516 Chapter 15
produced by the primary response have disappeared. Immu-
nizations, therefore, seem to produce a type of “learning” in
which the ability of the immune system to combat a particular
pathogen is improved by prior exposure.
The mechanisms by which secondary responses are pro-
duced are not completely understood; the clonal selection
theory, however, accounts for most of the evidence. Accord-
ing to this theory, B lymphocytes inherit the ability to produce
particular antibodies (and T lymphocytes inherit the ability
to respond to particular antigens). A given B lymphocyte can
produce only one type of antibody, with specificity for one
antigen. Because this ability is genetically inherited rather
than acquired, some lymphocytes can respond to smallpox, for
example, and produce antibodies against it even if the person
has never been previously exposed to this disease.
The inherited specificity of each lymphocyte is reflected
in the antigen receptor proteins on the surface of the lym-
phocyte’s plasma membrane. Exposure to smallpox antigens
thus stimulates these specific lymphocytes to divide many
times until a large population of genetically identical cells—a
clone —is produced. Some of these cells become plasma cells
that secrete antibodies for the primary response; others become
memory cells that can be stimulated to secrete antibodies dur-
ing the secondary response ( fig. 15.21 ). Memory cells live
longer than naive lymphocytes, are activated more easily, and
are more effective once they are activated. The clonal selection
theory is summarized in table 15.8.
Long-lived memory T cells of different subtypes, specific
for the antigen that caused their generation, are the most abun-
dant lymphocytes in an adult. They are located in the circulation
and in different lymphoid organs, and their numbers increase
through childhood to middle age, providing greater protection
from pathogens. Their numbers decline after about age 70, and
people’s susceptibility to infectious diseases increases.
Secondary lymphoid organs, such as the lymph nodes and
spleen, contain germinal centers following exposure to anti-
gens. A germinal center develops from a B cell that has been
stimulated by an antigen and activated by helper T cells. This
B cell then undergoes extremely rapid mitotic cell division to
become the founder of a germinal center that contains a clone
of memory cells and plasma cells, which secrete antibodies for
the secondary immune response. These plasma cells are longer-
lived than those outside of germinal centers, which produce
less effective antibodies for the primary response. The prolif-
erating B cells in the germinal center undergo somatic hyper-
mutation (previously described), which generates a diversity
of new antibodies. This could include antibodies that have a
higher affinity for the stimulating antigen, thereby improving
the immune response.
Active Immunity
The development of a secondary response provides active
immunity against the specific pathogens. The development of
active immunity requires prior exposure to the specific anti-
gens, at which time the sluggishness of the primary response
Figure 15.21 The clonal selection theory as applied
to B lymphocytes. Most members of the B lymphocyte clone
become memory cells, but some become antibody-secreting
plasma cells.B lymphocyteNucleusCytoplasmEndoplasmic
reticulumRibosomesFirst daySecond dayThird dayFourth dayFifth dayPlasma cellMemory cellsDevelopment of clonemay cause the person to develop the disease. For example, chil-
dren who get measles, chicken pox, or mumps will probably be
immune to them as adults, when these diseases are potentially
more serious.
Clinical immunization programs induce primary responses
by inoculating people with pathogens whose virulence has
been attenuated or destroyed (such as Pasteur’s heat-inactivated
anthrax bacteria) or by using closely related strains of