The Lymphatic System and Immunity PDF

CHAPTER 22 The Lymphatic System and Immunity The Lymphatic System, Disease Resistance, and Homeostasis The lymphatic system contributes to homeostasis by draining interstitial fluid as well as providing the mechanisms for defense against disease. The environment in which we live is filled wit...

CHAPTER 22 The Lymphatic System and Immunity The Lymphatic System, Disease Resistance, and Homeostasis The lymphatic system contributes to homeostasis by draining interstitial fluid as well as providing the mechanisms for defense against disease. The environment in which we live is filled with microbes that have the disease-producing microbes. In this chapter you will learn about the ability to cause disease if given the right opportunity. If we did not resist organization and components of the lymphatic system and its role in these microbes, we would be ill constantly or even die. Fortunately, we keeping us healthy. have a number of defenses that keep microbes from either entering our bodies or combat them if they do gain entrance. The lymphatic system Q Did you ever wonder how cancer can spread from one part is one of the principal body systems that helps to defend us against of the body to another? 808  22.3 Lymphatic Vessels and Lymph Circulation 809 22.1 The Concept of Immunity Components of the Lymphatic System The lymphatic or lymphoid system (lim-FAT-ik) consists of a fluid called lymph, vessels called lymphatic vessels that transport the OBJECTIVES lymph, a number of structures and organs containing lymphatic tis- sue (lymphocytes within a filtering tissue), and red bone marrow (Fig- Define immunity. ure 22.1). The lymphatic system assists in circulating body fluids and Compare the two basic types of immunity. helps defend the body against disease-causing agents. As you will see shortly, most components of blood plasma filter through blood capil- lary walls to form interstitial fluid. After interstitial fluid passes into Maintaining homeostasis in the body requires continual combat against lymphatic vessels, it is called lymph (LIMF = clear fluid). The major harmful agents in our internal and external environments. Despite constant difference between interstitial fluid and lymph is location: Interstitial exposure to a variety of pathogens (PATH-ō-jens)—disease-producing fluid is found between cells, and lymph is located within lymphatic microbes such as bacteria and viruses—most people remain healthy. vessels and lymphatic tissue. The body surface also endures cuts and bumps, exposure to ultraviolet Lymphatic tissue is a specialized form of reticular connective tis- rays, chemical toxins, and minor burns with an array of defensive ploys. sue (see Table 4.4) that contains large numbers of lymphocytes. Re- Immunity (i-MŪ-ni-tē) or resistance is the ability to ward off dam- call from Chapter 19 that lymphocytes are agranular white blood cells age or disease through our defenses. Vulnerability or lack of resis- (see Section 19.4). Two types of lymphocytes participate in adaptive tance is termed susceptibility. The two general types of immunity are immune responses: B cells and T cells (described shortly). (1) innate and (2) adaptive. Innate (nonspecific) immunity refers to defenses that are present at birth. Innate immunity does not involve specific recognition of a microbe and acts against all microbes in the Functions of the Lymphatic System same way. Among the components of innate immunity are the first line of defense (the physical and chemical barriers of the skin and The lymphatic system has three primary functions: mucous membranes) and the second line of defense (antimicrobial substances, natural killer cells, phagocytes, inflammation, and fever). 1. Drains excess interstitial fluid. Lymphatic vessels drain excess in- Innate immune responses represent immunity’s early warning system terstitial fluid from tissue spaces and return it to the blood. This and are designed to prevent microbes from entering the body and to function closely links it with the cardiovascular system. In fact, help eliminate those that do gain access. without this function, the maintenance of circulating blood volume Adaptive (specific) immunity refers to defenses that involve spe- would not be possible. cific recognition of a microbe once it has breached the innate immu- 2. Transports dietary lipids. Lymphatic vessels transport lipids and nity defenses. Adaptive immunity is based on a specific response to a lipid-soluble vitamins (A, D, E, and K) absorbed by the gastrointes- specific microbe; that is, it adapts or adjusts to handle a specific mi- tinal tract. crobe. Adaptive immunity involves lymphocytes (a type of white 3. Carries out immune responses. Lymphatic tissue initiates highly blood cell) called T lymphocytes (T cells) and B lymphocytes (B cells). specific responses directed against particular microbes or abnor- The body system responsible for adaptive immunity (and some mal cells. aspects of innate immunity) is the lymphatic system. This system is closely allied with the cardiovascular system, and it also func- Checkpoint tions with the digestive system in the absorption of fatty foods. In this chapter, we explore the mechanisms that provide defenses against 3. What are the components and functions of the lymphatic system? intruders and promote the repair of damaged body tissues. Checkpoint 1. What is a pathogen? 22.3 Lymphatic Vessels and 2. Now are innate and adaptive immunity different? Lymph Circulation 22.2 Overview of the Lymphatic OBJECTIVES System Describe the organization of lymphatic vessels. Explain the formation and flow of lymph. OBJECTIVES List the components of the lymphatic system. Lymphatic vessels begin as lymphatic capillaries. These capillaries, Describe the functions of the lymphatic system. which are located in the spaces between cells, are closed at one end (Figure 22.2). Just as blood capillaries converge to form venules and FIGURE 22.1 Components of the lymphatic system. The lymphatic system consists of lymph, lymphatic vessels, lymphatic tissues, and red bone marrow. Functions 1. Drains excess interstitial fluid. 2. Transports dietary lipids from the gastrointestinal tract to the blood. 3. Protects against invasion through immune responses. Palatine tonsil Submandibular node Cervical node Left internal jugular vein Right internal jugular vein Left subclavian vein Right lymphatic duct Right subclavian vein Thoracic duct Thymus Axillary node Lymphatic vessel Thoracic duct Spleen Cisterna chyli Intestinal node Aggregated lymphatic follicle (b) Areas drained by Small intestine right lymphatic and Large intestine thoracic ducts Appendix Iliac node Area drained by Inguinal node right lymphatic duct Red bone Area drained by marrow thoracic duct Lymphatic vessel (a) Anterior view of principal components of lymphatic system Q What tissue contains stem cells that develop into lymphocytes? 810  22.3 Lymphatic Vessels and Lymph Circulation 811 FIGURE 22.2 Lymphatic capillaries. Lymphatic Capillaries Lymphatic capillaries are found throughout the body except in avascu- Lymphatic capillaries have greater permeability than blood capillar- lar tissues, the central nervous system, portions of the spleen, and bone ies and thus can absorb large molecules such as proteins and lipids. marrow. Lymphatic capillaries are also slightly larger in diameter than blood capillaries and have a unique one-way structure that permits intersti- tial fluid to flow into them but not out. The ends of endothelial cells that make up the wall of a lymphatic capillary overlap (Figure 22.2b). Blood When pressure is greater in the interstitial fluid than in lymph, the capillary cells separate slightly, like the opening of a one-way swinging door, Venule and interstitial fluid enters the lymphatic capillary. When pressure is greater inside the lymphatic capillary, the cells adhere more closely, Tissue cell Arteriole and lymph cannot escape back into interstitial fluid. The pressure is relieved as lymph moves further down the lymphatic capillary. Blood Blood Attached to the lymphatic capillaries are anchoring filaments, which contain elastic fibers. They extend out from the lymphatic capillary, attaching lymphatic endothelial cells to surrounding tissues. When Lymph excess interstitial fluid accumulates and causes tissue swelling, the Lymphatic anchoring filaments are pulled, making the openings between cells Interstitial fluid capillary even larger so that more fluid can flow into the lymphatic capillary. In the small intestine, specialized lymphatic capillaries called lacteals (LAK-tē-als; lact- = milky) carry dietary lipids into lymphatic (a) Relationship of lymphatic capillaries to tissue cells and blood capillaries vessels and ultimately into the blood (see Figure 24.20). The pres- ence of these lipids causes the lymph draining from the small intes- tine to appear creamy white; such lymph is referred to as chyle (KĪL = juice). Elsewhere, lymph is a clear, pale-yellow fluid. Lymph Endothelium of lymphatic Lymph Trunks and Ducts capillary As you have already learned, lymph passes from lymphatic capillaries Tissue cell into lymphatic vessels and then through lymph nodes. As lymphatic Interstitial fluid vessels exit lymph nodes in a particular region of the body, they unite Anchoring to form lymph trunks. The principal trunks are the lumbar, intestinal, filament bronchomediastinal, subclavian, and jugular trunks (see Figure Opening 22.3). The lumbar trunks drain lymph from the lower limbs, the wall and viscera of the pelvis, the kidneys, the adrenal glands, and the abdominal wall. The intestinal trunk drains lymph from the stom- ach, intestines, pancreas, spleen, and part of the liver. The broncho- mediastinal trunks (brong-kō-mē′-dē-as-TĪ-nal) drain lymph from the thoracic wall, lung, and heart. The subclavian trunks drain the upper limbs. The jugular trunks drain the head and neck. (b) Details of a lymphatic capillary The lymph passage from the lymph trunks to the venous system Q Is lymph more similar to blood plasma or to interstitial differs on the right and left sides of the body. On the right side the three fluid? Why? lymph trunks (right jugular trunk, right subclavian trunk, and right then veins, lymphatic capillaries unite to form larger lymphatic bronchomediastinal trunk) usually open independently into the vessels (see Figure 22.1), which resemble small veins in structure but venous system on the anterior surface of the junction of the internal have thinner walls and more valves. At intervals along the lymphatic jugular and subclavian veins (Figure 22.3). Rarely, the three trunks will vessels, lymph flows through lymph nodes, encapsulated bean- join to form a short right lymphatic duct that forms a single junction shaped organs consisting of masses of B cells and T cells. In the skin, with the venous system. On the left side of the body, the largest lymph lymphatic vessels lie in the subcutaneous tissue and generally follow vessel, the thoracic (left lymphatic) duct forms the main duct for the same route as veins; lymphatic vessels of the viscera generally fol- return of lymph to the blood. This long duct, approximately 38–45 cm low arteries, forming plexuses (networks) around them. Tissues that (15–18 in.), begins as a dilation called the cisterna chyli (sis-TER-na lack lymphatic capillaries include avascular tissues (such as cartilage, KI-le; cisterna = cavity or reservoir) anterior to the second lumbar ver- the epidermis, and the cornea of the eye), portions of the spleen, and tebra. The cisterna chyli receives lymph from the right and left lumbar red bone marrow. trunks and from the intestinal trunk. In the neck, the thoracic duct also 812 CH APTE R 2 2 The Lymphatic System and Immunity FIGURE 22.3 Routes for drainage of lymph from lymph trunks into the thoracic and right lymphatic ducts. All lymph returns to the bloodstream through the thoracic (left) lymphatic duct and right lymphatic duct. Right internal jugular vein Left internal jugular vein Right Left jugular trunk jugular Thoracic (left lymphatic) duct trunk Left subclavian trunk Right subclavian trunk Left subclavian vein Right subclavian First rib vein Left brachiocephalic vein Accessory hemiazygos vein Left broncho- Right brachiocephalic mediastinal trunk vein Thoracic (left Right broncho- lymphatic) duct mediastinal trunk Superior vena cava Hemiazygos vein Rib Intercostal muscle Azygos vein Cisterna chyli Right lumbar trunk Left lumbar trunk Inferior vena cava Intestinal trunk (a) Overall anterior view Right internal Left internal jugular vein jugular vein Right jugular trunk Left jugular trunk Left subclavian trunk Right subclavian trunk Left subclavian vein Right subclavian vein Thoracic (left lymphatic) duct Right brachiocephalic Left bronchomediastinal trunk vein Right bronchomediastinal trunk Left brachiocephalic vein Superior vena cava (b) Detailed anterior view of thoracic and right lymphatic duct Q Which lymphatic vessels empty into the cisterna chyli, and which duct receives lymph from the cisterna chyli?  22.3 Lymphatic Vessels and Lymph Circulation 813 receives lymph from the left jugular and left subclavian trunks before level outside) opposes such movement. The proteins can, however, opening into the anterior surface of the junction of the left internal move readily through the more permeable lymphatic capillaries into jugular and subclavian veins. The left bronchomediastinal trunk joins lymph. Thus, an important function of lymphatic vessels is to return the anterior surface of the subclavian vein independently and does not the lost plasma proteins and plasma to the bloodstream. join the thoracic duct. As a result of these pathways, lymph from the Like some veins, lymphatic vessels contain valves, which ensure upper right quadrant of the body returns to the superior vena cava the one-way movement of lymph. As noted previously, lymph drains from the right brachiocephalic vein, while all the lymph form the left into venous blood through the right lymphatic duct and the thoracic upper side of the body and the entire body below the diaphragm duct at the junction of the internal jugular and subclavian veins returns to the superior vena cava via the left brachiocephalic vein. (Figure 22.3). Thus, the sequence of fluid flow is blood capillaries (blood) → interstitial spaces (interstitial fluid) → lymphatic capillaries (lymph) → lymphatic vessels (lymph) → lymphatic trunks or ducts Formation and Flow of Lymph (lymph) → junction of the internal jugular and subclavian veins (blood). Figure 22.4 illustrates this sequence, along with the relation- Most components of blood plasma, such as nutrients, gases, and hor- ship of the lymphatic and cardiovascular systems. Both systems form mones, filter freely through the capillary walls to form interstitial fluid, a very efficient circulatory system. but more fluid filters out of blood capillaries than returns to them by The same two “pumps” that aid the return of venous blood to the reabsorption (see Figure 21.7). The excess filtered fluid—about 3 liters heart maintain the flow of lymph. per day—drains into lymphatic vessels and becomes lymph. Because most plasma proteins are too large to leave blood vessels, interstitial 1. Respiratory pump. Lymph flow is also maintained by pressure fluid contains only a small amount of protein. Proteins that do leave changes that occur during inhalation (breathing in). Lymph flows blood plasma cannot return to the blood by diffusion because the con- from the abdominal region, where the pressure is higher, toward centration gradient (high level of proteins inside blood capillaries, low the thoracic region, where it is lower. When the pressures reverse FIGURE 22.4 Schematic diagram showing the relationship of the lymphatic system to the cardiovascular system. Arrows indicate the direction of flow of lymph and blood. The sequence of fluid flow is blood capillaries (blood) → interstitial spaces (interstitial fluid) → lymphatic capillaries (lymph) → lymphatic vessels (lymph) → lymphatic trunks or ducts (lymph) → junction of the internal jugular and subclavian veins (blood). SYSTEMIC CIRCULATION PULMONARY CIRCULATION Lymph node Lymphatic ducts (thoracic Lymphatic capillaries duct, right lymphatic duct) empty lymph into the junction of jugular and subclavian veins of the cardiovascular system. Subclavian vein Pulmonary blood capillaries Lymphatic vessels pass lymph to Veins lymphatic ducts. Valve ensures one-way flow of lymph. Heart Arteries Efferent lymphatic vessels carry lymph from lymph nodes. Lymph nodes remove foreign substances through Systemic blood capillaries filtering lymph, phagocytosis, and immune reactions. Blood plasma is filtered from blood Afferent lymphatic capillaries into vessels carry lymph from Lymphatic capillaries interstitial spaces lymphatic capillaries to lymph absorb interstitial fluid and to become nodes. pass lymph to afferent interstitial fluid. lymphatic vessels. Q Does inhalation promote or hinder the flow of lymph? 814 CH APTE R 2 2 The Lymphatic System and Immunity during exhalation (breathing out), the valves in lymphatic vessels and begin to mature. Dendritic cells (den-DRIT-ik; dendr- = a tree), prevent backflow of lymph. In addition, when a lymphatic vessel which are derived from monocytes (and so named because they have distends, the smooth muscle in its wall contracts, which helps long, branched projections that resemble the dendrites of a neuron), move lymph from one segment of the vessel to the next. assist the maturation process. As you will see shortly, dendritic cells in 2. Skeletal muscle pump. The “milking action” of skeletal muscle other parts of the body, such as lymph nodes, play another key role in contractions (see Figure 21.9) compresses lymphatic vessels (as immune responses. Each of the specialized epithelial cells in the well as veins) and forces lymph toward the junction of the internal cortex has several long processes that surround and serve as a frame- jugular and subclavian veins. work for as many as 50 T cells. These epithelial cells help “educate” the pre-T cells in a process known as positive selection (see Figure 22.22). Additionally, they produce thymic hormones that are thought to aid in Checkpoint the maturation of T cells. Only about 2% of developing T cells survive 4. How do lymphatic vessels differ in structure form veins? in the cortex. The remaining cells die via apoptosis (programmed cell death). Thymic macrophages (MAK-rō-fā-jez) help clear out the debris 5. Diagram the route of lymph circulation. of dead and dying cells. The surviving T cells enter the medulla. The medulla consists of widely scattered, more mature T cells, epithelial cells, dendritic cells, and macrophages (Figure 22.5c). Some of the epithelial cells become arranged into concentric layers of 22.4 Lymphatic Organs flat cells that degenerate and become filled with keratohyalin granules and keratin. These clusters are called thymic (Hassall’s) corpuscles. and Tissues Although their role is uncertain, they may serve as sites of T cell death in the medulla. T cells that leave the thymus via the blood migrate to lymph nodes, the spleen, and other lymphatic tissues, where they OBJECTIVE colonize parts of these organs and tissues. Because of its high content of lymphoid tissue and a rich blood Distinguish between primary and secondary lymphatic organs. supply, the thymus has a reddish appearance in a living body. With age, however, fatty infiltrations replace the lymphoid tissue and the The widely distributed lymphatic organs and tissues are classified into thymus takes on more of the yellowish color of the invading fat, giving two groups based on their functions. Primary lymphatic organs are the the false impression of reduced size. However, the actual size of the sites where stem cells divide and become immunocompetent (im′-ū-nō- thymus, defined by its connective tissue capsule, does not change. In KOM-pe-tent), that is, capable of mounting an immune response. The infants, the thymus has a mass of about 70 g (2.3 oz). It is after puberty primary lymphatic organs are the red bone marrow (in flat bones and the that adipose and areolar connective tissue begin to replace the thymic epiphyses of long bones of adults) and the thymus. Pluripotent stem cells tissue. By the time a person reaches maturity, the functional portion of in red bone marrow give rise to mature, immunocompetent B cells and to the gland is reduced considerably, and in old age the functional portion pre-T cells. The pre-T cells in turn migrate to the thymus, where they may weigh only 3 g (0.1 oz). Before the thymus atrophies, it populates become immunocompetent T cells. The secondary lymphatic organs the secondary lymphatic organs and tissues with T cells. However, and tissues are the sites where most immune responses occur. They some T cells continue to proliferate in the thymus throughout an indi- include lymph nodes, the spleen, and lymphatic nodules (follicles). The vidual’s lifetime, but this number decreases with age. thymus, lymph nodes, and spleen are considered organs because each is surrounded by a connective tissue capsule; lymphatic nodules, in con- trast, are not considered organs because they lack a capsule. Lymph Nodes Located along lymphatic vessels are about 600 bean-shaped lymph Thymus nodes. They are scattered throughout the body, both superficially and deep, and usually occur in groups (see Figure 22.1). Large groups The thymus is a bilobed organ located in the mediastinum between the of lymph nodes are present near the mammary glands and in the axil- sternum and the aorta. It extends from the top of the sternum or the lae and groin. inferior cervical region to the level of the fourth costal cartilages, ante- Lymph nodes are 1–25 mm (0.04–1 in.) long and, like the thymus, rior to the top of the heart and its great vessels (Figure 23.5a). An envel- are covered by a capsule of dense connective tissue that extends into oping layer of connective tissue holds the two lobes closely together, the node (Figure 22.6). The capsular extensions, called trabeculae, but a connective tissue capsule encloses each lobe separately. Exten- divide the node into compartments, provide support, and provide a sions of the capsule, called trabeculae (tra-BEK-ū-lē = little beams), route for blood vessels into the interior of a node. Internal to the cap- penetrate inward and divide each lobe into lobules (Figure 23.5b). sule is a supporting network of reticular fibers and fibroblasts. The Each thymic lobule consists of a deeply staining outer cortex and capsule, trabeculae, reticular fibers, and fibroblasts constitute the a lighter-staining central medulla (Figure 22.5b). The cortex is com- stroma (supporting framework of connective tissue) of a lymph node. posed of large numbers of T cells and scattered dendritic cells, epithe- The parenchyma (functioning part) of a lymph node is divided lial cells, and macrophages. Immature T cells (pre-T cells) migrate from into a superficial cortex and a deep medulla. The cortex consists of an red bone marrow to the cortex of the thymus, where they proliferate outer cortex and an inner cortex. Within the outer cortex are  22.4 Lymphatic Organs and Tissues 815 FIGURE 22.5 Thymus. The bilobed thymus is largest at puberty and then the functional portion atrophies with age. Thyroid gland Trachea Right common carotid artery Brachiocephalic veins Superior vena cava Right lung Thymus Left lung Fibrous pericardium Diaphragm (a) Thymus of adolescent Capsule Lobule: Cortex T cell Thymic (Hassall’s) corpuscle Medulla Thymic (Hassall’s) corpuscle Epithelial cell Trabecula Courtesy Michael Ross, University of Florida LM 30x Courtesy Michael Ross, University of Florida LM 385x (b) Thymic lobules (c) Details of the thymic medulla Q Which type of lymphocytes mature in the thymus? egg-shaped aggregates of B cells called lymphatic nodules (follicles). “present” an antigen (described later in the chapter), B cells proliferate A lymphatic nodule consisting chiefly of B cells is called a primary lym- and develop into antibody-producing plasma cells or develop into phatic nodule. Most lymphatic nodules in the outer cortex are second- memory B cells. Memory B cells persist after an initial immune re- ary lymphatic nodules (Figure 22.6), which form in response to an sponse and “remember” having encountered a specific antigen. antigen (a foreign substance) and are sites of plasma cell and memory B cells that do not develop properly undergo apoptosis (programmed B cell formation. After B cells in a primary lymphatic nodule recognize cell death) and are destroyed by macrophages. The region of a an antigen, the primary lymphatic nodule develops into a secondary secondary lymphatic nodule surrounding the germinal center is lymphatic nodule. The center of a secondary lymphatic nodule con- composed of dense accumulations of B cells that have migrated away tains a region of light-staining cells called a germinal center. In the from their site of origin within the nodule. germinal center are B cells, follicular dendritic cells (a special type The inner cortex does not contain lymphatic nodules. It consists of dendritic cell), and macrophages. When follicular dendritic cells mainly of T cells and dendritic cells that enter a lymph node from 816 CH APTE R 2 2 The Lymphatic System and Immunity FIGURE 22.6 Structure of a lymph node. Green arrows indicate the direction of lymph flow through a lymph node. Lymph nodes are present throughout the body, usually clustered in groups. Cells of inner cortex Cells around germinal center Cells in germinal center of of outer cortex outer cortex T cells B cells B cells Follicular Macrophages Dendritic cells dendritic cells Cells of medulla Subcapsular sinus Reticular fiber Trabecula Trabecular sinus Outer cortex: B cells Plasma Macrophages Germinal center cells in secondary lymphatic nodule Cells around germinal Valve center Inner cortex Medulla Medullary sinus Reticular fiber Afferent lymphatic vessels Efferent lymphatic vessels Valve Hilum Route of lymph flow through a lymph node: Afferent lymphatic vessel Subcapsular sinus Trabecular sinus Afferent Capsule lymphatic vessels Medullary sinus Efferent lymphatic vessel (a) Partially sectioned lymph node  22.4 Lymphatic Organs and Tissues 817 Macrophage Lymphocyte Capsule Medullary Subcapsular sinus sinus Reticular Outer cortex fiber Steve Gschmeissner/Science Source Images SEM 100x Trabecular sinus (c) Portion of the medullary sinus of a lymph node Germinal center in secondary lymphatic nodule Efferent lymphatic vessels Trabecula Nerve Skeletal muscle Inner cortex Lymph node Medullary sinus Afferent lymphatic vessels Medulla Mark Nielsen LM 40x Dissection Shawn Miller, Photograph Mark Nielsen (b) Portion of a lymph node (d) Anterior view of an inguinal lymph node Q What happens to foreign substances in lymph that enter a lymph node? other tissues. The dendritic cells present antigens to T cells, causing sinuses drain into one or two efferent lymphatic vessels (EF-er-ent; their proliferation. The newly formed T cells then migrate from the efferent = to carry away), which are wider and fewer in number than lymph node to areas of the body where there is antigenic activity. afferent vessels. They contain valves that open away from the center of The medulla of a lymph node contains B cells, antibody-producing the lymph node to convey lymph, antibodies secreted by plasma cells, plasma cells that have migrated out of the cortex into the medulla, and activated T cells out of the node. Efferent lymphatic vessels emerge and macrophages. The various cells are embedded in a network of from one side of the lymph node at a slight depression called a hilum reticular fibers and reticular cells. (HĪ-lum). Blood vessels also enter and leave the node at the hilum. As you have already learned, lymph flows through a node in one Lymph nodes function as a type of filter. As lymph enters one end direction only (Figure 22.6a). It enters through several afferent lym- of a lymph node, foreign substances are trapped by the reticular fibers phatic vessels (AF-er-ent; afferent = to carry toward), which penetrate within the sinuses of the node. Then macrophages destroy some for- the convex surface of the node at several points. The afferent vessels eign substances by phagocytosis, while lymphocytes destroy others contain valves that open toward the center of the node, directing the by immune responses. The filtered lymph then leaves the other end of lymph inward. Within the node, lymph enters sinuses, a series of irregu- the lymph node. Since there are many afferent lymphatic vessels that lar channels that contain branching reticular fibers, lymphocytes, and bring lymph into a lymph node and only one or two efferent lymphatic macrophages. From the afferent lymphatic vessels, lymph flows into the vessels that transport lymph out of a lymph node, the slow flow of subcapsular sinus (sub-KAP-soo-lar), immediately beneath the cap- lymph within the lymph nodes allows additional time for lymph to be sule. From here the lymph flows through trabecular sinuses (tra-BEK-ū- filtered. Additionally, all lymph flows through multiple lymph nodes lar), which extend through the cortex parallel to the trabeculae, and into on its path through the lymph vessels. This exposes the lymph to mul- medullary sinuses, which extend through the medulla. The medullary tiple filtering events before returning to the blood. 818 CH APTE R 2 2 The Lymphatic System and Immunity travel in the blood or lymph and establish new tumors where they lodge. Clinical Connection When metastasis occurs via lymphatic vessels, secondary tumor sites can be predicted according to the direction of lymph flow from the primary Metastasis through Lymphatic Vessels tumor site. Cancerous lymph nodes feel enlarged, firm, nontender, and Metastasis (me-TAS-ta-sis; meta- = beyond; -stasis = to stand), the spread fixed to underlying structures. By contrast, most lymph nodes that are of a disease from one part of the body to another, can occur via lymphatic enlarged due to an infection are softer, tender, and movable. vessels. All malignant tumors eventually metastasize. Cancer cells may FIGURE 22.7 Structure of the spleen. The spleen is the largest single mass of lymphatic tissue in the body. SUPERIOR Splenic vein Splenic artery Colic impression Gastric impression Hilum ANTERIOR Renal impression (a) Visceral surface Red pulp Trabecula Splenic artery Splenic vein White pulp Red pulp: Venous sinus White pulp Splenic cord Central artery Central artery Trabecula Capsule Mark Nielsen LM 100x (b) Internal structure (c) Portion of the spleen Clinical Connection Ruptured Spleen The spleen is the organ most often damaged in cases of abdominal trauma. Severe blows over the inferior left chest or superior abdomen can fracture the protecting ribs. Such crushing injury may result in a ruptured spleen, which causes significant hemorrhage and shock. Prompt removal of the spleen, called a splenectomy (splē-NEK-tō-mē), is needed to prevent death due to bleeding. Other structures, particularly red bone marrow and the liver, can take over some functions normally carried out by the spleen. Immune functions, however, decrease in the absence of a spleen. The spleen’s absence also places the patient at higher risk for sepsis (a blood infection) due to loss of the filtering and phagocytic functions of the spleen. To reduce the risk of sepsis, patients who have undergone a splenectomy take prophylactic (preventive) antibiotics before any invasive procedures. Q After birth, what are the main functions of the spleen?  22.5 Development of Lymphatic Tissues 819 Spleen The oval spleen is the largest single mass of lymphatic (LIN-gwal), located at the base of the tongue, may also require re- tissue in the body. It is a soft, encapsulated organ of variable size, but moval during a tonsillectomy. on average it fits in a person’s open hand and measures about 12 cm (5 in.) in length (Figure 22.7a). It is located in the left hypochondriac Clinical Connection region between the stomach and diaphragm. The superior surface of the spleen is smooth and convex and conforms to the concave Tonsillitis surface of the diaphragm. Neighboring organs make indentations in Tonsillitis is an infection or inflammation of the tonsils. Most often, it is the visceral surface of the spleen—the gastric impression (stomach), caused by a virus, but it may also be caused by the same bacteria that the renal impression (left kidney), and the colic impression (left colic cause strep throat. The principal symptom of tonsillitis is a sore throat. flexure of large intestine). Like lymph nodes, the spleen has a hilum. Additionally, fever, swollen lymph nodes, nasal congestion, difficulty in Through it pass the splenic artery, splenic vein, and efferent lymphatic swallowing, and headache may also occur. Tonsillitis of viral origin usually vessels. resolves on its own. Bacterial tonsillitis is typically treated with anti- A capsule of dense connective tissue surrounds the spleen and is biotics. Tonsillectomy (ton-si-LEK-tō-mē; ectomy = incision), the removal covered in turn by a serous membrane, the visceral peritoneum. Tra- of a tonsil, may be indicated for individuals who do not respond to other treatments. Such individuals usually have tonsillitis lasting for more than beculae extend inward from the capsule. The capsule plus trabecu- 3 months (despite medication), obstructed air pathways, and difficulty in lae, reticular fibers, and fibroblasts constitute the stroma of the swallowing and talking. It appears that tonsillectomy does not interfere spleen; the parenchyma of the spleen consists of two different kinds with a person’s response to subsequent infections. of tissue called white pulp and red pulp (Figure 22.7b, c). White pulp is lymphatic tissue, consisting mostly of lymphocytes and mac- rophages arranged around branches of the splenic artery called cen- tral arteries. The red pulp consists of blood-filled venous sinuses Checkpoint and cords of splenic tissue called splenic cords or Billroth’s cords. 6. What is the role of the thymus in immunity? Splenic cords consist of red blood cells, macrophages, lymphocytes, plasma cells, and granulocytes. Veins are closely associated with the 7. What functions do lymph nodes, the spleen, and the tonsils serve? red pulp. Blood flowing into the spleen through the splenic artery enters the central arteries of the white pulp. Within the white pulp, B cells and T cells carry out immune functions, similar to lymph nodes, while spleen macrophages destroy blood-borne pathogens by phago- 22.5 Development of c ytosis. Within the red pulp, the spleen performs three functions re- lated to blood cells: (1) removal by macrophages of ruptured, worn Lymphatic Tissues out, or defective blood cells and platelets; (2) storage of platelets, up to one-third of the body’s supply; and (3) production of blood cells OBJECTIVE (hemopoiesis) during fetal life. Describe the development of lymphatic tissues. Lymphatic Nodules Lymphatic nodules (follicles) are egg- shaped masses of lymphatic tissue that are not surrounded by a capsule. Because they are scattered throughout the lamina propria Lymphatic tissues begin to develop by the end of the fifth week of (connective tissue) of mucous membranes lining the gastrointestinal, embryonic life. Lymphatic vessels develop from lymph sacs that arise urinary, and reproductive tracts and the respiratory airways, from developing veins, which are derived from mesoderm. lymphatic nodules in these areas are also referred to as mucosa- The first lymph sacs to appear are the paired jugular lymph sacs associated lymphatic tissue (MALT). at the junction of the internal jugular and subclavian veins (Figure 22.8). Although many lymphatic nodules are small and solitary, some From the jugular lymph sacs, lymphatic capillary plexuses spread occur in multiple large aggregations in specific parts of the body. to the thorax, upper limbs, neck, and head. Some of the plexuses Among these are the tonsils in the pharyngeal region and the aggre- enlarge and form lymphatic vessels in their respective regions. Each gated lymphatic follicles (Peyer’s patches) in the ileum of the small jugular lymph sac retains at least one connection with its jugular vein, intestine. Aggregations of lymphatic nodules also occur in the ap- the left one developing into the superior portion of the thoracic duct pendix. Usually there are five tonsils, which form a ring at the junc- (left lymphatic duct). tion of the oral cavity and oropharynx and at the junction of the nasal The next lymph sac to appear is the unpaired retroperitoneal - cavity and nasopharynx (see Figure 23.2b). The tonsils are strategi- lymph sac (re′-trō-per′-i-tō-NE-al) at the root of the mesentery of cally positioned to participate in immune responses against inhaled the intestine. It develops from the primitive vena cava and meso- or ingested foreign substances. The single pharyngeal tonsil nephric (primitive kidney) veins. Capillary plexuses and lymphatic (fa-RIN-jē-al) or adenoid is embedded in the posterior wall of the vessels spread from the retroperitoneal lymph sac to the abdomi- nasopharynx. The two palatine tonsils (PAL-a-tīn) lie at the posterior nal viscera and diaphragm. The sac establishes connections with region of the oral cavity, one on either side; these are the tonsils the cisterna chyli but loses its connections with neighboring commonly removed in a tonsillectomy. The paired lingual tonsils veins. 820 CH APTE R 2 2 The Lymphatic System and Immunity FIGURE 22.8 Development of lymphatic tissues. It also includes various internal defenses, such as antimicrobial substances, natural killer cells, phagocytes, inflammation, and fever. Lymphatic tissues are derived from mesoderm. First Line of Defense: Skin and Mucous Membranes Internal jugular vein The skin and mucous membranes of the body are the first line of Jugular lymph sac Subclavian defense against pathogens. These structures provide both physical vein and chemical barriers that discourage pathogens and foreign Thoracic duct substances from penetrating the body and causing disease. Cisterna chyli Inferior With its many layers of closely packed, keratinized cells, the outer Retroperitoneal vena cava epithelial layer of the skin—the epidermis—provides a formidable lymph sac physical barrier to the entrance of microbes (see Figure 5.1). In Posterior addition, periodic shedding of epidermal cells helps remove microbes lymph sac at the skin surface. Bacteria rarely penetrate the intact surface of healthy epidermis. If this surface is broken by cuts, burns, or punc- tures, however, pathogens can penetrate the epidermis and invade adjacent tissues or circulate in the blood to other parts of the body. Q When do lymphatic tissues begin to develop? The epithelial layer of mucous membranes, which line body cavities, secretes a fluid called mucus that lubricates and moistens At about the time the retroperitoneal lymph sac is developing, the cavity surface. Because mucus is slightly viscous, it traps many another lymph sac, the cisterna chyli, develops inferior to the dia- microbes and foreign substances. The mucous membrane of the nose phragm on the posterior abdominal wall. It gives rise to the inferior has mucus-coated hairs that trap and filter microbes, dust, and pol- portion of the thoracic duct and the cisterna chyli of the thoracic duct. lutants from inhaled air. The mucous membrane of the upper respira- Like the retroperitoneal lymph sac, the cisterna chyli also loses its tory tract contains cilia, microscopic hairlike projections on the connections with surrounding veins. surface of the epithelial cells. The waving action of cilia propels The last of the lymph sacs, the paired posterior lymph sacs, inhaled dust and microbes that have become trapped in mucus toward develop from the iliac veins. The posterior lymph sacs produce capillary the throat. Coughing and sneezing accelerate movement of mucus plexuses and lymphatic vessels of the abdominal wall, pelvic region, and its entrapped pathogens out of the body. Swallowing mucus and lower limbs. The posterior lymph sacs join the cisterna chyli and sends pathogens to the stomach, where gastric juice destroys them. lose their connections with adjacent veins. Other fluids produced by various organs also help protect epithe- With the exception of the anterior part of the sac from which the cis- lial surfaces of the skin and mucous membranes. The lacrimal ap- terna chyli develops, all lymph sacs become invaded by mesenchymal paratus (LAK-ri-mal) of the eyes (see Figure 17.6) manufactures and cells (me-SENG-kī-mal) and are converted into groups of lymph nodes. drains away tears in response to irritants. Blinking spreads tears over The spleen develops from mesenchymal cells between layers of the surface of the eyeball, and the continual washing action of tears the dorsal mesentery of the stomach. The thymus arises as an out- helps to dilute microbes and keep them from settling on the surface of growth of the third pharyngeal pouch (see Figure 18.20a). the eye. Tears also contain lysozyme (LĪ-sō-zīm), an enzyme capable of breaking down the cell walls of certain bacteria. Besides tears, Checkpoint lysozyme is present in saliva, perspiration, nasal secretions, and tis- sue fluids. Saliva, produced by the salivary glands, washes microbes 8. What are the names of the four lymph sacs from which lymphatic from the surfaces of the teeth and from the mucous membrane of the vessels develop? mouth, much as tears wash the eyes. The flow of saliva reduces colo- nization of the mouth by microbes. The cleansing of the urethra by the flow of urine retards microbial 22.6 Innate Immunity colonization of the urinary system. Vaginal secretions likewise move microbes out of the body in females. Defecation and vomiting also expel microbes. For example, in response to some microbial toxins, OBJECTIVE the smooth muscle of the lower gastrointestinal tract contracts vigor- ously; the resulting diarrhea rapidly expels many of the microbes. Describe the components of innate immunity. Certain chemicals also contribute to the high degree of resistance of the skin and mucous membranes to microbial invasion. Sebaceous (oil) glands of the skin secrete an oily substance called sebum that Innate (nonspecific) immunity includes the external physical and forms a protective film over the surface of the skin. The unsaturated chemical barriers provided by the skin and mucous membranes. fatty acids in sebum inhibit the growth of certain pathogenic bacteria  22.6 Innate Immunity 821 and fungi. The acidity of the skin (pH 3–5) is caused in part by the se- substances in blood, the next nonspecific defense consists of natural cretion of fatty acids and lactic acid. Perspiration helps flush mi- killer cells and phagocytes. About 5–10% of lymphocytes in the blood crobes from the surface of the skin. Gastric juice, produced by the are natural killer (NK) cells. They are also present in the spleen, glands of the stomach, is a mixture of hydrochloric acid, enzymes, lymph nodes, and red bone marrow. NK cells lack the membrane and mucus. The strong acidity of gastric juice (pH 1.2–3.0) destroys molecules that identify B and T cells, but they have the ability to many bacteria and most bacterial toxins. Vaginal secretions also are kill a wide variety of infected body cells and certain tumor cells. NK slightly acidic, which discourages bacterial growth. cells attack any body cells that display abnormal or unusual plasma membrane proteins. The binding of NK cells to a target cell, such as an infected human Second Line of Defense: Internal Defenses cell, causes the release of granules containing toxic substances from NK cells. Some granules contain a protein called perforin (PER-for-in) When pathogens penetrate the physical and chemical barriers of the that inserts into the plasma membrane of the target cell and creates skin and mucous membranes, they encounter a second line of channels (perforations) in the membrane. As a result, extracellular defense: internal antimicrobial substances, phagocytes, natural killer fluid flows into the target cell and the cell bursts, a process called cells, inflammation, and fever. cytolysis (sī-TOL-i-sis; cyto- = cell; -lysis = loosening). Other granules of NK cells release granzymes (GRAN-zīms), which are protein- Antimicrobial Substances There are four main types of anti- digesting enzymes that induce the target cell to undergo apoptosis, or microbial substances that discourage microbial growth: interferons, self-destruction. This type of attack kills infected cells, but not the complement, iron-binding proteins, and antimicrobial proteins. microbes inside the cells; the released microbes, which may or may not be intact, can be destroyed by phagocytes. 1. Lymphocytes, macrophages, and fibroblasts infected with viruses Phagocytes (FAG-ō-sīts; phago- = eat; -cytes = cells) are special- - - produce proteins called interferons (IFNs) (in′-ter-FER-ons). Once ized cells that perform phagocytosis (fag-ō-sī-TO-sis; -osis = process), released by virus-infected cells, IFNs diffuse to uninfected neigh- the ingestion of microbes or other particles such as cellular debris boring cells, where they induce synthesis of antiviral proteins that (see Figure 3.13). The two major types of phagocytes are neutrophils interfere with viral replication. Although IFNs do not prevent viruses and macrophages. When an infection occurs, neutrophils and mono- from attaching to and penetrating host cells, they do stop repli- cytes migrate to the infected area. During this migration, the mono- cation. Viruses can cause disease only if they can replicate within cytes enlarge and develop into actively phagocytic macrophages body cells. IFNs are an important defense against infection by many called wandering macrophages. Other macrophages, called fixed different viruses. The three types of interferons are alpha-, beta-, macrophages, stand guard in specific tissues. Among the fixed and gamma-IFN. macrophages are histiocytes (HIS-tē-ō-sīts) (connective tissue 2. A group of normally inactive proteins in blood plasma and on plas- macrophages), stellate reticuloendothelial cells (STEL-āt re-tik′-ū-lō- - ma membranes makes up the complement system. When acti- en-dō-THE-lē-al) or Kupffer cells (KOOP-fer) in the liver, alveolar mac- vated, these proteins “complement” or enhance certain immune rophages in the lungs, microglial cells in the nervous system, and reactions (see Section 22.9). The complement system causes cy- tissue macrophages in the spleen, lymph nodes, and red bone tolysis (bursting) of microbes, promotes phagocytosis, and contrib- marrow. In addition to being an innate defense mechanism, phagocy- utes to inflammation. tosis plays a vital role in adaptive immunity, as discussed later in 3. Iron-binding proteins inhibit the growth of certain bacteria by re- the chapter. ducing the amount of available iron. Examples include transferrin (found in blood and tissue fluids), lactoferrin (found in milk, saliva, and mucus), ferritin (found in the liver, spleen, and red bone mar- Clinical Connection row), and hemoglobin (found in red blood cells). Microbial Evasion of Phagocytosis 4. Antimicrobial proteins (AMPs) are short peptides that have a broad spectrum of antimicrobial activity. Examples of AMPs are Some microbes, such as the bacteria that cause pneumonia, have extra- dermicidin (der-ma-SĪ-din) (produced by sweat glands), defen- cellular structures called capsules that prevent adherence. This makes it sins and cathelicidins (cath-el-i-SĪ-dins) (produced by neutrophils, physically difficult for phagocytes to engulf the microbes. Other microbes, such as the toxin-producing bacteria that cause one kind of food poison- macrophages, and epithelia), and thrombocidin (throm′-bō-SĪ- ing, may be ingested but not killed; instead, the toxins they produce (leu- din) (produced by platelets). In addition to killing a wide range of kocidins) may kill the phagocytes by causing the release of the phagocyte’s microbes, AMPs can attract dendritic cells and mast cells, which own lysosomal enzymes into its cytoplasm. Still other microbes—such as participate in immune responses. Interestingly enough, microbes the bacteria that cause tuberculosis—inhibit fusion of phagosomes and exposed to AMPs do not appear to develop resistance, as often lysosomes and thus prevent exposure of the microbes to lysosomal en- happens with antibiotics. zymes. These bacteria apparently can also use chemicals in their cell walls to counter the effects of lethal oxidants produced by phagocytes. Sub- sequent multiplication of the microbes within phagosomes may eventually Natural Killer Cells and Phagocytes When microbes destroy the phagocyte. penetrate the skin and mucous membranes or bypass the antimicrobial 822 CH APTE R 2 2 The Lymphatic System and Immunity Phagocytosis occurs in five phases: chemotaxis, adherence, 5 Killing. The chemical onslaught provided by lysozyme, digestive ingestion, digestion, and killing (Figure 22.9): enzymes, and oxidants within a phagolysosome quickly kills many types of microbes. Any materials that cannot be degraded 1 Chemotaxis. Phagocytosis begins with chemotaxis (kē-mō-TAK- further remain in structures called residual bodies. sis), a chemically stimulated movement of phagocytes to a site of damage. Chemicals that attract phagocytes might come from invading microbes, white blood cells, damaged tissue cells, or Inflammation Inflammation is a nonspecific, defensive res- activated complement proteins. ponse of the body to tissue damage. Among the conditions that may 2 Adherence. Attachment of the phagocyte to the microbe or other produce inflammation are pathogens, abrasions, chemical irritations, foreign material is termed adherence (ad-HER-ents). The binding distortion or disturbances of cells, and extreme temperatures. of complement proteins to the invading pathogen enhances Inflammation is an attempt to dispose of microbes, toxins, or foreign adherence. material at the site of injury, to prevent their spread to other tissues, and to prepare the site for tissue repair in an attempt to restore 3 Ingestion. The plasma membrane of the phagocyte extends tissue homeostasis. There are certain signs-symptoms associated projections, called pseudopods (SOO-dō-pods), that engulf the with inflammation and these can be recalled by using the following microbe in a process called ingestion. When the pseudopods acronym: PRISH. meet they fuse, surrounding the microorganism with a sac called a phagosome (FAG-ō-sōm). P is for pain due to the release of certain chemicals. R is for redness because more blood is rushed to the affected area. 4 Digestion. The phagosome enters the cytoplasm and merges I is for immobility that results from some loss of function in severe with lysosomes to form a single, larger structure called a inflammations. phagolysosome (fag-ō-LĪ-sō-sōm). The lysosome contributes S is for swelling caused by an accumulation of fluids. lysozyme, which breaks down microbial cell walls, and other H is for heat which is also due to more blood rushed to the affected digestive enzymes that degrade carbohydrates, proteins, lipids, area. and nucleic acids. The phagocyte also forms lethal oxidants, such as superoxide anion (O2−), hypochlorite anion (OCl−), Because inflammation is one of the body’s nonspecific defense and hydrogen peroxide (H2O2), in a process called an oxidative mechanisms, the response of a tissue to a cut is similar to the response burst. to damage caused by burns, radiation, or bacterial or viral invasion. In FIGURE 22.9 Phagocytosis of a microbe. The major types of phagocytes are neutrophils and macrophages. 1 Chemotaxis Microbe Phagocyte 2 Adherence 3 Ingestion Phagocyte Pseudopod Phagosome Lysosome 4 Digestion Digested microbe Plasma in phagolysosome membrane Residual body 5 Killing (contains indigestible Microbe Digestive material) enzymes Juergen Berger/Science Source Images SEM 1800x (a) Phases of phagocytosis (b) Phagocyte (white blood cell) engulfing microbe. Q What chemicals are responsible for killing ingested microbes?  22.6 Innate Immunity 823 each case, the inflammatory response has three basic stages: (1) vas- Kinins. Polypeptides formed in blood from inactive precursors odilation and increased permeability of blood vessels, (2) emigration called kininogens, (kinins), induce vasodilation and increased (movement) of phagocytes from the blood into interstitial fluid, and, permeability and serve as chemotactic agents for phagocytes. An ultimately, (3) tissue repair. example of a kinin is bradykinin. Prostaglandins. Prostaglandins (PGs) (pros′-ta-GLAN-dins), es- VASODILATION AND INCREASED BLOOD VESSEL PERMEABILITY Two pecially those of the E series, are released by damaged cells and immediate changes occur in the blood vessels in a region of tissue intensify the effects of histamine and kinins. PGs also may stimulate injury: vasodilation (increase in the diameter) of arterioles and the emigration of phagocytes through capillary walls. increased permeability of capillaries (Figure 22.10). Increased per- meability means that substances normally retained in blood are per- Leukotrienes. Produced by basophils and mast cells, leukotrienes mitted to pass from the blood vessels. Vasodilation allows more blood (LTs) (loo′-kō-TRĪ-ēns) cause increased permeability; they also func- to flow through the damaged area, and increased permeability permits tion in adherence of phagocytes to pathogens and as chemotactic defensive proteins such as antibodies and clotting factors to enter the agents that attract phagocytes. injured area from the blood. The increased blood flow also helps Complement. Different components of the complement system remove microbial toxins and dead cells. stimulate histamine release, attract neutrophils by chemotaxis, Among the substances that contribute to vasodilation, increased and promote phagocytosis; some components can also destroy permeability, and other aspects of the inflammatory response are the bacteria. following: Dilation of arterioles and increased permeability of capillaries Histamine. In response to injury, mast cells in connective tissue and produce three of the signs and symptoms of inflammation: heat, red- basophils and platelets in blood release histamine. Neutrophils and ness (erythema), and swelling (edema). Heat and redness result from macrophages attracted to the site of injury also stimulate the release the large amount of blood that accumulates in the damaged area. As of histamine, which causes vasodilation and increased permeability the local temperature rises slightly, metabolic reactions proceed of blood vessels. more rapidly and release additional heat. Edema results from in- FIGURE 22.10 Inflammation. creased permeability of blood vessels, which permits more fluid to move from blood plasma into tissue spaces. The three stages of inflammation are as follows: (1) vasodilation and Pain is a prime symptom of inflammation. It results from injury to increased permeability of blood vessels, (2) phagocyte emigration, neurons and from toxic chemicals released by microbes. Kinins affect and (3) tissue repair. some nerve endings, causing much of the pain associated with inflam- Tissue injury mation. Prostaglandins intensify and prolong the pain associated with inflammation. Pain may also be due to increased pressure from edema. The increased permeability of capillaries allows leakage of blood- clotting factors into tissues. The clotting sequence is set into motion, and fibrinogen is ultimately converted to an insoluble, thick mesh of fibrin threads that localizes and traps invading microbes and blocks their spread. EMIGRATION OF PHAGOCYTES Within an hour after the inflammatory Chemotaxis Microbe process starts, phagocytes appear on the scene. As large amounts of blood accumulate, neutrophils begin to stick to the inner surface of the endothelium (lining) of blood vessels (Figure 22.10). Then the neutrophils begin to squeeze through the wall of the blood vessel to Phagocytes reach the damaged area. This process, called emigration (em′-i-GRĀ- Emigration shun), depends on chemotaxis. Neutrophils attempt to destroy the invading microbes by phagocytosis. A steady stream of neutrophils is ensured by the production and release of additional cells from red bone marrow. Such an increase in white blood cells in the blood is - termed leukocytosis (loo-kō-sī-TO-sis). Vasodilation Although neutrophils predominate in the early stages of infec- and increased tion, they die off rapidly. As the inflammatory response continues, permeability monocytes follow the neutrophils into the infected area. Once in the tissue, monocytes transform into wandering macrophages that add to the phagocytic activity of the fixed macrophages already present. Phagocytes migrate from blood to site of tissue injury True to their name, macrophages are much more potent phagocytes Q What causes each of the following signs and symptoms of than neutrophils. They are large enough to engulf damaged tissue, inflammation: redness, pain, heat, and swelling? worn-out neutrophils, and invading microbes. 824 CH APTE R 2 2 The Lymphatic System and Immunity Eventually, macrophages also die. Within a few days, a pocket of TA B L E 22. 1 Summary of Innate Defenses dead phagocytes and damaged tissue forms; this collection of dead cells and fluid is called pus. Pus formation occurs in most inflam- COMPONENT FUNCTIONS matory responses and usually continues until the infection subsides. FIRST LINE OF DEFENSE: SKIN AND MUCOUS MEMBRANES At times, pus reaches the surface of the body or drains into an internal Physical Factors cavity and is dispersed; on other occasions the pus remains even after the infection is terminated. In this case, the pus is gradually destroyed Epidermis of skin Forms physical barrier to entrance of over a period of days and is absorbed. microbes. Mucous membranes Inhibit entrance of many microbes, but not as effective as intact skin. Clinical Connection Mucus Traps microbes in respiratory and gastrointestinal tracts. Abscesses and Ulcers Hairs Filter out microbes and dust in nose. If pus cannot drain out of an inflamed region, the result is an abscess—an Cilia Together with mucus, trap and excessive accumulation of pus in a confined space. Common examples are remove microbes and dust from upper pimples and boils. When superficial inflamed tissue sloughs off the surface respiratory tract. of an organ or tissue, the resulting open sore is called an ulcer. People with Lacrimal apparatus Tears dilute and wash away irritating poor circulation—for instance, diabetics with advanced atherosclerosis— substances and microbes. are susceptible to ulcers in the tissues of their legs. These ulcers, which Saliva Washes microbes from surfaces of teeth are called stasis ulcers, develop because of poor oxygen and nutrient and mucous membranes of mouth. supply to tissues that then become very susceptible to a very mild injury or infection. Urine Washes microbes from urethra. Defecation Expel microbes from body. and vomiting Inflammation can be classified as acute or chronic depending on Chemical Factors a number of factors. In acute inflammation the signs and symptoms Sebum Forms protective acidic film over skin develop rapidly and usually last for a few days or even a few weeks. It surface that inhibits growth of many microbes. is usually mild and self-limiting and the principal defensive cells are neutrophils. Examples of acute inflammation are a sore throat, ap- Lysozyme Antimicrobial substance in perspiration,