Section D – Antibodies
partly to facilitate protection against microbes entering at the different sites and with different properties. There is some overlap in their function and in where they are produced, but generally there is a division of labor among the different antibody classes, e.g. IgA is the most common antibody in mucosal secretions while IgM is mainly found in the plasma, and both are most effective at those locations.
IgG Immunoglobulins of the IgG class have a MW of 150 kDa and are found both in vascular and extravascular spaces as well as in secretions. IgG is the most abun- dant immunoglobulin in the blood (see Table 1 in Topic D1), provides the bulk of immunity to most bloodborne infectious agents and is the only antibody class to cross the placenta to provide passive humoral immunity to the develop- ing fetus and thus to the infant on its birth. IgG has two H-chains (referred to as γ chains) with either two κ or two λ L-chains. Furthermore, there are four different subclasses of IgG (designated IgG1, IgG2, IgG3, IgG4), which have slightly different sequences in their H-chains and corresponding differences in their functional activities.
IgA This immunoglobulin is present in the serum as a 170 kDa, four polypeptide (two L and two H) chain protein. More important, it is the major immunoglobu- lin present in external secretions such as colostrum, milk, and saliva where it exists as a 420 kDa dimer (Fig. 1). In addition to the κor λL-chains and the IgA heavy chain (designated α), which distinguishes it from IgG or other antibody classes, secreted IgA also contains two other polypeptide chains – secretory component (SC) and J-chain (Joining chain). SC is part of the poly-Ig receptor involved in the transepithelial transport of exocrine IgA and stabilizes IgA against proteolytic degradation. The two four-chain units composing secretory IgA are held together by the J-chain through disulfide bridges. Most IgA is synthesized locally by plasma cells in mammary and salivary glands, and along the respiratory, gastrointestinal and genitourinary tracts (Topic E4). It is then transported through epithelial cells to the lumen. This antibody is a first line of
66 Section D – Antibodies
B cell surface receptor IgD
Allergic responses (Enhances acute inflammation) IgE
IgM immunoglobulin J-chain
L-chain H-chain
Secretory IgA
Secretory component
IgA Immunoglobulins
Circulatory IgA H-chain
L-chain J-chain
Fig. 1. Chain structures of different classes of immunoglobulins.
defense against microbial invaders at mucosal surfaces. Of the two subclasses of IgA, IgA2 rather than IgA1 is primarily found in mucosal secretions.
IgM IgM is the first antibody produced by, and expressed on the surface of, a B cell.
It acts as an antigen receptor for these cells, and is also present as a soluble molecule in the blood. On the B cell surface this molecule is expressed as a four-chain unit – two µ H-chains and two L-chains. In the blood, IgM is composed of five four-chain units held together by disulfide bridges at the carboxy-terminal end of the µchains (Fig. 1). J-chain is also associated with IgM in the blood and initiates the polymerization of its subunits at the time of its secretion from a plasma cell. Because of its size (900 kDa), IgM is found prima- rily in the intravascular space (i.e. in the bloodstream). As IgM is the first anti- body produced in an immune response, its efficiency in combining with antigen is of particular importance until sufficient quantities of IgG antibody have been synthesized. Although IgM antibodies usually have low-affinity binding sites for antigen, they have ten combining sites per molecule which can synergize with each other on the same molecule when it binds to a microbe. Thus, the overall tightness of binding of an IgM molecule (avidity) to a microbe is quite high, making antibodies of this class very effective in removal of the microbe.
IgD IgD is present in low quantities in the circulation (0.3 mg/ml in adult serum).
Its primary function is that of an antigen receptor on B lymphocytes (Fig. 1), but it is probably also involved in regulating B cell function when it encounters antigen. B cells thus can express both IgM and IgD and both are specific for the same antigen. When IgM and IgD expressed on a B cell interact with an antigen for which they are specific, the antigen is internalized, and processed and presented to helper T cells which trigger the B cells to proliferate and differenti- ate into plasma cells, thus initiating the development of a humoral immune response.
IgE IgE is present in the serum at very low levels (nanograms per milliliter), but plays a significant role in enhancing acute inflammation, in protection from infection by worms, and in allergic reactions (Topics B4, H2, K2). Antibody- mediated allergy is predominantly associated with IgE. After stimulation of the development of IgE-producing plasma cells by an antigen, the IgE produced binds to receptors on mast cells which are specific for the Fc region of IgE.
When antigen is reintroduced into an individual with such ‘armed’ mast cells, it binds to the antigen-binding site of the IgE molecule on the mast cell, and as a result of this interaction, the mast cell is triggered to release pharmacologically active agents (e.g., histamine). IgE antibodies are thus important components of immediate hypersensitivity syndromes such as hay fever and asthma (Topic K2, Fig. 1).
D2 – Antibody classes 67
Section D – Antibodies