Clinical Pharmacology and Therapeutics

CHAPTER 50
CLINICAL
IMMUNOPHARMACOLOGY
● Introduction 399
● Immunity and hypersensitivity 399
● Immunosuppressive agents 400
● Chemical mediators of the immune response and
drugs that block their actions 404
● Drugs that enhance immune system function 407
● Vaccines 407
● Immunoglobulins as therapy 407
INTRODUCTION
The introduction of a foreign antigen into the body may provoke
an immune reaction. Antigens (usually proteins, glycoproteins
or high-molecular-weight carbohydrates) usually have a
molecular weight 5000 Da. They are typically processed by
macrophages before presentation to T lymphocytes. The effector
limb of the immune response is initiated by interaction of the
presented antigen with receptors on the surface of the lymphocytes.
Immune responses are of two types, namely humoral (via
B lymphocytes, plasma cells and antibody) or cellular (via T
lymphocytes).
The immune response is an essential defence mechanism.
However, it may be defective, disorganized or overactive. The
body has the potential to stimulate its own immune system so
that antibodies are produced against itself. Normally this situation
is prevented, for example, by tolerance, but if this fails
then autoimmune disease results. Deficiencies in the immune
system may be congenital or result from disease (notably AIDS
from HIV-1 infection) or the use of immunosuppressant drugs,
particularly cytotoxic agents (e.g. cyclophosphamide, 6-mercaptopurine),
glucocorticosteroids and immunophilins (e.g.
ciclosporin and its analogues). By the same token, these are
the very drugs that are used clinically as immunosuppressants
when it is necessary to damp down an inappropriate immune
response.
IMMUNITY AND HYPERSENSITIVITY
2. secondary reactions – these occur with subsequent exposure
to the antigen. The rise in antibody titre is greater and
persists for a long period. The antibody consists mainly of
IgG. This reaction requires the interaction of helper T cells
and B lymphocytes.
CELLULAR IMMUNITY
This is mediated by sensitized T lymphocytes which recognize
and bind the antigen and subsequently release a cascade of
lymphokines which control and amplify both humoral and
cellular immune responses. The effector arm of cellular immunity
consists of cytotoxic T cells.
ACTIVE IMMUNITY
This consists of immunity that is developed either in response
to infection or following inoculation with an attenuated strain
of organism, or with a structural protein or toxic protein to
which the host produces protective antibodies.
PASSIVE IMMUNITY
This is immunity that is transferred by the administration of
preformed antibodies (e.g. immune globulin/serum) either
from another host or from recombinant techniques in vitro.
HUMORAL IMMUNITY
The humoral response occurs in two stages:
1. primary reactions – these occur with the first exposure to
the antigen. There is a small and short-lived rise in
antibody titre which consists largely of IgM;
HYPERSENSITIVITY
Sometimes the immune response to an antigen results in damage
to the tissue; this is known as hypersensitivity. There are
four types of hypersensitivity.