Describe the structure and classes of immunoglobulins with their functions.

Basic Structure

• Light chains — kappa or lambda (about 2:1 in man); a single molecule carries only one type
• Heavy chains determine the class — gamma (IgG), mu (IgM), alpha (IgA), epsilon (IgE), delta (IgD)
• Each chain has variable and constant regions; the variable regions of one heavy and one light chain form the antigen-binding site, with three hypervariable (complementarity-determining) regions making the contact
• The hinge region allows the arms to move, so epitopes at different spacings can be gripped
• Fab and Fc — PAPAIN gives two Fab and one Fc; pepsin gives one bivalent F(ab')2 and digests the Fc

The Five Classes Compared

Special Features

• Secretory IgA — a dimer joined by a J chain, with a secretory component added by the epithelial cell as it is transported across. That component protects it from proteolysis in the gut and secretions, which is why it survives where other antibodies would not
• Total daily production of IgA exceeds that of all other classes combined, reflecting the size of the mucosal surface it defends
• IgG subclasses — IgG1 and IgG3 fix complement well and cross the placenta best; IgG2 responds chiefly to polysaccharide antigens and its deficiency causes recurrent infection with capsulated organisms; IgG4 does not fix complement
• Immunoglobulin variants — isotype (the class, present in all members of a species), allotype (genetic differences between individuals), and idiotype (variation in the variable region, unique to a clone)
• Monoclonal antibodies are produced by hybridoma technology, fusing an antibody-producing B cell with a myeloma cell to give an immortal clone; they are now central to diagnosis and to therapy

Applied Aspects

• IgM in cord blood or neonatal serum means intrauterine infection, since maternal IgM cannot cross the placenta — the basis of diagnosing congenital rubella, syphilis, toxoplasmosis and cytomegalovirus
• IgM indicates recent infection; IgG indicates past exposure or immunity, and both are measured in dengue, hepatitis and antenatal screening
• Maternal IgG protects for 3 to 6 months and then wanes, which sets both the timing of primary immunisation and the age at which infections such as pneumococcal disease begin
• Selective IgA deficiency is the commonest primary immunodeficiency; many are asymptomatic, but some develop recurrent respiratory and gut infection, and they may react anaphylactically to blood products containing IgA
• Multiple myeloma produces a monoclonal band on electrophoresis with free light chains in urine (Bence Jones protein), while the other classes are suppressed — hence the paradox of a high total protein with recurrent infection
• Anti-D immunoglobulin is IgG, and works by removing fetal red cells from the maternal circulation before the mother can mount her own response