Immunoglobulins are glycoproteins in the immunoglobulin superfamily that function as antibodies. The terms antibody and immunoglobulin are often used interchangeably. They are found in the blood and tissue fluids, as well as many secretions. In structure, they are globulins (in the γ-region of protein electrophoresis). They are synthesized and secreted by plasma cells that are derived from the B cells of the immune system. B cells are activated upon binding to their specific antigen and differentiate into plasma cells. In some cases, the interaction of the B cell with a T helper cell is also necessary.
Types of Immunoglobulins
IgG is a monomeric immunoglobulin, built of two heavy chains γ and two light chains. Each molecule has two antigen binding sites. This is the most abundant immunoglobulin and is approximately equally distributed in blood and in tissue liquids. This is the only isotype that can pass through the placenta, thereby providing protection to the fetus in its first weeks of life before its own immune system has developed. It can bind to many kinds of pathogens, for example viruses, bacteria, and fungi, and protects the body against them by complement activation (classic pathway), opsonization for phagocytosis and neutralisation of their toxins. There are 4 subclasses: IgG1 (66%), IgG2 (23%), IgG3 (7%) and IgG4 (4%). -IgG1, IgG3 and IgG4 cross the placenta easily. -IgG3 is the most effective complement activator, followed by IgG1 and then IgG2. IgG4 does not activate complement. - IgG1 and IgG3 bind with high affinity to Fc receptors on phagocytic cells. IgG4 has intermediate affinity and IgG2 affinity is extremely low.
IgG (along with IgA below) gluten specific antibodies are one of the two main antibodies which are measured in patients with coeliac(gb)/celiac(am) disease.
IgA represents about 15% to 20% of immunoglobulins in the blood, although it is primarily secreted across the mucosal tract into the stomach and intestines. It is also found in maternal milk, tears and saliva. This immunoglobulin helps to fight against pathogens that contact the body surface, are ingested, or are inhaled. It does not activate complement, and opsonises only weakly. Its heavy chains are of the type α. It exists in two forms, IgA1 (90%) and IgA2 (10%) that differ in the structure. IgA1 is composed like other proteins, however in IgA2 the heavy and light chains are not linked with disulfide but with noncovalent bonds. Though IgA2 is less in serum, it accounts for major secretory antibody.
The IgA found in secretions have a special form. They are dimeric molecules, linked by two additional chains. One of these is the J chain (from join), which is a polypeptide of molecular mass 1,5 kD, rich with cysteine and structurally completely different from other immunoglobulin chains. This chain is formed in the antibodies secreting cells. The dimeric form of IgA in the outer secretions has also a polypeptide of the same molecular mass (1,5 kD) that is called the secretory chain and is produced by the epithelial cells. It is also possible to find trimeric and even tetrameric IgA.
Decreased or absent IgA, termed selective IgA deficiency, can be a clinically significant immunodeficiency.
IgM forms polymers where multiple immunoglobulins are covalently linked together with disulfide bonds, normally as a pentamer or occasionally as a hexamer. It has a large molecular mass of approximately 900 kD (in its pentamer form). The J chain is attached to most pentamers, while hexamers do not possess the J chain due to space constraints in the complex. Because each monomer has two antigen binding sites, an IgM has 10 of them, however it cannot bind 10 antigens at the same time because they hinder each other. Because it is a large molecule, it cannot diffuse well, and is found in the interstitium only in very low quantities. IgM is primarily found in serum; however, because of the J chain, it is also important as a secretory immunoglobulin. Due to its polymeric nature, IgM possesses high avidity, and is particularly effective at complement activation. It is also a so-called "natural antibody": it is found in the serum without any evidence of prior contact with antigen.
In germline cells, the gene segment encoding the μ constant region of the heavy chain is positioned first among other constant region gene segments. For this reason, IgM is the first immunoglobulin expressed by mature B cells.
IgD makes up about 1% of proteins in the plasma membranes of mature naive B-lymphocytes (coexpressed with IgM) and is also found in serum in very small amounts. It is monomeric and incorporates the δ heavy chain in its structure. IgD's function is currently unknown, as mice lacking IgD seem to retain normal immune responses (implying redundancy if not lack of function), and IgD ceases to be expressed in activated B-lymphocytes. It may function as a regulatory antigen receptor.
IgE is a monomeric immunoglobulin with the heavy chain ε. It contains a high proportion of carbohydrates. Its molecular mass is 190 kD. It can be found on the surface of the plasma membrane of basophils and mast cells of connective tissue. IgE plays a role in immediate hypersensitivity and the defense against parasites such as worms. The IgE antibodies are present also in outer excretions. They do not activate complement. Only IgE is heat-labile.