Page 529 - Review of Medical Microbiology and Immunology ( PDFDrive )

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mebooksfree.com mebooksfree.com mebooksfree.com disease (asthma). IL-13 is made by Th-2 cells and binds to mebooksfree.com
PART VII Immunology
518
IL-1 is endogenous pyrogen, which acts on the hypothala-
(8) IL-13 is implicated as the mediator of allergic airway
mus to cause the fever associated with infections and other
a receptor that shares a chain with the IL-4 receptor. In
inflammatory reactions. (Exogenous pyrogen is endotoxin,
a lipopolysaccharide found in the cell wall of gram-negative
animals, IL-13 was shown to be necessary and sufficient to
bacteria [see Chapter 7].)
cause asthma. IL-13 is involved in producing the airway
(2) IL-2 is produced mainly by helper T cells. It stimulates
both helper and cytotoxic T cells to grow. IL-2 is T-cell
the amount of IgE.
growth factor. Resting T cells are stimulated by antigen (or
(9) The main function of transforming growth factor-β
(TGF-β) is to inhibit the growth and activation of T cells.
other stimulators) both to produce IL-2 and to display IL-2 hyperresponsiveness seen in asthma but not in increasing
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receptors on their surface, thereby acquiring the capacity to
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It is an “anti-inflammatory” cytokine. Although it is a
“negative regulator” of the immune response, it stimulates
respond to IL-2. Interaction of IL-2 with its receptor stimu-
wound healing by enhancing the synthesis of collagen. It is
lates DNA synthesis, allowing cell division to occur.
(3) IL-4 is produced by the Th-2 class of helper T cells.
and macrophages. In summary, the role of TGF-β is to
IL-4 stimulates the development of Th-2 cells from T cells
that have been activated by exposure to antigen. It also
dampen or suppress the immune response when it is no
induces class switching to IgE. IL-4 is the “signature” (most
longer needed after an infection and to promote the healing
characteristic) cytokine produced by Th-2 cells (Figure 58–3
process.
and Table 58–5).
(4) IL-5 is produced by the Th-2 class of helper T cells.
It induces class switching to IgA, thereby increasing muco-
& Monocytes
sal immunity. It also increases the number and activity of
Chemokines are a group of cytokines that can attract either
eosinophils. Eosinophils are an important host defense Cytokines Affecting Macrophages
macrophages or neutrophils to the site of infection. The
against many helminths (worms), (e.g., Strongyloides) (see
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term chemokine is a contraction of chemotactic and cyto-
Chapter 56) and are increased in immediate hypersensitiv-
kine. Chemokines are produced by various cells in the
ity (allergic) reactions (see Chapter 65).
(5) IL-6 is produced mainly by macrophages. It is a pro-
phages. The circulating neutrophils and macrophages
inflammatory cytokine that induces fever by affecting the
(monocytes) are attracted to the site by an increasing gradi-
hypothalamus and induces the production of acute-phase
ent of chemokines and then bind to selectins on the endo-
proteins by the liver. Acute-phase proteins are described on
thelial cell surface. Chemokines also activate integrins on
page 481.
the surface of the neutrophils and macrophages that bind to
(6) IL-7 is produced by stromal cells in the thymus and
ICAM proteins on the endothelial cell surface. The interac-
bone marrow. It is required for stem cells to differentiate into
T cells and B cells. A mutation in the gene for the γ chain of
of the white cells into the tissue to reach the infected area.
the IL-7 receptor results in severe combined immunodefi-
Approximately 50 chemokines have been identified;
ciency because neither T cells nor B cells are formed.
they are small polypeptides ranging in size from 68 to 120
(7) IL-10 and IL-12 regulate the production of Th-1 tion between integrin and ICAM facilitates the movement
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amino acids. The alpha-chemokines have two adjacent
cells, the cells that mediate delayed hypersensitivity (See
cysteines separated by another amino acid (Cys-X-Cys),
Figure 58–3). IL-12 is produced by macrophages and pro-
whereas the beta-chemokines have two adjacent cysteines
motes the development of Th-1 cells, whereas IL-10 is
produced by Th-2 cells and inhibits the development of
trophils and are produced by activated mononuclear cells.
Th-1 cells. The relative amounts of IL-4, IL-10, and IL-12
IL-8 is a very important member of this group. The beta-
drive the differentiation of Th-1 and Th-2 cells and there-
chemokines attract macrophages and monocytes and are
fore enhance either cell-mediated or humoral immunity,
produced by activated T cells. RANTES and MCAF are
respectively. This is likely to have important medical conse-
important beta-chemokines.
quences because the main host defense against certain
There are specific receptors for chemokines on the sur-
infections is either cell-mediated or humoral immunity. For
example, Leishmania infections in mice are lethal if a
tion of the chemokine with its receptor results in changes in
humoral response predominates but are controlled if a vig-
cell surface proteins that allow the cell to adhere to and
orous cell-mediated response occurs. face of cells, such as neutrophils and monocytes. Interac-
migrate through the endothelium to the site of infection.
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The IL-12–gamma interferon axis is very important in
the ability of our host defenses to control infections by
Cytokines Affecting
intracellular pathogens, such as M. tuberculosis and
L. monocytogenes. IL-12 increases the number of Th-1 cells,
and Th-1 cells produce the gamma interferon that activates
(1) TNF activates the phagocytic and killing activities of
the macrophages that phagocytose and kill the intracellular
bacterial pathogens mentioned earlier.
neutrophils and increases the synthesis of adhesion
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