C h a p t e r 1 5
Innate and Adaptive Immunity
333
as well as aiding in antibody production. High concen-
trations of mature T and B lymphocytes are found in the
lymph nodes, spleen, skin, and mucosal tissues, where
they can respond to antigen.
B and T lymphocytes possess all of the key
properties associated with the adaptive immune
response—specificity, diversity, memory, and self–
nonself recognition. These cells can exactly recognize
and target a specific antigen and differentiate it from
other substances that may be similar. The approximately
10
12
lymphocytes in the body have tremendous diver-
sity. They can respond to the millions of different kinds
of antigens encountered daily. This diversity occurs
because an enormous variety of lymphocyte popula-
tions have been programmed and selected during devel-
opment, each to respond to a different antigen. After
responding, they can acquire immunologic memory. The
memory B and T lymphocytes that are generated remain
in the body for a longer time and can respond more
rapidly on repeat exposure than naive cells. Because of
this heightened state of immune reactivity, the immune
system usually can respond to commonly encountered
microorganisms so efficiently that we are unaware of
the response.
Adaptive immune responses are initiated when the
antigen receptors of lymphocytes recognize antigens. The
key trigger for the activation of B and T cells is the recog-
nition of the antigen by unique surface receptors. B-cell
antigen receptors (membrane-bound antibodies) and
the antibodies that B cells secrete are able to recognize a
broad range of structurally different molecules of varied
sizes. This enables antibodies to detect diverse microbes
and toxins. In contrast, the T-cell receptor recognizes
only peptides, and only when these peptides are dis-
played on antigen-presenting cells bound to membrane
proteins encoded by the MHC gene. Thus, T cells are
only able to detect cell-associated microbes and antigens.
Activation of the lymphocytes depends on appropri-
ate processing and presentation of antigen to T lympho-
cytes by antigen-presenting cells such as macrophages
and dendritic cells (Fig. 15-7). On recognition of antigen
and after additional stimulation by cytokines, the B and
T lymphocytes divide several times to form clonal cell
populations that continue to differentiate into effector
and memory cells. After antigen binds to a B-cell recep-
tor, the cell proliferates and differentiates into plasma
cells that secrete antibodies that are a form of the B-cell
receptor and have identical antigen specificity. Thus, the
antigen that activates a given B cell becomes the target
of the antibody produced by the cell’s progeny. After
a T cell is activated by its first encounter with an anti-
gen, it proliferates and differentiates into helper or cyto-
toxic T cells. Helper T cells provide signals that activate
antigen-stimulated B cells to differentiate and produce
antibody. Some helper T cells also activate macrophages
to become more efficient at killing engulfed pathogens.
Cytotoxic T cells kill cells that are infected with viruses
or other intracellular pathogens.
Major Histocompatibility Complex Molecules
Major histocompatibility complex molecules are
membrane-bound proteins encoded by a MHC gene
locus that display peptides for recognition by T lympho-
cytes. Although first identified as antigens that evoke
rejection of transplanted organs, histocompatibility
(i.e., tissue compatibility) molecules are now known to
be extremely important for induction and regulation of
immune responses. Recall that T cells (in contrast to
B cells) can only recognize membrane-bound antigens,
and hence histocompatibility molecules are critical to
the induction of T-cell immunity. In humans, the genes
encoding the most important MHC molecules are clus-
tered on a small segment of chromosome 6.
The MHC molecules involved in self-recognition and
cell-to-cell communication fall into two classes, class
I and class II (Fig. 15-8).
Class I MHC
(MHC-I) mol-
ecules, which are expressed on all nucleated cells and
platelets, are cell surface molecules that interact with the
receptor–antigen peptide complex on CD8
+
cytotoxic
T cells.
Class II MHC
(MHC-II) molecules, which are
expressed mainly on dendritic cells, macrophages, and
B lymphocytes, communicate with the antigen receptor
and the CD4 molecule on helper T cells.
Although the MHC-I and MHC-II proteins differ in
subunit composition, they are similar in overall structure,
and each contains a peptide-binding cleft on the extra-
cellular portion of the molecule. The MHC-I molecule
contains a cleft that accommodates a peptide fragment
of antigen. Cytotoxic T cells can become activated only
Thymus
Bone marrow
or fetal liver
Pluripotent
stem cell
Lymphocyte
stem cell
B cell
Lymphoid tissue (lymph
nodes, spleen, mucosal tissue, blood, and
lymph)
T cell
FIGURE 15-6.
Pathway forT- and B-cell differentiation.
