Figure 3 Summary of antibody functions.

3. Functions of the Crystallizable Fragment

Although the Fab fragments bind antigen, the Fc fragment has a different binding function. In most classes of immunoglobulin, the proximal end of Fc contains an effector molecule that can bind to certain receptors on the membrane of cells, such as macrophages, neutrophils, eosinophils, mast cells, basophils, and lymphocytes. The effect on an antibody’s Fc fragment binding to a cell receptor depends upon that cell’s role. In the case of opsonization, the attachment of antibody to foreign cells and viruses exposes the Fc fragments to phagocytes. Certain antibodies have receptors on the Fc portion for fixing complement, and in some immune reactions, the binding of Fc causes the release of cytokines. For example, the antibody of allergy (IgE) binds to basophils and mast cells, which causes the release of allergic mediators such as histamine. The size and amino acid composition of Fc also determine an antibody’s permeability, its distribution in the body, and its class.

4. Accessory Molecules on Immunoglobulins

All antibodies contain molecules in addition to the basic polypeptides. Varying amounts of carbohydrates are affixed to the constant regions in most instances (table 1). Two additional accessory molecules are the J chain that joins the monomers of IgA and IgM, and the secretory component, which helps move Ig across mucous membranes. These proteins occur only in certain immunoglobulin classes.

5. The Classes of Immunoglobulins

Immunoglobulins exist as structural and functional classes called isotypes (compared and contrasted in table 1). The differences in these classes are due primarily to variations in the Fc fragment and its accessory molecules. The classes are differentiated with shorthand names (Ig, followed by a letter: IgG, IgA, IgM, IgD, IgE).

The structure of IgG has already been presented. It is a monomer produced by memory cells responding the second time to a given antigenic stimulus. It is by far the most prevalent antibody circulating throughout the tissue fluids and blood. It has numerous functions: It neutralizes toxins, opsonizes, and fixes complement, and it is the only antibody capable of crossing the placenta.

Table 1

Characteristics of the Immunoglobulin (Ig) Classes

The two forms of IgA are: (1) a monomer that circulates in small amounts in the blood and (2) a dimer that is a significant component of the mucous and serous secretions of the salivary glands, intestine, nasal membrane, breast, lung, and genitourinary tract. The dimer, called secretory IgA, is formed in a plasma cell by two monomers attached by a J piece. To facilitate the transport of IgA across membranes, a secretory piece is later added by the gland cells themselves. IgA coats the surface of these membranes and appears free in saliva, tears, and mucus. It confers the most important specific local immunity to enteric, respiratory, and genitourinary pathogens. It protects newborns who derive it passively from nursing.

IgM (M for macro) is a huge molecule composed of five monomers (making it a pentamer) attached by the Fc receptors to a central J chain. With its 10 binding sites, this molecule has tremendous avidity for antigen (avidity means the capacity to bind antigens). It is the first class synthesized by a plasma cell following its first encounter with antigen. Its complement-fixing and opsonizing qualities make it an important antibody in many immune reactions. It circulates mainly in the blood and is far too large to cross the placental barrier.

IgD is a monomer found in miniscule amounts in the serum, and it does not fix complement, opsonize, or cross the placenta. Its main function is to serve as a receptor for antigen on B cells, usually along with IgM. It seems to be the triggering molecule for B-cell activation, and it can also play a role in immune suppression.

IgE is also an uncommon blood component unless one is allergic or has a parasitic worm infection. Its Fc region interacts with receptors on mast cells and basophils. Its biological significance is to stimulate an inflammatory response through the release of potent physiological substances by the basophils and mast cells. Because inflammation would enlist blood cells such as eosinophils and lymphocytes to the site of infection, it would certainly be one defense against parasites. Unfortunately, IgE has another, more insidious effect – that of mediating anaphylaxis, asthma, and certain other allergies.