Wiley; Monash University (Australia)
Immunoglobulins (antibodies) are the glycoproteins involved in the immune response. As well as the adaptive immunity these molecules are the evolutionary invention of the vertebrates. These proteins can recognize and bind to the hazardous agents (bacteria, fungi, viruses, protozoa, worms, own tumor cells, toxins), triggering a cascade of other processes aimed at destroying them.The organism can generate a specific antibody to any antigen it encounters: about 10 billion unique immunoglobulin species can be synthesized in a period of the human life (1).
However, only three genetic loci are responsible for the immunoglobulins synthesis. The huge diversity of antibodies is possible because of the specific mechanisms of gene rearrangements and introduction of point mutations (2, 3). Immunoglobulins are found both on the surfaces of the B-lymphocytes where they are synthesized and in blood, tissue fluid, mucous membranes, saliva, tears or breast milk. Average human produces about 2-3 grams of antibodies per day. Two-thirds of this amount are produced in digestive, respiratory and urogenital tracts (4).
Immunoglobulins consist of two identical heavy and two identical light polypeptide chains, connected by the disulfide bonds. Heavy chains are glycosylated. There are five types of heavy chains (α-, γ-, δ-, ε- and μ-chains) and two types of light chains (κ-chain and λ-chain). Both heavy and light chains are divided into domains (4 and 2, respectively). One of the domains is variable and the other(s) are constant. The part of the molecule that is bound to the antigen is called FAB (Fragment Antigen Binding), There are two FABs in each monomeric antibody. These fragments are formed by the whole light chain and two domains (one variable and one constant) of the heavy chain. Thus all variable segments are part of the antigen binding regions. The constant part of the immunoglobulin (FC — Fragment crystallizable) is formed by the heavy chains constant domains. FABs are flexibly attached to the FC by the hinge region. This gives the molecule its Y- or T-shape.There are 5 classes of antibodies that differ in functions, structure, size and glycosylation pattern: IgG, IgD, IgE, IgA, and IgM.
Molecules of the IgG, IgD, IgE and the serum IgA work as monomers, but the secreted IgA (found in saliva) is a dimer and the IgM molecules form pentamers (2, 4). IgGs, the most common human immunoglobulins, represent 75% of all plasma immunoglobulins and have several functions including triggering the complement system (the proteolytic plasma enzyme cascade involved in antigen degradation in the blood).
The model presented provides a view of the common IgG1 protein. Light chains are shown in red, heavy chains are in gray, disulfide bridges linking the chains are in yellow, and the oligosaccharide is in dark gray.