The Immune System: Innate and Adaptive Body Defenses
cells that will deal with the antigens. Te major types of cells act-
ing as APCs are
are found at the body’s frontiers (skin, for ex-
ample) where they act as mobile sentinels. With their long,
wispy extensions, dendritic cells are very eﬃcient antigen catch-
. Once they have internalized antigens by
phagocytosis, they enter nearby lymphatics to get to a lymph
node where they will present the antigens to ± cells.
Migration of dendritic cells to secondary lymphoid organs
is now recognized as the most important way of ensuring that
lymphocytes encounter invading antigens. Indeed, dendritic
cells are the most eﬀective antigen presenter known—it’s their
only job. Tis early alert spares the body a good deal of tissue
damage that might otherwise occur.
Dendritic cells are one of the key links between innate and
adaptive immunity. Tey initiate adaptive immune responses
tailored to the type of pathogen they have encountered.
Macrophages are widely distributed throughout the lymphoid
organs and connective tissues. Although macrophages, like den-
dritic cells, can activate naive ± cells, macrophages oFen present
antigens to ± cells for another reason—to be activated them-
selves. Certain eﬀector ± cells release chemicals that prod mac-
rophages to become
, true “killers” that
are insatiable phagocytes and secrete bactericidal chemicals.
Unlike dendritic cells and macrophages, B cells do not activate
naive ± cells. Instead, they present antigens to a certain kind of
± cell (called a helper ± cell) in order to obtain “help” in their
own activation. We will discuss this more on p. 787.
When an antigen binds to the particular lymphocyte that
has a receptor for it, the antigen selects that lymphocyte for fur-
ther development. Tis is called
. If the proper
signals (which we describe later) are present, the selected lym-
phocyte will activate to complete its diﬀerentiation.
Proliferation and Differentiation (Figure 21.8
tivated, the lymphocyte rapidly proliferates to form an army of
cells all exactly like itself and bearing the same antigen-speciﬁc
receptors. Tis army of identical cells, all descended from the
ancestor cell, is called a
Most members of the clone become
, the cells
that actually do the work of ﬁghting infection. A few members
of the clone become
that are able to respond
quickly aFer any subsequent encounter with the same antigen.
B and ± memory cells and eﬀector ± cells circulate throughout
the body on continuous patrol.
Generation of Antigen Receptor Diversity
We know that lymphocytes become immunocompetent
meeting the antigens they may later attack.
Our genes, not an-
tigens we encounter, determine which speciﬁc foreign substances
our immune system will be able to recognize and resist.
words, the immune cell receptors represent our genetically ac-
quired knowledge of the microbes that are likely to be in our
environment. An antigen simply determines which existing ±
or B cells will proliferate and mount the attack against it.
Only some of the antigens our lymphocytes are programmed
to resist will ever invade our bodies. Consequently, only some
members of our army of immunocompetent cells are mobilized
in our lifetime. Te others are forever idle.
Our lymphocytes make up to a billion diﬀerent types of anti-
gen receptors. Tese receptors, like all other proteins, are speci-
ﬁed by genes, so you might think that an individual must have
billions of genes. Not so; each body cell only contains about
25,000 genes that code for all the proteins the cell must make.
How can a limited number of genes generate a seemingly lim-
itless number of diﬀerent antigen receptors? Molecular genetic
studies have shown that the genes that dictate the structure of
each antigen receptor are not present as such in lymphocyte stem
cells. Instead of a complete set of “antigen receptor genes,” stem
cells contain a few hundred genetic bits and pieces that can be
thought of as a “Lego set” for antigen receptor genes. As each
lymphocyte becomes immunocompetent, these gene segments
are shuﬄed and combined in diﬀerent ways, a process called
. Te information of the newly assembled
genes is then expressed as the surface receptors of B and ± cells
and as the antibodies later released by the B cell’s “oﬀspring.”
Antigen-Presenting Cells (APCs)
Antigen-presenting cells (APCs)
engulf antigens and then
present fragments of them, like signal ﬂags, on their own sur-
faces where ± cells can recognize them. Naive ± cells can only
be activated by antigens that are presented to them on MHC
proteins by APCs. In other words, APCs
Scanning electron micrograph (1050