A Textbook of Clinical Pharmacology and Therapeutics

●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

CHAPTER 50

CLINICAL

IMMUNOPHARMACOLOGY

INTRODUCTION

The introduction of a foreign antigen into the body may pro-
voke an immune reaction. Antigens (usually proteins, glycopro-
teins 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 lympho-
cytes. 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 situ-
ation 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-mer-
captopurine), glucocorticosteroids and immunophilins (e.g.
ciclosporinand 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

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;

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 immu-

nity 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.

HYPERSENSITIVITY

Sometimes the immune response to an antigen results in dam-

age to the tissue; this is known as hypersensitivity. There are

four types of hypersensitivity.