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- Heavy-chain sequence analysis of an immunoglobulin molecule revealed five basic sequence patterns.
- These five basic sequences correspond to five different heavy-chain constant (C) regions named with Greek letters: 渭 (mu), 饾浛 (delta), 纬 (gamma), 蔚 (epsilon), and 伪 (alpha).
- Each of these five different heavy chains is called an isotype which determines the class of the given antibody molecule.
- There are five major classes of antibodies: IgM, IgG, IgA, IgD and IgE.
- Minor differences in the amino acid sequences of the heavy chains (伪 and 纬), leads to further classification of the heavy chains into sub-isotypes.
- Sub-isotypes determine the subclass of the antibody molecules they constitute.
- The molecular properties and biological activities of the immunoglobulin classes are summarized below:
1. Immunoglobulin G (IgG):
- IgG consists of two Gamma(纬) heavy-chains (50 KDa each) and two Kappa (k) or two Lambda (位) light-chains (25 KDa each).
- Total molecular weight: 150 KDa
- It is the most abundant class of Immunoglobulin in serum constituting of about 80% of total serum immunoglobulin.
- There are four human IgG subclasses based on the differences in Y-chain (Y1, Y2, y3 and Y4) constant region sequences which are numbered according to their decreasing average serum concentrations: IgG1, IgG2, IgG3 and IgG4,
- Each of IgG subclasses has a molecular weight of about 150 KDa.
- It has the longest half-life (23 days) among all antibodies.
Biological activities:
- IgG1, IgG3 and IgG4 readily cross the placenta and provide immunity to the developing fetus up to 6 months.
- IgG also activates complement proteins. IgG3 is the most effective complement activator followed by IgG1 and IgG2. IgG4 cannot activate complement proteins.
- IgG1 and IgG3 mediate opsonization by binding with Fc receptors on phagocytic cells.
- IgG helps in bacterial immobilization.
- It also neutralizes toxin and viruses.
- It is the major antibody produced during secondary immune response.
2. Immunoglobulin M (IgM):
- It exists as a pentamer (900 KDa) in which five monomeric units (180 KDa each) are held together by disulfide bonds.
- It consists of 10 Mu (碌) heavy-chains (65 KDa each) and 10 k or 10 位 light-chains (25 KDa each).
- There are 10 antigen binding sites (Fab) in a pentameric IgM molecule but due to steric hindrance it cannot bind to all 10 complete antigens at the same time.
- The average serum concentration of IgM is about 1.5mg/dl that accounts for about 5-10% of total serum Immunoglobulin.
- Each pentamer contains an additional Fc-linked polypeptide chain called the J-chain which is required for the polymerization of IgM.
- It is secreted by plasma cells and expressed as membrane-bound antibody on B-cells.
Biological activities:
- IgM is the first antibody produced during a primary immune response.
- It is also the first antibody class produced by neonates.
- Since IgM is in a pentameric form, it has higher number of antigen binding sites.
- IgM is very effective in agglutination reaction. It takes 100 to 1000 times more molecules of IgG than of IgM to achieve the same level of agglutination.
- IgM is more efficient than IgG in complement activation.
- The presence of J-chain allows IgM to bind to the receptors on secretory cells and cross the epithelial linings to enter the external secretions.
![](https://onlinesciencenotes.com/wp-content/uploads/2021/06/isotypes-of-antibodies.jpg)
Image Credit:
https://www.notesonzoology.com/immunology/antibody-meaning-structures-and-classification/4678
3. Immunoglobulin A (IgA):
- It primarily exists as a monomer in blood and consists of two Alpha (伪) heavy chains (55 KDa each) and two k or two 位 light chains (25 KDa each).
- Dimeric, trimeric and some tetrameric forms of IgA are present in body secretions.
- Its molecular weight ranges from 150 KDa to 600 KDa depending on its form.
- IgA constitutes about 10-15% of total serum immunoglobulin.
- Dimeric form of IgA contains J-chain and a secretory chain. Secretory chain helps IgA cross the epithelial layer and enter into body secretions, a process called transcytosis.
- Capable of transcytosis, IgA is present in external secretions like breast milk, saliva, tears and mucus of bronchial, genitourinary and digestive tracts.
- There are two sub-classes of IgA based on sub-isotypes of 伪 heavy chain. i.e. IgA1 and IgA2.
Biological activities:
- IgA provides local immunity in GI tracts, respiratory tract, genital tract etc. since it can cross the epithelial layer and enter into body secretion.
- Binding of secretory IgA to bacterial and viral surface antigens prevents further attachment of the pathogens to the mucosal cells, thus inhibiting viral infection and bacterial colonization.
4. Immunoglobulin E (IgE):
- It consists of two Epsilon (蔚) heavy-chains (70 KDa each) and two k or two 位 light chains (25 KDa each).
- Total molecular weight: 190 KDa.
- IgE constitutes about 0.3% of total serum Immunoglobulin.
- Level of IgE in blood of normal individual is very low and its level increases during parasitic infection and in allergic reactions.
- Because of its involvement in allergic reactions, it is also called a reagenic antibody.
- Fc region of IgE present in Ag-Ab complex binds on blood basophils and tissue mast cells. This cross reaction causes degranulation of mast cell and basophils releasing histamine. Histamine is responsible for symptoms of allergy.
Biological activities:
- IgE mediates immediate hypersensitivity reaction and responsible for symptoms like hay fever, asthma, anaphylactic shocks, etc.
- IgE provides immunity against parasites by antibody dependent cell mediated cytotoxicity (ADCC).
5. Immunogloublin D (IgD):
- It contains two Delta (饾浛) heavy chains (65 KDa each) and two k or two 位 light chains (25 KDa each).
- Molecular weight is 180 KDa.
- It constitutes about 0.2% of total serum immunoglobulin.
Biological activities:
- IgD, together with IgM, is the major membrane-bound immunoglobulin expressed by mature B-cells.
- IgD plays an important role in maturation and proliferation of B-cell.
- No other biological effector function has been identified for IgD.
![](https://onlinesciencenotes.com/wp-content/uploads/2021/06/table.jpg)
Five major classes of Antibodies and their Biological Activities:
References:
- https://www.ncbi.nlm.nih.gov/books/NBK27144/Immunobiology: The Immune System in Health and Disease. 5th edition
- Kindt T. J, Goldsby R. A & Osbotne B. A,聽 (sixth edition).聽Kuby Immunology,聽New York , NY: W.H. Freeman and Company, 2007