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Immunoglobulin is composed of a pair of light and heavy chains linked by disulfide bonds.  The light chain contains a variable region and a constant region; the heavy chain contains a variable region and 3 or 4 constant regions (C_H1-4).  The functional structure of the immunoglobulin is broadly divided into the 2 following components:

• The Fab fragment is the entire light chain plus the variable and first constant (C_H1) regions of the heavy chain; Fab fragments bind to specific epitopes on antigens using a hypervariable cluster of 110-130 amino acids in the variable portion of the molecule (Choices D and E).

• The Fc fragment is the remaining constant regions of the heavy chain; the Fc fragment is the effector portion of the immunoglobulin that interacts with complement and immune cells.

IgG, the most prevalent immunoglobulin in serum, is the immunoglobulin primarily responsible for controlling most recurrent bacterial infections.  It binds to bacterial epitopes with the Fab fragment and then exerts its bactericidal effects with the second and third heavy chain constant regions of the Fc fragment, as follows:

• Complement activation:  The second heavy-chain constant region serves as a platform for activation of the classical complement cascade.  This generates membrane attack complexes and opsonizing C3b ligands for the CR1 receptor on erythrocytes and reticuloendothelial phagocytes.

• Direct phagocytosis:  The third heavy-chain constant region is the ligand for the Fc receptor (CD16) on the surface of phagocytic cells.  Binding results in phagocytosis of the immunoglobulin-covered bacteria and subsequent destruction.

(Choice B)  The constant region of the light chain is bound to the first constant region of the heavy chain with disulfide bonds.  It does not play a significant role in opsonization or phagocyte binding.

(Choice C)  Immunoglobulins have hinge regions between the Fab and Fc fragments that provide flexibility to the Fab arms.  Longer hinge regions are associated with increased antibody avidity because the Fab fragments can reach antigens that are farther apart on the bacteria.  The hinge region does not bind to the Fc receptor on phagocytes.

Educational objective:
Immunoglobulin contains a Fab fragment that binds to antigen and an Fc fragment that activates complement and/or interacts with immune cells.  The Fc fragment of IgG activates the classical complement cascade (constant heavy chain region 2) and serves as a ligand for the Fc receptor on phagocytes (constant heavy chain region 3).