Defense Mechanisms of the Body
eign molecule that can trigger a speciﬁ c immune response
against itself or the cell bearing it is called an
immunologists prefer the more technically correct term
) Most antigens are either proteins or very large
polysaccharides. The term
is a functional term; that is,
any molecule, regardless of its location or function, that can
induce a speciﬁ
c immune response against itself is by deﬁ ni-
tion an antigen. Thus, it is any molecule or cell that the host
does not recognize as self. Antigens include the protein coats
of viruses, speciﬁ c proteins on foreign cells, cancer cells, or
transplanted cells, and toxins. It is the ability of lymphocytes
to distinguish one antigen from another that confers speciﬁ c-
ity upon the immune responses in which they participate.
A typical speciﬁ c immune response can be divided into
three stages: (1) the encounter and recognition of an antigen
by lymphocytes, (2) lymphocyte activation, and (3) the attack
launched by the activated lymphocytes and their secretions.
During its development, each lymphocyte
synthesizes and inserts into its plasma membrane
a single type of receptor that can bind to a speciﬁ c
antigen. If, at a later time, the lymphocyte ever
encounters that antigen, the antigen becomes
bound to the receptors. This binding is the
physicochemical meaning of the word
in immunology. As a result, the ability of
lymphocytes to distinguish one antigen from
another is determined by the nature of their plasma
Each lymphocyte is speciﬁ
just one type of antigen.
The progeny of this speciﬁ c
antigen-stimulated lymphocyte are called
is estimated that in a typical person the lymphocyte
population expresses more than 100 million
distinct antigen receptors, each with the potential
to form a different clone.
The binding of antigen to receptor must occur
Upon binding to an
antigen, the lymphocyte undergoes a cell division,
and the two resulting daughter cells then also
divide (even though only one of them still has
the antigen attached to it) and so on. In other
words, the original binding of antigen by a single
lymphocyte speciﬁ c for that antigen triggers
multiple cycles of cell divisions. As a result, many
lymphocytes form that are identical to the one that
started the cycles and can recognize the antigen;
this is called
some lymphocytes will function as effector
lymphocytes to carry out the attack response.
Others will be set aside as
recognize the antigen if it returns in the future.
The activated effector lymphocytes launch an attack
against all antigens of the kind that initiated the
immune response. Theoretically, it takes only one
or two antigen molecules to
the speciﬁ c
immune response that will then result in an attack
on all of the other antigens of that speciﬁ c kind in
the body. One group of lymphocytes, activated B
cells, differentiate into plasma cells, which secrete
antibodies into the blood. These antibodies
then recruit and guide other molecules and cells
to perform the actual attack. Another type of
lymphocyte, activated cytotoxic T cells, directly
attack and kill the cells bearing the antigens. Once
the attack is successfully completed, the great
majority of the B cells, plasma cells, helper T cells,
and cytotoxic T cells that participated in it die by
apoptosis. The timely death of these effector cells is
a homeostatic response that prevents the immune
defense from becoming excessive and possibly
destroying its own tissues. However, memory cells
persist even after the immune response has been
Lymphoid Organs and Lymphocyte Origins
Our ﬁ rst task is to describe the organs and tissues in which
lymphocytes originate and come to reside. Then the various
types of lymphocytes alluded to in the overview and summa-
rized in Table 18–1 will be described.
Like all leukocytes, lymphocytes circulate in the blood. At any
moment, the great majority of lymphocytes are not actually in
the blood, however, but in a group of organs and tissues col-
lectively called the
These are subdivided
into primary and secondary lymphoid organs.
primary lymphoid organs
are the bone marrow and
thymus. These organs supply the secondary lymphoid organs
with mature lymphocytes—that is, lymphocytes already pro-
grammed to perform their functions when activated by antigen.
The bone marrow and thymus are not normally sites in which
lymphocytes undergo activation during an immune response.
secondary lymphoid organs
include the lymph
nodes, spleen, tonsils, and lymphocyte accumulations in the
linings of the intestinal, respiratory, genital, and urinary tracts.
It is in the secondary lymphoid organs that lymphocytes are
activated to participate in speciﬁ c immune responses.
We have stated that the bone marrow and thymus supply
mature lymphocytes to the secondary lymphoid organs. Most
of the lymphocytes in the secondary organs are not, however,
the same cells that originated in the primary lymphoid organs.
The explanation of this seeming paradox is that, once in the
secondary organ, a mature lymphocyte coming from the bone
marrow or thymus can undergo cell division to produce addi-
tional identical lymphocytes, which in turn undergo cell divi-
sion and so on. In other words, all lymphocytes are
from ancestors that matured in the bone marrow or thymus
but may not themselves have arisen in those organs. Recall
that all the progeny cells derived by cell division from a single
lymphocyte constitute a lymphocyte clone.
A distinction must be made between the lymphoid
organs and the lymphatic system, described in Chapter 12.
The latter is a network of lymphatic vessels and the lymph
nodes found along these vessels. Of all the lymphoid organs,
only the lymph nodes also belong to the lymphatic system.