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UNIT 4
Maintenance of the Body
21
maturation process in the thymus. B cells become immuno-
competent and self-tolerant in the bone marrow. Te lymphoid
organs where the lymphocytes become immunocompetent—
thymus and bone marrow—are called
primary lymphoid
organs
. All other lymphoid organs are referred to as
secondary
lymphoid organs
.
Te selection process (education) that lymphocytes undergo
is best understood in ± cells, so we will explore it first. ± cell edu-
cation consists of positive and negative selection
(Figure 21.9)
,
both of which occur in the thymus.
1.
Positive selection
is the first of two tests a developing ±
lymphocyte must pass. It ensures that
only
± cells that are
able to recognize self-MHC proteins survive. Remember
that ± cells cannot bind antigens unless the antigens are
presented on self-MHC proteins. ± cells that are unable to
recognize self-MHC are eliminated by apoptosis.
2.
Negative selection
, the second test, ensures that ± cells do
not recognize self-antigens displayed on self-MHC. If they
do, they are eliminated by apoptosis. Negative selection
is the basis for immunologic self-tolerance, making sure
that ± cells don’t attack the body’s own cells, which would
cause autoimmune disorders.
Tis education of ± cells is expensive indeed—only about 2% of
± cells survive it and continue to become successful immuno-
competent, self-tolerant ± cells.
Less is known about the factors that control B cell matura-
tion, but a similar selection process is thought to occur in the
bone marrow. B cells that successfully make antigen receptors
are positively selected and those whose antigen receptors are
self-reactive are eliminated (
clonal deletion
). However, selection
is not perfect for either B or ± cells—some self-reactive lym-
phocytes survive.
Seeding Secondary Lymphoid Organs and Circulation (Fig-
ure 21.8
3
)
Immunocompetent B and ± cells that have not
yet been exposed to antigen are called
naive
. Naive B cells and
± cells are exported from the primary lymphoid organs to seed
(colonize) the secondary lymphoid organs—lymph nodes,
spleen, and so on—where they are likely to encounter antigens.
Lymphocytes, especially the ± cells (which account for 65–85%
of bloodborne lymphocytes), circulate continuously throughout
the body. Circulating greatly increases a lymphocyte’s chance of
coming into contact with antigens located in different parts of the
body, as well as with huge numbers of macrophages and other
lymphocytes. For example, a ± cell circulates through lymph and
blood and back to a lymph node about once a day. Although lym-
phocyte circulation appears to be random, lymphocyte movement
into the tissues is highly specific, regulated by homing signals
(CAMs) displayed on vascular endothelial cells.
Antigen Encounter and Activation (Figure 21.8
4
)
Te first
encounter between an immunocompetent but naive lymphocyte
and an invading antigen usually takes place in a lymph node or
the spleen, but it may happen in any secondary lymphoid organ.
Immune cells in lymph nodes are in a strategic position to en-
counter a large variety of antigens because lymphatic capillaries
pick up proteins and pathogens from nearly all body tissues.
of receptor on their surface. Tese receptors (some 10
5
per
cell) enable the lymphocyte to recognize and bind a specific
antigen. Once these receptors appear, the lymphocyte is com-
mitted to react to one (and only one) distinct antigenic deter-
minant because
all
of its antigen receptors are the same. Te
receptors on B cells are in fact membrane-bound antibodies.
Te receptors on ± cells are not antibodies but are products of
the same gene superfamily and have similar functions.
Self-tolerance.
Each lymphocyte must be relatively unre-
sponsive to self-antigens so that it does not attack the body’s
own cells. Tis is called
self-tolerance
.
B and ± cells acquire immunocompetence and self-tolerance in
different parts of the body. ± cells undergo this two- to three-day
Adaptive defenses
T cells
must
recognize self major histocompatibility proteins (self-MHC)
Antigen-
presenting
thymic cell
Failure to recognize self-
MHC results in
apoptosis
(death by cell suicide).
Recognizing self-MHC
results in survival.
Survivors proceed
to negative selection.
Recognizing self-antigen
results in
apoptosis
. This
eliminates self-reactive
T cells that could cause
autoimmune diseases.
Failure to recognize (bind
tightly to) self-antigen
results in survival and
continued maturation.
Self-MHC
Self-antigen
T cell receptor
Developing
T cell
Cellular immunity
T cells
must not
recognize self-antigens
1. Positive Selection
2. Negative Selection
Figure 21.9
T cell education in the thymus.
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