C h a p t e r 1 5
Innate and Adaptive Immunity
339
which activates macrophages and stimulates B cells to
produce IgG antibodies that activate complement and
coat pathogens for phagocytosis. T
H
2 cells produce
IL-4, which stimulates B cells to differentiate into IgE-
secreting plasma cells; IL-5, which activates eosinophils;
and IL-13, which activates mucosal epithelial cells to
secrete mucus and expel microbes. Differentiated CD4
+
T cells of the T
H
1 subset recognize microbial peptides on
macrophages and have the dual function of stimulating
the production of IgG antibodies and eliminating cells
infected with certain pathogenic intracellular microbes
such as mycobacteria; whereas those of the T
H
2 subset
tend to recognize protein antigens or chemicals that
stimulate the production of IgE and development of
allergies. Activated T
H
17 produces the cytokine IL-17,
which promotes inflammation, and plays a role in the
adaptive immune response and in some T cell–mediated
inflammatory disorders.
In most immune responses, a balanced response of
T
H
1 and T
H
2 cells occurs, but immunization or exposure
to antigen can skew the response to one or the other sub-
set. For example, the extensive exposure to an allergen
in atopic individuals has been shown to shift the naive
CD4
+
T cell toward a T
H
2 response, with the production
of the cytokines that influence IgE production and mast
cell priming. An appreciation of these processes has led
to clinical research that suggests that redirection of an
allergic T
H
2 response to a nonallergic T
H
1 response can
occur in atopic individuals through modified immuniza-
tion protocols.
CytotoxicT Cells
Activated CD8
+
lymphocytes become cytotoxic T cells
after recognition of class I MHC–antigen complexes on
target cell surfaces, such as body cells infected by viruses
or transformed by cancer (Fig. 15-13). The recognition
of class I MHC–antigen complexes on infected target
cells ensures that neighboring uninfected host cells,
which express class I MHC molecules alone or with
self-peptide, are not indiscriminately destroyed. The
CD8
+
cytotoxic T cells perform their killing function
by injecting preformed cytotoxic proteins into target
cells, thereby triggering apoptosis or programmed cell
death (see Chapter 2). Cytotoxic T cells also produce
and release cytokines, such as IFN-
γ
, which inhibits
viral replication and is an important inducer of MHC
class 1 molecule expression and macrophage activation.
The CD8
+
cytotoxic T cells are especially important in
controlling replicating viruses and intracellular bacteria
because antibodies cannot readily penetrate the mem-
brane of living cells.
RegulatoryT Cells
A recently defined type of T lymphocyte is the
regula-
tory T cell,
which has CD4 and CD25 expressed on
its cell membrane. Regulatory T cells, in contrast to
CD4
+
helper T cells, suppress immune responses by
inhibiting the proliferation of other potentially harm-
ful self-reactive lymphocytes. The actions of regulatory
T cells are antigen specific. Activation of a regulatory
T-cell receptor by the antigen prompts the secretion of
the cytokine IL-10 and transforming growth factor-
β
(TGF-
β
). These cytokines inhibit the proliferation and
activation of lymphocytes and macrophages. There is
also recent evidence that regulatory CD8
+
T cells can
selectively down-regulate T cells that are activated by
either self or foreign antigens. These cells are thought
to differentiate into effector cells during the primary
immune response and function as suppressor cells dur-
ing the secondary or memory phases of immunity, and
are primarily involved in self–nonself discrimination.
The potential clinical importance of regulatory T cells
is suggested from animal studies showing inhibition
of inflammatory bowel disease, experimental allergic
encephalitis, and autoimmune diabetes by increased
activity of regulatory T cells.
Cell-Mediated Immunity
Cell-mediated immunity functions against microbes,
including bacteria, parasites, and all viruses that rep-
licate inside cells where they cannot be destroyed by
antibodies. Both CD8
+
and CD4
+
cells contribute to the
response, with each having different effector mecha-
nisms for the eradication of the infection.
The effector functions of CD8
+
cytotoxic T cells,
which act against cells infected with viruses, are the most
direct. Antigens derived from the virus multiply inside
IL-2
receptor
Antigen
TCR
CD8
MHC-I
CD4
TCR (already triggered)
Activated
helper
T cell
Cytotoxic
T cell
Target
cell
(cell death)
Cytokines
Perforins
Toxic cytokines
IL-2
FIGURE 15-13.
Destruction of target cell by cytotoxicT cell.
Cytokines released from the activated helperT cell enhance the
potential of the cytotoxicT cell in destruction of the target cell.
IL, interleukin; MHC, major histocompatibility class;TCR,T-cell
receptor.
