The main biological features of the human antibodies are summarized in Table 4.6. Different classes of antibody tend to predominate at different sites. The major functions of antibody are:

• elimination of infective organisms by:
• binding to prevent adhesion and invasion of organisms (e.g. preventing the entry of poliovirus and other enteroviruses)
• opsonization of particles for phagocytosis
• lysis (in combination with complement)
• antitoxin activity (e.g. in prevention of tetanus)
• sensitization of cells for antibody-dependent cell cytotoxicity (ADCC)
• immune regulation, acting as the antigen receptor on B cells and presenting the antigen to helper T cells.

Table 4-6. Characteristics of the immunoglobulins

	IgG Dominant class of antibody	IgM Produced first in immune response	IgA Found in mucous membrane secretions	IgE Responsible for symptoms of allergy; used in defence against nematode parasites	IgD Found almost solely on lymphocyte membrane
Heavy chain Mean adult serum levels (mg/mL):	γ IgG (total) = 8-16 G1 = 6.5 G2 = 2.5 G3 = 0.7 G4 = 0.3	μ 0.5-2	α IgA (total) = 1.4-4 A1 = 1.5 A2 = 0.2	ε 17-450 ng/mL	δ 0-0.4
Half-life (days)	21	10	6	2	3
Complement fixation
Classical	++	+++	-	-	-
Alternative	-	-	+	-	-
Binding to mast cells	-	-	-	+	-
Crosses placenta	+	-	-	-	-

IgM

The antibody is confined mainly to the intravascular pool. It is a large pentameric molecule, bound together by the joining ‘J’ chain. It does not cross the placenta, and is not normally produced in the child until after birth. Therefore, if present in the newborn infant, antigen-specific IgM is a good marker for intrauterine infection. It is usually a sign of acute infections.

IgG

This is the most abundant immunoglobulin in serum, present as a monomer. IgG is the antibody of secondary response, and has high antigen affinity. It is the only antibody to cross the placenta in significant quantities. There are four subclasses: IgG1, IgG2, IgG3 and IgG4. IgG1 and IgG3 are produced mainly in response to protein antigens, such as viruses. These subclasses are good opsonins, binding Fc receptors on neutrophils and activating complement. IgG2 and IgG4 are produced in response to polysaccharide antigen (e.g. the capsule of bacteria such as pneumococcus and Haemophilus influenzae) and are the major opsonins for such organisms. IgG antibody is involved in resistance to infection, as patients who are lacking in IgG suffer with recurrent, even life-threatening bacterial infections. Those with isolated IgA or IgM deficiency have much less severe problems.

IgA

This is mainly the antibody of secretions, being present in the respiratory, gastrointestinal and urinary tracts. There are two subclasses, IgA1 and IgA2; their functions appear to be similar. IgA is mainly monomeric in the serum, but dimeric in secretions, the two molecules being complexed by a joining (J) chain. The mechanism for transport from serum to intestinal mucosal surface is well established. IgA in serum binds to a poly-Fc receptor for IgA and IgM on the basal surface of enterocytes and hepatocytes. Transcellular transport delivers the immunoglobulin to the luminal surface where it is secreted still bound to the receptor, which is termed the secretory component (SC). For IgA responses, localized antigen exposure gives rise to generalized mucosal immunity, which is of importance in vaccination.

IgD

Serum levels are very low and its function at this site is uncertain. IgD is present on the surface of B lymphocytes, and may have an immunoregulatory role. Levels are high in conditions with B-cell activation such as systemic lupus erythematosus (SLE), HIV infection and Hodgkin’s disease.

IgE

IgE is a monomer that is normally present in very low levels in serum, as most is membrane-bound to the high-affinity receptors on mast cells and basophils. Its main physiological role is its antinematode activity, but its most common clinical relevance is in the pathogenesis of type 1 hypersensitivity (atopic or allergic) disease.

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