminates the unique and critical function IgA plays in humoral immunity.
Unlike other antibody isotypes, IgA exists in mutiple oligomeric states, the a monomeric, a dimeric, and secretory forms being most common Cite error: Invalid <ref> tag;
refs with no name must have content, Cite error: Invalid <ref> tag;
refs with no name must have content. At least two isotypes exist, termed IgA1 and IgA2. IgA2 can further be categorized into 2 allotypes: IgA2 m(1) and IgA2 m(2). The receptors for IgA include the Fcα Receptor (FcαRI; CD89) and the polyimmunologlobulin receptor (pIgRI). When binding to FcαRI results in the dimerization, the consequent signaling results in effector functions, including respiratory burst, phaocytosis, and eosinophil degranulation. Binding to the pIgR results in transoocytosis and IgA secretion Cite error: Invalid <ref> tag;
refs with no name must have content. At the mucosal surface, an approximately equal ratio of secretory IgA1 (sIgA1) to secretory IgA2 (sIgA2) reside at the mucosal surface, with the exception of the colon, where the majority is sIgA2 Cite error: Invalid <ref> tag;
refs with no name must have content. In the serum, about 90% of the IgA is monomeric IgA1 Cite error: Invalid <ref> tag;
refs with no name must have content.
Structure
- Immunoglobulin Structure
Antibodies are composed of a heavy chain and a light chain.
Fab fragment
- Forms of IgA
Dimeric Structure
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- Secretory Component
IgA1 and IgA2
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Secretory Component
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Insights into Function
Evolution
Implications in Science and Medicine
Limitations of the Current Studies
- Because of the nature of the IgA molecule, crystalizing this structure was not possible. Therefore, many of these structures are based on models and not actual crystal structures. Because ...., the models were depositable in the PDB. I tried to include other crystallographic data when available, supporting the proposed models- as the authors did in the original papers.
Questions for the Future
- Because of the limitating resolution of these models, many details concerning the binding residues and residue interactions are left unknown. Crystallographic structure will yield further insights into the structure of IgA, the interactions between IgA and other molecules, and ....
Links
IgA
- Monomeric
- Fab and Fc Fragments
- Refined crystal structure of the galactan-binding immunoglobulin fab j539 at 1.95-angstroms resolution 2fbj
- Phosphocholine binding immunoglobulin fab mc/pc603. an x-ray diffraction study at 2.7 angstroms 1mcp
- Phosphocholine binding immunoglobulin fab mc/pc603. an x-ray diffraction study at 3.1 angstroms 2mcp
- Crystal structure of human FcaRI bound to IgA1-Fc 1ow0
- Refined crystal structure of a recombinant immunoglobulin domain and a complementarity-determining region 1-grafted mutant 2imm and2imn
- Dimeric and Secretory
Receptors
- Crystal Structure of a Ligand-Binding Domain of the Human Polymeric Ig Receptor, pIgR 1XED
- Crystal structure of human FcaRI 10vz
- Crystal structure of a Staphylococcus aureus protein (SSL7) in complex with Fc of human IgA1 2qej
Other Isotypes (for comparison)
- IgM: Solution structure of human Immunoglobulin M 2rcj
- IgG:
- IgD:
- IgE:
