Immunoglobulin Classes: IgG, IgA, IgM, IgD and IgE
Immunoglobulin Classes
Immunoglobulins provide a structural and chemical concept. All antibodies are immunoglobulins, but all immunoglobulins may not be antibodies. Human serum contains five classes of immunoglobulins-IgG, IgA, IgM, IgD and IgE in the desending order of the concentration.
Immunoglobulin G (IgG)
- This is the major immunoglobulin in human serum, accounting for about 80% of the total immunoglobulin pool.
- It has a sedimentation coeffient of 7S and a molecular weight of 150,000.
- It contains less carbohydrate than other immunoglobulins.
- The normal serum concentration of IgG is about 8-16 mg per mL.
- It has a half-life of 23 days—the longest of all of the immunoglobulin isotypes.
- IgG is the predominant immunoglobulin in blood, lymph, peritoneal fluid and cerebrospinal fluid, and it is distributed nearly equally between extra- and intravascular spaces.
- Four subclasses of IgG (Ig1, Ig2, Ig3, Ig4) have been recognized.
- Catabolism of IgG is unique in that it varies with its serum concentration. When its level is raised, as in chronic malaria, kala-azar or myeloma, the IgG synthesized against a particular antigen will be catabolized rapidly and may result in the particular antibody deficiency. Conversely, in hypogammaglobulinemia, the IgG given for treatment will be catabolized only slowly.
Functions of IgG: IgG is a very versatile molecule. It may be considered a general-purpose antibody, protective against those infectious agents, which are active in the blood and tissues.
Examples of its Functions
- Transfer from mother to fetus: IgG is the only class of Igs that can cross the placenta and is responsible for the protection of the infant during the first few months of life.
- Opsonization: IgG binds to microorganisms and enhances their phagocytosis.
- Fixing to guinea pig skin.
- Immunological reactions: IgG participates in complement fixation, precipitation and neutralization of toxins and viruses.
- Immobilize bacteria.
- Suppresses the homologous antibody synthesis: Passively administered IgG suppresses the homologous antibody synthesis by a feedback process.
Immunoglobulin A (IgA)
- It is the second most abundant class, constituting about 10–13 per cent of serum immunoglobulins.
- The normal serum level is 0.6–4.2 mg per mL.
- It has a half life of 6–8 days.
- IgA is the primary immunoglobulin found in external secretions, such as mucus, tears, saliva, gastric fluid, colostrum and sweat. It exists in different forms in these various solutions.
- IgA occurs in two forms. Serum IgA and secretory IgA (SIgA).
Serum IgA: Serum IgA is monomeric (one four chain unit) 7S molecule (MW about 160,000).
Secretory IgA (SIgA): In contrast, IgA found on mucosal surfaces and in secretions is a dimer formed by two monomer units joined together at their carboxy terminals by a glycopeptide termed as the J chain (J for joining). This dimeric form is more important form, known as secretory IgA (SIgA). Dimeric SIgA is synthesized by plasma cells situated near the mucosal or glandular epithelium. J chains are also found in other polymeric immunoglobulins such as IgM.
Secretory component: Secretory IgA (SIgA) contains another glycine-rich polypeptide called the secretory component or secretory piece. This is not produced by lymphoid cells but by mucosal or glandular epithelial cells.
The secretory piece is believed to protect IgA from denaturation by bacterial proteases in sites such as the intestinal mucosa which have a rich and varied bacterial flora. Subclasses: There are two subclasses of IgA in humans: IgA1 and IgA2.
Functions of IgA
- Local immunity: Secretory IgA (SIgA) is believed to play an important role in local immunity against respiratory and intestinal pathogens.
- Prevention of organisms’ entry into body tissues.
- Newborn protection: IgA present in breast milk provides the newborn with protection against infection.
- Agglutination.
- Alternative pathways activation.
- Phagocytosis and intracellular killing.
Immunoglobulin M (IgM)
- About 10% of normal serum Igs consists of this class.
- It is a heavy molecule (19S; MW 900,000 to 1,000,000 daltons, hence called ‘millionaire molecule’).
- The normal serum level of IgM is 1.2 mg/mL.
- It has a half-life of about 5 days.
- IgM is the first immunoglobulin to appear after exposure to an antigen.
- In the circulation, IgM exists as a pentamer of five four-chain units. The five identical IgM monomers are connected to each other by a polypeptide joining (J) chain.
- Polymerization of the subunits depends upon the presence of the J chain as with IgA.
- Most of IgM (80%) is intravascular in distribution.
- IgM is the first class of antibody produced during the primary immune response. It is also the earliest to be synthesized by fetus beginning by about 20 weeks of age. As it cannot cross the placental barrier, the presence of IgM in the fetus or newborn indicates intrauterine infection.
- They are relatively short lived, hence their demonstration in the serum indicates recent infection.
- Treatment of serum with 0.12 M 2-mercaptoethanol selectively destroys IgM without affecting IgG antibodies.
- Isohemagglutinins (anti-A and anti-B) and antibodies to S. Typhi O antigen and Wassermann reaction antibodies in syphilis are usually IgM.
- IgM agglutinates bacteria activates complement by the classical pathway, and enhances the ingestion of pathogens by phagocytic cells.
- IgM is normally restricted to the intravascular space because of its high molecular weight.
Immunoglobulin D (IgD)
- IgD has a monomer structure similar to IgG.
- Its molecular weight is 180,000 daltons.
- IgD is an immunoglobulin found in trace amounts in the blood serum (0.03 mg/mL).
- Half-life is about 3 days.
- IgD antibodies are abundant in combination with IgM on the surface of B cells and bind antigens, thus signaling the B cell to start
antibody production. - Two subclasses of IgD (IgD1 and IgD2) are known.
Immunoglobulin E (IgE)
- It resembles IgG structurally and also known as reagin antibody.
- IgE is an 8S molecule (MW 19,000) and half life of two days.
- It is present in extremely low amounts in serum.
- It exhibits unique properties such as heat lability (inactivated at 56°C in one hour).
- It is susceptible to mercaptoethanol.
- It does not pass the placental barrier.
- IgE does not activate complement nor agglutinate antigens.
- Allergic reactions: IgE may be elevated in allergic (atopic) individuals, and is responsible for many of the symptoms of allergies, bronchial asthma, and even systemic anaphylaxis. Allergy mediated by IgE is termed as type I hypersensitivity response.
- Immunity against helminthic parasites: Children living in insanitary conditions, with a high load of intestinal parasites, have high serum levels of IgE.
- Extravascular: It is mostly found extravascularly in the lining of the respiratory and intestinal tracts.
- Protection against pathogens: The physiological role of IgE appears to be protection against pathogens by mast cell degranulation and release of inflammatory mediators.
Role of Different Immunoglobulin Classes
- IgG: Protects the body fluids.
- IgA: Protects the body surfaces.
- IgM: Protects the bloodstream.
- IgE: Mediates type I hypersensitivity.
- IgD: Role not known.
Abnormal Immunoglobulins
Other structurally similar proteins are seen in serum in many pathological processes, and sometimes even in healthy persons apart from
antibodies in the following pathological conditions:
- Multiple myeloma
- Heavy chain disease
- Cryoglobulinemia
Multiple Myeloma
The abnormal plasma cells are myeloma cells which also collect in the solid part of the bone. The disease is called “multiple myeloma”. Myeloma is a plasma cell dyscrasia in which there is unchecked proliferation of one clone of plasma cells, resulting in the excessive production of the particular immunoglobulin synthesized by the clone. Such immunoglobulins are, therefore, called monoclonal.
Waldenstrom’s macroglobulinemia: Multiple myeloma may affect plasma cells synthesizing IgG, IgA, IgD or IgE. Myeloma involving IgMproducing cells (lympho-plasmacytoid cells) is known as Waldenstrom’s macroglobulinemia. In this condition, there occurs excessive production of the respective myeloma proteins (M proteins) and of their light chains (Bence-Jones proteins).
Bence-Jones proteins: In most patients, the myeloma cells also secrete excessive amounts of light chains. These excess light chains were first discovered in the urine of myeloma patients and were named Bence-Jones proteins, for their discoverer Bence Jones (1847). Bence Jones proteins can be identified in urine by its characteristic property of coagulation when heated to 50°C but redissolving at 70°C. These proteins are the light chains of immunoglobulins and so may occur as the kappa or lambda forms. But in any one patient, the chain is either kappa or lambda only, and never both, being uniform in all other respects also.
Heavy Chain Disease
It is a lymphoid neoplasia characterized by the overproduction of the Fc parts of the immunoglobulin heavy chains.
Cryoglobulinemia
It is a condition in which there is the formation of a gel or a precipitate on cooling the serum, which redissolves on warming. It may not always be associated with disease but is often found in myelomas, macroglobulinemias and autoimmune conditions such as systemic lupus erythematosus. Most cryoglobulins consist of either IgG, IgM or mixture of the two.
Reference and Sources
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