Page 517 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART VII Immunology
506
by producing IL-17 rather than the typical cytokines pro-
duced by Th-1 cells, namely gamma interferon, and Th-2
protein, is presented to the receptor on the CD4-positive
helper cell. This plus the action of costimulators (see later)
cells, namely IL-4. IL-17 acts to recruit neutrophils to the
site of bacterial infections. Th-17 cells develop from naïve
activates the helper T cell.
Th-0 cells in the presence of IL-6 and TGF-β produced by
Note that APCs (e.g., dendritic cells) are typically under
dendritic cells.
One clinical finding related to Th-17 cells is that they
nodes. How do the two cells get together? After the APC
are selectively killed by human immunodeficiency virus
ingests the microbe, it produces a chemokine receptor
called CCR7. T cells in the lymph node continuously pro-
(HIV). The loss of Th-17 cells results in a high rate of an epithelial surface, whereas T cells are primarily in lymph
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duce the chemokine CCL21, and the dendritic cell migrates
bloodstream infections caused by colonic bacteria, such as
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from the epithelium to the lymph node via the lymphatics
Escherichia coli and Klebsiella. IL-17 also contributes to our
by ascending the gradient of CCL21.
host defenses against certain fungal infections, such as
chronic mucocutaneous candidiasis. The signature cyto-
The activation of cytotoxic T cells can occur when the
kines produced by the subsets of CD4-positive helper T
cells are described in Table 58–5.
synthesized and then presented on the surface in associa-
tion with class I MHC proteins. Activation of cytotoxic T
CD8 lymphocytes perform cytotoxic functions (i.e.,
cells can also occur when the APC ingests pieces of a dying
they kill virus-infected tumor and allograft cells). They kill
by either of two mechanisms, namely, the release of perfo-
virus-infected cell. Viral antigens from the infected cell are
rins, which destroy cell membranes, or the induction of
programmed cell death (apoptosis). CD8 cells predominate
process called cross-presentation.
Similarly, within a virus-infected cell that is not an APC,
in human bone marrow and gut lymphoid tissue and con-
stitute about 35% of peripheral T cells. then presented in association with class I MHC proteins, a
the newly synthesized viral peptide associates with class I
MHC protein and the complex is transported to the sur-
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Activation of T Cells
face, where the viral antigen is presented to the receptor on
a CD8-positive cytotoxic cell. Remember the rule of eight:
The activation of helper T cells requires that their TCR
recognize a complex on the surface of antigen-presenting
interact with class I (8 × 1 = 8).
cells (APCs) (e.g., dendritic cells) consisting of both the
There are many different alleles within the class I and
antigen and a class II MHC protein. The activation of
class II MHC genes; hence, there are many different MHC
cytotoxic T cells requires that their TCR recognize a com-
proteins. These various MHC proteins bind to different
plex on the surface of APCs consisting of both the antigen
peptide fragments. The polymorphism of the MHC genes
and class I MHC protein. Note that this can occur because
and the proteins they encode are a means of presenting
APCs have both class I and class II proteins on their sur-
face. Dendritic cells, macrophages, and B cells are the
class II MHC proteins can only present peptides; other
most important antigen-presenting cells (i.e., have class
types of molecules do not bind and therefore cannot be
II proteins on their surface). many different antigens to the TCR. Note that class I and
presented. Note also that MHC proteins present peptides
The activation of helper T cells begins with the ingestion
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derived from self proteins as well as from foreign proteins;
of the foreign protein (or microbe) into the APC. Within
therefore, whether an immune response occurs is deter-
the cytoplasm of the APC, the foreign protein is cleaved
into small peptides that associate with the class II MHC
that peptide has survived the positive and negative selec-
proteins. The complex is transported to the surface of the
tion processes in the thymus.
Costimulation Is Required to
Activate T Cells
TABLE 58–5 Signature Cytokine Produced by
Subsets of CD4-Positive Helper T Cells
cytotoxic T cells. The first signal in the activation pro-
Subset of
cess is the interaction of the antigen and the MHC pro-
CD4-Positive
Cytokine
Helper T Cells Signature Function of Cytokine Two signals are required to activate both helper and
tein with the TCR specific for that antigen (Figure 58–4
left). Note that when the TCR interacts with the antigen-
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Activates macrophages to kill
Gamma
Th-1 cells
MHC protein complex, the CD4 protein on the surface
interferon
intracellular microbes
of the helper T cell also interacts with the class II MHC
Stimulates development of Th-2
Interleukin-4
Th-2 cells
(IL-4)
cells; enhances class switching
to IgE
with the MHC class II protein, other proteins interact to
help stabilize the contact between the T cell and the APC
Th-17 cells
Interleukin-17
infection
(IL-17)
(e.g., lymphocyte function-associated antigen 1 [LFA-1]
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