338
U N I T 4
Infection and Immunity
receptors on CD4
+
helper T cells recognize the antigenic
peptide–class II MHC molecules, the T cells become acti-
vated and produce cytokines to further stimulate and
direct the immune system. In humoral immunity, acti-
vated CD4
+
helper T cells trigger B cells to proliferate
and differentiate into a clone of plasma cells that produce
antibody. This activation process takes 1 to 2 weeks, but
once generated, detectable antibody continues to rise for
several weeks. Recovery from many infectious diseases
occurs during the primary response when the antibody
concentration is reaching its peak.
The
secondary
or
memory response
occurs on sec-
ond or subsequent exposures to the antigen. During the
primary response, a fraction of activated B cells does
not differentiate into plasma cells but instead forms a
pool of memory B cells. In a secondary response, the
rise in antibody occurs sooner and reaches a higher level
because of these available memory cells. The booster
immunization given for some diseases, such as tetanus,
makes use of the memory response. For a person who
has been previously immunized, administration of a
booster shot causes an almost immediate rise in anti-
body to a level sufficient to prevent development of the
disease. Activated T cells can also generate primary and
secondary cell-mediated immune responses.
T Lymphocytes and Cell-Mediated
Immunity
T lymphocytes function in the activation of other T cells
and B cells, in the control of intracellular viral infections,
in the rejection of foreign tissue grafts, and in delayed
hypersensitivity reactions (see Chapter 16). Collectively,
these immune responses are referred to as
cell-mediated
or
cellular immunity.
T lymphocytes arise from bone marrow stem cells, but
unlike B cells, pre-T cells migrate to the thymus for their
maturation. There the immature T lymphocytes undergo
rearrangement of the genes needed for expression of a
unique T-cell antigen receptor similar to but distinct from
the B-cell receptor. The T-cell receptor is composed of two
polypeptide chains that form a groove that recognizes the
processed antigen peptide–MHC molecules (Fig. 15-12).
Maturation of subpopulations of T cells (i.e., CD4
+
and
CD8
+
) also occurs in the thymus. Mature T cells migrate
to the peripheral lymphoid tissues and, upon encoun-
tering antigen, multiply and differentiate into memory
T cells and various mature T-cell populations. The two
main populations of mature T cells are CD4
+
(helper) and
CD8
+
(cytotoxic) T cells.
Helper T Cells
The CD4
+
helper T cell serves as a master regulator for
the immune system. Activation of CD4
+
helper T cells
depends on the recognition of antigen in association
with class II MHC molecules. Once activated, the helper
T cells secrete cytokines that influence the function of
nearly all other cells of the immune system. Differences
in the types of cytokines made by the CD4
+
helper T cell
produce different types of immune responses. These
cytokines activate and regulate B cells, cytotoxic T cells,
NK cells, macrophages, and other immune cells.
The activated CD4
+
helper T cell can differenti-
ate into distinct subpopulations of helper T cells (e.g.,
T
H
1, T
H
2, and T
H
17) based on the cytokines secreted
by the antigen-presenting cell at the site of activation.
The cytokine IL-12 produced by macrophages and den-
dritic cells directs the maturation of CD4
+
helper T cells
toward T
H
1 cells. The cytokine IL-4 produced by mast
cells and T cells induces differentiation toward T
H
2 cells.
The cytokines IL-6 and transforming growth factor-beta
(TGF-
β
), notably in the absence of either IL-4 or IL-12,
will induce differentiation toward T
H
17 cells.
The distinct pattern of cytokines secreted by mature
T
H
1 and T
H
2 cells defines these subpopulations of
T cells and determines their functions. Activated T
H
1
cells stimulate phagocyte-mediated ingestion and kill-
ing of microbes. T
H
1 cells produce the cytokine IFN-
γ
,
8
10
12
6
4
2
Weeks
Antigen
Antigen
Primary
response
Secondary
response
Activated
B cell
Activated
B cell
Memory
B cell
Naive
B cell
FIGURE 15-11.
Primary and secondary or memory phases of
the humoral immune response to the same antigen.
Peptide
MHC molecule
CD4
TCR
CD4
+
T cell
Antigen-presenting cell
FIGURE 15-12.
TheT-cell receptor (TCR) on a CD4
+
T cell and
the interaction of the major histocompatibility complex (MHC)
on the antigen-presenting cell. Note that theTCR recognizes
the peptide fragment of antigen bound to the MHC class II
molecule.The CD4 molecule binds to a portion of the MHC
molecule, stabilizing the interaction.
