Immunotherapy for Infectious Diseases

10 Nara
Fig. 4. Primary (dotted line, vaccination; IgM) and secondary (solid line, booster; IgG) antibody
responses.
Thus the secondary response requires the phenomenon known as class switching.
This requires cooperation with T-cells of various types, which release cocktails of substances
called cytokines. These cytokines induce gene rearrangements culminating in
class switching (described below).
This phenomenon is possible because the immune system possesses specific memory
for antigens. It occurs because during the primary response, some B-lymphocytes,
in addition to those differentiating into antibody-secreting plasma cells, become memory
cells, which are long lived.
GENERATION OF ANTIBODY DIVERSITY
A major question is how antibodies recognize so many different epitopes. The
antigen-combining site of the antibody molecule is in the variable region of Fab. Actually,
this site is even more variable than the immediately adjacent sites and is known
as the hypervariable region. The bond with antigen is of a physical, non-covalent
nature.
As mentioned before, variable (V), and constant (C) regions are genetically encoded.
If we bear in mind that we need to be capable of responding to something on the order
of 1018 antigens, we can appreciate the need for the enormous number of genes necessary
to provide this. In fact, the amount of DNA that this would involve would be
quite profligate, and nature has solved this problem very ingeniously by a neat little
trick.
In the germline DNA, the V genes encoding the antigen-combining sites need to
combine with the C genes. Additional interposed genes bring about diversity of speci-