Lymph
Lymph
Lymph
AND IMMUNITY
22
T H E LY M P H AT I C S Y S T E M , D I S E A S E R E S I S T A N C E , A N D H O M E O S T A S I S
The lymphatic system contributes to homeostasis by draining interstitial fluid as well as providing
the mechanisms for defense against disease. •
Maintaining homeostasis in the body requires continual combat against harmful agents in our inter-
nal and external environment. 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 in sunlight,
chemical toxins, and minor burns with an array of defensive ploys.
Immunity or resistance is the ability to ward off damage or disease through our de-
fenses. Vulnerability or lack of resistance 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. They are always present and available to provide rapid responses to
protect us against disease. Innate immunity does not involve specific recognition of a mi-
crobe and acts against all microbes in the same way. In addition, innate immunity does not
have a memory component; that is, it cannot recall a previous contact with a foreign mole-
cule. 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 gaining access into the body and to help eliminate those that do gain access.
Adaptive (specific) immunity refers to defenses that involve specific recognition of a
microbe once it has breached the innate immunity defenses. Adaptive immunity is based on a
specific response to a specific microbe; that is, it adapts or adjusts to handle a specific microbe.
Unlike innate immunity, adaptive immunity is slower to respond, but it does have a memory com-
ponent. 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 functions
with the digestive system in the absorption of fatty foods. In this chapter, we will explore the mecha-
nisms that provide defenses against intruders and promote the repair of damaged body tissues.
831
832 CHAPTER 22 • THE LYMPHATIC SYSTEM AND IMMUNITY
LYMPHATIC SYSTEM STRUCTURE sels lie in the subcutaneous tissue and generally follow the same
route as veins; lymphatic vessels of the viscera generally follow
AND FUNCTION arteries, forming plexuses (networks) around them. Tissues that
OBJECTIVES lack lymphatic capillaries include avascular tissues (such as car-
• List the components and major functions of the lymphatic tilage, the epidermis, and the cornea of the eye), the central ner-
system. vous system, portions of the spleen, and red bone marrow.
• Describe the organization of lymphatic vessels.
• Explain the formation and flow of lymph.
Lymphatic Capillaries
• Compare the structure and functions of the primary and Lymphatic capillaries are slightly larger in diameter than blood
secondary lymphatic organs and tissues. capillaries and have a unique one-way structure that permits
interstitial fluid to flow into them but not out. The ends of
The lymphatic system (lim-FAT-ik) consists of a fluid called endothelial cells that make up the wall of a lymphatic capillary
lymph, vessels called lymphatic vessels that transport the lymph, overlap (Figure 22.2b). When pressure is greater in the inter-
a number of structures and organs containing lymphatic tissue, stitial fluid than in lymph, the cells separate slightly, like the
and red bone marrow, where stem cells develop into the various opening of a one-way swinging door, and interstitial fluid enters
types of blood cells, including lymphocytes (Figure 22.1). It the lymphatic capillary. When pressure is greater inside the lym-
assists in circulating body fluids and helps defend the body phatic capillary, the cells adhere more closely, and lymph cannot
against disease-causing agents. As you will see shortly, most escape back into interstitial fluid. The pressure is relieved as
components of blood plasma filter through blood capillary walls lymph moves further down the lymphatic capillary. Attached to
to form interstitial fluid. After interstitial fluid passes into lym- the lymphatic capillaries are anchoring filaments, which contain
phatic vessels, it is called lymph (LIMF clear fluid). The elastic fibers. They extend out from the lymphatic capillary,
major difference between interstitial fluid and lymph is location: attaching lymphatic endothelial cells to surrounding tissues.
Interstitial fluid is found between cells, and lymph is located When excess interstitial fluid accumulates and causes tissue
within lymphatic vessels and lymphatic tissue. swelling, the anchoring filaments are pulled, making the open-
Lymphatic tissue is a specialized form of reticular con- ings between cells even larger so that more fluid can flow into
nective tissue (see Table 4.4C on page 129) that contains large the lymphatic capillary.
numbers of lymphocytes. Recall from Chapter 19 that lympho- In the small intestine, specialized lymphatic capillaries called
cytes are agranular white blood cells (see page 699). Two types lacteals (LAK-tē-als; lact- milky) carry dietary lipids into
of lymphocytes participate in adaptive immune responses: B lymphatic vessels and ultimately into the blood. The presence of
cells and T cells. these lipids causes the lymph draining from the small intestine to
appear creamy white; such lymph is referred to as chyle (KĪ L
Functions of the Lymphatic System juice). Elsewhere, lymph is a clear, pale-yellow fluid.
The lymphatic system has three primary functions:
Lymph Trunks and Ducts
1. Drains excess interstitial fluid. Lymphatic vessels drain As you have already learned, lymph passes from lymphatic
excess interstitial fluid from tissue spaces and return it to the blood. capillaries into lymphatic vessels and then through lymph nodes.
2. Transports dietary lipids. Lymphatic vessels transport lipids As lymphatic vessels exit lymph nodes in a particular region of
and lipid-soluble vitamins (A, D, E, and K) absorbed by the gas- the body, they unite to form lymph trunks. The principal trunks
trointestinal tract. are the lumbar, intestinal, bronchomediastinal, subclavian, and
3. Carries out immune responses. Lymphatic tissue initiates jugular trunks (Figure 22.3 on page 835). The lumbar trunks
highly specific responses directed against particular microbes drain lymph from the lower limbs, the wall and viscera of the
or abnormal cells. pelvis, the kidneys, the adrenal glands, and the abdominal wall.
The intestinal trunk drains lymph from the stomach, intestines,
pancreas, spleen, and part of the liver. The bronchomediastinal
Lymphatic Vessels and Lymph Circulation trunks drain lymph from the thoracic wall, lung, and heart. The
Lymphatic vessels begin as lymphatic capillaries. These tiny subclavian trunks drain the upper limbs. The jugular trunks
vessels, which are located in the spaces between cells, are closed drain the head and neck.
at one end (Figure 22.2 on page 834). Just as blood capillaries Lymph passes from lymph trunks into two main channels, the
converge to form venules and then veins, lymphatic capillaries thoracic duct and the right lymphatic duct, and then drains into
unite to form larger lymphatic vessels (see Figure 22.1), which venous blood. The thoracic (left lymphatic) duct is
resemble veins in structure but have thinner walls and more about 38– 45 cm (15–18 in.) long and begins as a dilation called
valves. At intervals along the lymphatic vessels, lymph flows the cisterna chyli (sis-TER-na KĪ -lē; cisterna cavity or reser-
through lymph nodes, encapsulated bean-shaped organs consist- voir) anterior to the second lumbar vertebra. The thoracic duct is
ing of masses of B cells and T cells. In the skin, lymphatic ves- the main duct for the return of lymph to blood. The cisterna
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Palatine tonsil
Submandibular node Left internal jugular vein
Cervical node
Left subclavian vein
Right internal jugular vein
Right lymphatic duct
Right subclavian vein
Thoracic duct
Thymus
Axillary node
Lymphatic vessel
Thoracic duct
Spleen
Functions
Lymphatic vessel
1. Drains excess interstitial fluid.
2. Transports dietary lipids from the gastrointestinal tract to the blood.
3. Protects against invasion through immune responses.
Lymph
Blood
capillary Endothelium
of lymphatic
Venule capillary
chyli receives lymph from the right and left lumbar trunks and such movement. The proteins can, however, move readily
from the intestinal trunk. In the neck, the thoracic duct also through the more permeable lymphatic capillaries into lymph.
receives lymph from the left jugular, left subclavian, and left Thus, an important function of lymphatic vessels is to return the
bronchomediastinal trunks. Therefore, the thoracic duct re- lost plasma proteins to the bloodstream.
ceives lymph from the left side of the head, neck, and chest, Like veins, lymphatic vessels contain valves, which ensure
the left upper limb, and the entire body inferior to the ribs the one-way movement of lymph. As noted previously, lymph
(see Figure 22.1b). The thoracic duct in turn drains lymph into drains into venous blood through the right lymphatic duct and
venous blood at the junction of the left internal jugular and left the thoracic duct at the junction of the internal jugular and sub-
subclavian veins. clavian veins (Figure 22.3). Thus, the sequence of fluid flow
The right lymphatic duct (Figure 22.3) is about 1.2 cm (0.5 is blood capillaries (blood) : interstitial spaces (interstitial
in.) long and receives lymph from the right jugular, right subcla- fluid) : lymphatic capillaries (lymph) : lymphatic vessels
vian, and right bronchomediastinal trunks. Thus, the right lym- (lymph) : lymphatic ducts (lymph) : junction of the internal
phatic duct receives lymph from the upper right side of the body jugular and subclavian veins (blood). Figure 22.4 on page 837
(see Figure 22.1b). From the right lymphatic duct, lymph drains illustrates this sequence, along with the relationship of the lym-
into venous blood at the junction of the right internal jugular and phatic and cardiovascular systems.
right subclavian veins. The same two “pumps” that aid the return of venous blood to
the heart maintain the flow of lymph.
Formation and Flow of Lymph
Most components of blood plasma filter freely through the capil- 1. Skeletal muscle pump. The “milking action” of skeletal
lary walls to form interstitial fluid, but more fluid filters out muscle contractions (see Figure 21.9 on page 774) compresses
of blood capillaries than returns to them by reabsorption (see lymphatic vessels (as well as veins) and forces lymph toward the
Figure 21.7 on page 771). The excess filtered fluid—about junction of the internal jugular and subclavian veins.
3 liters per day—drains into lymphatic vessels and becomes 2. Respiratory pump. Lymph flow is also maintained by
lymph. Because most plasma proteins are too large to leave pressure changes that occur during inhalation (breathing in).
blood vessels, interstitial fluid contains only a small amount of Lymph flows from the abdominal region, where the pressure is
protein. Proteins that do leave blood plasma cannot return to the higher, toward the thoracic region, where it is lower. When the
blood by diffusion because the concentration gradient (high level pressures reverse during exhalation (breathing out), the valves
of proteins inside blood capillaries, low level outside) opposes prevent backflow of lymph. In addition, when a lymphatic vessel
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LEFT BRONCHO-
RIGHT LYMPHATIC MEDIASTINAL TRUNK
DUCT
Right brachiocephalic THORACIC (LEFT
vein LYMPHATIC) DUCT
RIGHT BRONCHO-
MEDIASTINAL TRUNK
Hemiazygos vein
Superior vena cava
Rib
Intercostal
muscle
Azygos vein
LEFT LUMBAR
CISTERNA CHYLI TRUNK
RIGHT LUMBAR
TRUNK
Inferior vena cava INTESTINAL
TRUNK
? Which lymphatic vessels empty into the cisterna chyli, and which duct receives lymph from the cisterna chyli?
836 CHAPTER 22 • THE LYMPHATIC SYSTEM AND IMMUNITY
Figure 22.4 Schematic diagram showing the relationship of the lymphatic system to the cardiovascular system.
The arrows indicate the direction of flow of lymph and blood.
The sequence of fluid flow is blood capillaries (blood) : interstitial spaces (interstitial fluid) : lymphatic
capillaries (lymph) : lymphatic vessels (lymph) : lymphatic ducts (lymph) : junction of the internal
jugular and subclavian veins (blood).
SYSTEMIC CIRCULATION PULMONARY CIRCULATION
Lymph node
Lymphatic capillaries
Lymphatic
duct
Subclavian vein Pulmonary blood
capillaries
Veins
Lymphatic vessel
Valve
Heart Arteries
Lymph node
Systemic blood capillaries
Lymphatic capillaries
distends, the smooth muscle in its wall contracts, which helps Thymus
move lymph from one segment of the vessel to the next. The thymus is a bilobed organ located in the mediastinum
between the sternum and the aorta (Figure 22.5a). An envelop-
ing layer of connective tissue holds the two lobes closely
Lymphatic Organs and Tissues
together, but a connective tissue capsule separates the two.
The widely distributed lymphatic organs and tissues are clas- Extensions of the capsule, called trabeculae (tra-BEK-ū-lē
sified into two groups based on their functions. Primary little beams), penetrate inward and divide each lobe into lobules
lymphatic organs are the sites where stem cells divide and (Figure 22.5b).
become immunocompetent, that is, capable of mounting an im- Each thymic lobule consists of a deeply staining outer cortex
mune response. The primary lymphatic organs are the red bone and a lighter-staining central medulla (Figure 22.5b). The cortex
marrow (in flat bones and the epiphyses of long bones of adults) is composed of large numbers of T cells and scattered dendritic
and the thymus. Pluripotent stem cells in red bone marrow give cells, epithelial cells, and macrophages. Immature T cells (pre-T
rise to mature, immunocompetent B cells and to pre-T cells. The cells) migrate from red bone marrow to the cortex of the thymus,
pre-T cells in turn migrate to the thymus, where they become where they proliferate and begin to mature. Dendritic cells
immunocompetent T cells. The secondary lymphatic organs (dendr- a tree), which are derived from monocytes, and so
and tissues are the sites where most immune responses occur. named because they have long, branched projections that resem-
They include lymph nodes, the spleen, and lymphatic nodules ble the dendrites of a neuron, assist the maturation process. As
(follicles). The thymus, lymph nodes, and spleen are considered you will see shortly, dendritic cells in other parts of the body,
organs because each is surrounded by a connective tissue cap- such as lymph nodes, play another key role in immune re-
sule; lymphatic nodules, in contrast, are not considered organs sponses. Each of the specialized epithelial cells in the cortex has
because they lack a capsule. several long processes that surround and serve as a framework
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Blood vessels
Capsule
Lobule:
Cortex
Thymic (Hassall’s)
corpuscle
Thyroid Medulla
Brachiocephalic
gland veins Trabecula
Trachea
Right common Thymus
carotid artery
Superior Parietal
vena cava pericardium
LM 30x
Right Left
lung lung
T cell
Thymic (Hassall’s)
corpuscle
Epithelial cell
Diaphragm
for as many as 50 T cells. These epithelial cells help “educate” In infants, the thymus is large, with a mass of about 70 g (2.3 oz).
the pre-T cells in a process known as positive selection (see After puberty, adipose and areolar connective tissue begin to re-
Figure 22.22). Additionally, they produce thymic hormones that place the thymic tissue. By the time a person reaches maturity,
are thought to aid in the maturation of T cells. Only about 2% of the gland has atrophied considerably, and in old age it may
developing T cells survive in the cortex. The remaining cells die weigh only 3 g (0.1 oz). Before the thymus atrophies, it popu-
via apoptosis (programmed cell death). Thymic macrophages lates the secondary lymphatic organs and tissues with T cells.
help clear out the debris of dead and dying cells. The surviving However, some T cells continue to proliferate in the thymus
T cells enter the medulla. throughout an individual’s lifetime.
The medulla consists of widely scattered, more mature
T cells, epithelial cells, dendritic cells, and macrophages (Figure Lymph Nodes
22.5c). Some of the epithelial cells become arranged into Located along lymphatic vessels are about 600 bean-shaped
concentric layers of flat cells that degenerate and become filled lymph nodes. They are scattered throughout the body, both
with keratohyalin granules and keratin. These clusters are called superficially and deep, and usually occur in groups (see Figure
thymic (Hassall’s) corpuscles. Although their role is uncertain, 22.1). Large groups of lymph nodes are present near the mam-
they may serve as sites of T cell death in the medulla. T cells mary glands and in the axillae and groin.
that leave the thymus via the blood migrate to lymph nodes, the Lymph nodes are 1–25 mm (0.04–1 in.) long and, like the
spleen, and other lymphatic tissues where they colonize parts of thymus, are covered by a capsule of dense connective tissue that
these organs and tissues. extends into the node (Figure 22.6). The capsular extensions,
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Figure 22.6 Structure of a lymph node. Arrows indicate the direction of lymph flow through a lymph node.
Lymph nodes are present throughout the body, usually clustered in groups.
Outer Cortex
Cells of inner cortex Cells around germinal center Cells in germinal center
Cells of medulla
Subcapsular sinus
Reticular fiber
Trabecula
Efferent lymphatic
vessels
Valve
Hilum
Subcapsular sinus
Trabecular sinus
Capsule
Afferent
lymphatic vessel Medullary sinus
Capsule
Subcapsular sinus
Trabecula
Trabecular sinus
Nerve
Outer cortex
Skeletal muscle
Germinal center in
secondary lymphatic
nodule Lymph node
Inner cortex
Lymphatic vessel
Medullary sinus
Medulla
LM 55x
(b) Portion of a lymph node (c) Anterior view of an inguinal lymph node
called trabeculae, divide the node into compartments, provide T cells, causing their proliferation. The newly formed T cells
support, and provide a route for blood vessels into the interior then migrate from the lymph node to areas of the body where
of a node. Internal to the capsule is a supporting network of there is antigenic activity.
reticular fibers and fibroblasts. The capsule, trabeculae, reticular The medulla of a lymph node contains B cells, antibody
fibers, and fibroblasts constitute the stroma (supporting connec- producing plasma cells that have migrated out of the cortex into
tive tissue) of a lymph node. the medulla, and macrophages. The various cells are embedded
The parenchyma (functioning part) of a lymph node is in a network of reticular fibers and reticular cells.
divided into a superficial cortex and a deep medulla. The cortex As you have already learned, lymph flows through a node in
consists of an outer cortex and an inner cortex. Within the outer one direction only (Figure 22.6a). It enters through afferent
cortex are egg-shaped aggregates of B cells called lymphatic lymphatic vessels (afferent to carry toward), which penetrate
nodules (follicles). A lymphatic nodule consisting chiefly of B the convex surface of the node at several points. The afferent
cells is called a primary lymphatic nodule. Most lymphatic nod- vessels contain valves that open toward the center of the
ules in the outer cortex are secondary lymphatic nodules (Figure node, directing the lymph inward. Within the node, lymph enters
22.6), which form in response to an antigenic challenge and are sinuses, a series of irregular channels that contain branching
sites of plasma cell and memory B cell formation. After B cells reticular fibers, lymphocytes, and macrophages. From the affer-
in a primary lymphatic nodule recognize an antigen, the primary ent lymphatic vessels, lymph flows into the subcapsular sinus,
lymphatic nodule develops into a secondary lymphatic nodule. immediately beneath the capsule. From here the lymph flows
The center of a secondary lymphatic nodule contains a region of through trabecular sinuses, which extend through the cortex
light-staining cells called a germinal center. In the germinal cen- parallel to the trabeculae, and into medullary sinuses, which
ter are B cells, follicular dendritic cells (a special type of den- extend through the medulla. The medullary sinuses drain into
dritic cell), and macrophages. When follicular dendritic cells one or two efferent lymphatic vessels (efferent to carry
“present” an antigen (described later in the chapter), B cells pro- away), which are wider and fewer in number than afferent
liferate and develop into antibody-producing plasma cells or de- vessels. They contain valves that open away from the center of
velop into memory B cells. Memory B cells persist after an ini- the lymph node to convey lymph, antibodies secreted by plasma
tial immune response and “remember” having encountered a cells, and activated T cells out of the node. Efferent lymphatic
specific antigen. B cells that do not develop properly undergo vessels emerge from one side of the lymph node at a slight
apoptosis (programmed cell death) and are destroyed by depression called a hilum (HĪ -lum). Blood vessels also enter
macrophages. The region of a secondary lymphatic nodule sur- and leave the node at the hilum.
rounding the germinal center is composed of dense accumula- Lymph nodes function as a type of filter. As lymph enters one
tions of B cells that have migrated away from their site of origin end of a lymph node, foreign substances are trapped by the retic-
within the nodule. ular fibers within the sinuses of the lymph node. Then
The inner cortex does not contain lymphatic nodules. It con- macrophages destroy some foreign substances by phagocytosis
sists mainly of T cells and dendritic cells that enter a lymph while lymphocytes destroy others by immune responses. The
node from other tissues. The dendritic cells present antigens to filtered lymph then leaves the other end of the lymph node.
840 CHAPTER 22 • THE LYMPHATIC SYSTEM AND IMMUNITY
Figure 22.7 Structure of the spleen. (See Tortora, A Photographic Atlas of the Human Body, Second Edition, Figure 7.3a.)
The spleen is the largest single mass of lymphatic tissue in the body.
SUPERIOR
Splenic vein
Splenic artery
Colic impression
Gastric impression
Hilum
POSTERIOR ANTERIOR
Renal impression
Splenic vein
White pulp
Red pulp:
Venous sinus Red pulp
Splenic cord
Central artery
White pulp
Trabecula
Central artery
Capsule
Trabecula
LM 25x
(c) Portion of the spleen
The spleen is the organ most often damaged in cases of abdominal Lymphatic tissues begin to develop by the end of the fifth
trauma. Severe blows over the inferior left chest or superior abdomen week of embryonic life. Lymphatic vessels develop from lymph
can fracture the protecting ribs. Such crushing injury may result in a sacs that arise from developing veins, which are derived
ruptured spleen, which causes significant hemorrhage and shock. from mesoderm.
Prompt removal of the spleen, called a splenectomy, is needed to pre- The first lymph sacs to appear are the paired jugular
vent death due to bleeding. Other structures, particularly red bone mar- lymph sacs at the junction of the internal jugular and subcla-
row and the liver, can take over some functions normally carried out by vian veins (Figure 22.8). From the jugular lymph sacs, lym-
the spleen. Immune functions, however, decrease in the absence of a phatic capillary plexuses spread to the thorax, upper limbs,
spleen. The spleen’s absence also places the patient at higher risk for
sepsis (a blood infection) due to loss of the filtering and phagocytic
functions of the spleen. To reduce the risk of sepsis, patients who have
undergone a splenectomy take prophylactic (preventive) antibiotics be- Figure 22.8 Development of lymphatic tissues.
fore any invasive procedures. • Lymphatic tissues are derived from mesoderm.
Lymphatic Nodules
Lymphatic nodules (follicles) are egg-shaped masses of lym-
phatic tissue that are not surrounded by a capsule. Because
they are scattered throughout the lamina propria (connective Jugular
tissue) of mucous membranes lining the gastrointestinal, urinary, lymph sac Subclavian
and reproductive tracts and the respiratory airways, lymphatic vein
nodules in these areas are also referred to as mucosa-associated Thoracic
lymphatic tissue (MALT). duct
Inferior
Although many lymphatic nodules are small and solitary, Cisterna vena cava
some occur in multiple large aggregations in specific parts of the chyli
body. Among these are the tonsils in the pharyngeal region and Posterior
the aggregated lymphatic follicles (Peyer’s patches) in the ileum lymph sac
of the small intestine. Aggregations of lymphatic nodules also
occur in the appendix. Usually there are five tonsils, which form
a ring at the junction of the oral cavity and oropharynx and at the
junction of the nasal cavity and nasopharynx (see Figure 23.2b).
The tonsils are strategically positioned to participate in immune ? When do lymphatic tissues begin to develop?