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Home , Cisterna chyli, Hilum (anatomy), Lumen (anatomy), Lymphatic system, Lymphatic vessel, Lymph capillary

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24.1 Functions of the 725 24.2 and Lymph Vessels 726 24 24.2a Lymphatic 726 24.2b Lymphatic Vessels 726 24.2c Lymphatic Trunks 727 24.2d Lymphatic Ducts 727 Lymphatic 24.3 Lymphatic Cells 729 24.3a Types and Functions of 729 24.3b 734 24.4 Lymphatic Structures 735 System 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: LYMPHATIC SYSTEM

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e have seen in chapters 21–23 how the cardiovascular system W transports 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 maintain- ing 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 and cells. Lymphatic structures contain certain cells that initiate an immune Axillary response to abnormal materials. Without the primary immune response by the lymphatic system, the body would be unable to fight lymph nodes and keep itself healthy. In this chapter we examine the lymph vessels, lymphatic Thoracic duct structures, and lymphatic organs of the body, and learn how each of these components plays an important role in keeping us healthy. Mucosa- associated lymphatic (MALT) (in small 24.1 Functions of the Lymphatic intestine) System Inguinal Learning Objective: lymph nodes 1. Explain how the lymphatic system aids fluid homeostasis and guards the health of body cells and tissues. The lymphatic (lim- ́ik) system involves several organs Red marrow as well as a system of lymphatic cells and lymph vessels located throughout the body (figure 24.1). Together, these structures Lymph vessels 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 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 extracel- lular 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 (e-dē ḿă ; 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 Figure 24.1 of control and helps maintain blood volume levels. Lymphatic System. The lymphatic system consists of lymph vessels, Lymph vessels also transport dietary . Although most lymphatic cells, and lymphatic organs that work together to pick up nutrients are absorbed directly into the bloodstream, some larger and transport interstitial fluid back to the blood and to mount an materials, such as lipids and -soluble vitamins, are unable to immune response when needed. enter the bloodstream directly from the gastrointestinal (GI) tract. These materials are transported through tiny lymph vessels called producing), which are any substances perceived as abnormal to the , which drain into larger lymph vessels and eventually into body, such as bacteria, viruses, and even cancer cells. If the bloodstream. are discovered, lymphatic cells initiate a systematic defense against ū ́ Lymphatic organs house lymphocytes, a type of leukocyte (see the antigens, called an immune (i-m n ) response. Some of the cells chapter 21). While some lymphocytes circulate in the bloodstream, produce soluble called that bind to the foreign or most are located in the lymphatic structures and organs. Some lym- abnormal agent, thus damaging it or identifying it to other elements phatic organs assist in these cells’ maturation, while others serve as of the . Other cells attack and destroy the a site for replication (mitosis). directly. Still other cells become memory cells, which remember the Finally, the lymphatic system cells generate an immune past antigen encounters and initiate an even faster and more power- response and increase the lymphocyte population when necessary. ful response should the same antigen appear again. Lymphatic structures contain T-lymphocytes, B-lymphocytes, and ( that have migrated from the bloodstream WHATW DID YOU LEARN? into other tissues). These cells are constantly monitoring the blood ●1 What is the “immune response,” and how does the lymphatic and the interstitial fluid for antigens (an ti-gen;́ anti(body) + gen = system initiate it?

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When the pressure increases in the lymphatic capillary, the cell wall 24.2 Lymph and Lymph Vessels margin pushes back into place next to the adjacent endothelial cell. The fluid that is now “trapped” in the cannot be Learning Objectives: released back into the interstitial spaces. This process is analogous 1. Identify the components of lymph. to the movement of the entryway door to your house or apartment. 2. Outline the path of lymph from interstitial tissues to the Imagine that the door is unlocked and the knob is turned. Putting bloodstream. 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 Excess interstitial fluid and solutes are returned to the blood- to the inside so you can enter. Once inside, pressure applied to the stream through a lymph vessel network. When the combination inside surface of the door (or fluid pressure against the inside lym- of interstitial fluid, solutes, and sometimes foreign material enters phatic capillary surface) causes it to close. the lymph vessels, the liquid mixture is called lymph (limf; lym- The (part of the GI tract) contains special pha = clear spring water). The lymph vessel network is composed types of lymphatic capillaries called lacteals (lak t́ē -ăl; lactis = of increasingly larger vessels, as follows (from smallest to largest milk). Lacteals pick up not only interstitial fluid, but also dietary in diameter): lymphatic capillaries, lymphatic vessels, lymphatic lipids and lipid-soluble vitamins (vitamins that must be dissolved trunks, and lymphatic ducts. Thus, the term “lymph vessel” is a in lipids before they can be absorbed). The lymph from the GI tract general term to describe all of these specific lymphatic capillaries, has a milky color due to the lipid, and for this reason the GI tract lymphatic vessels, trunks, and ducts. lymph is also called (kı̄l; chylos = juice). 24.2a Lymphatic Capillaries The lymph vessel network begins with microscopic vessels called 24.2b Lymphatic Vessels lymphatic capillaries. Lymphatic capillaries are closed-ended tubes Lymphatic capillaries merge to form larger structures called lym- that are interspersed among most blood capillary networks (figure phatic vessels. Lymphatic vessels resemble small , in that 24.2), except those within the red and central ner- both contain three tunics (intima, media, and externa) and both vous system. In addition, avascular tissues (such as epithelia) lack have valves within the . Since the lymph vessel network is lymphatic capillaries. A lymphatic capillary is similar to a blood a low-pressure system, valves prevent lymph from pooling in the capillary in that its wall is an . However, and help prevent lymph backflow (figure 24.3). These capillaries tend to be larger in diameter, lack a basement mem- valves are especially important in areas where lymph flow is brane, and have overlapping endothelial cells. Anchoring filaments against the direction of gravity. Contraction of nearby skeletal help hold these endothelial cells to the nearby structures. These muscles also helps move lymph through the vessels. overlapping endothelial cells act as one-way flaps; when interstitial Some lymphatic vessels connect directly to lymphatic organs fluid pressure rises, the margins of the endothelial cells push into called lymph nodes. Afferent lymphatic vessels bring lymph to a the lymphatic capillary lumen and allow interstitial fluid to enter. where it is filtered for foreign or pathogenic material.

Interstitial space Capillary bed

Endothelium of lymphatic capillary Lymphatic capillary

Interstitial fluid Tissue cell

Opening

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 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 one- way flaps in its endothelial lining.

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Overlapping endothelial cells

Valve open Lymph (lymph flows forward)

Direction of Valve closed lymph flow (backflow of lymph is prevented) LM 100x

Valve Lymphatic vessel (a) Lymphatic vessel, longitudinal section (b) Lymphatic vessel, cross section

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 lym- right , and right side of the (figure 24.4b). The phatic vessels. Lymph nodes are often found in clusters, so after thoracic duct is the largest lymph vessel, with a length of about one lymph node receives and filters lymph, the lymph is passed to 37.5 to 45 centimeters (15 to 18 inches). At the base of the thoracic another lymph node in the cluster, then to another lymph node, duct and anterior to the L2 vertebra is a rounded, saclike structure and so on. Thus, lymph is repeatedly examined for the presence of called the cisterna chyli (sis-ter ńă kı̄ ́lı̄; cistern) (figure 24.4a). foreign or pathogenic materials. The cisterna chyli gets its name from the milky lymph called chyle it receives from the small intestine. Left and right intestinal and 24.2c Lymphatic Trunks lumbar trunks drain into the cisterna chyli. The thoracic duct Left and right lymphatic trunks form from merging lymphatic travels superiorly from the cisterna chyli and lies directly anterior vessels (figure 24.4). Each lymphatic trunk drains lymph from a to the vertebral bodies. It passes through the aortic opening of the major body region, as follows: diaphragm, and then it ascends to the left of the vertebral body midline. It drains lymph into the junction of the left subclavian ■ Jugular trunks drain lymph from the head and neck. and left . The thoracic duct receives ■ Subclavian trunks drain lymph from the upper limbs, lymph from most regions of the body, including the left side of the , and superficial thoracic wall. head and neck, left upper limb, left thorax, and all body regions ■ Bronchomediastinal trunks drain deep thoracic structures. inferior to the diaphragm (including the right lower limb and right ■ Intestinal trunks drain most abdominal structures. side of the abdomen). ■ Lumbar trunks drain the lower limbs, abdominopelvic wall, and pelvic organs.

24.2d Lymphatic Ducts WHATW DID YOU LEARN? Lymphatic trunks drain into the largest vessels, called lymphatic ducts. The two lymphatic ducts empty lymph back into the venous ●2 What is lymph? circulation. The right lymphatic duct, located near the right ●3 Describe the structure of lymphatic capillaries. Into what , returns the lymph into the junction of the right subclavian structures do they drain? vein and the right internal jugular vein. It receives lymph from the ●4 Which major body regions drain lymph to the right lymphatic trunks that drain the right side of the head and neck, lymphatic duct?

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Right jugular trunk Right subclavian trunk Right lymphatic duct Left internal jugular vein Right bronchomediastinal trunk Left 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 Right lumbar trunk Intestinal trunk

(a) Posterior thoracic wall, anterior view

Thoracic duct

Thyroid gland Left internal jugular vein Area drained by Left vertebral vein (cut) right lymphatic duct Left subclavian vein Left vertebral Right brachiocephalic vein Left brachiocephalic Brachiocephalic artery Area drained vein by thoracic duct

Superior vena cava

Thoracic duct

Azygos vein Hemiazygos 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 in the of the foot, which is why many cases of lymphedema in the foot are seen. However, mosquitoes are the most common vector for Lymphedema (limf ́e-de¯ ́ma˘) refers to an accumulation of interstitial transmitting . Once the mature worms have entered the body, fluid that occurs due to interference with lymphatic drainage in a they become permanent “residents.” An affected body part can swell part of the body. As the interstitial fluid accumulates, the affected to many times its normal size. In these extreme cases, the condition area swells and becomes painful. If lymphedema is left untreated, the also is known as elephantiasis (el-e˘-fan-tı¯ a˘-sis;́ elephas = ). -rich interstitial fluid may interfere with wound healing and Patients are treated with medications to kill the filarial worms, although can even contribute to an infection by acting as a growth medium the damage to the lymphatic system may be irreversible. for bacteria. 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., cancer surgery when the 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. ■ may cause scar formation that interferes with lymphatic drainage. Elephantiasis () of the lower limb. ■ Trauma or infection of the lymph vessels obstructs lymphatic drainage. Lymphedema has no cure, but it can be controlled. Patients may In addition, millions of individuals in Southeast Asia and Africa have wear compression stockings or other compression garments to reduce developed lymphedema as a result of infection by threadlike parasitic swelling and assist interstitial fluid return to the circulation. Certain filarial worms. Lymphatic filariasis (fil-a˘-rı¯ a˘-sis;́ filum = thread) is a exercise regimens may improve lymphatic drainage as well. Ideally, an type of lymphedema whereby filarial worms lodge in the lymphatic sys- individual with any symptoms of lymphedema, such as swelling and pain tem, live and reproduce there for years, and eventually obstruct lymphatic in a body region or skin feeling tight, should seek medical assistance drainage. Some filarial worms gain entrance to the body through cracks quickly in order for treatment to be most effective.

24.3a Types and Functions of Lymphocytes 24.3 Lymphatic Cells The three types of lymphocytes are T-lymphocytes (also called T-cells B-cells Learning Objectives: ), B-lymphocytes (also called ), and natural killer (NK) cells. All three types migrate through the lymphatic system 1. List and describe the types of lymphatic cells. and search for antigens. 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 Study Tip! both the lymphatic system and the cardiovascular system. The lymphatic cells work together to elicit an immune response. Lymphocytes are identified according to the tissue or where Among the types of lymphatic cells are macrophages, some epithe- they mature: lial cells, dendritic cells, and lymphocytes. T-lymphocytes mature in the Thymus. = = Macrophages (mak ŕō -faj; macros large, phago to eat) are B-lymphocytes mature in the Bone marrow. monocytes that have migrated into the lymphatic system from the bloodstream; they are responsible for phagocytosis of foreign sub- stances. They also may present antigens to other lymphatic cells. Special epithelial cells (also called nurse cells) are found in the thy- mus, where they secrete thymic hormones. Dendritic (den-drit ́ik) T-lymphocytes cells are found in the lymphatic nodules; they internalize antigens T-lymphocytes make up about 70–85% of body lymphocytes. from the lymph and present them to other lymphatic cells. These The lymphocyte plasma membrane contains a coreceptor that cells are the main antigen-presenting cell of the immune system. can recognize a particular antigen. (Coreceptors are named with (Recall from chapter 5 that dendritic cells within the skin epidermis the letters “CD” followed by a number.) There are several types perform the same function.) Lymphocytes are the most abundant of T-lymphocytes, each with a particular kind of coreceptor. cells in the lymphatic system. There are three types of lymphocytes, The two main groups are helper T-lymphocytes and cytotoxic and each has a specific job in the overall immune response. T-lymphocytes (figure 24.5).

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(a) Helper T-lymphocyte

Stimulates B-lymphocyte Foreign cell with antigen to produce antibodies

CD4 coreceptor

Cytokine Mitosis Regulates cytotoxic T-lymphocyte activity

Helper T-lymphocyte Encourages formation Helper of more macrophages T-lymphocytes

1 Helper T-lymphocyte recognizes antigen. 2 Helper T-lymphocyte secretes and 3 Cytokines secreted by helper T-lymphocytes begins to undergo mitosis to form more initiate and control the immune response. helper T-lymphocytes.

(b) Cytotoxic T-lymphocyte

CD8 coreceptor

Cytotoxic T-lymphocyte Foreign cell Dead foreign cell Cytotoxic T-lymphocyte Foreign cell

1 In response to a signal from a helper 2 Cytotoxic T-lymphocyte detaches from 3 Foreign cell dies. T-lymphocyte, CD8 coreceptors in cytotoxic foreign cell. T-lymphocyte attach to a foreign cell and initiate processes for cell death. 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 (sı̄ t́ō -kin; kinesis = movement), which are chemical signals that bind defense against antigens. They primarily contain the CD4 corecep- to receptors on other lymphatic cells and activate them. tor. For this reason, helper T-lymphocytes are also called CD4+ cells, Cytotoxic T-lymphocytes, also called CD8+ cells or T8 cells, or T4 cells. There are many kinds of helper T-lymphocytes in the primarily contain the CD8 coreceptor. These lymphocytes come in body, and each is activated by and responds to one type of antigen direct contact with infected or foreign cells and kill them. Each type only. For example, one type of helper T-lymphocyte may respond of cytotoxic T-lymphocyte responds to one type of antigen only. to the chickenpox virus, but this same helper T-lymphocyte will Cytotoxic T-lymphocytes can kill in either of two ways: by secret- not be activated if it comes across Streptococcus bacteria. Helper ing substances into abnormal cells that cause unregulated entry of T-lymphocytes initiate and oversee the immune response; in material into the cell, which may cause cell swelling and bursting, other words, they are the “conductors” in the immune response or by triggering cell death directly. A cytotoxic T-lymphocyte acts “symphony.” Helper T-lymphocytes regulate the immune response only after it is activated by a helper T-lymphocyte. using two methods. The first method is to present an antigen to In addition to the two main groups, other subsets of other lymphatic cells. The second method is to secrete cytokines T-lymphocytes include memory T-lymphocytes and regulatory

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Cytokines 1 Helper T-lymphocyte secretes cytokines and presents an antigen to Helper T-lymphocyte a B-lymphocyte. Antigen

B-lymphocyte

Mitosis 2 B-lymphocyte divides, differentiating into plasma cells and memory B-lymphocytes.

Plasma cells Memory B-lymphocyte

3 Short-lived plasma cells secrete antibodies that attach to the antigen. Memory B-lymphocytes remain to Secreted protect against future attacks by the antibodies same antigen. 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 IgE. These immunoglobulins act by forming antigen- coreceptor and appear to “turn off” the immune response once complexes that help destroy or neutralize specific foreign anti- it has been activated to help regulate its performance. Memory gens. Typically, a B-lymphocyte cannot be activated without T-lymphocytes arise from T-lymphocytes that have encountered a helper T-lymphocyte. Once it is activated, the B-lymphocyte a foreign antigen. They patrol the body, and if they encounter the undergoes cell division and differentiates into one of two types same antigen again, they mount an even faster immune response of B-lymphocytes: plasma cells or memory B-lymphocytes than occurred at the first exposure to the antigen. (figure 24.6). Most of the activated lymphocytes become plasma (plaz ma)́ B-lymphocytes cells, mature cells that produce and secrete large amounts of anti- B-lymphocytes make up about 15–30% of the lymphocytes bodies. Plasma cells may be either short-lived or long-lived. The in the body. B-lymphocytes contain antigen receptors that short-lived plasma cells have a life span of less than a week, while respond to one particular antigen and stimulate the produc- long-lived plasma cells can live for months or years. tion of immunoglobulins (Ig) (im ú¯-nō -glob ú¯-lin), or anti- A few of the activated B-lymphocytes do not differentiate bodies, that respond to that particular antigen. There are five into plasma cells and instead become memory B-lymphocytes. main classes of immunoglobulins based on the order of amino These cells “remember” the initial antigen attack and stand guard acids in their composition. These classes, from most common to mount a faster, more efficient immune response should the in the plasma to least common, are IgG, IgA, IgM, IgD, and same antigen strike again. If the antigen does strike again, the

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CLINICAL VIEW: In Depth HIV and AIDS HOW HIV CAUSES DAMAGE HIV consists of two identical copies of a single strand of genetic mate- AIDS (acquired syndrome) is a life-threatening rial (RNA) surrounded by an outer protein coat. A small part of this disease that results from infection by the immunodeficiency protein coat binds to the CD4 coreceptor on a helper T-lymphocyte. virus (HIV). HIV targets helper T-lymphocytes; the loss of these cells (Some macrophages also have a CD4 coreceptor, so HIV can bind to gives rise to the devastating effects of AIDS. them as well.) After HIV attaches to the helper T-lymphocyte, it enters the helper T-lymphocyte, the protein coat is shed, and the EPIDEMIOLOGY HIV RNA is released into the helper T-lymphocyte. A DNA copy is HIV can be found in the body fluids of an infected person, including made of the HIV RNA, and then the HIV DNA is incorporated into the blood, semen, vaginal , and breast milk. The virus is trans- helper T-lymphocyte’s DNA. Thus, the helper T-lymphocyte becomes mitted during activities that allow intimate contact with these body an “HIV factory” as it divides and produces new HIV that will travel fluids, such as unprotected vaginal or anal intercourse, sharing through the body and destroy other helper T-lymphocytes. Since helper hypodermic needles with other intravenous drug users, or breast- T-lymphocytes oversee the body’s immune response, their decrease feeding an infant. Current evidence indicates that HIV is not spread results in a loss of normal immune function. Thus, the infected by casual kissing, sharing eating utensils, using a public toilet, or individual is prone to certain types of cancer and opportunistic other nonintimate types of physical contact. Although HIV was first , diseases that would normally be eradicated by a healthy seen in the early 1980s among the homosexual male population and IV immune system. drug users, it is now a major disease among heterosexual populations. The United Nations program on AIDS (UNAIDS) estimates that 90% EARLY SYMPTOMS of all HIV infections are currently transmitted heterosexually. Prior Several weeks to several months after initial HIV infection, many indi- to 1985, before HIV and AIDS were well known, HIV could be trans- viduals experience flulike symptoms, while others have no symptoms at mitted through the donated blood supply. Individuals who received all. Typically, the early symptoms disappear after a few weeks. Healthy blood transfusions sometimes received HIV-infected blood, thereby helper T-lymphocytes divide to replace the cells that were lost in the becoming infected as well. This discovery led to more stringent initial phase of infection. However, in the long run, HIV continues to screening of blood donors. 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 Since the early 1980s, over 60 million people have become infected T-lymphocytes drops to a dangerous level, setting the stage for AIDS. with HIV, and more than 27 million have died. The incidence of AIDS is increasing throughout the world, but the disease is particularly HIV BLOOD TESTS rampant on the continents of Africa and Asia. Southern Sub-Saharan HIV blood tests detect the presence of HIV antibodies in the blood. It Africa has been hit especially hard with estimated infection rates of can take as long as 6 months for antibody levels in the blood to rise to 15–18%. The AIDS epidemic in Africa has led to massive numbers of a point where they can be detected by the blood test. Thus, individuals deaths, and children are frequently orphaned as both parents succumb who have been exposed to HIV, but are tested within the first 6 months, to the disease. Asian countries are also seeing a surge of new HIV may receive a false-negative result simply because the antibodies have and AIDS cases in recent years. Health officials are concerned that not yet reached the detectable level. Even though the antibody test is these numbers will quickly multiply unless preventive measures are negative at this early stage, the person can still infect others. taken soon. WHEN DOES HIV BECOME AIDS? PREVENTION HIV is diagnosed as AIDS when a person’s helper T-lymphocyte count The key to limiting the spread of HIV infection is to refrain from behaviors drops to below 200 cells per cubic milliliter, when an opportunistic that allow the virus to be transmitted. Unprotected intercourse (especially infection or related illness develops, or when a particular type of malig- anal intercourse) and oral sex can spread HIV, so individuals should either nancy develops. Common opportunistic infections include Pneumocystis practice abstinence or protect themselves by using condoms. (Other jiroveci pneumonia (PCP) and histoplasmosis. Malignancies that tend to contraceptives, such as birth control pills, do not protect an individual occur in people whose immune systems are weakened include Kaposi from HIV infection.) Both partners in a monogamous relationship should and non-Hodgkin . Opportunistic infections and be tested for HIV via a simple blood test before engaging in sexual inter- malignancies account for up to 80% of all AIDS-related deaths. In addi- course. Intravenous drug users should not share needles. As a precaution, tion, many AIDS patients have some form of CNS complications, includ- health-care workers should wear gloves and be careful around patients’ ing meningitis, encephalitis, neurologic deficits, and neuropathies. body fluids. HIV-infected pregnant women need special prenatal care to keep from transmitting the virus to their fetuses, and HIV-infected TREATMENT OPTIONS mothers are discouraged from breast-feeding, because the virus is pres- HIV infection is a lifelong illness; there is no cure. Current pharmaceutic ent in breast milk. treatments alleviate symptoms or help prevent the spread of HIV infection

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in the body, but they cannot eradicate HIV from an infected individual. Unfortunately, HIV drugs are expensive and not widely available In addition, most of these drugs have numerous unpleasant side effects. in developing countries, where the need for them is greatest. One hopeful sign is that pharmaceutical companies are negotiating The first HIV drug treatment was zidovudine (AZT, Retrovir), which with the governments of developing countries to make cheaper helps prevent the HIV RNA from being transcribed into viral DNA. forms of these drugs available. In addition, pharmaceutical com- AZT can help contain the infection, but the HIV often develops panies are starting to work together to create better and easier- resistance to it. Other newer HIV drugs target other cellular activi- to-use medications. For example, in July 2006, the FDA approved ties of HIV, helping prevent HIV from replicating in the helper an HIV medication that combines three of the “cocktail” HIV T-lymphocytes. Combinations of these different drugs (called “drug drugs— efavirenz, emtricitabine, and tenofovir—in a single pill. cocktails”) are often given to HIV patients to retard the develop- This pill is marketed under the brand name Atripla and was produced ment of drug resistance and to ensure more effective elimination of through the collaboration of several drug companies. The single the viral copies from the blood (called viral load). Patients taking a daily dose medication will make treating HIV in foreign countries triple combination of drugs typically experience a dramatic reduc- much easier, since these drugs will be easier to distribute than tion in viral load and even a slight rise in their helper T-lymphocyte multiple pills and patients will be more likely to comply with the count. However, they must take these drugs for life, or else the HIV simpler dosing schedule. and AIDS will progress.

HIV HIV genetic material

CD4 coreceptors DNA

RNA

DNA RNA HIV genetic material HIV DNA in helper T-lymphocyte Helper T-lymphocyte DNA

1 HIV targets and attaches to CD4 coreceptor 2 HIV releases its genetic material into helper 3 HIV DNA is made from HIV RNA. on helper T-lymphocyte. T-lymphocyte.

Helper T-lymphocyte Nuclear envelope nucleus Helper T-lymphocyte nucleus HIV DNA HIV RNA Helper T-lymphocyte DNA

HIV (human immunodeficiency virus) targets New HIV virus helper T-lymphocytes in a multistep process.

4 HIV DNA incorporates itself into the helper 5 The helper T-lymphocyte becomes an T-lymphocyte DNA. "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 T-LYMPHOCYTE 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 Responds to a single antigen T-lymphocyte fi rst Memory T-lymphocyte A type of T-lymphocyte that has already encountered an Responds to a single antigen antigen; patrols the body looking for the same antigen again Regulatory T-lymphocyte Helps “turn off” the immune response once it has been Responds to a single antigen activated

B-LYMPHOCYTE Produces and secretes antibodies Responds to a single antigen Memory B-lymphocyte Remembers an initial antigen attack and mounts a faster, more Responds to a single antigen effi cient response should the same antigen type attack again

NK (NATURAL KILLER) CELL NK (natural killer) cell Kills a wide variety of infected and cancerous cells Responds to multiple antigens

body responds so quickly that no symptoms may occur. Memory NK Cells B-lymphocytes have a much longer life span than plasma cells; NK (natural killer) cells, also called large granular lymphocytes, some live for months or even years. make up the remaining small percentage of body lymphocytes. NK Some vaccines (e.g., vaccine, flu vaccine) introduce cells tend to have CD16 receptors. Unlike T- and B-lymphocytes, modified or dead forms of an antigen so that memory cells may which respond to one particular antigen only, NK cells can kill a be formed and the body can fight and eliminate the illness before wide variety of infected cells and some cancerous cells. any symptoms ever develop. Depending upon the life span of the Table 24.1 reviews the main types of lymphocytes and their particular memory B-lymphocytes, the vaccine may provide life- functions. long , or periodic booster shots may be needed to ensure continued protection against the antigen. 24.3b Lymphopoiesis WHAT DO YOU THINK? Lymphopoiesis (lim-fō -poy-ē sis)́ is the process of lymphocyte develop- ment and maturation. When a lymphocyte fully matures, it becomes ●1 Tetanus (commonly known as lockjaw) is a severe illness that immunocompetent, meaning that the lymphocyte is fully able to causes painful muscle spasms and convulsions and can lead to death. If adults are advised to get a tetanus booster shot about participate in the immune response. Immature lymphocytes cannot once every 10 years, what is the probable life span of the tetanus- participate in the immune response. All lymphocyte types originate in detecting memory B-lymphocytes? the red bone marrow, but their maturation sites differ (figure 24.7).

Red Bone Marrow

Hemopoietic stem cell Thymus

Lymphoid Lymphoid stem cell Figure 24.7 stem cell Lymphopoiesis. (a) B-lymphocytes Lymphoid stem cell Migrate to and NK cells mature in the red bone thymus marrow. (b) T-lymphocytes mature and differentiate in the thymus under the influence of thymic hormones. NK cells Thymic hormones help differentiate T-lymphocytes B-lymphocytes

(a) B-lymphocyte and NK cell maturation (b) T-lymphocyte maturation (in red bone marrow) (in thymus)

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In the red bone marrow, a hemopoietic stem cell gives rise 24.4a Lymphatic Nodules to several types of immature blood precursor cells, including lym- Lymphatic nodules (nod ́ūl; nodulus = knot), or lymphatic follicles, phoid (lim ́foyd) stem cells (a slightly more differentiated type are ovoid clusters of lymphatic cells with some extracellular con- of stem cell). Some lymphoid stem cells remain in the red bone nective tissue matrix that are not surrounded by a connective tissue marrow and mature into B-lymphocytes and NK cells. Once the capsule. The pale center of a lymphatic nodule is called the ger- B-lymphocytes and NK cells mature, they migrate from the bone minal (jer mi-ń ăl; germen = bud) center; it contains proliferating marrow, travel through the bloodstream, and enter lymphatic B-lymphocytes and some macrophages. T-lymphocytes are located structures and lymphatic organs. outside the . Lymphatic nodules filter and attack Other lymphoid stem cells leave the red bone marrow and antigens. Individually, a lymphatic nodule is small. However, in migrate to the thymus for subsequent maturation. Under the influ- some areas of the body, many lymphatic nodules group together to ence of thymic hormones, these stem cells mature and differenti- form larger structures, such as mucosa-associated lymphatic tissue ate into specific types of T-lymphocytes. Once the maturation and (MALT) or tonsils. differentiation process is complete, the T-lymphocytes migrate to the other lymphatic structures in the body. The T-lymphocyte MALT (Mucosa-Associated Lymphatic Tissue) maturation process primarily takes place from childhood until Large collections of lymphatic nodules are located in the lamina puberty. Thereafter, the thymus regresses and becomes almost propria of the mucosa of the gastrointestinal, respiratory, genital, nonfunctional in the adult. and urinary tracts. Together, these collections of lymphatic nod- Most lymphocytes have long life spans, and some can live for ules are called MALT (mucosa-associated lymphatic tissue). As many years. Once lymphocytes leave their maturation sites, they food, air, and urine enter their respective tracts, the lymphatic cells can proliferate through cell division. However, note that each type of in the MALT detect antigens and initiate an immune response. lymphocyte can only replicate its own kind—that is, a B-lymphocyte MALT is very prominent in the mucosa of the small intestine, pri- cannot produce a T-lymphocyte, only other B-lymphocytes. In addi- marily in the . There, collections of lymphatic nodules called tion, mature helper T-lymphocytes can only divide into other mature Peyer patches can become quite large and bulge into the gut lumen helper T-lymphocytes, not other types of T-lymphocytes. (figure 24.8a). WHATW DID YOU LEARN? Tonsils ●5 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 com- ●6 List and describe the functions of the different types of T-lymphocytes and B-lymphocytes. pletely surrounded by a connective tissue capsule (figure 24.8b, c). Tonsils consist of multiple germinal centers and have invaginated ●7 How and where are lymphocytes formed? outer edges called crypts. Crypts help trap material and facilitate its identification by lymphocytes. Several groups of tonsils are found in the (throat): Pharyngeal tonsils, or 24.4 Lymphatic Structures (ad ́ĕ -noydz; aden = gland), are in the posterior wall of the naso- Learning Objectives: pharynx; palatine tonsils are in the posterolateral region of the oral cavity; and are along the posterior one-third 1. Describe the structure and functions of lymphatic nodules. of the . 2. List the organs of the lymphatic system, and explain their functions. WHAT DO YOU THINK? In addition to the lymph vessels, the lymphatic system ●2 If your tonsils are removed, how does your body develop an consists of lymphatic nodules and various lymphatic organs (see immune response against antigens in the throat? Are any other figure 24.1). sources of lymphatic cells or structures located there?

CLINICAL VIEW Tonsillitis and Tonsillectomy with antibiotics such as penicillin or amoxicillin. If tonsillitis is caused by a virus, measures to relieve the (such as pain medication Because the tonsils are designed to protect the pharynx from infec- and/or gargling) are advised, since standard antibiotics are not effec- tion, they frequently become inflamed and infected, a condition tive against viruses. called acute tonsillitis (ton ́si-lı¯ ́tis). The palatine tonsils are most Persistent or recurrent infections can lead to permanent enlarge- commonly affected. The tonsils redden and enlarge—in severe cases, ment of the tonsils and a condition known as chronic tonsillitis. to the point that they partially obstruct the pharynx and may cause If medical treatment does not help the chronic tonsillitis, surgical respiratory distress. removal of the tonsils (tonsillectomy) may be indicated. Typically, Tonsils may be infected by viruses (such as adenoviruses) or bacteria medical guidelines suggest performing a tonsillectomy only if the (most commonly Streptococcus). Streptococcal tonsillitis often results in person has had six to seven tonsillar infections in 1 year, or two very red tonsils that have whitish specks (called whitish exudate). The to three infections per year for several years running. Research symptoms of tonsillitis include fever, chills, sore throat, and difficulty indicates that tonsillectomy does not significantly affect the body’s swallowing. Bacterial tonsillitis (e.g., “strep throat”) is successfully treated response to new infections.

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Pharyngeal Opening of auditory tube Palate Lingual tonsil

LM 140x

Simple columnar MALT (Peyer patches) (b) Tonsils of small intestine (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) of tonsil

24.4b Lymphatic Organs and an inner medulla (figure 24.9b). These distinct zones A lymphatic organ consists of lymphatic cells within an extracel- support different stages of T-lymphocyte development. The cortex lular connective tissue matrix, and is completely surrounded by contains immature T-lymphocytes, nurse cells, and some macro- a connective tissue capsule. The main lymphatic organs are the phages. The medulla contains epithelial cells and T-lymphocytes thymus, lymph nodes, and spleen. 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 Thymus nurse cells) (figure 24.9c). The thymus (thı̄ ḿŭ s) is a bilobed organ located in the anterior The thymus functions as a site for T-lymphocyte maturation . In infants and young children, the thymus is quite and differentiation. Immature lymphocytes migrate to the thymus large and extends into the superior mediastinum as well (figure during embryonic development. These immature cells then reside 24.9a). The thymus continues to grow until puberty, when it in the cortex of each lobule. The nurse cells in the cortex secrete reaches a maximum weight of 30 to 50 grams. After reaching this several thymic hormones that stimulate T-lymphocyte maturation size, cells of the thymus regress, and much of the functional thy- and differentiation. T-lymphocytes within the thymus do not par- mus is eventually replaced by adipose connective tissue. In adults, ticipate in the immune response and are protected from antigens in the thymus atrophies and becomes almost nonfunctional. the body by a well-formed blood-thymus barrier around the blood In its prime, the thymus consists of two fused thymic lobes, vessels in the cortex. When the T-lymphocytes differentiate (e.g., each surrounded by a connective tissue capsule. Fibrous exten- mature into helper T-lymphocytes or cytotoxic T-lymphocytes), sions of the capsule, called trabeculae (tră-bek ́ū-lē ) or septa, they migrate to the medulla of each lobule. No blood-thymus bar- subdivide the thymic lobes into lobules; each lobule has an outer rier is present in the medulla, so the mature T-lymphocytes enter

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Trabecula

Thyroid gland

Right Left lung

Thymus Capsule Cortex Lobule Medulla

Diaphragm LMLM 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 Lymphocytes prominent in children. (b) A micrograph of a child’s thymus shows Thymic the arrangement of the cortex and the central medulla within a corpuscle lobule. (c) A thymic corpuscle is visible within the medulla of the Epithelial cells thymus in this micrograph.

LM 320x

(c) Thymic corpuscle

the bloodstream and migrate to other lymphatic system structures. lymph and present them to the T-lymphocytes. The lymph node The T-lymphocyte maturation and differentiation process occurs medulla has strands of lymphatic cells (primarily B-lymphocytes primarily when we are young. Once adulthood is reached, differ- and macrophages) supported by connective tissue fibers called entiated T-lymphocytes can be produced by cell division only, not medullary cords. The medulla also contains lymphatic sinuses by maturation of new cells in the thymus. called medullary sinuses. The primary function of a lymph node is to filter antigens Lymph Nodes from lymph and initiate an immune response when necessary. Lymph nodes are small, round or ovoid structures located along Afferent lymphatic vessels carry lymph to the lymph node, where it the pathways of lymph vessels (see figure 24.1). They range in slowly percolates through the cortical sinuses and then the medul- length from 1 to 25 millimeters, and typically are found in clusters lary sinuses. Macrophages line the lymphatic sinuses and remove that receive lymph from selected body regions. For example, the foreign debris from the lymph. Lymph then exits the lymph node cluster of lymph nodes in the armpit, called the axillary lymph by way of one or two efferent lymphatic vessels. Efferent lymphatic nodes, receives lymph from the breast, , and upper limb. vessels originate at the indented portion of the lymph node called Lymph nodes clustered in the , called , the (hı̄ ́lŭm) or hilus. receive lymph from the lower limb and . Cervical lymph If antigens are presented to lymphocytes, an immune nodes receive lymph from the head and neck. In addition to these response is generated. The lymphocytes undergo cell division clusters, lymph nodes are found individually throughout the body. (especially in the germinal centers), and these new lymphocytes Each lymph node is surrounded by a tough connective tis- eventually travel to the bloodstream, where they can help fight sue capsule (cap ́sool) (figure 24.10a). The capsule projects infection. When a person is sick (e.g., influenza or strep throat), internal extensions called trabeculae into the node, subdivid- some of the lymph nodes are often swollen and tender to the touch. ing the node into compartments. The trabeculae also provide This is a sign that lymphocytes are proliferating and beginning to a pathway through which blood vessels and may enter fight the infection. the lymph node. Lymphatic cells surround the trabeculae, and Cancerous cells from other areas of the body can travel easily tiny open channels called lymphatic sinuses provide a pathway through the lymphatic system (a process called ), and through which lymph flows. become entrapped in lymph nodes. These cancerous cells can pro- The lymph node regions deep to the capsule are subdivided liferate and also contribute to enlarged lymph nodes. A lymph node into an outer cortex and an inner medulla. The cortex consists of enlarged by cancer tends to be firm and nontender, as opposed to lymphatic nodules and lymphatic sinuses called cortical sinuses. a lymph node that is swollen and tender due to an infection. If an Remember that lymphatic nodules contain an outer region of individual is diagnosed with a cancer, the lymph nodes that drain T-lymphocytes surrounding an inner germinal center that houses the affected organ or body region are examined to determine if the proliferating B-lymphocytes and some macrophages. In addition, cancer has spread. For example, if cancer is detected in a breast, dendritic cells within these lymph nodes collect antigens from the the axillary lymph nodes are examined.

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Medullary sinus Medulla T-lymphocytes Medullary cord B-lymphocytes Germinal center

Dendritic cells

Lymphatic nodule Trabeculae Afferent lymphatic vessels

Capsule Lymphatic nodule

Cortex Germinal center

Cortical sinus Hilum

Valve

Efferent lymphatic Medullary cords vessel 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.

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CLINICAL VIEW Lymphoma (or Hodgkin disease) is characterized by the pres- ence of the Reed-Sternberg cell, a large cell whose two nuclei resemble A lymphoma (lim-fo¯ má˘; oma = tumor) is a malignant that owl eyes, surrounded by lymphocytes within the affected lymph node. develops from lymphatic structures. Usually (but not always) a lym- Hodgkin lymphoma affects young adults (ages 16–35) and people over phoma presents as a nontender, enlarged lymph node, often in the 60. It arises in a lymph node and then spreads to other nearby lymph neck or axillary region. Some patients have no further symptoms, nodes. If caught early, Hodgkin lymphoma can be treated and cured while others may experience night sweats, fever, and unexplained by excision of the tumor, radiation, and/or . weight loss in addition to the nodal enlargement. are Non-Hodgkin lymphomas are much more common than Hodgkin lympho- grouped into two categories: Hodgkin lymphoma and non-Hodgkin mas. These lymphomas typically develop in lymphatic structures, usually lymphoma. 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.

Reed-Sternberg cell, a The AIDS epidemic is associated with a significant rise in aggressive characteristic of Hodgkin B-lymphocyte non-Hodgkin lymphomas, prompting the Centers for lymphoma. 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 LM 1000x health in further jeopardy.

Spleen some plasma cells. One of the functions of the spleen is to serve as The largest lymphatic organ in the body is the spleen, which is a blood reservoir, whereby the formed elements are stored in these located in the left upper quadrant of the abdomen, inferior to the splenic cords. In situations where more erythrocytes (and thus, diaphragm and adjacent to 9–11. This deep red organ lies greater oxygen delivery) are needed, such as during exercise, these lateral to the left and posterolateral to the . The erythrocytes reenter the bloodstream. Since the spleen contains a spleen can vary considerably in size and weight, but typically is large amount of blood, severe trauma to the spleen results in mas- about 12 centimeters long and 7 centimeters wide. The spleen’s sive hemorrhage. posterolateral aspect (called the diaphragmatic surface) is convex Among the splenic cords, the splenic sinusoids act like and rounded, while the concave anteromedial border (the visceral enlarged capillaries that carry blood. These vessels have a dis- surface) contains the hilum (or hilus), where blood vessels and continuous basal lamina, so blood cells can easily enter and exit nerves enter and leave the spleen (figure 24.11a, d). A splenic across the vessel wall. Macrophages lining the sinusoid lumen (splen ́ik) artery delivers blood to the spleen, while blood returns phagocytize (1) bacteria and foreign debris from the blood, and to the circulation by way of a splenic vein. (2) old and defective erythrocytes and (a process called = The spleen is surrounded by a dense irregular connective hemolysis (hē -mol ́i-sis; lysis destruction). Old erythrocytes tissue capsule. The capsule sends extensions called trabeculae can rupture or become trapped in the sinusoids, making them into the organ. Within these trabeculae extend branches of the a target for these macrophages. Sinusoids merge to form small splenic artery and vein called trabecular vessels. The spleen lacks veins, and eventually the filtered blood leaves the spleen via the a cortex and medulla. Rather, the cells around the trabeculae are splenic vein. subdivided into white and . Red pulp surrounds each In summary, the spleen performs the following functions: cluster of (figure 24.11b, c). ■ Initiates an immune response when antigens are found in The white pulp is associated with the arterial supply of the blood (a white pulp function) the spleen and consists of circular clusters of lymphatic cells ■ Serves as a reservoir for erythrocytes and platelets (a red (T-lymphocytes, B-lymphocytes, and macrophages). In the cen- pulp function) ter of each cluster is a central artery. As blood enters the spleen ■ Phagocytizes old, defective erythrocytes and platelets (a red and flows through the central , the white pulp lymphatic pulp function) cells monitor the blood for foreign materials, bacteria, and other ■ Phagocytizes bacteria and other foreign materials antigens. If antigens are found, the T- and B-lymphocytes elicit an immune response. Thus, while lymph nodes monitor lymph for Table 24.2 summarizes the lymphatic structures and organs antigens, the spleen monitors blood for antigens. and their functions. The red pulp is associated with the venous supply of the spleen, since blood that enters the spleen in the central arter- ies then travels through blood vessels in the red pulp. Red pulp WHAT DO YOU THINK? consists of splenic cords and splenic sinusoids. The splenic cords ●3 If your spleen were removed (), would you be able to (cords of Bilroth) contain erythrocytes, platelets, macrophages, and 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 Capsule surface

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 (cut) Left kidney

(d) , 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, , and kidney. In this photo, the pancreas has been moved inferiorly to show the splenic vessels more clearly.

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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 Structure Filter and attack antigens in food, air, or Within walls of GI, respiratory, genital, lymphatic tissue) urine and urinary tracts Tonsils Structure Protect against inhaled and ingested Within pharynx materials Thymus Organ Site of T-lymphocyte maturation Superior mediastinum (in adults); anterior and differentiation; stores maturing and superior mediastinum (in children) lymphocytes 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 In left upper quadrant of abdomen, near and platelets; serves as a blood reservoir; 9th–11th ribs and inferior to diaphragm houses lymphocytes; mounts immune response to foreign antigens in the blood

1 A lymphatic structure is unencapsulated or has an incomplete connective tissue capsule, while a lymphatic organ has a complete connective tissue capsule encircling it.

WHATW DID YOU LEARN? WHATW DID YOU LEARN?

●8 What is MALT, and where is it found? ●12 Why are elderly individuals more prone to illnesses? ●9 Describe the main function of the thymus, and explain how the blood-thymus barrier supports this function. 24.6 Development of the Lymphatic ●10 Describe the basic structure and function of a lymph node. ●11 How do the white pulp and red pulp of the spleen differ with System respect to both cell population and function? Learning Objective: 1. Outline the lymphatic system formation in the developing 24.5 Aging and the Lymphatic embryo and fetus. The origin of the lymph vessels is poorly understood. Some System anatomists believe they originate from the endothelium of veins, Learning Objective: while others support the theory that they originate from local meso- derm. Despite this conflict, we know that the first lymphatic struc- 1. Explain how aging affects the lymphatic system. tures (called primary ) appear during the sixth week of Some lymphatic system functions are not affected by aging. development. A total of six primary lymph sacs form: Two jugular For example, the body effectively continues to transport lymph lymph sacs develop near each junction of the subclavian and future back to the bloodstream and absorb dietary lipids from the small internal jugular veins; two posterior lymph sacs develop near intestine. However, other functions change as we age. First, when each junction of the external and internal iliac veins; a retroperito- an individual reaches adulthood, the thymus no longer matures and neal (re tŕō -per ́i-tō -nē ́ăl) lymph sac forms in the digestive system differentiates T-lymphocytes. New T-lymphocytes can be produced ; and a cisterna chyli forms dorsal to the (figure only by division (mitosis) of preexisting lymphocytes. Second, the 24.12a). lymphatic system’s ability to provide immunity and fight disease Paired lymph vessels connect the lymph sacs by the ninth decreases as we get older. Helper T-lymphocytes do not respond week (figure 24.12b). Eventually, portions of the paired lymph ves- to antigens as well, and do not always reproduce rapidly. Reduced sels are obliterated, and a single thoracic duct forms that travels numbers of helper T-lymphocytes lead to fewer B-lymphocytes from the cisterna chyli, along the bodies of the vertebrae, and emp- and other kinds of T-lymphocytes. Therefore, the body’s ability to ties into the union of the left subclavian and left internal jugular acquire immunity and resist infection decreases, making elderly veins. The right lymphatic duct is formed from some other lymph people more susceptible to illnesses and more likely to become vessels. Additional smaller lymph vessels form during and after sicker than younger adults. Older individuals are advised to get a the embryonic period. pneumococcal vaccine or yearly influenza vaccinations because of During the fetal period, connective tissue subdivides the their increased risk of developing Streptococcus pneumoniae infec- lymph sacs (except the cisterna chyli) into rounded structures that tions or the flu, respectively. The faltering immune system may later become the lymph nodes (figure 24.12c). Lymphocytes within also be less able to target and eliminate malignant cells, suggesting the developing lymph sacs eventually form the cortex and medulla one reason why the elderly tend to be more prone to cancer. of each lymph node.

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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 Developing thoracic duct thoracic duct

Cisterna chyli Cisterna chyli

Posterior Posterior lymph sac lymph sac

(b) Week 9: Lymph vessels connect (c) Fetal period: Right lymphatic and thoracic ducts to the lymph sacs 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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Pharynx Pharynx

Fourth pharyngeal Superior parathyroid Third pharyngeal pouch (dorsal portion) glands pouch Developing trachea Thyroid (dorsal portion) and larynx Inferior parathyroid Thyroid glands Right third Left third pharyngeal pharyngeal pouch pouch (ventral portion) Trachea (ventral portion)

Thymus Aortic Developing bronchi arch

(a) Week 5: Ventral portions of left and right third (b) Week 7: Left and right third pharyngeal (c) Fetal period: Thymus is pharyngeal pouches migrate inferiorly pouches fuse to form the bilobed thymus 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 During the second trimester, T-lymphocytes and B-lymphocytes right third pharyngeal pouches (figure 24.13). These pouches are enter the organ, helping form the characteristic red pulp and the internal, endodermal portions of the third pharyngeal arches. white pulp. During weeks 4–7 of development, the left and right third pouches The palatine tonsils form from endoderm from the left and migrate inferiorly from the pharynx to their final position poste- right second pharyngeal pouches and the second pharyngeal arch rior to the . There, the two ventral portions fuse to form . During months 3–5 of development, lymphatic cells a single thymus gland. Lymphocytes begin infiltrating the gland enter the tonsils. Other tonsils (e.g., pharyngeal tonsils, lingual shortly after its formation. By the fetal period, the thymus gland tonsils) and lymphatic structures such as MALT form from aggre- is large and located within the mediastinum, superior to the heart gations of lymphatic cells and connective tissue. and anterior to the aortic arch and trachea. The spleen is formed from mesoderm that condenses in the WHATW DID YOU LEARN? future greater omentum during the fifth week of development. Initially, the spleen functions solely as a -producing organ. ●13 When does the spleen begin to develop?

Clinical Terms

autoimmune disease Disease in which the body’s immune system (angeion = vessel) Inflammation of the lymph mistakenly attacks its own healthy tissues. Examples include vessels. systemic erythematosus (SLE), multiple sclerosis (splē-n ō -meg ́ă-lē; mega = large) Enlarged (MS), , type 1 diabetes mellitus, and spleen, often seen in association with infection (e.g., . mononucleosis). (lim-fad-ĕ-nek t́ō -mē; aden = gland) Removal or excision of lymph nodes.

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Chapter Summary

24.1 Functions ■ The lymphatic system carries interstitial fluid back to the bloodstream, transports dietary lipids, houses and develops of the Lymphatic lymphocytes, and generates an immune response. System 725

24.2 Lymph and ■ Lymph is interstitial fluid containing solutes and sometimes foreign material that is transported through lymph vessels to Lymph Vessels 726 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 726 ■ 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 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.

24.3 Lymphatic ■ Lymphatic cells include macrophages that phagocytize foreign substances, epithelial cells that secrete thymic hormones, Cells 729 dendritic cells that filter antigens from lymph, and lymphocytes that perform specific functions in the immune response. 24.3a Types and Functions of Lymphocytes 729 ■ 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 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.

24.4 Lymphatic ■ Lymphatic structures include lymphatic nodules and various lymphatic organs. Structures 735 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 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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24.5 Aging and ■ The lymphatic system’s ability to provide immunity and fight disease decreases as we get older. the Lymphatic System 741

24.6 Development ■ The primary lymph sacs eventually give rise to lymph nodes. of the Lymphatic ■ The thymus forms from the ventral portions of the left and right third pharyngeal pouches. System 741 ■ The spleen forms from mesodermal condensations during week 5 of development. ■ The palatine tonsils are derived from the second pharyngeal pouches.

Challenge Yourself

Matching ______3. Which statement is false about lymphatic nodules? a. The center has proliferating B-lymphocytes and Match each numbered item with the most closely related lettered some macrophages. item. b. T-lymphocytes are located along the periphery. ______1. lymph node a. receives lymph from some c. Lymphatic nodules are completely surrounded by lymphatic trunks ______2. antibody a connective tissue capsule. b. former that d. Lymphatic nodules in the ileum of the small ______3. helper T-lymphocyte phagocytizes foreign debris intestine are called Peyer patches. ______4. spleen ______4. What is the function of the blood-thymus barrier? c. B-lymphocytes mature and a. It protects maturing T-lymphocytes from antigens ______5. red bone marrow differentiate here in the blood. ______6. d. smallest type of lymph vessel b. It filters the blood and starts an immune response when necessary. ______7. lymphatic capillary e. attaches to an antigen c. It subdivides the thymus into a cortex and a ______8. thymus f. T-lymphocytes mature and medulla. differentiate here d. It forms thymic corpuscles. ______9. lymphatic vessel g. filters lymph ______5. Which type of lymph vessel consists solely of an ______10. thoracic duct endothelium and has one-way flaps that allow h. drains directly into and out of interstitial fluid to enter? lymph nodes a. lymphatic vessel i. removes old and defective b. lymphatic capillary erythrocytes c. lymphatic duct d. lymphatic trunk j. cell type that regulates the ______6. Which statement is true about lymph nodes? immune response a. Cancerous lymph nodes are swollen and tender to Multiple Choice the touch. b. The medulla of a lymph node contains lymphatic Select the best answer from the four choices provided. nodules. ______1. Lymph from which of the following body regions c. Lymph enters the lymph node through afferent drains into the thoracic duct? lymphatic vessels. a. right side of the thorax d. Lymphatic sinuses are located in the cortex of a b. right upper limb lymph node only. c. right lower limb ______7. In an early Streptococcus infection of the throat, all d. right side of the head of the following structures may swell except the ______2. Which type of lymphatic cell is responsible for a. pharyngeal tonsil. producing antibodies? b. spleen. a. macrophage c. cervical lymph node. b. helper T-lymphocyte d. palatine tonsil. c. plasma cell d. NK cell

mck78097_ch24_724-746.indd 745 2/25/11 2:18 PM 746 Chapter Twenty-Four Lymphatic System

______8. Which of the following is a function of the white 7. Describe how the thymus’s anatomy and function change pulp of the spleen? from infancy on. a. phagocytizes erythrocytes 8. Describe the basic anatomy of a lymph node, how lymph b. serves as a blood cell reservoir enters and leaves the node, and the functions of this organ. c. elicits an immune response if antigens are 9. Compare and contrast the red and white pulp of the spleen detected in the blood with respect to the anatomy and functions of each. d. serves as a site for hemopoiesis during fetal life 10. Describe how lymph vessels and lymph nodes develop. ______9. The primary lymph sacs form the a. thoracic duct. Developing Critical Reasoning b. right lymphatic duct. c. spleen. 1. Arianna was diagnosed with mononucleosis, an infectious d. lymph nodes. disease that targets B-lymphocytes. When she went to the doctor, he palpated her left side, just below the ______10. What change occurs to the adult lymphatic system cage. The doctor told Arianna she was checking to see if a as we get older? certain organ was enlarged, a complication that can occur a. The body produces and transports less lymph. with mononucleosis. What lymphatic organ was the doctor b. Greater numbers of B-lymphocytes are produced. checking, and why would it become enlarged? Include some c. Helper T-lymphocytes do not respond as well to explanation of the anatomy and histology of this organ in antigens. your answer. d. The lymph nodes enlarge. 2. Why is HIV infection so devastating to the body? In your Content Review answer, explain what cells are infected and why the body cannot produce more mature, noninfected cells. 1. List the functions of the lymphatic system. Also explain how AIDS affects the way the body fights 2. Describe what lymph is, and draw a flowchart that infection, and give some examples of ailments that are illustrates what structures the lymph travels through to common among AIDS patients. return to the bloodstream. 3. Jordan has an enlarged lymph node along the side of 3. Which body regions have their lymph drained to the his neck, and he is worried that the structure may be a thoracic duct? lymphoma. What are some criteria to help distinguish 4. Compare and contrast the types of lymphatic cells with between infected lymph nodes and malignant lymph respect to their appearance, function, and place of maturation. nodes? If the lymph node were cancerous, how would 5. Describe how the lymphatic cells elicit an immune response. a physician determine if the cancer has spread to other parts of the body? 6. Describe the basic composition of a lymphatic nodule, and give examples in the body where lymphatic nodules may be found.

Answers to “What Do You Think?”

1. If you need a booster shot about once every 10 years, that 3. Most individuals who have their removed can indicates a maximum 10-year life span of tetanus-detecting fight off illness and infections effectively, because the memory B-lymphocytes. Many of these cells may die off other lymphatic tissues and organs take over the immune before the 10 years is up, which is why a physician gives functions previously handled by the spleen. However, the you a tetanus booster earlier if you have been exposed to risk for severe bacterial infection is greater, since there is tetanus—for example, by piercing your foot on a rusty nail no spleen to filter bacteria from the blood. For this reason, that could carry tetanus bacteria. individuals who have undergone splenectomies may need 2. If the tonsils are removed, other lymphatic tissue and to be vaccinated against certain bacteria and undergo long- lymphatic organs in the head and neck, such as lymph term (years or even lifelong) antibiotic therapy. nodes, can mount an immune response to antigens in the throat. Also, the lymphocytes circulating in the bloodstream can detect antigens in the throat.

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.

mck78097_ch24_724-746.indd 746 2/25/11 2:18 PM