Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

OVERVIEW OF THE ADAPTIVE IMMUNE SYSTEM
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lymphoid follicle
(mainly B cells)
paracortex
(mainly T cells)
germinal center
vein
afferent lymphatic vessels
artery
medulla
efferent
lymphatic vessel
3 mm
postcapillary
venule
marginal sinus
medullary sinus
Figure 24–20 A simplified drawing of a
human lymph node. B cells are primarily
clustered in structures called lymphoid
follicles, whereas T cells are found mainly
in the paracortex. Chemokines attract both
types of lymphocytes into the lymph node
from the blood via postcapillary venules
(see Figure 24–19). B and T cells then
migrate to their respective areas, attracted
by different chemokines. If they do not
encounter their specific antigen, both B
cells and T cells then enter the medullary
sinuses and leave the node via the efferent
lymphatic vessel. This vessel ultimately
empties into the bloodstream, allowing
the lymphocytes to begin another cycle of
circulation through a peripheral lymphoid
organ (see Figure 24–18). During an
infection, proliferation of pathogen-specific
B cells produces a germinal center in some
lymphoid follicles.
Unless they encounter their antigen, both B and T cells soon leave the lymph
node via efferent lymphatic vessels. If they encounter their antigen, however, they
are stimulated to display adhesion receptors that trap the cells in the node; the
cells accumulate at the junction between the B cell and T cell areas, where the
rare antigen-specific B and MBoC6 T cells m25.16/24.21
can interact, leading to their proliferation and
differentiation into either effector cells or memory cells. Many of the effector cells
leave the node, expressing different chemokine receptors that help guide them to
their new destinations—effector plasma B cells to the bone marrow and effector
T cells to sites of infection.
Immunological Self-Tolerance Ensures That B and T Cells Do Not
Attack Normal Host Cells and Molecules
As discussed earlier, cells of the innate immune system use PRRs to distinguish
microbial molecules from self molecules made by the host. The adaptive immune
system has the far more difficult recognition task of responding specifically to an
almost unlimited number of foreign molecules while not responding to the large
number of self molecules. How does it accomplish this feat? It helps that self molecules
normally do not induce the innate immune reactions required to activate
adaptive immune responses. But even when an infection or tissue injury triggers
innate reactions, the vast majority of self molecules normally still fail to induce an
adaptive immune response. Why?
One important reason is that the adaptive immune system “learns” not to
respond to self molecules. Normal mice, for example, cannot mount an immune
response against one of their own protein components of the complement system
called C5 (see Figure 24–7). However, mutant mice that lack the gene encoding C5
but are otherwise genetically identical to normal mice of the same strain can make
a strong immune response to this blood protein when immunized with it. The
immunological self-tolerance exhibited by normal mice persists only for as long
as the self molecule remains in the body: if a self molecule such as C5 is experimentally
removed from an adult mouse, the animal gains the ability to respond
to it after a few weeks or months, as new B and T cells develop in the absence of
C5. Thus, the adaptive immune system is genetically capable of responding to self
molecules, but it learns not to do so.
Self-tolerance depends on a number of distinct mechanisms, including the
following (Figure 24–21):
1. In receptor editing, developing B cells that recognize self molecules change
their antigen receptors so that the cells no longer do so.
2. In clonal deletion, potentially self-reactive B and T cells die by apoptosis
when they encounter their particular self molecule.