3.3.2. Properties of Immunoglobulins

General. All immunoglobulins appear to be glycoproteins but the carbohydrate content ranges from 2-3% for IgG to 12-14% for IgM, IgD and IgE. The physicochemical proper-ties of the immunoglobulins are summarized in Table 3.2. Each class possesses a characteristic type of heavy chain. Thus IgG possesses g chains; IgM, m chains; IgA, achains, IgD, dchains and IgE, echains. Variation in heavy chain structure within a class gives rise to immunoglobulin subclasses. For example the human IgG pool consists of four subclasses reflecting four distinct types of g heavy chain. The physicochemical properties of the immunoglobulins vary between the different classes. Note that IgA occurs in a dimeric form {sigA) in association with a protein chain termed the secretory piece. The diversity of structure of the different classes suggests that they perform different functions, in addition to their primary function of antigen binding. In spite of this diver-sity all antibodies have a common basic structure. The structures of IgG, and IgA1 are shown in Fig. 3.11.

IgG. IgG is the major immunoglobulin in normal human serum accounting for 70-75% of the total immuno-globulin pool. IgG is a monomeric protein with a sedimentation coefficient of 7S and a molecular weight of 146,000. However, studies of IgG subclasses have indicated that IgG3 proteins are slightly larger than the other subclasses and this increase is due to the slightly heavier y3 chain. The IgG class is distributed evenly between the intra- and extravascular pools, is the major antibody of secondary immune responses and the exclusive anti-toxin class.

IgM. IgM accounts for about 10% of the immunoglobulin pool. The molecule has a pentameric structure in which individual heavy chains have a molecular weight of approximately 65,000 and the whole molecule has a molecular weight of 970,000. This protein is largely confined to the intravascular pool and is the predominant 'early' antibody frequently directed against antig,enically complex infectious organisms.

IgA. IgA represents 15-20% of the human serum immuno-globulin pool . In man more than 80% of IgA occurs as the basic four chain monomer but in most mammals the IgA in serum is mainly polymeric, occurring mostly as a dimer. IgA is the predominant immunoglobulin in sero-mucous secretions such as saliva, tracheobronchial secretions, colostrum, milk and genito-urinary secretions. Secretory IgA (sigA) which may be of either subclass, exists mainly in the 1 15, dimeric form and has a molecu-lar weight of 385,000. sigA is abundant in

Table 3.2. Physicochemical properties of human immunoglobulins.

Immunoglobulin	IgG1	IgG2	IgG3	IgG4	IgM	IgA1	IgA2	sigA	IgD	IgE
name of heavy chain	g1	g1	g1	g1	m	a1	a1	a1 or a2	d	e
concentration, mg/mL	9	3	1	0.5	1.5	3	0.5	0.05	0.03	0.00005
sedimentation constant	7S	7S	7S	7S	19S	7S	7S	11S	7S	8S
molecular weight, x1000	146	146	170	146	970	160	160	385	184	188
MW of heavy chain, x1000	51	51	60	51	65	56	52	52-56	69.7	72.5
# of heavy chain domains	4	4	4	4	5	4	4	4	4	5
carbohydrates, %	2-3	2-3	2-3	2-3	12	7-11	7-11	7-11	9-14	12

seromucous secretions and is protected from proteolysis by combina-tion with another protein - the secretory component.

IgD. IgD accounts for less than 1% of the total plasma immunoglobulin but it is known to be present in large quantities on the membrane of many circulating B Iymphocytes. The precise biological function of this class is not known but it may play a role-in antigen-triggered Iymphocyte differentiation.

IgE. IgE though a trace serum protein, is found on the surface membrane of basophils and mast cells in all individuals. This class may play a role in active immunity to helminthic parasites but in Western countries is more commonly associated with immediate hypersensitivity diseases such as asthma and hayfever.