The Role of the Lymphatic System in Maintaining Immunity Understanding the Complex Interplay between Lymphocytes Lymph Nodes and Immune Responses
The Role of the Lymphatic System in Maintaining Immunity: Understanding the Complex Interplay between Lymphocytes, Lymph Nodes, and Immune Responses
The Lymphatic System, Disease Resistance,
and Homeostasis
The environment in which we live is filled with microbes that have the
ability to cause disease if given the right opportunity. If we did not resist
these microbes, we would be ill constantly or even die. Fortunately, we
have a number of defenses that keep microbes from either entering our
bodies or combat them if they do gain entrance. The lymphatic system
is one of the principal body systems that helps to defend us against
disease-producing microbes. In this chapter you will learn about the
organization and components of the lymphatic system and its role in
keeping us healthy.
Q Did you ever wonder how cancer can spread from one part
of the body to another?
The Concept of Immunity
OBJECTIVES
• Define immunity.
• Compare the two basic types of immunity.
Maintaining homeostasis in the body requires continual combat against
harmful agents in our internal and external environments. Despite constant
exposure to a variety of pathogens (PATH-ō-jens)—disease-producing
microbes such as bacteria and viruses—most people remain healthy.
The body surface also endures cuts and bumps, exposure to ultraviolet
rays, chemical toxins, and minor burns with an array of defensive ploys.
Immunity (i-MŪ-ni-tē) or resistance is the ability to ward off dam-
age or disease through our defenses. Vulnerability or lack of resis-
tance is termed susceptibility. The two general types of immunity are
(1) innate and (2) adaptive. Innate (nonspecific) immunity refers to
defenses that are present at birth. Innate immunity does not involve
specific recognition of a microbe and acts against all microbes in the
same way. Among the components of innate immunity are the first
line of defense (the physical and chemical barriers of the skin and
mucous membranes) and the second line of defense (antimicrobial
substances, natural killer cells, phagocytes, inflammation, and fever).
Innate immune responses represent immunity’s early warning system
and are designed to prevent microbes from entering the body and to
help eliminate those that do gain access.
Adaptive (specific) immunity refers to defenses that involve spe-
cific recognition of a microbe once it has breached the innate immu-
nity defenses. Adaptive immunity is based on a specific response to a
specific microbe; that is, it adapts or adjusts to handle a specific mi-
crobe. Adaptive immunity involves lymphocytes (a type of white
blood cell) called T lymphocytes (T cells) and B lymphocytes (B cells).
The body system responsible for adaptive immunity (and some
aspects of innate immunity) is the lymphatic system. This system
is closely allied with the cardiovascular system, and it also func –
tions with the digestive system in the absorption of fatty foods. In this
chapter, we explore the mechanisms that provide defenses against
intruders and promote the repair of damaged body tissues.
Overview of the Lymphatic
System
OBJECTIVES
• List the components of the lymphatic system.
• Describe the functions of the lymphatic system.
Components of the Lymphatic System
The lymphatic or lymphoid system (lim-FAT-ik) consists of a fluid
called lymph, vessels called lymphatic vessels that transport the
lymph, a number of structures and organs containing lymphatic tis-
sue (lymphocytes within a filtering tissue), and red bone marrow (Fig-
ure 22.1). The lymphatic system assists in circulating body fluids and
helps defend the body against disease-causing agents. As you will see
shortly, most components of blood plasma filter through blood capil-
lary walls to form interstitial fluid. Aft er interstitial fluid passes into
lymphatic vessels, it is called lymph (LIMF = clear fluid). The major
diff erence between interstitial fluid and lymph is location: Interstitial
fluid is found between cells, and lymph is located within lymphatic
vessels and lymphatic tissue.
Lymphatic tissue is a specialized form of reticular connective tis-
sue (see Table 4.4) that contains large numbers of lymphocytes. Re-
call from Chapter 19 that lymphocytes are agranular white blood cells
(see Section 19.4). Two types of lymphocytes participate in adaptive
immune responses: B cells and T cells (described shortly).
Functions of the Lymphatic System
The lymphatic system has three primary functions:
1. Drains excess interstitial fluid. Lymphatic vessels drain excess in-
terstitial fluid from tissue spaces and return it to the blood. This
function closely links it with the cardiovascular system. In fact,
without this function, the maintenance of circulating blood volume
would not be possible.
2. Transports dietary lipids. Lymphatic vessels transport lipids and
lipid-soluble vitamins (A, D, E, and K) absorbed by the gastrointes-
tinal tract.
3. Carries out immune responses. Lymphatic tissue initiates highly
specific responses directed against particular microbes or abnor-
mal cells.
Lymphatic Vessels and
Lymph Circulation
OBJECTIVES
• Describe the organization of lymphatic vessels.
• Explain the formation and flow of lymph.
Lymphatic vessels begin as lymphatic capillaries. These capillaries,
which are located in the spaces between cells, are closed at one end
(Figure 22.2). Just as blood capillaries converge to form venules and
Q Is lymph more similar to blood plasma or to interstitial
fluid? Why?
then veins, lymphatic capillaries unite to form larger lymphatic
vessels (see Figure 22.1), which resemble small veins in structure but
have thinner walls and more valves. At intervals along the lymphatic
vessels, lymph flows through lymph nodes, encapsulated bean-
shaped organs consisting of masses of B cells and T cells. In the skin,
lymphatic vessels lie in the subcutaneous tissue and generally follow
the same route as veins; lymphatic vessels of the viscera generally fol-
low arteries, forming plexuses (networks) around them. Tissues that
lack lymphatic capillaries include avascular tissues (such as cartilage,
the epidermis, and the cornea of the eye), portions of the spleen, and
red bone marrow.
Lymphatic Capillaries
Lymphatic capillaries have greater permeability than blood capillar-
ies and thus can absorb large molecules such as proteins and lipids.
Lymphatic capillaries are also slightly larger in diameter than blood
capillaries and have a unique one-way structure that permits intersti-
tial fluid to flow into them but not out. The ends of endothelial cells
that make up the wall of a lymphatic capillary overlap (Figure 22.2b).
When pressure is greater in the interstitial fluid than in lymph, the
cells separate slightly, like the opening of a one-way swinging door,
and interstitial fluid enters the lymphatic capillary. When pressure is
greater inside the lymphatic capillary, the cells adhere more closely,
and lymph cannot escape back into interstitial fluid. The pressure is
relieved as lymph moves further down the lymphatic capillary.
Attached to the lymphatic capillaries are anchoring filaments, which
contain elastic fibers. They extend out from the lymphatic capillary,
attaching lymphatic endothelial cells to surrounding tissues. When
excess interstitial fluid accumulates and causes tissue swelling, the
anchoring filaments are pulled, making the openings between cells
even larger so that more fluid can flow into the lymphatic capillary.
In the small intestine, specialized lymphatic capillaries called
lacteals (LAK-tē-als; lact- = milky) carry dietary lipids into lymphatic
vessels and ultimately into the blood (see Figure 24.20). The pres-
ence of these lipids causes the lymph draining from the small intes-
tine to appear creamy white; such lymph is referred to as chyle (KĪL =
juice). Elsewhere, lymph is a clear, pale-yellow fluid.
Lymph Trunks and Ducts
As you have already learned, lymph passes from lymphatic capillaries
into lymphatic vessels and then through lymph nodes. As lymphatic
vessels exit lymph nodes in a particular region of the body, they unite
to form lymph trunks. The principal trunks are the lumbar, intestinal,
bronchomediastinal, subclavian, and jugular trunks (see Figure
22.3). The lumbar trunks drain lymph from the lower limbs, the wall
and viscera of the pelvis, the kidneys, the adrenal glands, and the
abdominal wall. The intestinal trunk drains lymph from the stom-
ach, intestines, pancreas, spleen, and part of the liver. The broncho-
mediastinal trunks (brong-kō-mē′-dē-as-TĪ-nal) drain lymph from
the thoracic wall, lung, and heart. The subclavian trunks drain the
upper limbs. The jugular trunks drain the head and neck.
The lymph passage from the lymph trunks to the venous system
diff ers on the right and left sides of the body. On the right side the three
lymph trunks (right jugular trunk, right subclavian trunk, and right
bronchomediastinal trunk) usually open independently into the
venous system on the anterior surface of the junction of the internal
jugular and subclavian veins (Figure 22.3). Rarely, the three trunks will
join to form a short right lymphatic duct that forms a single junction
with the venous system. On the left side of the body, the largest lymph
vessel, the thoracic (left lymphatic) duct forms the main duct for
return of lymph to the blood. This long duct, approximately 38–45 cm
(15–18 in.), begins as a dilation called the cisterna chyli (sis-TER-na
KI-le; cisterna = cavity or reservoir) anterior to the second lumbar ver-
tebra. The cisterna chyli receives lymph from the right and left lumbar
trunks and from the intestinal trunk. In the neck, the thoracic duct also
Q Which lymphatic vessels empty into the cisterna chyli, and which duct receives lymph
from the cisterna chyli?
receives lymph from the left jugular and left subclavian trunks before
opening into the anterior surface of the junction of the left internal
jugular and subclavian veins. The left bronchomediastinal trunk joins
the anterior surface of the subclavian vein independently and does not
join the thoracic duct. As a result of these pathways, lymph from the
upper right quadrant of the body returns to the superior vena cava
from the right brachiocephalic vein, while all the lymph form the left
upper side of the body and the entire body below the diaphragm
returns to the superior vena cava via the left brachiocephalic vein.
Formation and Flow of Lymph
Most components of blood plasma, such as nutrients, gases, and hor-
mones, filter freely through the capillary walls to form interstitial fluid,
but more fluid filters out of blood capillaries than returns to them by
reabsorption (see Figure 21.7). The excess filtered fluid—about 3 liters
per day—drains into lymphatic vessels and becomes lymph. Because
most plasma proteins are too large to leave blood vessels, interstitial
fluid contains only a small amount of protein. Proteins that do leave
blood plasma cannot return to the blood by diff usion because the con-
centration gradient (high level of proteins inside blood capillaries, low
level outside) opposes such movement. The proteins can, however,
move readily through the more permeable lymphatic capillaries into
lymph. Thus, an important function of lymphatic vessels is to return
the lost plasma proteins and plasma to the bloodstream.
Like some veins, lymphatic vessels contain valves, which ensure
the one-way movement of lymph. As noted previously, lymph drains
into venous blood through the right lymphatic duct and the thoracic
duct at the junction of the internal jugular and subclavian veins
(Figure 22.3). Thus, the sequence of fluid flow is blood capillaries
(blood) → interstitial spaces (interstitial fluid) → lymphatic capillaries
(lymph) → lymphatic vessels (lymph) → lymphatic trunks or ducts
(lymph) → junction of the internal jugular and subclavian veins
(blood). Figure 22.4 illustrates this sequence, along with the relation-
ship of the lymphatic and cardiovascular systems. Both systems form
a very eff icient circulatory system.
The same two “pumps” that aid the return of venous blood to the
heart maintain the flow of lymph.
1. Respiratory pump. Lymph flow is also maintained by pressure
changes that occur during inhalation (breathing in). Lymph flows
from the abdominal region, where the pressure is higher, toward
the thoracic region, where it is lower. When the pressures reverse
during exhalation (breathing out), the valves in lymphatic vessels
prevent backflow of lymph. In addition, when a lymphatic vessel
distends, the smooth muscle in its wall contracts, which helps
move lymph from one segment of the vessel to the next.
2. Skeletal muscle pump. The “milking action” of skeletal muscle
contractions (see Figure 21.9) compresses lymphatic vessels (as
well as veins) and forces lymph toward the junction of the internal
jugular and subclavian veins.
Lymphatic Organs
and Tissues
OBJECTIVE
• Distinguish between primary and secondary lymphatic organs.
The widely distributed lymphatic organs and tissues are classified into
two groups based on their functions. Primary lymphatic organs are the
sites where stem cells divide and become immunocompetent (im′-ū-nō-
KOM-pe-tent), that is, capable of mounting an immune response. The
primary lymphatic organs are the red bone marrow (in flat bones and the
epiphyses of long bones of adults) and the thymus. Pluripotent stem cells
in red bone marrow give rise to mature, immunocompetent B cells and to
pre-T cells. The pre-T cells in turn migrate to the thymus, where they
become immunocompetent T cells. The secondary lymphatic organs
and tissues are the sites where most immune responses occur. They
include lymph nodes, the spleen, and lymphatic nodules (follicles). The
thymus, lymph nodes, and spleen are considered organs because each is
surrounded by a connective tissue capsule; lymphatic nodules, in con-
trast, are not considered organs because they lack a capsule.
Thymus
The thymus is a bilobed organ located in the mediastinum between the
sternum and the aorta. It extends from the top of the sternum or the
inferior cervical region to the level of the fourth costal cartilages, ante-
rior to the top of the heart and its great vessels (Figure 23.5a). An envel-
oping layer of connective tissue holds the two lobes closely together,
but a connective tissue capsule encloses each lobe separately. Exten-
sions of the capsule, called trabeculae (tra-BEK-ū-lē = little beams),
penetrate inward and divide each lobe into lobules (Figure 23.5b).
Each thymic lobule consists of a deeply staining outer cortex and
a lighter-staining central medulla (Figure 22.5b). The cortex is com-
posed of large numbers of T cells and scattered dendritic cells, epithe-
lial cells, and macrophages. Immature T cells (pre-T cells) migrate from
red bone marrow to the cortex of the thymus, where they proliferate
and begin to mature. Dendritic cells (den-DRIT-ik; dendr- = a tree),
which are derived from monocytes (and so named because they have
long, branched projections that resemble the dendrites of a neuron),
assist the maturation process. As you will see shortly, dendritic cells in
other parts of the body, such as lymph nodes, play another key role in
immune responses. Each of the specialized epithelial cells in the
cortex has several long processes that surround and serve as a frame-
work for as many as 50 T cells. These epithelial cells help “educate” the
pre-T cells in a process known as positive selection (see Figure 22.22).
Additionally, they produce thymic hormones that are thought to aid in
the maturation of T cells. Only about 2% of developing T cells survive
in the cortex. The remaining cells die via apoptosis (programmed cell
death). Thymic macrophages (MAK-rō-fā-jez) help clear out the debris
of dead and dying cells. The surviving T cells enter the medulla.
The medulla consists of widely scattered, more mature T cells,
epithelial cells, dendritic cells, and macrophages (Figure 22.5c).
Some of the epithelial cells become arranged into concentric layers of
flat cells that degenerate and become filled with keratohyalin granules
and keratin. These clusters are called thymic (Hassall’s) corpuscles.
Although their role is uncertain, they may serve as sites of T cell death
in the medulla. T cells that leave the thymus via the blood migrate to
lymph nodes, the spleen, and other lymphatic tissues, where they
colonize parts of these organs and tissues.
Because of its high content of lymphoid tissue and a rich blood
supply, the thymus has a reddish appearance in a living body. With
age, however, fatty infiltrations replace the lymphoid tissue and the
thymus takes on more of the yellowish color of the invading fat, giving
the false impression of reduced size. However, the actual size of the
thymus, defined by its connective tissue capsule, does not change. In
infants, the thymus has a mass of about 70 g (2.3 oz). It is aft er puberty
that adipose and areolar connective tissue begin to replace the thymic
tissue. By the time a person reaches maturity, the functional portion of
the gland is reduced considerably, and in old age the functional portion
may weigh only 3 g (0.1 oz). Before the thymus atrophies, it populates
the secondary lymphatic organs and tissues with T cells. However,
some T cells continue to proliferate in the thymus throughout an indi-
vidual’s lifetime, but this number decreases with age.
Lymph Nodes
Located along lymphatic vessels are about 600 bean-shaped lymph
nodes. They are scattered throughout the body, both superficially
and deep, and usually occur in groups (see Figure 22.1). Large groups
of lymph nodes are present near the mammary glands and in the axil-
lae and groin.
Lymph nodes are 1–25 mm (0.04–1 in.) long and, like the thymus,
are covered by a capsule of dense connective tissue that extends into
the node (Figure 22.6). The capsular extensions, called trabeculae,
divide the node into compartments, provide support, and provide a
route for blood vessels into the interior of a node. Internal to the cap-
sule is a supporting network of reticular fibers and fibroblasts. The
capsule, trabeculae, reticular fibers, and fibroblasts constitute the
stroma (supporting framework of connective tissue) of a lymph node.
The parenchyma (functioning part) of a lymph node is divided
into a superficial cortex and a deep medulla. The cortex consists of an
outer cortex and an inner cortex. Within the outer cortex are
Q Which type of lymphocytes mature in the thymus?
mainly of T cells and dendritic cells that enter a lymph node from
“present” an antigen (described later in the chapter), B cells proliferate
and develop into antibody-producing plasma cells or develop into
memory B cells. Memory B cells persist aft er an initial immune re-
sponse and “remember” having encountered a specific antigen.
B cells that do not develop properly undergo apoptosis (programmed
cell death) and are destroyed by macrophages. The region of a
secondary lymphatic nodule surrounding the germinal center is
composed of dense accumulations of B cells that have migrated away
from their site of origin within the nodule.
The inner cortex does not contain lymphatic nodules. It consists
mainly of T cells and dendritic cells that enter a lymph node from
Q What happens to foreign substances in lymph that enter a lymph node?
other tissues. The dendritic cells present antigens to T cells, causing
their proliferation. The newly formed T cells then migrate from the
lymph node to areas of the body where there is antigenic activity.
The medulla of a lymph node contains B cells, antibody-producing
plasma cells that have migrated out of the cortex into the medulla,
and macrophages. The various cells are embedded in a network of
reticular fibers and reticular cells.
As you have already learned, lymph flows through a node in one
direction only (Figure 22.6a). It enters through several aff erent lym-
phatic vessels (AF-er-ent; afferent = to carry toward), which penetrate
the convex surface of the node at several points. The aff erent vessels
contain valves that open toward the center of the node, directing the
lymph inward. Within the node, lymph enters sinuses, a series of irregu-
lar channels that contain branching reticular fibers, lymphocytes, and
macrophages. From the aff erent lymphatic vessels, lymph flows into the
subcapsular sinus (sub-KAP-soo-lar), immediately beneath the cap-
sule. From here the lymph flows through trabecular sinuses (tra-BEK-ū-
lar), which extend through the cortex parallel to the trabeculae, and into
medullary sinuses, which extend through the medulla. The medullary
sinuses drain into one or two eff erent lymphatic vessels (EF-er-ent;
efferent = to carry away), which are wider and fewer in number than
aff erent vessels. They contain valves that open away from the center of
the lymph node to convey lymph, antibodies secreted by plasma cells,
and activated T cells out of the node. Eff erent lymphatic vessels emerge
from one side of the lymph node at a slight depression called a hilum
(HĪ-lum). Blood vessels also enter and leave the node at the hilum.
Lymph nodes function as a type of filter. As lymph enters one end
of a lymph node, foreign substances are trapped by the reticular fibers
within the sinuses of the node. Then macrophages destroy some for-
eign substances by phagocytosis, while lymphocytes destroy others
by immune responses. The filtered lymph then leaves the other end of
the lymph node. Since there are many aff erent lymphatic vessels that
bring lymph into a lymph node and only one or two eff erent lymphatic
vessels that transport lymph out of a lymph node, the slow flow of
lymph within the lymph nodes allows additional time for lymph to be
filtered. Additionally, all lymph flows through multiple lymph nodes
on its path through the lymph vessels. This exposes the lymph to mul-
tiple filtering events before returning to the blood.
Spleen The oval spleen is the largest single mass of lymphatic
tissue in the body. It is a soft , encapsulated organ of variable size, but
on average it fits in a person’s open hand and measures about 12 cm
(5 in.) in length (Figure 22.7a). It is located in the left hypochondriac
region between the stomach and diaphragm. The superior surface
of the spleen is smooth and convex and conforms to the concave
surface of the diaphragm. Neighboring organs make indentations in
the visceral surface of the spleen—the gastric impression (stomach),
the renal impression (left kidney), and the colic impression (left colic
flexure of large intestine). Like lymph nodes, the spleen has a hilum.
Through it pass the splenic artery, splenic vein, and eff erent lymphatic
vessels.
A capsule of dense connective tissue surrounds the spleen and is
covered in turn by a serous membrane, the visceral peritoneum. Tra-
beculae extend inward from the capsule. The capsule plus trabecu-
lae, reticular fibers, and fibroblasts constitute the stroma of the
spleen; the parenchyma of the spleen consists of two diff erent kinds
of tissue called white pulp and red pulp (Figure 22.7b, c). White pulp
is lymphatic tissue, consisting mostly of lymphocytes and mac-
rophages arranged around branches of the splenic artery called cen-
tral arteries. The red pulp consists of blood-filled venous sinuses
and cords of splenic tissue called splenic cords or Billroth’s cords.
Splenic cords consist of red blood cells, macrophages, lymphocytes,
plasma cells, and granulocytes. Veins are closely associated with the
red pulp.
Blood flowing into the spleen through the splenic artery enters
the central arteries of the white pulp. Within the white pulp, B cells
and T cells carry out immune functions, similar to lymph nodes, while
spleen macrophages destroy blood-borne pathogens by phago-
c ytosis. Within the red pulp, the spleen performs three functions re-
lated to blood cells: (1) removal by macrophages of ruptured, worn
out, or defective blood cells and platelets; (2) storage of platelets, up
to one-third of the body’s supply; and (3) production of blood cells
(hemopoiesis) during fetal life.
Lymphatic Nodules Lymphatic nodules (follicles) are egg-
shaped masses of lymphatic tissue that are not surrounded by a
capsule. Because they are scattered throughout the lamina propria
(connective tissue) of mucous membranes lining the gastrointestinal,
urinary, and reproductive tracts and the respiratory airways,
lymphatic nodules in these areas are also referred to as mucosa-
associated lymphatic tissue (MALT).
Although many lymphatic nodules are small and solitary, some
occur in multiple large aggregations in specific parts of the body.
Among these are the tonsils in the pharyngeal region and the aggre-
gated lymphatic follicles (Peyer’s patches) in the ileum of the small
intestine. Aggregations of lymphatic nodules also occur in the ap-
pendix. Usually there are five tonsils, which form a ring at the junc-
tion of the oral cavity and oropharynx and at the junction of the nasal
cavity and nasopharynx (see Figure 23.2b). The tonsils are strategi-
cally positioned to participate in immune responses against inhaled
or ingested foreign substances. The single pharyngeal tonsil
(fa-RIN-jē-al) or adenoid is embedded in the posterior wall of the
nasopharynx. The two palatine tonsils (PAL-a-tīn) lie at the posterior
region of the oral cavity, one on either side; these are the tonsils
commonly removed in a tonsillectomy. The paired lingual tonsils
(LIN-gwal), located at the base of the tongue, may also require re-
moval during a tonsillectomy.
