Fig. 1.10 Maturation and tissue distribution of lymphocytes. Lymphocytes develop from precursors in
B cells leave the bone marrow and complete their maturation in the spleen (not shown).
CHAPTER 1 Introduction to the Immune System 13
Naive cell Memory lymphocyte Activated or
Relatively low Increases during
Effector functions None Antibody secretion None
changes in migration patterns and types of immunoglobulin produced, are described in later chapters.
14 CHAPTER 1 Introduction to the Immune System
lymphoid organs, where they may stay and produce
antibodies. Small numbers of antibody-secreting cells
where they mature into long-lived plasma cells and
Effector CD4+ T cells (helper T cells) produce
later chapters. Effector CD8+ T cells (CTLs) have the
machinery to kill infected host cells. The development
and functions of these effector cells are also discussed
in later chapters. Effector T lymphocytes are short
lived and die as the antigen is eliminated.
• Memory cells, also generated from the progeny of
antigen-stimulated lymphocytes, can survive for long
an adult (Fig. 1.12). As individuals age, the gradual
accumulation of memory cells compensates for the
reduced output of new, naive T cells from the thymus,
When memory cells encounter the same antigen that
induced their development, the cells rapidly respond
to initiate secondary immune responses. The signals
that generate and maintain memory cells are not well
understood but include cytokines.
The common portals of entry for microbes—the skin
and gastrointestinal, respiratory, and genitourinary
This function of antigen capture and presentation is
system. Dendritic cells capture protein antigens of
microbes that cross epithelial barriers and transport
these antigens to regional lymph nodes, where they
display fragments of the proteins for recognition by T
lymphoid organs may be captured by dendritic cells or
macrophages that reside in these organs and presented
to lymphocytes. The process of antigen presentation to
T cells is described in Chapter 3.
Dendritic cells have another important feature that
gives them the ability to stimulate T cell responses. These
together with antigen, to activate naive T lymphocytes to
proliferate and differentiate into effector cells. Dendritic
cells express higher levels of these costimulatory proteins
than do other cell types and are thus the most potent
B lymphocytes may directly recognize the antigens of microbes (either released or on the surface of
the microbes), and macrophages and dendritic cells in
peripheral lymphoid organs may also capture antigens
and display them to B cells. A distinct type of cell called
Fig. 1.12 Change in proportions of naive and memory
T cells with age. The proportions of naive and memory T
cells are based on data from multiple healthy individuals. The
estimate of thymic output is an approximation. (Courtesy Dr.
Donna L. Farber, Columbia University College of Physicians and
CHAPTER 1 Introduction to the Immune System 15
differentiation of B cells in the follicles (see Chapter 7).
FDCs do not present antigens to T cells and differ from
the dendritic cells described earlier that function as
antigens, and the peripheral lymphoid organs, in
which adaptive immune responses to microbes are
initiated (see Fig. 1.10). Most of the lymphocytes in
a healthy human are found in lymphoid organs and
other tissues (Fig. 1.13). However, as we discuss later,
lymphocytes are unique among the cells of the body
because of their ability to recirculate, repeatedly going
through the blood to visit every secondary lymphoid
organ in the body. The generative (also called primary
or central) lymphoid organs are described in Chapter
features of peripheral (or secondary) lymphoid organs
that are important for the development of adaptive
Peripheral (Secondary) Lymphoid Organs and
The peripheral lymphoid organs and tissues, which
consist of the lymph nodes, the spleen, and the mucosal and cutaneous immune systems, are organized
in a way that promotes the development of adaptive
immune responses. T and B lymphocytes must locate
microbes that enter at any site in the body, then respond to
concentrate antigens in these organs and lymphocytes to
locate and respond to the antigens. This organization is
complemented by a remarkable ability of lymphocytes to
circulate throughout the body in such a way that naive
lymphocytes preferentially go to the peripheral lymphoid
organs and tissues, in which antigen is concentrated,
whereas most effector cells go to sites of infection where
microbes must be eliminated. Furthermore, different
peripheral lymphoid organs, helper T cells specific for an
antigen interact with and help B lymphocytes specific for
the same antigen, resulting in antibody production. An
important function of lymphoid organs is to bring these
rare cells together after stimulation by antigen so they
The major peripheral lymphoid organs share many
characteristics but also have some unique features.
• Lymph nodes are encapsulated nodular aggregates
of lymphoid tissues located along lymphatic channels
throughout the body (Fig. 1.14). Fluid constantly
leaks out of small blood vessels in all epithelia and
connective tissues and most parenchymal organs.
lymph contains a mixture of substances absorbed
from epithelia and tissues. As the lymph passes
through lymph nodes, APCs in the nodes are able
to sample the antigens of microbes that may enter
through epithelia into tissues. In addition, dendritic
cells pick up antigens of microbes from epithelia
and other tissues and transport these antigens to
the lymph nodes. The net result of these processes
of antigen capture and transport is that the antigens
of microbes entering through epithelia or colonizing tissues become concentrated in draining lymph
Fig. 1.13 Distribution of lymphocytes in lymphoid organs
and other tissues. Approximate numbers of lymphocytes in
different organs of healthy adults are shown.
16 CHAPTER 1 Introduction to the Immune System
• The spleen is a highly vascularized abdominal organ
that serves the same role in immune responses to
blood-borne antigens as that of lymph nodes in
responses to lymph-borne antigens (Fig. 1.15).
Blood entering the spleen flows through a network
of channels (sinusoids). Blood-borne antigens are
captured and concentrated by dendritic cells and
macrophages in the spleen. The spleen contains
abundant phagocytes that line the sinusoids, which
ingest and destroy microbes in the blood. These
macrophages also ingest and destroy old red blood
B, Light micrograph shows a cross section of a lymph node
with numerous follicles in the cortex, some of which contain
lightly stained central areas (germinal centers).
Fig. 1.15 Morphology of the spleen. A, Schematic diagram
shows a splenic arteriole surrounded by the periarteriolar
lymphoid sheath (PALS) and attached follicles. The PALS
and lymphoid follicles together constitute the white pulp.
The marginal zone with its sinus is the indistinct boundary
PALS and a follicle with a prominent germinal center. These
are surrounded by the red pulp, which is rich in vascular
CHAPTER 1 Introduction to the Immune System 17
• The cutaneous immune system and mucosal
immune system are specialized collections of lymphoid tissues and APCs located in and under the
epithelia of the skin and the gastrointestinal and
respiratory tracts, respectively. Although most
of the immune cells in these tissues are diffusely
scattered beneath the epithelial barriers, there
are discrete collections of lymphocytes and APCs
organized in a similar way as in lymph nodes. For
example, tonsils in the pharynx and Peyer patches
in the intestine are two anatomically defined
mucosal lymphoid tissues (Fig. 1.16). The immune
system of the skin consists of most of the cells of
innate and adaptive immunity, but without any
anatomically defined structures (Fig. 1.17). At any
time, at least a quarter of the body’s lymphocytes
are in the mucosal tissues and skin (reflecting the
large size of these tissues) (see Fig. 1.13), and many
T cell Plasma cell Macrophage B cell
Fig. 1.16 Mucosal immune system. Schematic diagram of the mucosal immune system uses the small
in the lamina propria, including dendritic cells, T lymphocytes, and macrophages, provide innate and
18 CHAPTER 1 Introduction to the Immune System
of these are memory cells. Cutaneous and mucosal
lymphoid tissues are sites of immune responses to
but do not react to the enormous numbers of usually harmless commensal microbes present at the
epithelial barriers. This is accomplished by several
mechanisms, including the action of regulatory T
cells and other cells that suppress rather than activate T lymphocytes.
cortex, of each node. If the B cells in a follicle have
recently responded to a protein antigen and received
signals from helper T cells, this follicle may contain
a central lightly staining region called a germinal
center. The germinal center has an important role in
the production of highly effective antibodies and is
paracortex. The follicles contain the FDCs described
earlier that are involved in the activation of B cells,
sheaths surrounding small arterioles, and B cells reside
The anatomic organization of peripheral lymphoid
organs is tightly regulated to allow immune responses
to develop after stimulation by antigens. B lymphocytes
are attracted to and retained in the follicles because of
the action of a class of cytokines called chemokines
(chemoattractant cytokines; chemokines and other
cytokines are discussed in more detail in later chapters).
FDCs in the follicles secrete a particular chemokine for
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