arise from these cells by cell division in the secondary lym-
phoid organs will be identical to the parent cells; that is, they
will be B-cell clones.
In contrast to the B cells, other lymphocytes leave the
bone marrow in an immature state during fetal and early neo-
natal life. They are carried to the thymus and mature there
before moving to the secondary lymphoid organs. These cells
Like B cells, T cells also
undergo cell division in secondary lymphoid organs, the prog-
eny being identical to the original T cells and thus part of that
In addition to the B and T cells, there is another distinct
population of lymphocytes,
natural killer (NK) cells.
cells arise in the bone marrow, but their precursors and life
history are still unclear. As we will see, NK cells, unlike B and
T cells, are not speciﬁ c to a given antigen.
Functions of B Cells and T Cells
Upon activation, B cells differentiate into plasma cells, which
proteins that travel all over the body to
reach antigens identical to those that stimulated their produc-
tion. In the body ﬂ uids outside of cells, the antibodies com-
bine with these antigens and guide an attack that eliminates
the antigens or the cells bearing them.
are also called
responses, the adjective humoral denoting communication
“by way of soluble chemical messengers” (in this case, anti-
bodies in the blood). Antibody-mediated responses have an
extremely wide diversity of targets and are the major defense
against bacteria, viruses, and other microbes in the extracel-
lular ﬂ uid, and against toxic molecules (toxins).
T cells constitute a family that has two major func-
tional subsets, called
cytotoxic T cells
helper T cells.
A third subset, called suppressor or regulatory T cells, have
been hypothesized to inhibit the function of both B cells and
cytotoxic T cells.
Another way to categorize T cells is not by function but
rather by the presence of certain proteins, called CD4 and
CD8, in their plasma membranes. Cytotoxic T cells have CD8
and so are also commonly called CD8+ cells; helper T cells
express CD4 and so are also commonly called CD4+ cells.
Cytotoxic T cells are “attack” cells. Following activa-
tion, they travel to the location of their target, bind to them
via antigen on these targets, and directly kill their targets via
secreted chemicals. Responses mediated by cytotoxic T cells
are directed against the body’s own cells that have become
cancerous or infected with viruses (or certain bacteria and
parasites that, like viruses, take up residence inside host cells).
It is worth emphasizing the important geographical dif-
ference in antibody-mediated responses and responses medi-
ated by cytotoxic T cells. The B cells (and plasma cells derived
from them) remain in whatever location the recognition and
activation steps occurred. The plasma cells send their antibod-
ies forth, via the blood, to seek out antigens identical to those
that triggered the response. Cytotoxic T cells must enter the
blood and seek out the targets.
We have now assigned roles to the B cells and cytotoxic
T cells. What role is performed by the helper T cells? As their
name implies, these cells do not themselves function as attack
cells but rather assist in the activation and function of both B
cells and cytotoxic T cells. Helper T cells go through the usual
ﬁ rst two stages of the immune response. First, they combine
with antigen and then undergo activation. Once activated,
they secrete cytokines that act on B cells and cytotoxic T cells
that have also bound antigen. This is a very important point.
With only a few exceptions, B cells and cytotoxic T cells can-
not function adequately unless they are stimulated by cyto-
kines from helper T cells.
Helper T cells will be considered as though they were
a homogeneous cell population, but in fact, there are differ-
ent subtypes of helper T cells, distinguished by the different
cytokines they secrete when activated. By means of these dif-
ferent cytokines, they help different sets of lymphocytes, mac-
rophages, and NK cells. Some of the cytokines secreted by
helper T cells also act as inﬂ
summarizes the basic interactions among
B, cytotoxic T, and helper T cells.
To repeat, the ability of lymphocytes to distinguish one antigen
from another is determined by the lymphocytes’ receptors.
Recall that once B cells are activated by antigen and helper
T-cell cytokines, they proliferate and differentiate into plasma
cells, which secrete antibodies. The plasma cells derived from a
particular B cell can secrete only one particular antibody. Each
B cell always displays on its plasma membrane copies of the
particular antibody its plasma cell progeny can produce. This
surface protein (glycoprotein, to be more accurate) acts as the
receptor for the antigen speciﬁ c to it.
B-cell receptors and plasma cell antibodies constitute the
family of proteins known as
themselves, even though they are identical to the antibodies
to be secreted by the plasma cell derived from the activated
B cell, are technically not antibodies because only
immunoglobulins are called antibodies. Each immunoglob-
ulin molecule is composed of four interlinked polypeptide
). The two long chains are called heavy
chains, and the two short ones, light chains. There are ﬁ ve
major classes of immunoglobulins, determined by the amino
acid sequences in the heavy chains and a portion of the light
chains. The classes are designated by the letters A, D, E, G,
and M following the symbol Ig for immunoglobulin; thus
IgA, IgD, and so on.
As illustrated in Figure 18–10, immunoglobulins have
a “stem” called the
portion and comprising the lower
half of the two heavy chains. The upper part of each heavy
chain and its associated light chain form an
—the amino acid sequences that bind antigen. The amino
acid sequences of the Fc portion are identical for all immu-
noglobulins of a single class (IgA, IgD, and so on). In con-
trast to the identical (or “constant”) regions of the heavy and
light chains, the amino acid sequences of the antigen bind-
ing sites vary from immunoglobulin to immunoglobulin in a
given class, and are thus known as variable ends. Each of the