Download 24. Lymphatic System

24
Lymphatic
System
O U T L I N E
24.1 Functions of the Lymphatic System
24.2 Lymph and Lymph Vessels 726
24.2a
24.2b
24.2c
24.2d
725
Lymphatic Capillaries 726
Lymphatic Vessels 726
Lymphatic Trunks 727
Lymphatic Ducts 727
24.3 Lymphatic Cells
729
24.3a Types and Functions of Lymphocytes
24.3b Lymphopoiesis 734
24.4 Lymphatic Structures
729
735
24.4a Lymphatic Nodules 735
24.4b Lymphatic Organs 736
24.5 Aging and the Lymphatic System 741
24.6 Development of the Lymphatic System 741
MODULE 10: LY MPHATIC SYSTEM
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e have seen in chapters 21–23 how the cardiovascular system
transports blood throughout the body, where it exchanges
gases and nutrients with the tissues. Another body system, called the
lymphatic system, aids the cardiovascular system by transporting
excess interstitial fluid through lymph vessels assisting in maintaining fluid homeostasis. Once this fluid enters the vessels, the fluid is
renamed lymph. Along the way, lymph is filtered and checked for
foreign or pathologic material, such as bacteria and cancer cells.
Lymphatic structures contain certain cells that initiate an immune
response to abnormal materials. Without the primary immune
response by the lymphatic system, the body would be unable to fight
infection and keep itself healthy.
In this chapter we examine the lymph vessels, lymphatic
structures, and lymphatic organs of the body, and learn how each
of these components plays an important role in keeping us healthy.
Lymphatic System
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W
Tonsils
Cervical lymph nodes
Right lymphatic duct
Thymus
Axillary
lymph nodes
Thoracic duct
Spleen
Cisterna chyli
Mucosaassociated
lymphatic tissue
(MALT) (in small
intestine)
24.1 Functions of the Lymphatic
System
Learning Objective:
Inguinal
lymph nodes
1. Explain how the lymphatic system aids fluid homeostasis
and guards the health of body cells and tissues.
The lymphatic (lim-fat ́ik) system involves several organs
as well as a system of lymphatic cells and lymph vessels located
throughout the body (figure 24.1). Together, these structures
transport fluids and help the body fight infection. However, not all
of these components of the lymphatic system are involved in each
function.
At the arterial end of a capillary bed, blood pressure forces
fluid from the blood into the interstitial spaces around cells. This
fluid is called interstitial fluid (not to be confused with extracellular fluid, a term that encompasses both interstitial fluid and
plasma [see chapter 2]). Most of this fluid is reabsorbed at the
venous end of the capillaries, but an excess of about 3 liters of
fluid per day remains in the interstitial spaces. A network of lymph
vessels (figure 24.1) reabsorbs this excess fluid and returns it to
the venous circulation. If this excess fluid were not removed, body
tissues would swell, a condition called edema (e-dē ́mă; oidema = a
swelling). Further, this excess fluid would accumulate outside the
bloodstream, causing blood levels to drop precipitously. Thus, the
lymphatic system prevents interstitial fluid levels from rising out
of control and helps maintain blood volume levels.
Lymph vessels also transport dietary lipids. Although most
nutrients are absorbed directly into the bloodstream, some larger
materials, such as lipids and lipid-soluble vitamins, are unable to
enter the bloodstream directly from the gastrointestinal (GI) tract.
These materials are transported through tiny lymph vessels called
lacteals, which drain into larger lymph vessels and eventually into
the bloodstream.
Lymphatic organs house lymphocytes, a type of leukocyte (see
chapter 21). While some lymphocytes circulate in the bloodstream,
most are located in the lymphatic structures and organs. Some lymphatic organs assist in these cells’ maturation, while others serve as
a site for lymphocyte replication (mitosis).
Finally, the lymphatic system cells generate an immune
response and increase the lymphocyte population when necessary.
Lymphatic structures contain T-lymphocytes, B-lymphocytes, and
macrophages (monocytes that have migrated from the bloodstream
into other tissues). These cells are constantly monitoring the blood
and the interstitial fluid for antigens (an ́ti-gen; anti(body) + gen =
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Red bone marrow
Lymph vessels
Figure 24.1
Lymphatic System. The lymphatic system consists of lymph vessels,
lymphatic cells, and lymphatic organs that work together to pick up
and transport interstitial fluid back to the blood and to mount an
immune response when needed.
producing), which are any substances perceived as abnormal to the
body, such as bacteria, viruses, and even cancer cells. If antigens
are discovered, lymphatic cells initiate a systematic defense against
the antigens, called an immune (i-mūn ́) response. Some of the cells
produce soluble proteins called antibodies that bind to the foreign or
abnormal agent, thus damaging it or identifying it to other elements
of the immune system. Other cells attack and destroy the antigen
directly. Still other cells become memory cells, which remember the
past antigen encounters and initiate an even faster and more powerful response should the same antigen appear again.
W H AT D I D Y O U L E A R N?
1
●
What is the “immune response,” and how does the lymphatic
system initiate it?
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24.2 Lymph and Lymph Vessels
Learning Objectives:
1. Identify the components of lymph.
2. Outline the path of lymph from interstitial tissues to the
bloodstream.
Excess interstitial fluid and solutes are returned to the bloodstream through a lymph vessel network. When the combination
of interstitial fluid, solutes, and sometimes foreign material enters
the lymph vessels, the liquid mixture is called lymph (limf; lympha = clear spring water). The lymph vessel network is composed
of increasingly larger vessels, as follows (from smallest to largest
in diameter): lymphatic capillaries, lymphatic vessels, lymphatic
trunks, and lymphatic ducts. Thus, the term “lymph vessel” is a
general term to describe all of these specific lymphatic capillaries,
lymphatic vessels, trunks, and ducts.
When the pressure increases in the lymphatic capillary, the cell wall
margin pushes back into place next to the adjacent endothelial cell.
The fluid that is now “trapped” in the lymph capillary cannot be
released back into the interstitial spaces. This process is analogous
to the movement of the entryway door to your house or apartment.
Imagine that the door is unlocked and the knob is turned. Putting
pressure on the outside of the door (like the pressure of interstitial
fluid on the outside of the lymphatic capillary wall) causes it to open
to the inside so you can enter. Once inside, pressure applied to the
inside surface of the door (or fluid pressure against the inside lymphatic capillary surface) causes it to close.
The small intestine (part of the GI tract) contains special
types of lymphatic capillaries called lacteals (lak ́tē-a ̆l; lactis =
milk). Lacteals pick up not only interstitial fluid, but also dietary
lipids and lipid-soluble vitamins (vitamins that must be dissolved
in lipids before they can be absorbed). The lymph from the GI tract
has a milky color due to the lipid, and for this reason the GI tract
lymph is also called chyle (kı̄ l; chylos = juice).
24.2a Lymphatic Capillaries
The lymph vessel network begins with microscopic vessels called
lymphatic capillaries. Lymphatic capillaries are closed-ended tubes
that are interspersed among most blood capillary networks (figure
24.2), except those within the red bone marrow and central nervous system. In addition, avascular tissues (such as epithelia) lack
lymphatic capillaries. A lymphatic capillary is similar to a blood
capillary in that its wall is an endothelium. However, lymphatic
capillaries tend to be larger in diameter, lack a basement membrane, and have overlapping endothelial cells. Anchoring filaments
help hold these endothelial cells to the nearby structures. These
overlapping endothelial cells act as one-way flaps; when interstitial
fluid pressure rises, the margins of the endothelial cells push into
the lymphatic capillary lumen and allow interstitial fluid to enter.
Interstitial space
Capillary bed
24.2b Lymphatic Vessels
Lymphatic capillaries merge to form larger structures called lymphatic vessels. Lymphatic vessels resemble small veins, in that
both contain three tunics (intima, media, and externa) and both
have valves within the lumen. Since the lymph vessel network is
a low-pressure system, valves prevent lymph from pooling in the
vessel and help prevent lymph backflow (figure 24.3). These
valves are especially important in areas where lymph flow is
against the direction of gravity. Contraction of nearby skeletal
muscles also helps move lymph through the vessels.
Some lymphatic vessels connect directly to lymphatic organs
called lymph nodes. Afferent lymphatic vessels bring lymph to a
lymph node where it is filtered for foreign or pathogenic material.
Venule
Endothelium of
lymphatic capillary
Lymphatic capillary
Interstitial fluid
Tissue cell
Opening
Arteriole
Lymph
Anchoring filament
(a) Capillary bed and lymphatic capillaries
(b) Lymphatic capillary
Figure 24.2
Lymphatic Capillaries. (a) Lymphatic capillaries arise as blind-ended vessels in connective tissue spaces among most blood capillary networks.
Here, the black arrows show blood flow and the green arrows show lymph flow. (b) A lymphatic capillary takes up interstitial fluid through oneway flaps in its endothelial lining.
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Overlapping
endothelial cells
Lymph
Valve open
(lymph flows forward)
Valve closed
(backflow of lymph is prevented)
Direction of
lymph flow
LM 100x
(a) Lymphatic vessel, longitudinal section
Valve
(b) Lymphatic vessel, cross section
Lymphatic vessel
Figure 24.3
Lymphatic Vessels and Valves. (a) Lymphatic vessels contain valves to prevent backflow of lymph. (b) Histologic cross section of a lymphatic
vessel.
Once filtered, the lymph exits the lymph node via efferent lymphatic vessels. Lymph nodes are often found in clusters, so after
one lymph node receives and filters lymph, the lymph is passed to
another lymph node in the cluster, then to another lymph node,
and so on. Thus, lymph is repeatedly examined for the presence of
foreign or pathogenic materials.
24.2c Lymphatic Trunks
Left and right lymphatic trunks form from merging lymphatic
vessels (figure 24.4). Each lymphatic trunk drains lymph from a
major body region, as follows:
■
■
■
■
■
Jugular trunks drain lymph from the head and neck.
Subclavian trunks drain lymph from the upper limbs,
breasts, and superficial thoracic wall.
Bronchomediastinal trunks drain deep thoracic structures.
Intestinal trunks drain most abdominal structures.
Lumbar trunks drain the lower limbs, abdominopelvic
wall, and pelvic organs.
right upper limb, and right side of the thorax (figure 24.4b). The
thoracic duct is the largest lymph vessel, with a length of about
37.5 to 45 centimeters (15 to 18 inches). At the base of the thoracic
duct and anterior to the L2 vertebra is a rounded, saclike structure
called the cisterna chyli (sis-ter ́na ̆ kı̄ ́lı̄; cistern) (figure 24.4a).
The cisterna chyli gets its name from the milky lymph called chyle
it receives from the small intestine. Left and right intestinal and
lumbar trunks drain into the cisterna chyli. The thoracic duct
travels superiorly from the cisterna chyli and lies directly anterior
to the vertebral bodies. It passes through the aortic opening of the
diaphragm, and then it ascends to the left of the vertebral body
midline. It drains lymph into the junction of the left subclavian
vein and left internal jugular vein. The thoracic duct receives
lymph from most regions of the body, including the left side of the
head and neck, left upper limb, left thorax, and all body regions
inferior to the diaphragm (including the right lower limb and right
side of the abdomen).
24.2d Lymphatic Ducts
Lymphatic trunks drain into the largest vessels, called lymphatic
ducts. The two lymphatic ducts empty lymph back into the venous
circulation. The right lymphatic duct, located near the right
clavicle, returns the lymph into the junction of the right subclavian
vein and the right internal jugular vein. It receives lymph from the
lymphatic trunks that drain the right side of the head and neck,
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W H AT D I D Y O U L E A R N?
2
●
3
●
4
●
What is lymph?
Describe the structure of lymphatic capillaries. Into what
structures do they drain?
Which major body regions drain lymph to the right
lymphatic duct?
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Right jugular trunk
Right subclavian trunk
Right lymphatic duct
Right bronchomediastinal trunk
Left internal jugular vein
Left subclavian vein
Left bronchomediastinal trunk
Superior vena cava
Thoracic duct
Lymph nodes
Azygos vein
Hemiazygos vein
Parietal pleura (cut)
Diaphragm
Cisterna chyli
Inferior vena cava
Left lumbar trunk
Intestinal trunk
Right lumbar trunk
(a) Posterior thoracic wall, anterior view
Thoracic duct
Thyroid gland
Area drained by
right lymphatic duct
Left internal jugular vein
Left vertebral vein
Left subclavian vein
Left vertebral artery
Trachea (cut)
Right brachiocephalic vein
Left brachiocephalic
vein
Brachiocephalic artery
Area drained
by thoracic duct
Superior vena cava
Thoracic duct
Hemiazygos vein
Azygos vein
(b) Lymph drainage pattern
(c) Thoracic duct
Figure 24.4
Lymphatic Trunks and Ducts. Lymph drains from lymphatic trunks into lymphatic ducts that each empty into the junctions of the internal
jugular and subclavian veins. (a) An anterior view of the posterior thoracic wall illustrates the major lymphatic trunks and ducts. (b) Pattern of
lymph drainage into the right lymphatic duct and the thoracic duct. (c) A cadaver photo of the thoracic duct.
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CLINICAL VIEW
Lymphedema
Lymphedema (limf ́e-dē ́mă) refers to an accumulation of interstitial
fluid that occurs due to interference with lymphatic drainage in a
part of the body. As the interstitial fluid accumulates, the affected
area swells and becomes painful. If lymphedema is left untreated, the
protein-rich interstitial fluid may interfere with wound healing and
can even contribute to an infection by acting as a growth medium
for bacteria.
in the skin of the foot, which is why many cases of lymphedema in the
foot are seen. However, mosquitoes are the most common vector for
transmitting filariasis. Once the mature worms have entered the body,
they become permanent “residents.” An affected body part can swell
to many times its normal size. In these extreme cases, the condition
also is known as elephantiasis (el-ĕ-fan-tı̄ ́ă-sis; elephas = elephant).
Patients are treated with medications to kill the filarial worms, although
the damage to the lymphatic system may be irreversible.
Most cases of lymphedema are obstructive, meaning they are caused
by blockage of lymph vessels. There are several causes of obstructive
lymphedema:
■
■
■
■
Any surgery that requires removal of a group of lymph nodes
(e.g., breast cancer surgery when the axillary lymph nodes are
removed) puts an individual at increased risk for lymphedema.
The spread of malignant tumors within the lymph nodes and/
or lymph vessels can obstruct lymphatic drainage.
Radiation therapy may cause scar formation that interferes
with lymphatic drainage.
Trauma or infection of the lymph vessels obstructs lymphatic
drainage.
In addition, millions of individuals in Southeast Asia and Africa have
developed lymphedema as a result of infection by threadlike parasitic
filarial worms. Lymphatic filariasis (fil-ă-rı̄ ́ă-sis; filum = thread) is a
type of lymphedema whereby filarial worms lodge in the lymphatic system, live and reproduce there for years, and eventually obstruct lymphatic
drainage. Some filarial worms gain entrance to the body through cracks
24.3 Lymphatic Cells
Learning Objectives:
1. List and describe the types of lymphatic cells.
2. Explain the function of lymphocytes in the body’s immune
response.
3. Outline lymphocyte formation.
Lymphatic cells (also called lymphoid cells) are located in
both the lymphatic system and the cardiovascular system. The
lymphatic cells work together to elicit an immune response.
Among the types of lymphatic cells are macrophages, some epithelial cells, dendritic cells, and lymphocytes.
Macrophages (mak ́rō-faj; macros = large, phago = to eat) are
monocytes that have migrated into the lymphatic system from the
bloodstream; they are responsible for phagocytosis of foreign substances. They also may present antigens to other lymphatic cells.
Special epithelial cells (also called nurse cells) are found in the thymus, where they secrete thymic hormones. Dendritic (den-drit ́ik)
cells are found in the lymphatic nodules; they internalize antigens
from the lymph and present them to other lymphatic cells. These
cells are the main antigen-presenting cell of the immune system.
(Recall from chapter 5 that dendritic cells within the skin epidermis
perform the same function.) Lymphocytes are the most abundant
cells in the lymphatic system. There are three types of lymphocytes,
and each has a specific job in the overall immune response.
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Elephantiasis (lymphatic filariasis) of the lower limb.
Lymphedema has no cure, but it can be controlled. Patients may
wear compression stockings or other compression garments to reduce
swelling and assist interstitial fluid return to the circulation. Certain
exercise regimens may improve lymphatic drainage as well. Ideally, an
individual with any symptoms of lymphedema, such as swelling and pain
in a body region or skin feeling tight, should seek medical assistance
quickly in order for treatment to be most effective.
24.3a Types and Functions of Lymphocytes
The three types of lymphocytes are T-lymphocytes (also called
T-cells), B-lymphocytes (also called B-cells), and natural killer
(NK) cells. All three types migrate through the lymphatic system
and search for antigens.
Study Tip!
Lymphocytes are identified according to the tissue or organ where
they mature:
T-lymphocytes mature in the Thymus.
B-lymphocytes mature in the Bone marrow.
T-lymphocytes
T-lymphocytes make up about 70–85% of body lymphocytes.
The lymphocyte plasma membrane contains a coreceptor that
can recognize a particular antigen. (Coreceptors are named with
the letters “CD” followed by a number.) There are several types
of T-lymphocytes, each with a particular kind of coreceptor.
The two main groups are helper T-lymphocytes and cytotoxic
T-lymphocytes (figure 24.5).
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(a) Helper T-lymphocyte
Stimulates B-lymphocyte
to produce antibodies
Foreign cell with antigen
CD4 coreceptor
Cytokine
secretion
Mitosis
Helper T-lymphocyte
Encourages formation
of more macrophages
Helper
T-lymphocytes
1 Helper T-lymphocyte recognizes antigen.
Regulates cytotoxic
T-lymphocyte activity
2 Helper T-lymphocyte secretes cytokines and
begins to undergo mitosis to form more
helper T-lymphocytes.
3 Cytokines secreted by helper T-lymphocytes
initiate and control the immune response.
(b) Cytotoxic T-lymphocyte
CD8 coreceptor
Cytotoxic T-lymphocyte
Cytotoxic T-lymphocyte
Foreign cell
Dead foreign cell
Foreign cell
1 In response to a signal from a helper
T-lymphocyte, CD8 coreceptors in cytotoxic
T-lymphocyte attach to a foreign cell and
initiate processes for cell death.
2 Cytotoxic T-lymphocyte detaches from
3 Foreign cell dies.
foreign cell.
Figure 24.5
Types of T-lymphocytes and Their Role in the Immune Response. (a) Helper T-lymphocytes recognize antigens and then secrete cytokines to
initiate both the maturation of immune defense cells and the immune response. (b) Cytotoxic T-lymphocytes recognize foreign antigens and directly
attack and kill foreign cells, thereby reducing threats by pathogens.
Helper T-lymphocytes are needed to begin an effective
defense against antigens. They primarily contain the CD4 coreceptor. For this reason, helper T-lymphocytes are also called CD4+ cells,
or T4 cells. There are many kinds of helper T-lymphocytes in the
body, and each is activated by and responds to one type of antigen
only. For example, one type of helper T-lymphocyte may respond
to the chickenpox virus, but this same helper T-lymphocyte will
not be activated if it comes across Streptococcus bacteria. Helper
T-lymphocytes initiate and oversee the immune response; in
other words, they are the “conductors” in the immune response
“symphony.” Helper T-lymphocytes regulate the immune response
using two methods. The first method is to present an antigen to
other lymphatic cells. The second method is to secrete cytokines
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(sı̄ ́tō-kin; kinesis = movement), which are chemical signals that bind
to receptors on other lymphatic cells and activate them.
Cytotoxic T-lymphocytes, also called CD8+ cells or T8 cells,
primarily contain the CD8 coreceptor. These lymphocytes come in
direct contact with infected or foreign cells and kill them. Each type
of cytotoxic T-lymphocyte responds to one type of antigen only.
Cytotoxic T-lymphocytes can kill in either of two ways: by secreting substances into abnormal cells that cause unregulated entry of
material into the cell, which may cause cell swelling and bursting,
or by triggering cell death directly. A cytotoxic T-lymphocyte acts
only after it is activated by a helper T-lymphocyte.
In addition to the two main groups, other subsets of
T-lymphocytes include memory T-lymphocytes and regulatory
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Cytokines
1 Helper T-lymphocyte secretes
cytokines and presents an antigen to
a B-lymphocyte.
Helper T-lymphocyte
Antigen presentation
Antigen
B-lymphocyte
Mitosis
2 B-lymphocyte divides, differentiating
into plasma cells and memory
B-lymphocytes.
Memory
B-lymphocyte
Plasma cells
3 Short-lived plasma cells secrete
antibodies that attach to the antigen.
Memory B-lymphocytes remain to
protect against future attacks by the
same antigen.
Secreted
antibodies
Memory B-lymphocyte responds to
reexposure of the antigen and initiates
a faster immune response than occurred
at first exposure to the antigen
Mitosis
4 If the same antigen enters the body at
a later time, the memory B-lymphocytes
divide to make more plasma cells and
memory cells.
Plasma cells
Secreted
antibodies
Memory
B-lymphocytes
Figure 24.6
B-lymphocytes and Their Role in the Immune Response. B-lymphocytes are activated by helper T-lymphocytes when presented with an
antigen. Their response to primary and secondary exposure to an antigen is shown here in a series of steps.
T-lymphocytes. Regulatory T-lymphocytes often contain the CD4
coreceptor and appear to “turn off” the immune response once
it has been activated to help regulate its performance. Memory
T-lymphocytes arise from T-lymphocytes that have encountered
a foreign antigen. They patrol the body, and if they encounter the
same antigen again, they mount an even faster immune response
than occurred at the first exposure to the antigen.
B-lymphocytes
B-lymphocytes make up about 15–30% of the lymphocytes
in the body. B-lymphocytes contain antigen receptors that
respond to one particular antigen and stimulate the production of immunoglobulins (Ig) (im ́ū -nō -glob ́ū -lin), or antibodies, that respond to that particular antigen. There are five
main classes of immunoglobulins based on the order of amino
acids in their composition. These classes, from most common
in the plasma to least common, are IgG, IgA, IgM, IgD, and
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IgE. These immunoglobulins act by forming antigen-antibody
complexes that help destroy or neutralize specific foreign antigens. Typically, a B-lymphocyte cannot be activated without
a helper T-lymphocyte. Once it is activated, the B-lymphocyte
undergoes cell division and differentiates into one of two types
of B-lymphocytes: plasma cells or memory B-lymphocytes
(figure 24.6).
Most of the activated lymphocytes become plasma (plaz ́ma)
cells, mature cells that produce and secrete large amounts of antibodies. Plasma cells may be either short-lived or long-lived. The
short-lived plasma cells have a life span of less than a week, while
long-lived plasma cells can live for months or years.
A few of the activated B-lymphocytes do not differentiate
into plasma cells and instead become memory B-lymphocytes.
These cells “remember” the initial antigen attack and stand guard
to mount a faster, more efficient immune response should the
same antigen strike again. If the antigen does strike again, the
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CLINICAL VIEW:
Lymphatic System
In Depth
HIV and AIDS
AIDS (acquired immunodeficiency syndrome) is a life-threatening
disease that results from infection by the human immunodeficiency
virus (HIV). HIV targets helper T-lymphocytes; the loss of these cells
gives rise to the devastating effects of AIDS.
EPIDEMIOLOGY
HIV can be found in the body fluids of an infected person, including
blood, semen, vaginal secretions, and breast milk. The virus is transmitted during activities that allow intimate contact with these body
fluids, such as unprotected vaginal or anal intercourse, sharing
hypodermic needles with other intravenous drug users, or breastfeeding an infant. Current evidence indicates that HIV is not spread
by casual kissing, sharing eating utensils, using a public toilet, or
other nonintimate types of physical contact. Although HIV was first
seen in the early 1980s among the homosexual male population and IV
drug users, it is now a major disease among heterosexual populations.
The United Nations program on AIDS (UNAIDS) estimates that 90%
of all HIV infections are currently transmitted heterosexually. Prior
to 1985, before HIV and AIDS were well known, HIV could be transmitted through the donated blood supply. Individuals who received
blood transfusions sometimes received HIV-infected blood, thereby
becoming infected as well. This discovery led to more stringent
screening of blood donors.
Since the early 1980s, over 60 million people have become infected
with HIV, and more than 27 million have died. The incidence of AIDS
is increasing throughout the world, but the disease is particularly
rampant on the continents of Africa and Asia. Southern Sub-Saharan
Africa has been hit especially hard with estimated infection rates of
15–18%. The AIDS epidemic in Africa has led to massive numbers of
deaths, and children are frequently orphaned as both parents succumb
to the disease. Asian countries are also seeing a surge of new HIV
and AIDS cases in recent years. Health officials are concerned that
these numbers will quickly multiply unless preventive measures are
taken soon.
PREVENTION
The key to limiting the spread of HIV infection is to refrain from behaviors
that allow the virus to be transmitted. Unprotected intercourse (especially
anal intercourse) and oral sex can spread HIV, so individuals should either
practice abstinence or protect themselves by using condoms. (Other
contraceptives, such as birth control pills, do not protect an individual
from HIV infection.) Both partners in a monogamous relationship should
be tested for HIV via a simple blood test before engaging in sexual intercourse. Intravenous drug users should not share needles. As a precaution,
health-care workers should wear gloves and be careful around patients’
body fluids. HIV-infected pregnant women need special prenatal care
to keep from transmitting the virus to their fetuses, and HIV-infected
mothers are discouraged from breast-feeding, because the virus is present in breast milk.
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HOW HIV CAUSES DAMAGE
HIV consists of two identical copies of a single strand of genetic material (RNA) surrounded by an outer protein coat. A small part of this
protein coat binds to the CD4 coreceptor on a helper T-lymphocyte.
(Some macrophages also have a CD4 coreceptor, so HIV can bind to
them as well.) After HIV attaches to the helper T-lymphocyte, it
enters the helper T-lymphocyte, the protein coat is shed, and the
HIV RNA is released into the helper T-lymphocyte. A DNA copy is
made of the HIV RNA, and then the HIV DNA is incorporated into the
helper T-lymphocyte’s DNA. Thus, the helper T-lymphocyte becomes
an “HIV factory” as it divides and produces new HIV that will travel
through the body and destroy other helper T-lymphocytes. Since helper
T-lymphocytes oversee the body’s immune response, their decrease
results in a loss of normal immune function. Thus, the infected
individual is prone to certain types of cancer and opportunistic
infections, diseases that would normally be eradicated by a healthy
immune system.
EARLY SYMPTOMS
Several weeks to several months after initial HIV infection, many individuals experience flulike symptoms, while others have no symptoms at
all. Typically, the early symptoms disappear after a few weeks. Healthy
helper T-lymphocytes divide to replace the cells that were lost in the
initial phase of infection. However, in the long run, HIV continues to
replicate at a faster rate than the immune system can replace the dying
infected cells. Over a period of months to years, the population of helper
T-lymphocytes drops to a dangerous level, setting the stage for AIDS.
HIV BLOOD TESTS
HIV blood tests detect the presence of HIV antibodies in the blood. It
can take as long as 6 months for antibody levels in the blood to rise to
a point where they can be detected by the blood test. Thus, individuals
who have been exposed to HIV, but are tested within the first 6 months,
may receive a false-negative result simply because the antibodies have
not yet reached the detectable level. Even though the antibody test is
negative at this early stage, the person can still infect others.
WHEN DOES HIV BECOME AIDS?
HIV is diagnosed as AIDS when a person’s helper T-lymphocyte count
drops to below 200 cells per cubic milliliter, when an opportunistic
infection or related illness develops, or when a particular type of malignancy develops. Common opportunistic infections include Pneumocystis
jiroveci pneumonia (PCP) and histoplasmosis. Malignancies that tend to
occur in people whose immune systems are weakened include Kaposi
sarcoma and non-Hodgkin lymphoma. Opportunistic infections and
malignancies account for up to 80% of all AIDS-related deaths. In addition, many AIDS patients have some form of CNS complications, including meningitis, encephalitis, neurologic deficits, and neuropathies.
TREATMENT OPTIONS
HIV infection is a lifelong illness; there is no cure. Current pharmaceutic
treatments alleviate symptoms or help prevent the spread of HIV infection
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733
Unfortunately, HIV drugs are expensive and not widely available
in developing countries, where the need for them is greatest. One
hopeful sign is that pharmaceutical companies are negotiating
with the governments of developing countries to make cheaper
forms of these drugs available. In addition, pharmaceutical companies are starting to work together to create better and easierto-use medications. For example, in July 2006, the FDA approved
an HIV medication that combines three of the “cocktail” HIV
drugs— efavirenz, emtricitabine, and tenofovir—in a single pill.
This pill is marketed under the brand name Atripla and was produced
through the collaboration of several drug companies. The single
daily dose medication will make treating HIV in foreign countries
much easier, since these drugs will be easier to distribute than
multiple pills and patients will be more likely to comply with the
simpler dosing schedule.
in the body, but they cannot eradicate HIV from an infected individual.
In addition, most of these drugs have numerous unpleasant side effects.
The first HIV drug treatment was zidovudine (AZT, Retrovir), which
helps prevent the HIV RNA from being transcribed into viral DNA.
AZT can help contain the infection, but the HIV often develops
resistance to it. Other newer HIV drugs target other cellular activities of HIV, helping prevent HIV from replicating in the helper
T-lymphocytes. Combinations of these different drugs (called “drug
cocktails”) are often given to HIV patients to retard the development of drug resistance and to ensure more effective elimination of
the viral copies from the blood (called viral load). Patients taking a
triple combination of drugs typically experience a dramatic reduction in viral load and even a slight rise in their helper T-lymphocyte
count. However, they must take these drugs for life, or else the HIV
and AIDS will progress.
HIV
HIV genetic material
CD4 coreceptors
DNA
RNA
HIV genetic material
HIV DNA in helper
T-lymphocyte
Helper T-lymphocyte
1 HIV targets and attaches to CD4 coreceptor
on helper T-lymphocyte.
2 HIV releases its genetic material into helper
DNA
DNA
3 HIV DNA is made from HIV RNA.
T-lymphocyte.
Helper T-lymphocyte
nucleus
Nuclear envelope
Helper T-lymphocyte
nucleus
HIV DNA
RNA
HIV RNA
Helper
T-lymphocyte
DNA
New HIV virus
4 HIV DNA incorporates itself into the helper
T-lymphocyte DNA.
mck78097_ch24_724-746.indd 733
HIV (human immunodeficiency virus) targets
helper T-lymphocytes in a multistep process.
5 The helper T-lymphocyte becomes an
"HIV factory," producing HIV that will be
released from the helper T-lymphocyte and
travel throughout the body.
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Table 24.1
Types of Lymphocytes
Cell Type
Function
Type of Antigen Response
Helper T-lymphocyte
Initiates and oversees the immune response
Responds to a single antigen
Cytotoxic T-lymphocyte
Directly kills foreign cells; must be activated by a helper
T-lymphocyte first
Responds to a single antigen
Memory T-lymphocyte
A type of T-lymphocyte that has already encountered an
antigen; patrols the body looking for the same antigen again
Responds to a single antigen
Regulatory T-lymphocyte
Helps “turn off” the immune response once it has been
activated
Responds to a single antigen
Plasma cell
Produces and secretes antibodies
Responds to a single antigen
Memory B-lymphocyte
Remembers an initial antigen attack and mounts a faster, more
efficient response should the same antigen type attack again
Responds to a single antigen
T-LYMPHOCYTE
B-LYMPHOCYTE
NK (NATURAL KILLER) CELL
NK (natural killer) cell
Kills a wide variety of infected and cancerous cells
body responds so quickly that no symptoms may occur. Memory
B-lymphocytes have a much longer life span than plasma cells;
some live for months or even years.
Some vaccines (e.g., polio vaccine, flu vaccine) introduce
modified or dead forms of an antigen so that memory cells may
be formed and the body can fight and eliminate the illness before
any symptoms ever develop. Depending upon the life span of the
particular memory B-lymphocytes, the vaccine may provide lifelong immunity, or periodic booster shots may be needed to ensure
continued protection against the antigen.
W H AT D O Y O U T H I N K ?
1
●
Tetanus (commonly known as lockjaw) is a severe illness that
causes painful muscle spasms and convulsions and can lead to
death. If adults are advised to get a tetanus booster shot about
once every 10 years, what is the probable life span of the tetanusdetecting memory B-lymphocytes?
Responds to multiple antigens
NK Cells
NK (natural killer) cells, also called large granular lymphocytes,
make up the remaining small percentage of body lymphocytes. NK
cells tend to have CD16 receptors. Unlike T- and B-lymphocytes,
which respond to one particular antigen only, NK cells can kill a
wide variety of infected cells and some cancerous cells.
Table 24.1 reviews the main types of lymphocytes and their
functions.
24.3b Lymphopoiesis
Lymphopoiesis (lim-fō-poy-ē ́sis) is the process of lymphocyte development and maturation. When a lymphocyte fully matures, it becomes
immunocompetent, meaning that the lymphocyte is fully able to
participate in the immune response. Immature lymphocytes cannot
participate in the immune response. All lymphocyte types originate in
the red bone marrow, but their maturation sites differ (figure 24.7).
Red Bone Marrow
Hemopoietic stem cell
Thymus
Lymphoid
stem cell
Figure 24.7
Lymphopoiesis. (a) B-lymphocytes
and NK cells mature in the red bone
marrow. (b) T-lymphocytes mature and
differentiate in the thymus under the
influence of thymic hormones.
Migrate to
thymus
Lymphoid stem cell
NK cells
B-lymphocytes
(a) B-lymphocyte and NK cell maturation
(in red bone marrow)
mck78097_ch24_724-746.indd 734
Lymphoid stem cell
Thymic hormones
help differentiate
T-lymphocytes
(b) T-lymphocyte maturation
(in thymus)
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Chapter Twenty-Four
In the red bone marrow, a hemopoietic stem cell gives rise
to several types of immature blood precursor cells, including lymphoid (lim ́foyd) stem cells (a slightly more differentiated type
of stem cell). Some lymphoid stem cells remain in the red bone
marrow and mature into B-lymphocytes and NK cells. Once the
B-lymphocytes and NK cells mature, they migrate from the bone
marrow, travel through the bloodstream, and enter lymphatic
structures and lymphatic organs.
Other lymphoid stem cells leave the red bone marrow and
migrate to the thymus for subsequent maturation. Under the influence of thymic hormones, these stem cells mature and differentiate into specific types of T-lymphocytes. Once the maturation and
differentiation process is complete, the T-lymphocytes migrate
to the other lymphatic structures in the body. The T-lymphocyte
maturation process primarily takes place from childhood until
puberty. Thereafter, the thymus regresses and becomes almost
nonfunctional in the adult.
Most lymphocytes have long life spans, and some can live for
many years. Once lymphocytes leave their maturation sites, they
can proliferate through cell division. However, note that each type of
lymphocyte can only replicate its own kind—that is, a B-lymphocyte
cannot produce a T-lymphocyte, only other B-lymphocytes. In addition, mature helper T-lymphocytes can only divide into other mature
helper T-lymphocytes, not other types of T-lymphocytes.
5
●
6
●
7
●
Lymphatic System
735
24.4a Lymphatic Nodules
Lymphatic nodules (nod ́ūl; nodulus = knot), or lymphatic follicles,
are ovoid clusters of lymphatic cells with some extracellular connective tissue matrix that are not surrounded by a connective tissue
capsule. The pale center of a lymphatic nodule is called the germinal (jer ́mi-na ̆l; germen = bud) center; it contains proliferating
B-lymphocytes and some macrophages. T-lymphocytes are located
outside the germinal center. Lymphatic nodules filter and attack
antigens. Individually, a lymphatic nodule is small. However, in
some areas of the body, many lymphatic nodules group together to
form larger structures, such as mucosa-associated lymphatic tissue
(MALT) or tonsils.
MALT (Mucosa-Associated Lymphatic Tissue)
Large collections of lymphatic nodules are located in the lamina
propria of the mucosa of the gastrointestinal, respiratory, genital,
and urinary tracts. Together, these collections of lymphatic nodules are called MALT (mucosa-associated lymphatic tissue). As
food, air, and urine enter their respective tracts, the lymphatic cells
in the MALT detect antigens and initiate an immune response.
MALT is very prominent in the mucosa of the small intestine, primarily in the ileum. There, collections of lymphatic nodules called
Peyer patches can become quite large and bulge into the gut lumen
(figure 24.8a).
W H AT D I D Y O U L E A R N?
Tonsils
List the main types of lymphatic cells.
Tonsils (ton ́sil; tonsilla = a stake) are large clusters of lymphatic
cells and extracellular connective tissue matrix that are not completely surrounded by a connective tissue capsule (figure 24.8b, c).
Tonsils consist of multiple germinal centers and have invaginated
outer edges called crypts. Crypts help trap material and facilitate
its identification by lymphocytes. Several groups of tonsils are
found in the pharynx (throat): Pharyngeal tonsils, or adenoids
(ad ́ĕ-noydz; aden = gland), are in the posterior wall of the nasopharynx; palatine tonsils are in the posterolateral region of the
oral cavity; and lingual tonsils are along the posterior one-third
of the tongue.
List and describe the functions of the different types of
T-lymphocytes and B-lymphocytes.
How and where are lymphocytes formed?
24.4 Lymphatic Structures
Learning Objectives:
1. Describe the structure and functions of lymphatic nodules.
2. List the organs of the lymphatic system, and explain their
functions.
In addition to the lymph vessels, the lymphatic system
consists of lymphatic nodules and various lymphatic organs (see
figure 24.1).
W H AT D O Y O U T H I N K ?
2
●
If your tonsils are removed, how does your body develop an
immune response against antigens in the throat? Are any other
sources of lymphatic cells or structures located there?
CLINICAL VIEW
Tonsillitis and Tonsillectomy
Because the tonsils are designed to protect the pharynx from infection, they frequently become inflamed and infected, a condition
called acute tonsillitis (ton ́si-lı̄ ́t is). The palatine tonsils are most
commonly affected. The tonsils redden and enlarge—in severe cases,
to the point that they partially obstruct the pharynx and may cause
respiratory distress.
Tonsils may be infected by viruses (such as adenoviruses) or bacteria
(most commonly Streptococcus). Streptococcal tonsillitis often results in
very red tonsils that have whitish specks (called whitish exudate). The
symptoms of tonsillitis include fever, chills, sore throat, and difficulty
swallowing. Bacterial tonsillitis (e.g., “strep throat”) is successfully treated
mck78097_ch24_724-746.indd 735
with antibiotics such as penicillin or amoxicillin. If tonsillitis is caused
by a virus, measures to relieve the inflammation (such as pain medication
and/or gargling) are advised, since standard antibiotics are not effective against viruses.
Persistent or recurrent infections can lead to permanent enlargement of the tonsils and a condition known as chronic tonsillitis.
If medical treatment does not help the chronic tonsillitis, surgical
removal of the tonsils (tonsillectomy) may be indicated. Typically,
medical guidelines suggest performing a tonsillectomy only if the
person has had six to seven tonsillar infections in 1 year, or two
to three infections per year for several years running. Research
indicates that tonsillectomy does not significantly affect the body’s
response to new infections.
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Pharyngeal
tonsil
Opening of
auditory tube
Palate
Palatine tonsil
Lingual tonsil
LM 140x
Simple columnar epithelium
of small intestine
MALT (Peyer patches)
(b) Tonsils
(a) MALT in small intestine
Figure 24.8
Lymphatic Nodules. (a) MALT (mucosa-associated lymphatic tissue)
in the ileum of the small intestine is called Peyer patches.
(b) Tonsils reside in the wall of the pharynx and are composed of
(c) lymphatic nodules.
LM 40x
Lymphatic nodules
(c) Histology of tonsil
24.4b Lymphatic Organs
A lymphatic organ consists of lymphatic cells within an extracellular connective tissue matrix, and is completely surrounded by
a connective tissue capsule. The main lymphatic organs are the
thymus, lymph nodes, and spleen.
Thymus
The thymus (thı̄ ́mŭs) is a bilobed organ located in the anterior
mediastinum. In infants and young children, the thymus is quite
large and extends into the superior mediastinum as well (figure
24.9a). The thymus continues to grow until puberty, when it
reaches a maximum weight of 30 to 50 grams. After reaching this
size, cells of the thymus regress, and much of the functional thymus is eventually replaced by adipose connective tissue. In adults,
the thymus atrophies and becomes almost nonfunctional.
In its prime, the thymus consists of two fused thymic lobes,
each surrounded by a connective tissue capsule. Fibrous extensions of the capsule, called trabeculae (tra -̆ bek ́ū-lē) or septa,
subdivide the thymic lobes into lobules; each lobule has an outer
mck78097_ch24_724-746.indd 736
cortex and an inner medulla (figure 24.9b). These distinct zones
support different stages of T-lymphocyte development. The cortex
contains immature T-lymphocytes, nurse cells, and some macrophages. The medulla contains epithelial cells and T-lymphocytes
that have completed maturation. In addition, the medulla contains
thymic corpuscles (or Hassall corpuscles), which are circular
aggregations of aged, degenerated epithelial cells (also known as
nurse cells) (figure 24.9c).
The thymus functions as a site for T-lymphocyte maturation
and differentiation. Immature lymphocytes migrate to the thymus
during embryonic development. These immature cells then reside
in the cortex of each lobule. The nurse cells in the cortex secrete
several thymic hormones that stimulate T-lymphocyte maturation
and differentiation. T-lymphocytes within the thymus do not participate in the immune response and are protected from antigens in
the body by a well-formed blood-thymus barrier around the blood
vessels in the cortex. When the T-lymphocytes differentiate (e.g.,
mature into helper T-lymphocytes or cytotoxic T-lymphocytes),
they migrate to the medulla of each lobule. No blood-thymus barrier is present in the medulla, so the mature T-lymphocytes enter
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737
Trabecula
Thyroid gland
Right
lung
Left lung
Thymus
Capsule
Cortex
Lobule
Medulla
Heart
Diaphragm
LM 20x
(b) Child’s thymus
(a) Child’s thorax, anterior view
Figure 24.9
Thymus. (a) The thymus is a bilobed lymphatic organ that is most
prominent in children. (b) A micrograph of a child’s thymus shows
the arrangement of the cortex and the central medulla within a
lobule. (c) A thymic corpuscle is visible within the medulla of the
thymus in this micrograph.
Lymphocytes
Thymic
corpuscle
Epithelial cells
LM 320x
(c) Thymic corpuscle
the bloodstream and migrate to other lymphatic system structures.
The T-lymphocyte maturation and differentiation process occurs
primarily when we are young. Once adulthood is reached, differentiated T-lymphocytes can be produced by cell division only, not
by maturation of new cells in the thymus.
Lymph Nodes
Lymph nodes are small, round or ovoid structures located along
the pathways of lymph vessels (see figure 24.1). They range in
length from 1 to 25 millimeters, and typically are found in clusters
that receive lymph from selected body regions. For example, the
cluster of lymph nodes in the armpit, called the axillary lymph
nodes, receives lymph from the breast, axilla, and upper limb.
Lymph nodes clustered in the groin, called inguinal lymph nodes,
receive lymph from the lower limb and pelvis. Cervical lymph
nodes receive lymph from the head and neck. In addition to these
clusters, lymph nodes are found individually throughout the body.
Each lymph node is surrounded by a tough connective tissue capsule (cap ́sool) (figure 24.10a). The capsule projects
internal extensions called trabeculae into the node, subdividing the node into compartments. The trabeculae also provide
a pathway through which blood vessels and nerves may enter
the lymph node. Lymphatic cells surround the trabeculae, and
tiny open channels called lymphatic sinuses provide a pathway
through which lymph flows.
The lymph node regions deep to the capsule are subdivided
into an outer cortex and an inner medulla. The cortex consists of
lymphatic nodules and lymphatic sinuses called cortical sinuses.
Remember that lymphatic nodules contain an outer region of
T-lymphocytes surrounding an inner germinal center that houses
proliferating B-lymphocytes and some macrophages. In addition,
dendritic cells within these lymph nodes collect antigens from the
mck78097_ch24_724-746.indd 737
lymph and present them to the T-lymphocytes. The lymph node
medulla has strands of lymphatic cells (primarily B-lymphocytes
and macrophages) supported by connective tissue fibers called
medullary cords. The medulla also contains lymphatic sinuses
called medullary sinuses.
The primary function of a lymph node is to filter antigens
from lymph and initiate an immune response when necessary.
Afferent lymphatic vessels carry lymph to the lymph node, where it
slowly percolates through the cortical sinuses and then the medullary sinuses. Macrophages line the lymphatic sinuses and remove
foreign debris from the lymph. Lymph then exits the lymph node
by way of one or two efferent lymphatic vessels. Efferent lymphatic
vessels originate at the indented portion of the lymph node called
the hilum (hı̄ ́lum
̆ ) or hilus.
If antigens are presented to lymphocytes, an immune
response is generated. The lymphocytes undergo cell division
(especially in the germinal centers), and these new lymphocytes
eventually travel to the bloodstream, where they can help fight
infection. When a person is sick (e.g., influenza or strep throat),
some of the lymph nodes are often swollen and tender to the touch.
This is a sign that lymphocytes are proliferating and beginning to
fight the infection.
Cancerous cells from other areas of the body can travel easily
through the lymphatic system (a process called metastasis), and
become entrapped in lymph nodes. These cancerous cells can proliferate and also contribute to enlarged lymph nodes. A lymph node
enlarged by cancer tends to be firm and nontender, as opposed to
a lymph node that is swollen and tender due to an infection. If an
individual is diagnosed with a cancer, the lymph nodes that drain
the affected organ or body region are examined to determine if the
cancer has spread. For example, if cancer is detected in a breast,
the axillary lymph nodes are examined.
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Medullary sinus
T-lymphocytes
Medullary cord
Medulla
B-lymphocytes
Germinal center
Dendritic cells
Lymphatic nodule
Trabeculae
Afferent lymphatic
vessels
Capsule
Lymphatic nodule
Cortex
Germinal center
Cortical sinus
Hilum
Valve
Efferent lymphatic
vessel
Medullary cords
Medullary sinus
Trabecula
Macrophage
(a) Lymph node and its components
Lymphocytes
Medulla
Trabecula
Capsule
Germinal center within
lymphatic nodule
Lymphatic vessels
Lymphatic nodule
Medullary sinuses
Lymph node
Medullary cords
Cortex
Blood vessels
Medulla
Muscle
LM 20x
(b) Lymph node section
(c) Lymph node and lymphatic vessels
Figure 24.10
Lymph Nodes. Lymph nodes are small, encapsulated structures that filter the lymph in lymphatic vessels. (a) Green arrows indicate the direction
of lymph flow into and out of the lymph node. (b) A micrograph of a lymph node shows the cortex and medulla. (c) A cadaver photo of a lymph
node and lymphatic vessels.
mck78097_ch24_724-746.indd 738
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CLINICAL VIEW
Lymphoma
A lymphoma (lim-fō ́mă; oma = tumor) is a malignant neoplasm that
develops from lymphatic structures. Usually (but not always) a lymphoma presents as a nontender, enlarged lymph node, often in the
neck or axillary region. Some patients have no further symptoms,
while others may experience night sweats, fever, and unexplained
weight loss in addition to the nodal enlargement. Lymphomas are
grouped into two categories: Hodgkin lymphoma and non-Hodgkin
lymphoma.
Reed-Sternberg cell, a
characteristic of Hodgkin
lymphoma.
LM 1000x
Spleen
The largest lymphatic organ in the body is the spleen, which is
located in the left upper quadrant of the abdomen, inferior to the
diaphragm and adjacent to ribs 9–11. This deep red organ lies
lateral to the left kidney and posterolateral to the stomach. The
spleen can vary considerably in size and weight, but typically is
about 12 centimeters long and 7 centimeters wide. The spleen’s
posterolateral aspect (called the diaphragmatic surface) is convex
and rounded, while the concave anteromedial border (the visceral
surface) contains the hilum (or hilus), where blood vessels and
nerves enter and leave the spleen (figure 24.11a, d). A splenic
(splen ́ik) artery delivers blood to the spleen, while blood returns
to the circulation by way of a splenic vein.
The spleen is surrounded by a dense irregular connective
tissue capsule. The capsule sends extensions called trabeculae
into the organ. Within these trabeculae extend branches of the
splenic artery and vein called trabecular vessels. The spleen lacks
a cortex and medulla. Rather, the cells around the trabeculae are
subdivided into white pulp and red pulp. Red pulp surrounds each
cluster of white pulp (figure 24.11b, c).
The white pulp is associated with the arterial supply of
the spleen and consists of circular clusters of lymphatic cells
(T-lymphocytes, B-lymphocytes, and macrophages). In the center of each cluster is a central artery. As blood enters the spleen
and flows through the central arteries, the white pulp lymphatic
cells monitor the blood for foreign materials, bacteria, and other
antigens. If antigens are found, the T- and B-lymphocytes elicit an
immune response. Thus, while lymph nodes monitor lymph for
antigens, the spleen monitors blood for antigens.
The red pulp is associated with the venous supply of the
spleen, since blood that enters the spleen in the central arteries then travels through blood vessels in the red pulp. Red pulp
consists of splenic cords and splenic sinusoids. The splenic cords
(cords of Bilroth) contain erythrocytes, platelets, macrophages, and
mck78097_ch24_724-746.indd 739
Hodgkin lymphoma (or Hodgkin disease) is characterized by the presence of the Reed-Sternberg cell, a large cell whose two nuclei resemble
owl eyes, surrounded by lymphocytes within the affected lymph node.
Hodgkin lymphoma affects young adults (ages 16–35) and people over
60. It arises in a lymph node and then spreads to other nearby lymph
nodes. If caught early, Hodgkin lymphoma can be treated and cured
by excision of the tumor, radiation, and/or chemotherapy.
Non-Hodgkin lymphomas are much more common than Hodgkin lymphomas. These lymphomas typically develop in lymphatic structures, usually
from abnormal B-lymphocytes, and less commonly from T-lymphocytes.
Some kinds of non-Hodgkin lymphoma are aggressive and often fatal,
whereas others are slow-growing and indolent. Treatment depends on
the type of non-Hodgkin lymphoma, the extent of its spread at the time
of discovery, and the rate of progression of the malignancy.
The AIDS epidemic is associated with a significant rise in aggressive
B-lymphocyte non-Hodgkin lymphomas, prompting the Centers for
Disease Control to revise the definition of AIDS to include HIV-infected
patients who have this type of lymphoma. AIDS-related non-Hodgkin
lymphomas are aggressive and difficult to treat, putting the patient’s
health in further jeopardy.
some plasma cells. One of the functions of the spleen is to serve as
a blood reservoir, whereby the formed elements are stored in these
splenic cords. In situations where more erythrocytes (and thus,
greater oxygen delivery) are needed, such as during exercise, these
erythrocytes reenter the bloodstream. Since the spleen contains a
large amount of blood, severe trauma to the spleen results in massive hemorrhage.
Among the splenic cords, the splenic sinusoids act like
enlarged capillaries that carry blood. These vessels have a discontinuous basal lamina, so blood cells can easily enter and exit
across the vessel wall. Macrophages lining the sinusoid lumen
phagocytize (1) bacteria and foreign debris from the blood, and
(2) old and defective erythrocytes and platelets (a process called
hemolysis (hē-mol ́ i-sis; lysis = destruction). Old erythrocytes
can rupture or become trapped in the sinusoids, making them
a target for these macrophages. Sinusoids merge to form small
veins, and eventually the filtered blood leaves the spleen via the
splenic vein.
In summary, the spleen performs the following functions:
■
■
■
■
Initiates an immune response when antigens are found in
the blood (a white pulp function)
Serves as a reservoir for erythrocytes and platelets (a red
pulp function)
Phagocytizes old, defective erythrocytes and platelets (a red
pulp function)
Phagocytizes bacteria and other foreign materials
Table 24.2 summarizes the lymphatic structures and organs
and their functions.
W H AT D O Y O U T H I N K ?
3
●
If your spleen were removed (splenectomy), would you be able to
fight off illness and infections effectively? Why or why not?
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Central artery
White pulp
Red pulp
Splenic
sinusoids
Trabecula
Splenic cords
Diaphragmatic
surface
Capsule
Diaphragm
(b) Red and white pulp of spleen
Trabeculae
Visceral surface
Hilum
Splenic artery
Red pulp
Splenic vein
(a) Anterior view of spleen
Central artery
White pulp
Capsule
LM 40x
(c) Histology of spleen
Diaphragm
Splenic artery
Inferior vena cava
Hilum of spleen
Spleen
Splenic vein
Pancreas
Liver (cut)
Left kidney
(d) Abdominal cavity, anterior view
Figure 24.11
Spleen. (a) An anterior view illustrates the hilum as well as the splenic artery and vein. (b) A diagram depicts the microscopic arrangement of
blood vessels, the red pulp, and the white pulp. (c) A micrograph of the spleen shows areas of white pulp and red pulp. (d) A cadaver photo shows
the spleen and its relationship to the diaphragm, pancreas, and kidney. In this photo, the pancreas has been moved inferiorly to show the splenic
vessels more clearly.
mck78097_ch24_724-746.indd 740
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1
Lymphatic System
741
Table 24.2
Lymphatic Structures and Organs
Component
Structure or Organ1
Functions
Location
Lymphatic nodules
Structure
Filter and attack antigens
Throughout body
MALT (mucosa-associated
lymphatic tissue)
Structure
Filter and attack antigens in food, air, or
urine
Within walls of GI, respiratory, genital,
and urinary tracts
Tonsils
Structure
Protect against inhaled and ingested
materials
Within pharynx
Thymus
Organ
Site of T-lymphocyte maturation
and differentiation; stores maturing
lymphocytes
Superior mediastinum (in adults); anterior
and superior mediastinum (in children)
Lymph nodes
Organ
Filter lymph; mount immune response
Throughout body; frequently in clusters in
the axillary, inguinal, and cervical regions
Spleen
Organ
Filters blood and recycles aged erythrocytes
and platelets; serves as a blood reservoir;
houses lymphocytes; mounts immune
response to foreign antigens in the blood
In left upper quadrant of abdomen, near
9th–11th ribs and inferior to diaphragm
A lymphatic structure is unencapsulated or has an incomplete connective tissue capsule, while a lymphatic organ has a complete connective tissue capsule encircling it.
W H AT D I D Y O U L E A R N?
8
●
9
●
10
●
11
●
What is MALT, and where is it found?
Describe the main function of the thymus, and explain how the
blood-thymus barrier supports this function.
Describe the basic structure and function of a lymph node.
How do the white pulp and red pulp of the spleen differ with
respect to both cell population and function?
24.5 Aging and the Lymphatic
System
Learning Objective:
1. Explain how aging affects the lymphatic system.
Some lymphatic system functions are not affected by aging.
For example, the body effectively continues to transport lymph
back to the bloodstream and absorb dietary lipids from the small
intestine. However, other functions change as we age. First, when
an individual reaches adulthood, the thymus no longer matures and
differentiates T-lymphocytes. New T-lymphocytes can be produced
only by division (mitosis) of preexisting lymphocytes. Second, the
lymphatic system’s ability to provide immunity and fight disease
decreases as we get older. Helper T-lymphocytes do not respond
to antigens as well, and do not always reproduce rapidly. Reduced
numbers of helper T-lymphocytes lead to fewer B-lymphocytes
and other kinds of T-lymphocytes. Therefore, the body’s ability to
acquire immunity and resist infection decreases, making elderly
people more susceptible to illnesses and more likely to become
sicker than younger adults. Older individuals are advised to get a
pneumococcal vaccine or yearly influenza vaccinations because of
their increased risk of developing Streptococcus pneumoniae infections or the flu, respectively. The faltering immune system may
also be less able to target and eliminate malignant cells, suggesting
one reason why the elderly tend to be more prone to cancer.
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W H AT D I D Y O U L E A R N?
12
●
Why are elderly individuals more prone to illnesses?
24.6 Development of the Lymphatic
System
Learning Objective:
1. Outline the lymphatic system formation in the developing
embryo and fetus.
The origin of the lymph vessels is poorly understood. Some
anatomists believe they originate from the endothelium of veins,
while others support the theory that they originate from local mesoderm. Despite this conflict, we know that the first lymphatic structures (called primary lymph sacs) appear during the sixth week of
development. A total of six primary lymph sacs form: Two jugular
lymph sacs develop near each junction of the subclavian and future
internal jugular veins; two posterior lymph sacs develop near
each junction of the external and internal iliac veins; a retroperitoneal (re ́trō-per ́i-tō-nē ́a l̆ ) lymph sac forms in the digestive system
mesentery; and a cisterna chyli forms dorsal to the aorta (figure
24.12a).
Paired lymph vessels connect the lymph sacs by the ninth
week (figure 24.12b). Eventually, portions of the paired lymph vessels are obliterated, and a single thoracic duct forms that travels
from the cisterna chyli, along the bodies of the vertebrae, and empties into the union of the left subclavian and left internal jugular
veins. The right lymphatic duct is formed from some other lymph
vessels. Additional smaller lymph vessels form during and after
the embryonic period.
During the fetal period, connective tissue subdivides the
lymph sacs (except the cisterna chyli) into rounded structures that
later become the lymph nodes (figure 24.12c). Lymphocytes within
the developing lymph sacs eventually form the cortex and medulla
of each lymph node.
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Chapter Twenty-Four
Lymphatic System
Jugular lymph sacs
Retroperitoneal lymph sac
Cisterna chyli
Posterior lymph sacs
(a) Week 6: Primary lymph sacs form
Developing
right lymphatic duct
Jugular lymph sac
Jugular
lymph sac
Superior vena cava
Superior vena cava
Developing
thoracic duct
Developing thoracic duct
Cisterna chyli
Cisterna chyli
Posterior
lymph sac
Posterior
lymph sac
(b) Week 9: Lymph vessels connect
to the lymph sacs
(c) Fetal period: Right lymphatic and thoracic ducts
form; lymph sacs will form lymph nodes
Figure 24.12
Development of the Lymphatic System. (a) Lymph sacs appear by week 6 of development. (b) Paired lymph vessels develop by week 9.
(c) During the fetal period, some of the lymph vessels enlarge and form the right lymphatic and thoracic ducts. Lymph sacs eventually develop into
lymph nodes.
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Chapter Twenty-Four
Pharynx
Third pharyngeal
pouch
(dorsal portion)
743
Pharynx
Fourth pharyngeal
pouch (dorsal portion)
Superior parathyroid
glands
Larynx
Thyroid
Developing trachea
and larynx
Inferior parathyroid
glands
Thyroid
Right third
pharyngeal pouch
(ventral portion)
Lymphatic System
Left third pharyngeal
pouch (ventral portion)
Trachea
Thymus
Aortic
arch
Developing bronchi
(a) Week 5: Ventral portions of left and right third
pharyngeal pouches migrate inferiorly
(b) Week 7: Left and right third pharyngeal
pouches fuse to form the bilobed thymus
(c) Fetal period: Thymus is
positioned in mediastinum
Figure 24.13
Development of the Thymus. The thymus originates from the ventral portions of the third pharyngeal pouches. (a) These pouches branch off the
pharynx and migrate inferiorly beginning in the fifth week. (b) The left and right pouches fuse in the future mediastinum during the seventh week,
forming the bilobed thymus. (c) By the fetal period, the thymus gland is large and is positioned within the mediastinum.
The thymus forms from the ventral portions of the left and
right third pharyngeal pouches (figure 24.13). These pouches are
the internal, endodermal portions of the third pharyngeal arches.
During weeks 4–7 of development, the left and right third pouches
migrate inferiorly from the pharynx to their final position posterior to the sternum. There, the two ventral portions fuse to form
a single thymus gland. Lymphocytes begin infiltrating the gland
shortly after its formation. By the fetal period, the thymus gland
is large and located within the mediastinum, superior to the heart
and anterior to the aortic arch and trachea.
The spleen is formed from mesoderm that condenses in the
future greater omentum during the fifth week of development.
Initially, the spleen functions solely as a blood cell-producing organ.
During the second trimester, T-lymphocytes and B-lymphocytes
enter the organ, helping form the characteristic red pulp and
white pulp.
The palatine tonsils form from endoderm from the left and
right second pharyngeal pouches and the second pharyngeal arch
mesoderm. During months 3–5 of development, lymphatic cells
enter the tonsils. Other tonsils (e.g., pharyngeal tonsils, lingual
tonsils) and lymphatic structures such as MALT form from aggregations of lymphatic cells and connective tissue.
W H AT D I D Y O U L E A R N?
13
●
When does the spleen begin to develop?
Clinical Terms
autoimmune disease Disease in which the body’s immune system
mistakenly attacks its own healthy tissues. Examples include
systemic lupus erythematosus (SLE), multiple sclerosis
(MS), rheumatoid arthritis, type 1 diabetes mellitus, and
scleroderma.
lymphadenectomy (lim-fad-ĕ-nek ́tō-mē; aden = gland) Removal
or excision of lymph nodes.
mck78097_ch24_724-746.indd 743
lymphangitis (angeion = vessel) Inflammation of the lymph
vessels.
splenomegaly (splē-nō-meg ́a-̆ lē; mega = large) Enlarged
spleen, often seen in association with infection (e.g.,
mononucleosis).
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Chapter Twenty-Four
Lymphatic System
Chapter Summary
24.1 Functions
of the Lymphatic
System 725
■
The lymphatic system carries interstitial fluid back to the bloodstream, transports dietary lipids, houses and develops
lymphocytes, and generates an immune response.
24.2 Lymph and
Lymph Vessels 726
■
Lymph is interstitial fluid containing solutes and sometimes foreign material that is transported through lymph vessels to
the blood.
■
There are many types of lymph vessels. From smallest to largest, they are lymphatic capillaries, lymphatic vessels,
lymphatic trunks, and lymphatic ducts.
24.2a Lymphatic Capillaries
■
Lymphatic capillaries, the smallest lymph vessels, are endothelium-lined vessels with overlapping internal edges of
endothelial cells that regulate lymph entry.
■
Lacteals are lymphatic capillaries in the small intestine; they pick up and transport the lymph (called chyle) from the
intestine.
24.2b Lymphatic Vessels
726
■
Lymphatic vessels form from merging lymphatic capillaries. They have valves to prevent lymph backflow.
■
Afferent lymphatic vessels conduct lymph to lymph nodes, and efferent lymphatic vessels conduct lymph away from
lymph nodes.
24.2c Lymphatic Trunks
■
727
Lymphatic trunks form from merging lymphatic vessels; each trunk drains a major body region into a lymphatic duct.
24.2d Lymphatic Ducts
24.3 Lymphatic
Cells 729
726
727
■
The right lymphatic duct drains the right side of the head and neck, the right upper limb, and the right side of the thorax.
It drains into the junction of the right subclavian vein and the right internal jugular vein.
■
The thoracic duct drains lymph from the left side of the head and neck, the left upper limb, the left thorax, and all body
regions inferior to the diaphragm. It drains into the junction of the left subclavian vein and left internal jugular vein.
■
Lymphatic cells include macrophages that phagocytize foreign substances, epithelial cells that secrete thymic hormones,
dendritic cells that filter antigens from lymph, and lymphocytes that perform specific functions in the immune response.
24.3a Types and Functions of Lymphocytes
Helper T-lymphocytes respond to one type of antigen only, and secrete cytokines, which are chemical signals that activate
other lymphatic cells.
■
Cytotoxic T-lymphocytes kill infected or foreign cells following direct contact with them.
■
Memory T-lymphocytes arise from T-lymphocytes that have encountered an antigen, and cause a faster immune response
than the first time.
■
Regulatory T-lymphocytes often “turn off” the immune response once it has been activated.
■
Activated B-lymphocytes respond to one particular antigen; they proliferate and differentiate into either plasma cells or
memory B-lymphocytes.
■
Plasma cells produce and secrete large numbers of antibodies.
■
Memory B-lymphocytes mount an even faster and more powerful immune response upon reexposure to an antigen.
■
NK cells respond to multiple antigens; they destroy infected cells and some cancerous cells.
24.3b Lymphopoiesis
24.4 Lymphatic
Structures 735
734
■
Some hemopoietic stem cells remain in the red bone marrow and mature into B-lymphocytes and NK cells. Other stem
cells exit the marrow and migrate to the thymus for subsequent maturation into T-lymphocytes.
■
Lymphatic structures include lymphatic nodules and various lymphatic organs.
24.4a Lymphatic Nodules
735
■
Lymphatic nodules are ovoid clusters of lymphatic cells and extracellular connective tissue matrix that are not contained
within a connective tissue capsule.
■
MALT (mucosa-associated lymphatic tissue) is composed of lymphatic nodules housed in the walls of the GI, respiratory,
genital, and urinary tracts.
■
Tonsils are large clusters of partially encapsulated lymphatic cells and extracellular connective matrix.
24.4b Lymphatic Organs
mck78097_ch24_724-746.indd 744
729
■
736
■
The lymphatic organs are composed of lymphatic structures completely surrounded by a connective tissue capsule.
■
The thymus is where T-lymphocytes mature and differentiate under stimulation by thymic hormones.
■
Lymph nodes are small structures that filter lymph.
■
The spleen is partitioned into white pulp (consists of clusters of lymphatic cells that generate an immune response when
exposed to antigens in the blood) and red pulp (consists of splenic cords that store blood and sinusoids containing
macrophages that phagocytize foreign debris, old erythrocytes, and platelets).
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Chapter Twenty-Four
Lymphatic System
24.5 Aging and
the Lymphatic
System 741
■
The lymphatic system’s ability to provide immunity and fight disease decreases as we get older.
24.6 Development
of the Lymphatic
System 741
■
The primary lymph sacs eventually give rise to lymph nodes.
■
The thymus forms from the ventral portions of the left and right third pharyngeal pouches.
■
The spleen forms from mesodermal condensations during week 5 of development.
■
The palatine tonsils are derived from the second pharyngeal pouches.
745
Challenge Yourself
Matching
Match each numbered item with the most closely related lettered
item.
______ 1. lymph node
______ 2. antibody
______ 3. helper T-lymphocyte
______ 4. spleen
a. receives lymph from some
lymphatic trunks
b. former monocyte that
phagocytizes foreign debris
______ 5. red bone marrow
c. B-lymphocytes mature and
differentiate here
______ 6. macrophage
d. smallest type of lymph vessel
______
e. attaches to an antigen
7. lymphatic capillary
______ 8. thymus
______ 9. lymphatic vessel
______ 10. thoracic duct
f. T-lymphocytes mature and
differentiate here
g. filters lymph
h. drains directly into and out of
lymph nodes
i. removes old and defective
erythrocytes
j. cell type that regulates the
immune response
Multiple Choice
Select the best answer from the four choices provided.
______ 1. Lymph from which of the following body regions
drains into the thoracic duct?
a. right side of the thorax
b. right upper limb
c. right lower limb
d. right side of the head
______ 2. Which type of lymphatic cell is responsible for
producing antibodies?
a. macrophage
b. helper T-lymphocyte
c. plasma cell
d. NK cell
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______ 3. Which statement is false about lymphatic nodules?
a. The center has proliferating B-lymphocytes and
some macrophages.
b. T-lymphocytes are located along the periphery.
c. Lymphatic nodules are completely surrounded by
a connective tissue capsule.
d. Lymphatic nodules in the ileum of the small
intestine are called Peyer patches.
______ 4. What is the function of the blood-thymus barrier?
a. It protects maturing T-lymphocytes from antigens
in the blood.
b. It filters the blood and starts an immune response
when necessary.
c. It subdivides the thymus into a cortex and a
medulla.
d. It forms thymic corpuscles.
______ 5. Which type of lymph vessel consists solely of an
endothelium and has one-way flaps that allow
interstitial fluid to enter?
a. lymphatic vessel
b. lymphatic capillary
c. lymphatic duct
d. lymphatic trunk
______ 6. Which statement is true about lymph nodes?
a. Cancerous lymph nodes are swollen and tender to
the touch.
b. The medulla of a lymph node contains lymphatic
nodules.
c. Lymph enters the lymph node through afferent
lymphatic vessels.
d. Lymphatic sinuses are located in the cortex of a
lymph node only.
______ 7. In an early Streptococcus infection of the throat, all
of the following structures may swell except the
a. pharyngeal tonsil.
b. spleen.
c. cervical lymph node.
d. palatine tonsil.
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Chapter Twenty-Four
Lymphatic System
______ 8. Which of the following is a function of the white
pulp of the spleen?
a. phagocytizes erythrocytes
b. serves as a blood cell reservoir
c. elicits an immune response if antigens are
detected in the blood
d. serves as a site for hemopoiesis during fetal life
______ 9. The primary lymph sacs form the
a. thoracic duct.
b. right lymphatic duct.
c. spleen.
d. lymph nodes.
7. Describe how the thymus’s anatomy and function change
from infancy on.
8. Describe the basic anatomy of a lymph node, how lymph
enters and leaves the node, and the functions of this organ.
9. Compare and contrast the red and white pulp of the spleen
with respect to the anatomy and functions of each.
10. Describe how lymph vessels and lymph nodes develop.
Developing Critical Reasoning
______ 10. What change occurs to the adult lymphatic system
as we get older?
a. The body produces and transports less lymph.
b. Greater numbers of B-lymphocytes are produced.
c. Helper T-lymphocytes do not respond as well to
antigens.
d. The lymph nodes enlarge.
Content Review
1. List the functions of the lymphatic system.
2. Describe what lymph is, and draw a flowchart that
illustrates what structures the lymph travels through to
return to the bloodstream.
3. Which body regions have their lymph drained to the
thoracic duct?
4. Compare and contrast the types of lymphatic cells with
respect to their appearance, function, and place of maturation.
5. Describe how the lymphatic cells elicit an immune response.
6. Describe the basic composition of a lymphatic nodule, and
give examples in the body where lymphatic nodules may
be found.
1. Arianna was diagnosed with mononucleosis, an infectious
disease that targets B-lymphocytes. When she went to
the doctor, he palpated her left side, just below the rib
cage. The doctor told Arianna she was checking to see if a
certain organ was enlarged, a complication that can occur
with mononucleosis. What lymphatic organ was the doctor
checking, and why would it become enlarged? Include some
explanation of the anatomy and histology of this organ in
your answer.
2. Why is HIV infection so devastating to the body? In your
answer, explain what cells are infected and why the
body cannot produce more mature, noninfected cells.
Also explain how AIDS affects the way the body fights
infection, and give some examples of ailments that are
common among AIDS patients.
3. Jordan has an enlarged lymph node along the side of
his neck, and he is worried that the structure may be a
lymphoma. What are some criteria to help distinguish
between infected lymph nodes and malignant lymph
nodes? If the lymph node were cancerous, how would
a physician determine if the cancer has spread to other
parts of the body?
Answers to “What Do You Think?”
1. If you need a booster shot about once every 10 years, that
indicates a maximum 10-year life span of tetanus-detecting
memory B-lymphocytes. Many of these cells may die off
before the 10 years is up, which is why a physician gives
you a tetanus booster earlier if you have been exposed to
tetanus—for example, by piercing your foot on a rusty nail
that could carry tetanus bacteria.
2. If the tonsils are removed, other lymphatic tissue and
lymphatic organs in the head and neck, such as lymph
nodes, can mount an immune response to antigens in
the throat. Also, the lymphocytes circulating in the
bloodstream can detect antigens in the throat.
3. Most individuals who have their spleens removed can
fight off illness and infections effectively, because the
other lymphatic tissues and organs take over the immune
functions previously handled by the spleen. However, the
risk for severe bacterial infection is greater, since there is
no spleen to filter bacteria from the blood. For this reason,
individuals who have undergone splenectomies may need
to be vaccinated against certain bacteria and undergo longterm (years or even lifelong) antibiotic therapy.
www.mhhe.com/mckinley3
Enhance your study with practice tests and
activities to assess your understanding. Your instructor may also recommend
the interactive eBook, individualized learning tools, and more.
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