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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 mck78097_ch24_724-746.indd 724 2/25/11 2:16 PM Chapter Twenty-Four 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 725 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 = mck78097_ch24_724-746.indd 725 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? 2/25/11 2:16 PM 726 Chapter Twenty-Four Lymphatic System 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. mck78097_ch24_724-746.indd 726 2/25/11 2:16 PM Chapter Twenty-Four Lymphatic System 727 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, mck78097_ch24_724-746.indd 727 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? 2/25/11 2:16 PM 728 Chapter Twenty-Four Lymphatic System 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. mck78097_ch24_724-746.indd 728 2/25/11 2:16 PM Chapter Twenty-Four Lymphatic System 729 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. mck78097_ch24_724-746.indd 729 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). 2/25/11 2:17 PM 730 Chapter Twenty-Four Lymphatic System (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 mck78097_ch24_724-746.indd 730 (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 2/25/11 2:17 PM Chapter Twenty-Four Lymphatic System 731 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 mck78097_ch24_724-746.indd 731 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 2/25/11 2:17 PM 732 Chapter Twenty-Four 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. mck78097_ch24_724-746.indd 732 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 2/25/11 2:17 PM Chapter Twenty-Four Lymphatic System 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. 2/25/11 2:17 PM 734 Chapter Twenty-Four Lymphatic System 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) 2/25/11 2:17 PM 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. 2/25/11 2:17 PM 736 Chapter Twenty-Four Lymphatic System 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 2/25/11 2:17 PM Chapter Twenty-Four Lymphatic System 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. 2/25/11 2:17 PM 738 Chapter Twenty-Four Lymphatic System 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 2/25/11 2:17 PM Chapter Twenty-Four Lymphatic System 739 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? 2/25/11 2:17 PM 740 Chapter Twenty-Four Lymphatic System 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 2/25/11 2:18 PM Chapter Twenty-Four 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. mck78097_ch24_724-746.indd 741 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. 2/25/11 2:18 PM 742 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. mck78097_ch24_724-746.indd 742 2/25/11 2:18 PM 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). 2/25/11 2:18 PM 744 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). 2/25/11 2:18 PM 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 mck78097_ch24_724-746.indd 745 ______ 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. 2/25/11 2:18 PM 746 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. mck78097_ch24_724-746.indd 746 2/25/11 2:18 PM