Page 522 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 58 Cellular Basis of the Immune Response
kill the organisms. A reduced ability to mount this response
of cell contents. Granzymes also activate caspases (a type of
manifests itself as a marked susceptibility to disease caused
by such microorganisms.
protease) that initiate apoptosis, resulting in cell death.
In the case of M. tuberculosis, a lipoprotein of the bacte-
After killing the virus-infected cell, the cytotoxic T cell
rium stimulates a specific Toll-like receptor on the macro-
itself is not damaged and can continue to kill other cells
phage, which signals the cell to synthesize IL-12. IL-12 then
induces naïve helper T cells to differentiate into the Th-1
effect on free virus, only on virus-infected cells.
Note that the effector functions of cytotoxic T cells do
type of helper T cells that participates in the delayed hyper-
not require costimulation. No B7-CD28 interaction is
sensitivity response. infected with the same virus. Cytotoxic T cells have no
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Th-1 cells produced gamma interferon, which activates
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required. This allows cytotoxic T cells to kill any virus-
macrophages, thereby enhancing their ability to kill M.
infected cell. The activation of the cytotoxic T cells by the
tuberculosis. This IL-12–gamma interferon axis is very
antigen-presenting cell (e.g., dendritic cell) does require
important in the ability of our host defenses to control
infections by intracellular pathogens, such as M. tuberculo-
Another mechanism by which cytotoxic T cells kill tar-
get cells is the Fas-Fas ligand (FasL) interaction. Fas is
sis and Listeria monocytogenes.
a protein displayed on the surface of many cells. When
a cytotoxic TCR recognizes an epitope on the surface of a
Th-2 Cells
target cell, FasL is induced in the cytotoxic T cell. When Fas
Th-2 cells and eosinophils are the main effectors of reactions
and FasL interact, apoptosis (death) of the target cell
that protect against helminths (worms) such as Schistosoma
and Strongyloides. The most important interleukins for these
induced apoptosis.
reactions are IL-4, which increases the production of IgE, and
In addition to direct killing by cytotoxic T cells, virus-
IL-5, which activates eosinophils. IgE binds to the surface of occurs. NK cells can also kill target cells by Fas-FasL–
infected cells can be destroyed by a combination of IgG and
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the worm. Eosinophils then bind to the heavy chain of IgE and
phagocytic cells. In this process, called antibody-dependent
secrete enzymes that destroy the worm.
cellular cytotoxicity (ADCC), antibody bound to the sur-
Th-17 Cells
the surface of phagocytic cells (e.g., macrophages or NK
Th-17 cells protect against the spread of bacterial infec-
cells), and the infected cell is killed. The ADCC process can
tions at mucosal surfaces by producing IL-17. IL-17 attracts
also kill helminths (worms). In this case, IgE is the antibody
neutrophils to the site of infection whereupon the bacteria
involved, and eosinophils are the effector cells. IgE binds to
are ingested and destroyed. Patients with a defective Th-17
surface proteins on the worm, and the surface of eosino-
response are predisposed to bloodstream infections caused
phils displays receptors for the epsilon heavy chain. The
by bacteria in the colon such as Escherichia and Klebsiella.
major basic protein located in the granules of the eosino-
A defective Th-17 response also predisposes to chronic
phils is released and damages the surface of the worm.
mucocutaneous candidiasis caused by C. albicans.
Many tumor cells develop new antigens on their surface.
These antigens bound to class I proteins are recognized by
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CD8 Cells
cytotoxic T cells, which are stimulated to proliferate by
CD8 cells mediate the cytotoxic response that is con-
IL-2. The resultant clone of cytotoxic T cells can kill the
cerned primarily with destroying virus-infected cells and
tumor cells, a phenomenon called immune surveillance.
tumor cells but also play an important role in graft rejec-
In response to allografts, cytotoxic (CD8) cells recog-
tion. In response to virus-infected cells, the CD8 lympho-
cytes must recognize both viral antigens and class I
eign cells. Helper (CD4) cells recognize the foreign class II
molecules on the surface of infected cells. To kill the virus-
molecules on certain cells in the graft (e.g., macrophages
infected cell, the cytotoxic T cell must be activated by IL-2
and lymphocytes). The activated helper cells secrete IL-2,
produced by a helper (CD4-positive) T cell. To become
which stimulates the cytotoxic cell to form a clone of cells.
activated to produce IL-2, helper T cells recognize viral
antigens bound to class II molecules on an APC (e.g., a
dendritic cell or macrophage). The activated helper T cells
Regulatory Functions of T Cells
secrete cytokines such as IL-2, which stimulates the virus- These cytotoxic cells kill the cells in the allograft.
T cells play a central role in regulating both the humoral
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specific cytotoxic T cell to form a clone of activated cyto-
(antibody) and cell-mediated arms of the immune system.
toxic T cells.
Activated cytotoxic T cells kill virus-infected cells pri-
marily by inserting perforins and degradative enzymes
called granzymes into the infected cell. Perforins form a
Antibody production by B cells usually requires the partici-
channel through the membrane, the cell contents are lost,
pation of helper T cells (T-cell–dependent response), but
antibodies to some antigens (e.g., polymerized [multivalent]
and the cell dies. Granzymes are proteases that degrade
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