The Immune System 509T cells and promote cell-mediated immunity against intra-
cellular pathogens. The lymphokines secreted by the T H 1
lymphocytes also stimulate nitric oxide production in macro-
phages, increasing their activity. The T H 2 lymphocytes secrete
interleukin-4, interleukin-5, interleukin-13, and other lym-
phokines that stimulate B lymphocytes to promote humoral
immunity against extracellular pathogens. Interleukin 4 and
other lymphokines secreted by T H 2 cells recruit eosinophils
to the site of the inflammation, help to clear parasitic infec-
tions, and induce IgE production in an allergic (immediate
hypersensitivity) reaction. For example, T H 2 lymphocytes and
the cytokines they secrete—IL-4, IL-5, and IL-13—play a key
role in most cases of allergic asthma.
In addition to the T H 1 and T H 2 subtypes of helper
T cells, there is another, more recently recognized subtypecalled T (^) H 17 cells. The TH17 cells secrete a different group
of lymphokines that include interleukin-17, which stimulates
a different kind of inflammatory response dominated by neu-
trophils. These cells are particularly important for fighting
infections in the skin, lungs, and other mucosal membranes.
Cytokines released by T H 17 cells promote neutrophil recruit-
ment and activation to combat bacteria. This is particularly
important in fighting infections at mucosal surfaces (of
the gut and lungs, for example) as well as in the skin. The
T H 17 cells also have roles in auto immune diseases, aller-
gic inflammation, and immune responses that affect tumor
growth.
CLINICAL APPLICATION
Acquired immune deficiency syndrome ( AIDS ) has killed
many millions of people worldwide, and millions more are
currently infected. AIDS is caused by the human immunode-
ficiency virus ( HIV; see fig. 15.3 ), which preferentially infects
and destroys helper T cells, particularly those in the gastro-
intestinal mucosa where up to 30% of helper T cells reside.
This results in decreased immunological function and greater
susceptibility to opportunistic infections and cancer.
HIV is classified as a retrovirus because its genetic
code is carried in its RNA. The enzyme reverse transcrip-
tase is needed to transcribe this viral RNA into complemen-
tary DNA for viral replication (see fig. 15.3 ). Antiretroviral
therapy ( ART ) involves drugs that inhibit this enzyme. Two
different reverse transcriptase inhibitors have been com-
bined with an inhibitor of protease (an enzyme needed to
assemble the viral coat) to produce a drug “cocktail” that
can suppress HIV replication indefinitely. This has proven to
be a very effective treatment, and even more so in people
who can begin this therapy very early after infection. How-
ever, ART does not cure AIDS because the HIV viral DNA
integrates itself into the host DNA of memory helper T cells.
When the ART drugs are stopped, the virus reappears.
Moreover, only a fraction of infected people worldwide
have access to these drugs that are required to maintain
their lives.
Hope has been raised because (1) early and continual
treatment of an infected person with the currently available
drugs can so lower HIV levels that the risk of infecting a
sexual partner may be reduced by 96%; (2) vaginal gels with
antiretroviral drugs reduce transmission of HIV to women;
(3) male circumcision significantly reduces the risk that
a man will be infected with HIV; and (4) vaccines against
HIV may be possible. It has proven exceedingly difficult
to develop anti-HIV vaccines, but scientists are working
on passive immunity antibody treatments and on design-
ing antigens that contain many different epitopes (antigenic
determinant sites) that hopefully will be effective in develop-
ing active immunity against HIV.
the brain, for example, and promote a fever). Interleukin-2 is
produced primarily by helper T lymphocytes residing in lymph
nodes and other secondary lymphoid organs, and is critically
important for the development and function of helper, killer,
and regulatory T lymphocytes. Interleukin-4 is required for the
proliferation and clone development of B cells. Interleukin-5
has a central role in eosinophil differentiation, proliferation,
and activation. Other interleukins will be described in conjunc-
tion with their functions.
Two subtypes of helper T lymphocytes are desig-
nated T (^) H 1 and T (^) H 2. Helper T lymphocytes of the T H 1 sub-
type produce interleukin-2 and gamma interferon. Because
they secrete these lymphokines, T H 1 cells activate killer
Cytokine Biological Functions
Interleukin-1 (IL-1) Induces proliferation and activation of
T lymphocytes
Interleukin-2 (IL-2) Induces proliferation of activated
T lymphocytes
Interleukin-3 (IL-3) Stimulates proliferation of bone
marrow stem cells and mast cells
Interleukin-4 (IL-4) Stimulates proliferation of activated
B cells; promotes production of
IgE antibodies; increases activity of
cytotoxic T cells
Interleukin-5 (IL-5) Induces activation of cytotoxic
T cells; promotes eosinophil
differentiation and serves as
chemokine for eosinophils
Interleukin-6 (IL-6) Stimulates proliferation and activation
of T and B lymphocytes
Granulocyte/
monocyte-macrophage
colony-stimulating
factor (GM-CSF)
Stimulates proliferation and
differentiation of neutrophils,
eosinophils, monocytes, and
macrophages
Table 15.7 | Some Cytokines That
Regulate the Immune System