LI CASE 5

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

The Concept 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 damage or disease through our
defenses. 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. 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 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. A
daptive 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.

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 tissue (lymphocytes within a filtering tissue), and red bone marrow (Figure 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
capillary 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 tissue (see Table 4.4) that contains
large numbers of lymphocytes. Recall 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 interstitial 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 gastrointestinal tract.
3. Carries out immune responses. Lymphatic tissue initiates highly specific responses directed
against particular microbes or abnormal cells.

Lymphatic Vessels and Lymph Circulation

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 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
beanshaped 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 follow 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.

Functions

1. Drains excess interstitial fluid.

2. Transports dietary lipids from the gastrointestinal tract to the blood.

3. Protects against invasion through immune responses.

Lymphatic capillaries are found throughout the body except in avascular tissues, the central
nervous system, portions of the spleen, and bone marrow.

Lymphatic Capillaries

Lymphatic capillaries have greater permeability than blood capillaries 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 interstitial 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
presence of these lipids causes the lymph draining from the small intestine 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 stomach, intestines, pancreas,
spleen, and part of the liver. The bronchomediastinal 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 vertebra. The cisterna chyli
receives lymph from the right and left lumbar trunks and from the intestinal trunk. In the neck,
the thoracic duct also 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 hormones, 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 concentration
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 relationship 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

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)
Lymphatic Organs and Tissues

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-nōKOM-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 contrast, 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, anterior to the top of the heart and its great vessels (Figure 23.5a). An enveloping
layer of connective tissue holds the two lobes closely together, but a connective tissue capsule
encloses each lobe separately. Extensions 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 composed of large numbers of T cells and scattered
dendritic cells, epithelial 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 framework 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 individual’s lifetime, but this number
decreases with age.

Lymph Nodes

Lymph nodes are present throughout the body, usually clustered in groups.

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 axillae 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 capsule 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 egg-shaped aggregates of B cells called
lymphatic nodules (follicles). A lymphatic nodule consisting chiefly of B cells is called a
primary lymphatic nodule. Most lymphatic nodules in the outer cortex are secondary lymphatic
nodules (Figure 22.6), which form in response to an antigen (a foreign substance) and are sites of
plasma cell and memory B cell formation. Aft er B cells in a primary lymphatic nodule recognize
an antigen, the primary lymphatic nodule develops into a secondary lymphatic nodule. The
center of a secondary lymphatic nodule contains a region of light-staining cells called a germinal
center. In the germinal center are B cells, follicular dendritic cells (a special type of dendritic
cell), and macrophages. When follicular dendritic cells “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 response 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 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 lymphatic 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 irregular 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 capsule. From here the lymph flows through
trabecular sinuses (tra-BEK-ūlar), 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 foreign 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
multiple 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. Trabeculae extend inward from the capsule. The capsule
plus trabeculae, 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
macrophages arranged around branches of the splenic artery called central 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 related 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 eggshaped 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 mucosaassociated
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 aggregated lymphatic follicles (Peyer’s patches) in the ileum 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 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 removal during a tonsillectomy