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
1311
antibodies in blood
(arbitrary units, Iog scale)
100
10
1
primary response
to antigen A
0 10 20 30 40 50 60
time (days)
first immunization
with antigen A
secondary
response to
antigen A
primary response
to antigen B
second immunization with antigen A
first immunization with antigen B
Figure 24–16 Immunological memory:
primary and secondary antibody
responses. The secondary response
induced by a second exposure to antigen
A is faster and greater than the primary
response and is specific for A, indicating
that the adaptive immune system has
specifically remembered its previous
encounter with antigen A. The same type
of immunological memory is observed in
T‐cell-mediated responses (not shown). As
we discuss later, the types of antibodies
produced in the secondary response
are different from those produced in the
primary response, and these antibodies
bind the antigen more tightly.
Thus, during the primary response, clonal expansion and differentiation of
antigen-stimulated naïve cells creates many memory cells, which are able to
respond to the same antigen more sensitively, rapidly, and effectively. And, unlike
most effector cells, which die within days or weeks, memory cells can persist for
the lifetime of the animal, even in the absence of their specific antigen, thereby
providing lifelong immunological memory. Although most effector B and T cells
MBoC6 m25.10/24.17
die after an immune response is over, some survive as effector cells and help provide
long-term protection against the pathogen. A small proportion of the plasma
cells produced in a primary B cell response, for example, can survive for many
months or years in the bone marrow, where they continue to secrete their specific
antibodies into the bloodstream.
Lymphocytes Continuously Recirculate Through Peripheral
Lymphoid Organs
Pathogens generally enter the body through an epithelial surface, usually through
the skin, gut, or respiratory tract. To induce an adaptive immune response,
microbes or their products must travel from these entry points to a peripheral
lymphoid organ, such as a lymph node or the spleen, which are the sites where
lymphocytes are activated (see Figure 24–11). The route and destination depend
on the site of entry. Lymphatic vessels carry antigens that enter through the skin
or respiratory tract to local lymph nodes; antigens that enter through the gut end
up in gut-associated peripheral lymphoid organs such as Peyer’s patches; and the
spleen filters out antigens that enter the blood (see Figure 24–12). As discussed
earlier (see Figure 24–11), in many cases, activated dendritic cells will carry the
antigen from the site of infection to the peripheral lymphoid organ, where they
play a crucial part in activating T cells, as we discuss later.
But only a tiny fraction of naïve B and T cells can recognize a particular microbial
antigen in a peripheral lymphoid organ, a reasonable estimate being between
1/10,000 and 1/1,000,000 of each class of lymphocyte, depending on the antigen.
How do these rare cells find an antigen-presenting cell displaying their specific
antigen? The answer is that the lymphocytes continuously recirculate between
one peripheral lymphoid organ and another via the lymph and blood. In a lymph
node, for example, lymphocytes continually leave the bloodstream by squeezing
out between specialized endothelial cells lining small veins called postcapillary
Figure 24–17 A model for the cellular basis of immunological memory.
When stimulated by their specific antigen and co-stimulatory signals, naïve
lymphocytes proliferate and differentiate. Most become effector cells, which
function and then usually die, while others become memory cells. During a
subsequent exposure to the same antigen, the memory cells respond more
readily, rapidly, and efficiently than did the naïve cells: they proliferate and give
rise to effector cells and to more memory cells. Some memory T cells also
develop from a minority of effector T cells (not shown). It is not known how
the decision to become an effector cell versus a memory cell is made.
first exposure to antigen
memory cells
second exposure
to antigen
memory cells
naïve cell
effector cells
effector cells