Immunotherapy for Infectious Diseases

4 Nara
Erlich introduced a number of ideas that were later to be proved correct. He hypothesized
that antibodies were distinct molecular structures with specialized receptor
areas. He believed that specialized cells encountered antigens and bound to them via
receptors on the cell surface. This binding of antigen then triggered a response and production
of antibodies to be released from the cell to attack the antigen. He understood
that antigen and antibody would fit together like a “lock and key.” A different key
would not fit the same lock and vice versa. However, he did get two important points
wrong. First, he suggested that the cells that produced antibody could make any type
of antibody. He saw the cell as capable of reading the structure of the antigen bound
to its surface and then making an antibody receptor to it in whatever shape was required
to bind the antigen. He also suggested that the antigen-antibody interaction took place
by chemical bonding rather than physically, like pieces of a jigsaw puzzle.
Thus, by 1900, the medical world was aware that the body had a comprehensive
defense system against infection based on the production of antibodies. They did not
know what these antibodies looked like, and they knew little about their molecular
interaction with antigens; however, another major step on the road had been made. We
can see that the antibody system of defense was ultimately a development of the
ancient Greek system of medicine that believed in imbalances in the body humors. The
antibody response later became known as the humoral arm of the immune system.
The term humoral (from the Latin word humors) refers to the fluids that pass through
the body like the blood plasma and lymph. The blood plasma is the noncellular portion
of the blood, and the lymph is the clear fluid that drains via lymph ducts to the
lymph glands and finally into the venous circulation. These fluids carry the antibodies,
which mediate the humoral immune response (Fig. 1).
BASIC STRUCTURE OF ANTIBODIES
Antibodies (immunoglobulins, abbreviated Ig) are proteins of molecular weight
150,000–900,000 kD. They are made up of a series of domains of related amino acid
sequence, which possess a common secondary and tertiary structure. This conserved
structure is frequently found in proteins involved in cell-cell interactions and is especially
important in immunology. Some examples of other members of the immunoglobulin
supergene family are the T-cell receptor; the adhesion molecules intercellular cell
adhesion molecule (ICAM)-1, -2, and -3 and vascular cell adhesion molecule (VCAM);
the coreceptors CD4 and CD8; the costimulatory pairs CD28, CTLA4, B7.1, and B7.2;
and all or parts of many other proteins. The proteins utilizing this structure are members
of the immunoglobulin supergene family. All antibodies have a similar overall
structure, with two light and two heavy chains. These are linked by both covalent
(disulphide bridges) and noncovalent forces.
One end of the Ig binds to antigens (the Fab portion, so called because it is the fragment
of the molecule that is antigen binding); the other end which is crystallizable, and
therefore called Fc, is responsible for effector functions (Fig. 2).
There are five classes (isotypes) of Ig: IgM, IgG, IgA, IgD, and IgE, plus four subtypes
of IgG (IgG1–4) and two subtypes of IgA (IgA1 and IgA2). Light chains exist
in two classes, � and �. Each antibody molecule has either � or � light chains, not both.
Igs are found in serum and in secretions from mucosal surfaces. They are produced and