Immunosuppressant drugs WORLD OF MICROBIOLOGY AND IMMUNOLOGY306•
to establish or consolidate an infection. Thus, immunomodu-
lation can be beneficial or detrimental to a host.
Many providers of nutritional supplements claim that a
product enhances certain aspects of the immune system so as
to more vigorously shield the body from infection or the
development of maladies such as cancer. However, rigorous
testing of these claims is typically lacking and so the claims of
nutritional links with immune system improvement are at
present tenuous.
A firmer link exists between exercise and immunomod-
ulation. Moderately active people are known to have
macrophages that are more capable of killing tumors, due to
the increased production of a compound called nitric oxide.
This population also displays lower incidence rates for cancer
and other chronic diseases. Even sporadic exercise increases
the ability of an immune system component called natural
killer cells to eradicate tumors.
Conversely, too much exercise is associated with
increased susceptibility to respiratory tract infections, indicat-
ing that the immune system is impaired in the ability to thwart
infections.
Immunomodulation by microorganisms is directed at
several aspects of the immune system. One target are the small
molecules known as cytokines, which function as messengers
of the immune system. In other words, cytokines stimulate
various immune responses such as inflammationof the manu-
facture of antibodies. Other cytokines are involved in down-
regulating the immune responses.
Some microorganisms are able to produce and excrete
proteins that mimic the structure and function of cytokines.
Often the result is a suppression of the host’s inflammatory
response. Examples of microbes that produce cytokine-like
molecules are the Epstein-Barr virus, poxvirus, vaccinia virus.
Other microbes, such as the protozoan Trypanosoma
cruziblocks the activation of cytokines by an as yet unknown
mechanism. The result is a severe suppression of the immune
system. Adenovirusesalso block cytokine expression, at the
level of transcription.
The manipulation of cytokine expression and action
may also be exploited to produce vaccines. For example, vac-
cines designed to nullify or enhance the activity of certain
cytokines could cause greater activity of certain components
of the immune system. While vaccines have yet to achieve this
level of activity, specific experimental targeting of deoxyri-
bonucleic acidhas suppressed certain cytokines.
Another portion of the immune system capable of
immunomodulation is complement. Herpessimplex virus types
1 and 2, the virusesresponsible for cold sores and genital her-
pes in humans, resist the action of complement. The presence of
specific viral proteins are required, and may act by disrupting a
key enzyme necessary for complement manufacture.
Vaccinia virus can also evade complement action, via a
protein that structurally resembles a host protein to which
complement binds. Also, another viral protein, called the
inflammation modulatory protein, acts to decrease the inflam-
matory response at the site of infection, thus preserving host
tissue from damage and providing the virus particles with rel-
atively undamaged cells in which to grow.The protozoan Trypanosoma cruzi can regulate the
activity of complement before infecting human cells. Once
inside the cells of the host, the parasite can evade an immune
response.
A variety of bacteria, viruses, and parasitesare also
able to modulate the immune system by affecting the way anti-
gens are exposed on their surfaces. Antigenpresentation is a
complex series of steps. By controlling or modulating even
one of these steps, the antigen presentation process can be dis-
rupted. The formation of antibodyis thus affected.
Aside from biological agents, physiological factors can
cause immunomodulation. For example, stress is known to be
capable of suppressing various aspects of the cellular immune
response. The release of various hormones may disrupt in the
normal expression of cytokines. Specifically, those cytokines
that suppress inflammation are more evident, either because of
their increased production or the decreased production of
cytokines that activate inflammation.See alsoImmunologic therapiesIMMUNOPRECIPITATION•seeANTIBODY-ANTIGEN,
BIOCHEMICAL AND MOLECULAR REACTIONSIImmunosuppressant drugsMMUNOSUPPRESSANT DRUGS
Immunosuppressant drugs are medications that reduce the
ability of the immune systemto recognize and respond to the
presence of foreign material. Such drugs were developed and
still have an important use as a means of ensuring that trans-
planted organs and tissues are not rejected by the recipient.
Rejection of transplanted organs or tissue is a natural
reaction of a person’s immune system. In a very real sense, the
transplanted material is foreign and is treated, as would be an
infectious microorganism. The immune system attacks and
tries to destroy the foreign matter. Suppressing the immune
system allows the transplanted material to be retained.
Drugs to suppress the immune system are available only
with a physician’s authorization. Some commonly prescribed
drugs are azathioprine, cyclosporine, prednisolone, and
tacrolimus. These can be taken orally, both in solid and liquid
forms, or can be injected.
The main target of such immunosuppressant drugs are
the white blood cells (which are also called lymphocytes). The
main function of lymphocytes is to patrol the body and root
out foreign material. Then these cells, in combination with
other immune system components, destroy the foreign mate-
rial.
Transplantation of animal kidneys into humans was
tried in the early 1900s, and human-to-human transplant
attempts were first made in 1933. These attempts were unsuc-
cessful. It was not until the years of World War II that the
immunological basis for these failures was deciphered. Then,
Peter Medawarobserved that a skin graft survived about a
week before being rejected, but a subsequent graft waswomi_I 5/6/03 3:23 PM Page 306