Gamma globulins (called immunoglobulins, or Igs, in current immunologic terminology) are not a homogeneous group. There are three main subdivisions: IgG, which migrates in the gamma region on electrophoresis; IgA, which migrates in the pregamma region or in the area between gamma and beta; and IgM, which migrates in the prebeta or beta region (Fig. 22-3). There are two additional groups called IgD and IgE. IgG comprises about 75% of serum immunoglobulins and has a normal 7S molecular weight. IgG constitutes the majority of the antibodies, especially the warm-temperature incomplete type. IgM accounts for 5%-7% of total immunoglobulins and is a macroglobulin (19S group). The IgM class includes the earliest antibodies produced against infectious organisms (later followed by IgG antibodies), cold agglutinins, ABO blood group isoagglutinins, and rheumatoid factor. IgA constitutes about 15% of immunoglobulins. Although most are 7S, some molecules are larger. It is found primarily in secretions, such as saliva, tears, gastrointestinal secretions from stomach and accessory organs, and secretions from the respiratory tract. Selective deficiency of IgA (the other immunoglobulins being normal) is the most common primary immunodeficiency, and is associated with frequent upper respiratory and GI infections. There is also increased frequency of autoimmune disease. Phenytoin (Dilantin) is reported to decrease IgA levels to some extent in 20%-85% of patients on long-term therapy. In one report, about 15% of patients had IgA levels below reference range, and about 4% had very low levels. IgD is a normal 7S molecular weight molecule that makes up less than 1% of the immunoglobulins; its function is not known. IgE also has a 7S weight and occurs with less than 1% frequency. It is elevated in certain allergic conditions, especially atopic disorders, and it is associated with reaginic antibody.

A normal Ig molecule is composed of two heavy chains (each chain of 50,000-dalton molecular weight) and two light chains (kappa and lambda, normally in 2:1 K/L ratio, each of 20,000-dalton molecular weight) connected by disulfide bridges. IgM is a pentomeric arrangement of five complete Ig units.