Please see attached.
For the second part of the discussion, you will apply what you have learned from the course materials in this module. By Thursday, create and post separately, two well-crafted questions for your classmates to answer. You must start each question post with “CLASSMATE QUESTION.” Please be sure to research your questions and add references in APA style format.
Module 3 – Google Slides
CHAPTER 19 Lymphatic and Immune Systems
STUDENT LEARNING OBJECTIVES
At the completion of this chapter, you should be able to do the following:
1.Briefly outline the components of the lymphatic and immune systems.
2.Contrast the composition of lymph with that of interstitial fluid.
3.Outline the general circulation of lymph through lymphatic vessels and nodes.
4.List several major groups of lymph nodes and their locations.
5.List the lymphatic functions of the following: tonsils, thymus, spleen.
6.Outline an overview of innate immunity.
7.List and briefly discuss the three lines of immune defense.
8.Discuss the significance of fever and inflammation.
9.Outline the roles of the following: macrophages, diapedesis, NK cells, interferon.
10.Give an overview of adaptive immunity.
11.Discuss the major types of immune system molecules and indicate how antibodies and complement proteins function.
12.Discuss the diversity of antibodies and their functions.
13.Discuss and contrast the development and functions of B and T cells.
14.Compare and contrast antibody-mediated and cell-mediated immunity.
LANGUAGE OF SCIENCE AND MEDICINE
Before reading the chapter, say each of these terms out loud. This will help you avoid stumbling over them as you read.
(ah-KWYERD ih-MYOO-nih-tee) [immun- free, -ity state]
(AK-tiv ih-MYOO-nih-tee) [actus- moving, immun- free, -ity state]
(ah-DAP-tiv ih-MYOO-nih-tee) [adapt- adjust, -ive relating to, immun- free, -ity state]
(ah-gloo-tin-AY-shun) [agglutin- glue, -ation process]
aggregated lymphoid nodule
(ag-rah-GAYT-ed LIM-foyd NOD-yool) [a(d)- to, -grega- collect, lymph- water, -oid like, nod- knot, -ule small]
(ah-nas-toh-MOH-sis) [ana- anew, -stomo- mouth, -osis conditions of] pl., anastomoses (ah-nas-toh-MOH-seez)
(AN-tih-bod-ee) [anti- against]
(AN-tih-bod-ee–MEE-dee-ayt-ed ih-MYOO-nih-tee) [anti- against, medi- middle, -ate process, immun- free, -ity state]
(AN-tih-bod-ee TYE-ter) [anti- against, titer proportion (in a solution)]
(AN-tih-jen) [anti- against, -gen produce]
(AN-tih-jen-AN-tih-bod-ee KOM-pleks) [anti- against, -gen produce, anti- against, complex embrace]
antigen-presenting cell (APC)
(AN-tih-jen sell) [anti- against, -gen produce, cell storeroom]
(aw-toh-ih-MYOO-nih-tee) [auto- self, -immun- free, -ity state]
axillary lymph node
(AK-sih-lair-ee limf) [axilla- wing, -ary relating to, lymph water, nod- knot]
[B bursa-equivalent tissue, cell storeroom]
(C-D SIS-tem) [C cluster, D differentiation, system organized whole]
(sell-MEE-dee-ayt-ed ih-MYOO-nih-tee) [cell storeroom, medi- middle, -ate process, immun- free, -ity state]
(SELL-yoo-lar ih-MYOO-nih-tee) [cell- storeroom, -ular relating to, immun- free, -ity state]
(kee-moh-TAK-sis) [chemo- chemical, -taxis movement]
(kile) [chyl- juice]
(klohn) [clon a plant cutting]
[comple- complete, -ment result of action]
(SYE-toh-kyne) [cyto- cell, -kine movement]
(dye-ah-peh-DEE-sis) [dia- through, -pedesis an oozing]
(eh-DEE-mah) [edema swelling]
(ah-FEK-tor sell) [effect- accomplish, -or agent, cell storeroom]
effector T cell
[effect- accomplish, -or agent, T thymus gland, cell storeroom]
(EP-ih-tope) [epi- on or upon, -tope place]
(JER-mih-nal SEN-ter) [germ- sprout, -al relating to]
hematopoietic stem cell
(hee-mah-toh-poy-ET-ik) [hema- blood, -poie- make, -ic relating to, cell storeroom]
(ih-MYOON SIS-tem) [immun- free, system organized whole]
(ih-myoo-nih-ZAY-shun) [immun- free (immunity), -tion process of]
(ih-myoo-noh-GLOB-yoo-lin) [immuno- free (immunity), -glob- ball, -ul- small, -in substance]
(in-FLAM-ah-toh-ree) [inflamm- set afire, -ory relating to]
(IN-ayt ih-MYOO-nih-tee) [innat- inborn, immun- free, -ity state]
(in-ter-FEER-on) [inter- between, -fer- strike, -on substance]
interstitial fluid (IF)
(in-ter-STISH-al FLOO-id) [inter- between, -stit- stand, -al relating to]
(LAK-tee-al) [lact- milk, -al relating to]
(LING-gwal TAHN-sil) [lingua- tongue, -al relating to]
(limf) [lymph water]
(lim-FAT-ik KAP-ih-lair-ee) [lymph- water, -atic relating to, capill- hair, -ary relating to]
(lim-FAT-ik SIS-tem) [lymph- water, -atic relating to, system organized whole]
(lim-FAT-ik) [lymph- water, -atic relating to]
(limf) [lymph water, nod- knot]
(LIM-foyd TISH-yoo) [lymph- water, -oid like, tissu fabric]
(MAK-roh-fayj) [macro- large, -phage eat]
major histocompatibility complex (MHC)
(his-toh-kom-pat-ih-BIL-ih-tee KOM-pleks) [histo- tissue, -compatibil- agreeable, -ity state, complex embrace]
(mass-TYE-tis) [mast- breast, -itis inflammation]
membrane attack complex (MAC)
(MEM-brayne KOM-pleks) [membran- thin skin, complex embrace]
memory B cell
[B bursa-equivalent tissue, cell storeroom]
memory T cell
[T thymus gland, cell storeroom]
(nye-EVE) [naïve natural]
naïve B cell
(nye-EVE B sell) [naïve natural, B bursa-equivalent tissue, cell storeroom]
natural killer (NK) cell
(NOO-troh-fil) [neuter- neither, -phil love]
(non-speh-SIF-ik ih-MYOO-nih-tee) [non- not, -specif- form or kind, -ic relating to, immun- free, -ity state]
(op-son-ih-ZAY-shun) [opson- condiment, -ization process]
(PAL-ah-tyne TAHN-sil) [palat- palate, -ine relating to]
(PAS-iv ih-MYOO-nih-tee) [immun- free, -ity state]
(fag-oh-sye-TOH-sis) [phago- eating, -cyt- cell, -osis condition]
(FAG-oh-sohm) [phago- eat, -some body]
(fah-RIN-jee-al TAHN-sil) [pharyng- throat, -al relating to]
(PLAZ-mah sell) [plasma something molded (blood plasma), cell storeroom]
(RAD-ih-kal mas-TEKtoh-mee) [radic- root, -al relating to, mast- breast, -ec- out, -tom- cut, -y action]
right lymphatic duct
(lim-FAT-ik) [lymph- water, -atic relating to]
(SPEE-sheez ree-ZIS-tens) [species form or kind]
(speh-SIF-ik ih-MYOO-nih-tee) [specif- form or kind, -ic relating to, immun- free, -ity state]
[T thymus gland, cell storeroom]
(thoh-RAS-ik) [thorac- chest (thorax), -ic relating to]
(THY-moh-syte) [thymo- thyme flower (thymus gland), -cyte cell]
(THY-moh-sin) [thymos- thyme flower (thymus gland), -in substance]
(THY-mus) [thymus thyme flower] pl., thymuses
(tahn-sih-LEK-toh-mee) [tonsil- tonsil, -ec- out, -tom- cut, -y action]
(tahn-sih-LYE-tis) [tonsil- tonsil, -itis inflammation]
(TOK-soyd) [tox- poison, -oid like]
(vak-sih-NAY-shun) [vaccin- cow (cowpox), -ation process]
KOSTAS remembered getting the flu (influenza) last winter: coughing, fever, achiness all over his body, watery eyes, and fatigue. He felt awful! But he argued, “What’s the point of a flu shot, when all it does is give you the flu?” Kostas did not understand that the injected flu vaccine is a combination of span inactivated (killed) viruses injected into muscles in your body (usually in your arm). No active viruses are injected. So, as for the injected form of the vaccine “causing” the flu—people who claim that could already have been exposed to a flu virus before the vaccination or could have been exposed to one of the strains not included in that year’s vaccine. Some people produce a mild immune reaction that can be mistaken for the flu. In the end, Kostas relented and got his flu shot!
We’re sure you’ll enjoy reading about your own immune system, and how your body is programmed to protect you from disease. At the end of this chapter, you should be able to answer some questions about Kostas and his flu shot.
Now that you have read this chapter, see if you can answer these questions about the flu shot Kostas received in the Introductory Story.
1. Which of Kostas’ cells will respond to the flu antigens introduced by the vaccine?
2. Which specific cell types will begin producing antibodies to the antigens?
a. Z cells
b. T cells
c. A cells
d. B cells
3. Which antibody is primarily involved in this response to vaccine?
4. Kostas’ fever during the previous winter’s flu was caused by the release of ___, molecules that help increase his body’s “set point” to higher than normal.
5. What would you call the specific type of immunity Kostas developed as a result of the vaccination?
a. Natural active immunity
b. Artificial active immunity
c. Natural passive immunity
d. Artificial passive immunity
To solve a case study, you may have to refer to the glossary or index, other chapters in this textbook, A&P Connect, Mechanisms of Disease, and other resources.
COMPONENTS OF THE LYMPHATIC AND IMMUNE SYSTEMS
We have combined two related systems in this chapter: the lymphatic system and the immune system.
The lymphatic system has at least three different functions. First, it serves to maintain the fluid balance of our internal body environment. Second, the lymphatic system serves to house the immune defenses of our body. Third, the lymphatic system also helps regulate the absorption of lipids from digested food in the small intestines and provides for their transport to the large systemic veins. As you will see, the vessels of the lymphatic system roughly parallel the vessels of the cardiovascular system.
The immune system serves to repel and destroy the hordes of microorganisms that threaten our lives every day. In addition, our immune system must defend us from our own abnormal cells that can cause cancerous tumors. Such tumors may damage surrounding tissues and spread cancer throughout the body. Without an internal “security force” to deal with such abnormal cells when they first appear, we would have very short lives indeed!
Overview of the Lymphatic System
Figure 19-1 gives you an excellent start to your understanding of the lymphatic system.
As you can see, plasma filters into interstitial spaces from blood flowing through the capillaries. Most of this interstitial fluid is absorbed by tissue cells or is reabsorbed by the blood before it flows out of the tissue. However, a small amount of the interstitial fluid remains behind. It seems insignificant, but if even small amounts of extra fluid continued to accumulate in the tissues over time, the result would be tremendous edema (swelling). This would be followed by tissue destruction. The lymphatic system solves the problem of fluid retention in our tissues. In fact, the entire system acts as a drainage system: It continuously collects excess tissue fluid and returns it to the venous blood just before it reaches the heart.
The lymphatic system consists of a moving fluid (lymph) derived from the blood and tissue fluid as well as a group of vessels (lymphatics) that return the lymph to the blood. In addition to lymph and lymphatic vessels, the system includes various structures that contain lymphoid tissue. This tissue, as we will see, contains lymphocytes and other defensive cells of the immune system. For example, lymph nodes are located along the paths of the collecting lymphatic vessels. Additional lymphoid tissue is found in the intestinal wall, appendix, tonsils, thymus, spleen, and bone marrow (Figure 19-2, A).
The lymphatic system provides a unique transport function. It returns tissue fluid, proteins, fats, and other substances to the general circulatory system. However, unlike the circulatory system, the lymphatic vessels do not form a closed
FIGURE 19-1 Role of the lymphatic system in fluid balance. Fluid from plasma flowing through the capillaries moves into interstitial spaces. Although most of this interstitial fluid is either absorbed by tissue cells or resorbed by capillaries, some of the fluid tends to accumulate in the interstitial spaces. As this fluid builds up, it drains into lymphatic vessels that eventually return the fluid to the venous blood.
system of vessels. Instead they begin blindly in the intercellular spaces of the soft tissue of the body (see Figure 19-1).
Lymph and Interstitial Fluid
Lymph is a clear fluid found in the lymphatic vessels, whereas interstitial fluid (IF) is the complex fluid that fills the spaces between the cells. Both lymph and interstitial fluid closely resemble blood plasma in composition. However, lymph cannot clot like blood. If the main lymphatic trunks in the thorax (see Figure 19-2) are damaged, the flow of lymph must be stopped surgically or death ensues.
Distribution of Lymphatic Vessels
Lymphatic vessels begin as microscopic blind-ended lymphatic capillaries. If the lymphatic vessels originate in the villi of the small intestine, they are called lacteals (see Chapter 21). The wall of each lymphatic capillary consists of a single layer of flattened endothelial cells. We have extensive networks of lymphatic capillaries that branch and then rejoin repeatedly to form an elaborate network throughout the interstitial spaces of our bodies.
The lymphatic capillaries merge to form larger and larger vessels until main lymphatic trunks are formed. These include the right lymphatic duct and the thoracic duct seen in Figure 19-2. Lymph from the entire body, except from the upper right quadrant, eventually drains into the thoracic duct. This in turn drains into the left subclavian vein at the point where it joins the left internal jugular vein (see Figure 19-2, B). Lymph from the upper right quadrant empties into the right lymphatic duct and then into the right subclavian vein.
Note that the thoracic duct is considerably larger than the right lymphatic duct. This is because most of the body’s lymph returns to the bloodstream via the thoracic duct.
Structure of Lymphatic Vessels
The walls of lymphatic capillaries have numerous openings or clefts between the cells. This makes them much more porous or permeable than blood capillaries. As lymph flows from the thin-walled lymphatic capillaries into vessels with larger diameters, the walls become thicker. Eventually these larger vessels have the three layers typical of arteries and veins.
One-way valves are abundant in lymphatic vessels of all sizes. These valves give the vessels a somewhat beaded appearance. Valves are present every few millimeters in large lymphatics and are even more numerous in the smaller vessels (Figure 19-3).
Function of Lymphatic Vessels
The lymphatics play a vital role in numerous homeostatic mechanisms. The great permeability of the lymphatic capillary wall permits very large molecules and even small particles to
FIGURE 19-2 Lymphatic system. A, Principal organs of the lymphatic system. B, The right lymphatic duct drains lymph from the upper right quadrant (dark blue) of the body into the right subclavian vein. The thoracic duct drains lymph from the rest of the body (yellow) into the left subclavian vein. The lymphatic fluid is thus returned to the systemic blood just before entering the heart.
be removed from the interstitial spaces. In fact, proteins that accumulate in the tissue spaces can return to blood only by the lymphatic system. This fact has great clinical importance. For example, if anything blocks the return of lymph for an extended period of time, blood protein concentration and blood osmotic pressure soon fall below normal. The result is fluid imbalance and death.
Lacteals from the villi of the small intestine are important in the absorption of fats and other nutrients. Chyle—the milky lymph found in lacteals after digestion—contains 1% to 2% fat.
Circulation of Lymph
Water and solutes continually filter out of capillary blood into the interstitial fluid (refer again to Figure 19-1). To balance this outflow from the system, fluid continually re-enters blood from the interstitial fluid. We now know that about 50% of the total blood protein leaks out of the capillaries into
FIGURE 19-3 Structure of a typical lymphatic capillary. Notice that interstitial fluid enters through clefts between overlapping endothelial cells that form the wall of the vessel. Valves ensure one-way flow of lymph out of the tissue.
the interstitial fluid and ultimately returns to the blood by way of the lymphatic vessels (Figure 19-4).
The Lymphatic Pump
Even without a pump like the heart, lymph moves slowly and steadily along in its lymphatic vessels into the general circulation at about 3 L/day. This occurs despite the fact that most of the flow is against gravity! It does so because of the large number of valves that permit fluid flow only in the general direction toward the heart.
Breathing movements and skeletal muscle contraction aid in this return movement of lymph to the circulatory system, just as they assist venous blood return, as we have seen (Chapter 10). During strenuous exercise, lymph flow may increase 10 to 15 times over normal because of skeletal muscle contraction. In this way, the continuous flow of lymph serves as an important homeostatic mechanism that maintains the constancy of our body fluids.
1. Where can you find lymphoid tissue?
2. Compare the composition of lymph and interstitial fluid.
3. Briefly describe the structure and function of lymphatic capillaries.
4. Briefly describe the factors that aid the movement of lymphatic fluid.
Structure of Lymph Nodes
Lymph nodes (lymph glands) are oval-shaped or bean-shaped structures (Figure 19-5) that are distributed widely throughout the body. Some are as small as a pinhead; others are as large as a lima bean. The vast system of lymph nodes is linked together by the lymphatic vessels. Note in Figure 19-5, C, that lymph moves into a node by way of several afferent lymphatic vessels and emerges by one or two efferent vessels, creating an effective biological filter. One-way valves keep lymph flowing only in one direction.
Fibrous partitions or trabeculae extend from the covering capsule toward the center of a lymph node, creating compartments called cortical nodules. Each cortical nodule within the lymph node is composed of packed lymphocytes that surround a less dense area, the germinal center (see Figure 19-5, C). When an infection is present, germinal centers enlarge and the node begins to release lymphocytes. Special leukocytes called B lymphocytes (B cells) begin their final stages of maturation within the germinal center of the nodule. They are then pushed into the denser outer layers to mature before becoming antibody-producing plasma cells.
The center, or medulla, of a lymph node is composed of sinuses that separate medullary cords composed of plasma
FIGURE 19-4 Circulation plan of lymphatic fluid. This diagram outlines the general scheme for lymphatic circulation. Fluids from the systemic and pulmonary capillaries leave the bloodstream and enter interstitial spaces, thus becoming part of the interstitial fluid (IF). The IF also exchanges materials with the surrounding tissues. Often, because less fluid is returned to the blood capillary than had left it, IF pressure increases—causing IF to flow into the lymphatic capillary. The fluid is then called lymph (lymphatic fluid) and is carried through one or more lymph nodes and finally to large lymphatic ducts. The lymph enters a subclavian vein, where it is returned to the systemic blood plasma. Thus fluid circulates through blood vessels, tissues, and lymphatic vessels in a sort of “open circulation.”
cells and B cells. Both the cortical and medullary sinuses are lined with macrophages ready for phagocytosis.
Locations of Lymph Nodes
Most lymph nodes occur in groups, or clusters (see Figure 19-2), in certain areas, especially the head and neck. A total of approximately 500 to 600 lymph nodes are located throughout our bodies. Before you continue, take a moment to review the locations of the major lymph nodes in Figure 19-2.
Function of Lymph Nodes
Our lymph nodes defend our bodies from invading pathogens and also provide sites for the maturation of some types of lymphocytes.
Lymph flow slows as it passes through the sinus channels of the lymph nodes. This gives the special cells that line the channels time to remove microorganisms and other injurious particles. Here, the offending material is engulfed in the process of phagocytosis and destroyed. Thus, lymph nodes are the sites of both biological and mechanical filtration.
Sometimes, however, the lymph nodes are overwhelmed by massive numbers of infectious microorganisms. The nodes themselves then become sites of infection. Most people have experienced the pain of swollen lymph nodes. In addition, cancer cells breaking away from a malignant tumor may also enter the lymphatic system. They travel to the lymph nodes and may create cancerous growths that block the flow of lymph. This leaves too few channels for lymph to return to the blood and swelling results. For example, if tumors block axillary lymph node channels (located under our arms), fluid accumulates in the interstitial spaces of the arm, causing swelling and pain from the edema. Even viruses such as human immunodeficiency virus (HIV) and other types of pathogens can infect or infest lymph nodes.
Lymphoid tissues of lymph nodes also serve as the site for the final stages of maturation of some types of lymphocytes and monocytes.
Lymphatic Drainage of the Breast
Distribution of Lymphatics in the Breast
The mammary glands and surrounding tissues of the breast are drained by two sets of lymphatic vessels. There are lymphatics that originate in and drain the surface area and skin over the breast (excluding the areola and nipple areas). There are also lymphatics that originate in and drain the underlying tissue of the breast itself (including the skin of the areola and nipple).
FIGURE 19-5 Structure of a lymph node. A, A lymph node is typically a small structure into which afferent lymphatic ducts empty their lymph. Efferent lymphatic ducts drain the lymph from the node. An outer fibrous capsule maintains the structural integrity of the node. B, Photograph of a dissected cadaver shows a lymph node and its associated lymphatic vessels, along with nearby muscles, nerves, and blood vessels. C, Internal structure of a lymph node. Several afferent valved lymphatics bring lymph to the node. In this example, a single efferent lymphatic leaves the node at a concave area called the hilum. Note that the artery and vein also enter and leave at the hilum. Arrows show direction of lymph movement.
FIGURE 19-6 Lymphatic drainage of the breast. Note the extensive network of lymphatic vessels and nodes that receive lymph from the breast. Surgical procedures called mastectomies, in which some or all of the breast tissues are removed, are sometimes performed to treat breast cancer. Because cancer cells can spread so easily through the extensive network of lymphatic vessels associated with the breast, the lymphatic vessels and their nodes are sometimes also removed. Occasionally, such procedures cause swelling, or lymphedema.
More than 85% of the lymph from the breast enters the lymph nodes of the axillary region (Figure 19-6). Most of the remainder enters lymph nodes along the lateral edges of the sternum. Several very large nodes in the axillary region physically contact extensions of breast tissue.
Lymph Nodes Associated with the Breast
There are many anastomoses (connections) between the superficial lymphatics from both breasts. These anastomoses can allow cancerous cells from one breast to invade normal tissue from the other breast. Removal of a wide area of deep fascia is therefore required in surgical treatment of advanced or diffuse breast malignancy. Such a surgical procedure is called a radical mastectomy. Cancer of the breast is one of the most common forms of malignancy in women. However, it can also be found (although rarely) in men.
Breast infections are also a serious health concern, especially among women who nurse their infants. Mastitis, for example, is an inflammation of the mammary gland, usually caused by infectious agents. Breast infections, like cancer, can also spread easily through lymphatic pathways associated with the breast.
5. Describe the overall structure of a typical lymph node.
6. How are lymph nodes generally distributed in your body?
7. What vital functions are performed by the lymph nodes?
8. How does the distribution of lymphatics in breast tissue and adjacent tissues relate to breast cancer and its spread?
Structure and Function of the Tonsils
Masses of lymphoid tissue, called tonsils, form a protective ring under the mucous membranes in the mouth and back of the throat (Figure 19-7). This ring of tonsils protects us against bacteria that may invade tissue in the area around the openings between the nasal and oral cavities. The palatine tonsils are located on each side of the throat. The pharyngeal tonsils (called adenoids when they become swollen) are near the posterior opening of the nasal cavity. A third type of tonsil, the lingual tonsils, lie near the base of the tongue. Other smaller tonsils are located near the opening of the auditory (eustachian) tube. Each tonsil has deep recesses that trap bacteria and expose them to the immune system.
FIGURE 19-7 Location of the tonsils. Small segments of the roof and floor of the mouth have been removed to show the protective ring of tonsils (pharyngeal lymphoid ring) around the internal openings of the nose and throat.
The tonsils are part of our first line of defense from the external environment. As such, they are subject to chronic infection, or tonsillitis. In these cases, tonsils may be surgically removed (tonsillectomy), if non-surgical treatments prove ineffective. However, because of the critical immunological role played by the lymphatic tissue, the number of tonsillectomies performed annually continues to decrease.
Structure and Function of Aggregated Lymphoid Nodules
Aggregated lymphoid nodules, also called Peyer patches, are groups of small oval patches or groups of lymph nodes that form a single protective layer in the mucous membrane of the small intestine, especially the ileum. Because the entire gastrointestinal tract is potentially open to the external environment via the mouth, these patches are in a great location to provide immune surveillance in an area where massive numbers of potentially pathogenic bacteria can be found. The macrophages and other cells of the immune system prevent most of these bacteria from penetrating the gut wall. Aggregated lymphoid nodules and other lymphoid tissues are sometimes called mucosa-associated lymphoid tissue (MALT).
Structure and Function of the Thymus
The thymus is a primary organ of the lymphatic system. It consists of two pyramid-shaped lobes. The thymus is located in the mediastinum, extending up into the neck, close to the thyroid gland (Figure 19-8). It is largest (relative to body size) in a child about 2 years old. After puberty, however, the thymus gradually atrophies. In advanced old age, it may be largely replaced by fat, becoming yellow in color.
FIGURE 19-8 Thymus. Location of a child’s thymus within the mediastinum.
The thymus plays a critical part in the body’s defenses against infection. Before birth, the thymus serves as the final site of lymphocyte development. Many lymphocytes leave the thymus and circulate to the spleen, lymph nodes, and other lymphoid tissue.
Soon after birth, the thymus assumes another function. It begins secreting a group of peptide hormones (collectively called thymosin) and other regulators that enable lymphocytes to develop into mature T cells. Only T lymphocytes that pass “immunological testing” are released into the bloodstream.
Structure and Function of the Spleen
The spleen is located below the diaphragm, just above most of the left kidney and behind the fundus of the stomach (see Figure 19-2). Roughly oval in shape (Figure 19-9), the spleen varies somewhat in size from individual to individual. For example, it enlarges (hypertrophies) during infectious disease and shrinks (atrophies) in old age.
FIGURE 19-9 Structure of the spleen. Medial aspect of the spleen. Notice the concave surface that fits against the stomach within the abdominopelvic cavity.
The spleen has a variety of functions, including defense, hematopoiesis, and erythrocyte and platelet destruction. It also serves as a reservoir for blood.
Defense is accomplished as blood passes through highly permeable, enlarged blood vessels, called sinusoids. Macrophages lining these venous spaces remove microorganisms from the blood and destroy them by phagocytosis. Hematopoiesis takes place when monocytes and lymphocytes complete their development and become “activated” in the spleen.
Before birth, red blood cells are also formed in the spleen. However, after birth, the spleen forms red blood cells only in cases of severe anemia. Macrophages lining the spleen’s sinusoids remove worn-out red blood cells and imperfectly formed platelets. Macrophages also break apart the hemoglobin molecules from the destroyed red blood cells. They salvage iron and globin content from destroyed erythrocytes and return these by-products of destruction to the bloodstream. From here, they are sent to storage in the bone marrow and liver.
Finally, the spleen and its venous sinuses hold a considerable amount of blood. This blood reservoir can rapidly be added back into the circulatory system if it is needed. However, if the spleen is ruptured, as when the ribs are broken and pushed into the spleen, significant internal bleeding can occur, followed by death. Surgical repair or removal of the spleen is often required to stop the blood loss and save the patient’s life.
Even though the spleen provides many useful functions, it is not a vital organ and can be removed without dire consequences.
9. Where are the major tonsils located? What is their role?
10. What major roles does the thymus play in immunity?
11. What are the major functions of the spleen? Is it a “vital” organ?
FIGURE 19-10 Lines of defense. Immune function—that is, defense of the internal environment against foreign cells, proteins, and viruses—includes three layers of protection. The first line of defense is a set of barriers between the internal and external environments. The second involves the innate inflammatory response (including phagocytosis). The third includes the adaptive immune responses and the innate defense offered by natural killer cells. Of course, tumor cells that arise within the body are not affected by the first two lines of defense and must be attacked by the third line of defense. This diagram is a simplification of the complex function of the immune system. In reality, a great deal of crossover of mechanisms occurs between these “lines of defense.”
Organization of the Immune System
Like any security force, the components and mechanisms of the immune system are organized in an efficient—almost military—manner. These forces are continually patrolling our bodies. We begin with a brief overview of how this important system is organized.
First, we must understand that all cells, viruses, and other particles have unique molecules on their surfaces that can be used to identify them. These molecules are called antigens. Like enemy aircraft with distinctive insignia, cells can be identified as being “self” or “nonself.” Foreign cells and particles have nonself antigen molecules that can serve as recognition markers for identification by our immune system. The ability of our immune system to attack abnormal or foreign cells while sparing our own cells is called self-tolerance.
Our bodies employ many different kinds of mechanisms to ensure the integrity and survival of our internal environment. All of these defense mechanisms are categorized either as innate (nonspecific) immunity or adaptive (specific) immunity.
Innate immunity is “in place” before you are exposed to a particular harmful particle or condition. It is naturally present at birth and is also called nonspecific immunity because it provides a general defense by acting against a wide variety of particles recognized as nonself.
Adaptive immunity, in contrast, involves mechanisms that program the body to recognize specific threatening agents. It “adapts” by targeting its response to these agents and to these agents alone. Because it targets only specific harmful particles, adaptive immunity is also called specific immunity. Adaptive immune mechanisms often take some time to recognize their targets before they can react with sufficient force to overcome the threat.
As in any body system, cells or substances made by cells do the work of the immune system. The primary types of cells involved in innate immunity are these: epithelial barrier cells, phagocytic cells (neutrophils, macrophages), and aptly named natural killer (NK) cells. The primary types of cells involved in adaptive immunity are two types of lymphocytes called T cells and B cells.
Cytokines are chemicals released from cells to trigger or regulate innate and adaptive immune responses. Examples of cytokines include interleukins (ILs), leukotrienes, and interferons (IFNs). We will describe interferons more fully later in this chapter.
Human immune systems are such that there is a type of species resistance in which the genomes of specific organisms may be resistant to particular pathogens. This species resistance protects us from diseases such as canine distemper. As you might expect, however, our closer living primate relatives such as chimpanzees and bonobos have immune systems almost identical to our own, which means that some of their infections also affect us.
Our internal army of cells and molecules can be described in one word: incredible. Over one trillion lymphocytes and over 100 million trillion plasma protein molecules (antibodies) patrol our internal environment every minute. The basic components of innate immunity and adaptive immunity will be explained in more detail in the following pages.
Overview of Innate Immunity
There are numerous aspects of our innate (nonspecific) defensive mechanisms. The major players in this system are discussed below.
Mechanical and Chemical Barriers
Our internal environment is protected by a continuous mechanical barrier created by the cutaneous membrane (skin) and mucous membranes, as we have seen in Chapter 7. Often called the first line of defense, these membranes provide several layers of densely packed cells and other material. Together these cells and materials form a sort of “castle wall” against entry (Figure 19-10).
Besides forming a protective barrier, the skin and mucous membranes provide additional immune functions. For example, substances such as skin surface film, sebum, mucus, enzymes, and even hydrochloric acid (produced by the stomach lining) all serve to deter or destroy invading pathogens. The epithelial barriers of our bodies are essentially innate, nonspecific defenses.
Inflammatory Response and Fever
If bacteria or other invaders break through our mechanical and chemical barriers formed by the membranes and their secretions, the body has a second line of defense ready: the inflammatory response (see Figure 19-10). The inflammatory response elicits a number of actions that promote returning your body to a normal state. You can follow a flowchart illustrating how a local inflammatory response works in Figure 19-11. The diagram shows bacteria causing tissue damage. In turn, this abnormal condition triggers the release of various inflammation mediators from cells such as mast cells found in connective tissues. These inflammation mediators include histamine, prostaglandins, leukotrienes, interleukins, and other related compounds. They function to attract
FIGURE 19-11 Example of the inflammatory response. Tissue damage caused by bacteria triggers a series of events that produce the inflammatory response. This promotes phagocytosis at the site of injury. These responses tend to inhibit or destroy the bacteria, eventually bringing the tissue back to its healthy state. Similar reactions will occur in the presence of other abnormal or injurious particles or conditions.
FIGURE 19-12 Chemotaxis and diapedesis. In this example, a neutrophil is attracted by agents released by a mast cell in a damaged or infected tissue. After adhering to the inside of the blood capillary, the neutrophil exits the capillary by diapedesis. Through chemotaxis (movement directed by chemical attraction), the neutrophil migrates toward the highest concentration of chemotactic factor—the site of the injury—where it can then begin its immune functions.
leukocytes to the area in a process called chemotaxis (Figure 19-12), which directs these cells to the site of inflammation. The characteristic signs of inflammation are heat, redness, pain, and swelling.
Besides local inflammation, systemic inflammation may occur when the inflammation mediators trigger responses that occur on a body-wide basis. A body-wide inflammatory response may be a fever—a state of elevated body temperature. Often a fever is accompanied by high neutrophil counts. A fever really results from a “reset” of the body’s thermostat in the hypothalamus. This temporarily increases the set point or target temperature to a higher-than-normal value. Our bodies may shiver and feel cold. An elevated body temperature may facilitate some immune reactions. High fevers may also inhibit the reproduction of some microbial pathogens. However, the truth is that we really don’t know for sure what fevers actually do!
Phagocytosis and Phagocytic Cells
A major component of the body’s second line of defense is phagocytosis—the ingestion and destruction of microorganisms and other small particles by cells called phagocytes. There are many types of phagocytes, but the basic mechanism of engulfing foreign substances is the same. Phagocytes extend footlike projections called pseudopods toward the invading organism. Soon the pseudopods encircle the pathogen and create a phagosome. The phagosome then moves into the interior of the cell. Here a lysosome fuses with it, releases digestive enzymes and hydrogen peroxide, and destroys the microorganism.
Because phagocytosis defends our bodies against a number of pathological agents, it is classified as an innate defense. As we will soon see, phagocytes play an important role in adaptive immunity as well.
The most numerous type of phagocyte is the neutrophil. Chemotactic factors (chemicals released at the site of infection) cause neutrophils and other phagocytes to adhere to the endothelial lining of capillaries servicing the affected area. The phagocytes then pass between the endothelial cells making up the capillary wall, dissolve the underlying basement membrane, and enter into the inflamed area. The movement of phagocytes from blood vessels to the site of inflammation is called diapedesis (see Figure 19-12).
Phagocytes have a very short life span. Dead phagocytic cells tend to “pile up” at the inflammation site, creating much of the white substance we call pus.
Another common type of phagocyte is the macrophage. These large phagocytic monocytes grow to several times their original size after migrating out of the bloodstream.
Other types of phagocytic cells are present in many areas of the body. For example, highly branched phagocytes called dendritic cells (DCs) are found in the interstitial fluid of most tissues of the body. Some phagocytes are even found on the outside surface of some mucous membranes (for example, in the respiratory tract).
Natural Killer Cells
Natural killer (NK) cells are large granular lymphocytes that patrol our blood and lymph and provide important innate defensive functions for our bodies. In fact, these cells kill many types of tumor cells and cells infected by different kinds of viruses. Natural killer cells are produced in the red bone marrow and make up about 15% of the total lymphocyte number. Because they have a broad-based action and do not have to be activated by specific foreign antigens to become active, we usually include NK cells among the body’s innate immune system. They are not phagocytic, however. They release chemicals called perforins that cause the targeted cell’s membrane to rupture and disintegrate.
Natural killer cells can attack a large range of invading cells simply by recognizing markers on the surface membrane of invading cells or defective cells. Some of the receptors on NK cells are “killer-inhibiting” in nature. If the killer-inhibiting receptor of an NK cell happens to bind to a major histocompatibility complex (MHC) protein also, then the killing action is stopped. (Box 19-1 explains that MHCs are surface proteins on all normal cells and are unique to each individual.) Thus, only abnormal and foreign cells fail to bind to the killer-inhibiting centers—and therefore are killed by the NK cell.
BOX 19-1 FYI
Major Histocompatibility Complex
The major histocompatibility complex (MHC) is a set of genes that code for antigen-presenting proteins and other immune system proteins. Antigens are proteins that potentially trigger a specific immune response. Their function is to present different protein fragments (peptides) at the surface of the cell for possible recognition as either self or nonself antigens by immune system cells.
The MHC class I proteins function to present protein fragments from within the cell at the surface as antigens. An immune cell will then recognize the presented antigen as a self-antigen or as a nonself-antigen (see figure). Self-antigens are normally ignored by the immune cell. Nonself-antigens are instead recognized as abnormal and attacked. If a normal cell becomes infected with a virus or becomes cancerous, it may present some abnormal antigens on the surface and thus be identified by the immune system. MHC class I proteins are also involved in the mechanism by which natural killer (NK) cells recognize abnormal cells.
MHC class II proteins are expressed in immune cells that specialize in presenting antigens. These “professional” antigen-presenting cells (APCs) include macrophages and dendritic cells (DCs), for example. The APCs use their MHC class II proteins to present fragments of proteins that they’ve brought in from outside the cell. Thus they alert the immune system to the presence of these invaders and trigger certain adaptive (specific) immune responses.
MHC class III proteins include a wide variety of different immune-related proteins such as complement components and a number of immune and nonimmune proteins.
The major histocompatibility complex (MHC) first came to the attention of researchers who were trying to find out why transplants and tissue grafts were often rejected by the recipient. They found that individuals with different MHC genes rejected tissues transplanted from one to the other. Thus they coined the term histocompatibility for this set of genes because the genes seemed to regulate the compatibility of transplants and grafts.
MHC function. This simplified diagram shows that the MHC protein displays an antigen (protein fragment or peptide) on the surface of the cell. A receptor on the surface of a T cell may then bind to the unique receptor-binding part of the MHC and to a complementary part of the T cell. Antigens (peptides) presented this way can then be recognized by immune cells as being “self” or “nonself.”
There are hundreds of different versions or alleles of the principal MHC genes—far more genetic variability than in any other group of genes in the human genome! Scientists are still trying to find a satisfactory explanation for this tremendous variation.
Several types of cells, if invaded by viruses, respond rapidly by synthesizing and releasing glycoproteins called interferons (IFNs). Interferon proteins interfere with the ability of viruses to replicate and cause disease in the host’s cells. These proteins induce the activation of antiviral genes in neighboring cells. In this way, interferons allow virus-infected cells to send out an “alarm” to nearby cells that protects the uninfected cells. The presence of interferons may also account for symptoms such as sore muscles, body aches, and fever when a virus invades our body.
Interferons come in several varieties, each with somewhat different antiviral actions. Three major types of interferons have now been produced with gene-splicing techniques, and studies exploring antiviral and anticancer activities are still being conducted.
Complement is a name that applies to a group of about 20 inactive enzymes found in the plasma and on cell membranes. Individual complement proteins are often designated by C (complement) followed by a number, such as C1, C2, and so on. Complement molecules are activated in a cascade of chemical reactions triggered by either adaptive or innate mechanisms. Ultimately, the complement lyses (breaks apart) the foreign cell that triggered the response. Complement also marks microbes for destruction by phagocytic cells. This process, called opsonization, promotes the inflammatory response in the body’s affected tissues.
12. Why are the skin and mucous membranes included as major players in the first line of defense?
13. Describe the basic inflammatory response. How does the inflammatory response protect the body?
14. What is phagocytosis? Name some phagocytic cells.
15. How do interferons and complement protect the body?
Overview of Adaptive Immunity
A variety of adaptive (specific) immune mechanisms are geared to attack specific agents that the body recognizes as abnormal or nonself. Adaptive immunity—part of the body’s third line of defense—is provided by two different types of lymphocytes (Figure 19-13). Lymphocytes originally are produced in the red bone marrow of the fetus from hematopoietic stem cells. However, the cells that eventually become lymphocytes follow two different developmental paths (Figure 19-14). For this reason, there are two major classes of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells).
B cells do not attack pathogens directly. Instead, they produce molecules called antibodies that attack the pathogens, or direct other cells, such as phagocytes, to attack them. B-cell mechanisms are therefore often classified as antibody-mediated immunity. Antibodies disperse freely in the blood plasma, where they perform their immune functions.
To help you understand the essential terms of immunity as you continue, we’ve created a short list of the most important ones in Box 19-2.
BOX 19-2 FYI
The Language of Adaptive Immunity
Learning the mechanisms of adaptive (specific) immunity will be easier if you first become familiar with these terms:
Antigens—macromolecules (large molecules) that induce the immune system to respond in specific ways. Most antigens are foreign proteins. However, some are polysaccharides and some are nucleic acids. Haptens, sometimes called “incomplete antigens,” are very small molecules that must first bind to a protein before they can induce an immune response. Many antigens that enter the body are macromolecules located in the walls or outer membranes of microorganisms or the outer coats of viruses. Of course, antigens on the surfaces of some tumor cells (tumor markers) are not really from outside the body but are “foreign” in the sense that they are recognized as “not belonging.” The membrane molecules that identify all the normal cells of the body are called major histocompatibility complex (MHC) antigens.
Antibodies—plasma proteins of the class called immunoglobulins. Unlike most antigens, all antibodies are native molecules; that is, they are normally present in the body.
Combining sites—two small concave regions on the surface of an antibody molecule. The unique shapes of the combining sites allow the antigen to bind to the antibody to form an antigen-antibody complex.
Clone—family of cells, all of which have descended from one cell.
Complement—a group of proteins that, when activated, work together to destroy foreign cells.
Effector cell—a B cell or T cell that is actively producing an immune response, such as secreting antibodies (effector B cells) or directly attacking other cells (effector T cells). Effector cells usually die during or just after their immune response. Effector B cells are also called plasma cells.
Memory cell—a B or T cell that has been activated (no longer naïve) but is not an effector cell producing an active response. A memory cell survives for a long period in the lymph nodes and, if later exposed to the same specific antigen, forms a clone of cells that rapidly produce a specific immune response.
Naïve—refers to a B or T cell that is inactive, because it has not yet been exposed to (or had an opportunity to react with) a specific antigen. The term is synonymous with “inactive.”
Because T cells attack pathogens more directly, we classify their mechanism of operation as cell-mediated immunity or cellular immunity (Figure 19-15). Lymphocytes bear proteins on their cellular surfaces called surface markers. Some of these proteins are unique
FIGURE 19-13 Lymphocytes. Color-enhanced scanning electron micrograph showing lymphocytes in yellow, red blood cells in red, and platelets in green.
FIGURE 19-14 Development of B cells and T cells. Both types of lymphocytes originate from stem cells in the red bone marrow. Pre-B cells that are formed by dividing stem cells develop in the special tissues of the yolk sac, fetal liver, and bone marrow. Pre-T cells migrate to the thymus, where they continue developing. Once they are formed, B cells and T cells circulate to the lymph nodes and spleen.
to lymphocytes; some are shared by other types of cells. B cells and T cells each have some unique surface markers that not only distinguish B cells from T cells, but also subdivide these categories even further into subsets.
There is actually an international system for naming the subset of surface markers on blood cells. It’s called the CD system (CD stands for cluster of differentiation). The number after “CD” refers to a single, defined surface marker protein. For example, the number of cells in the CD4 and CD8 T-cell subsets are clinically important in diagnosing AIDS (Figure 19-16).
The densest populations of lymphocytes occur in the bone marrow, thymus gland, spleen, and lymph nodes. Lymphocytes pour into the bloodstream from these structures. In this way they are distributed throughout the body. After meandering through the tissue spaces, they eventually find their way into lymphatic capillaries. Lymph flow then transports the lymphocytes through a succession of lymph nodes and lymph vessels and then, as we have seen, they empty into the thoracic and right lymphatic ducts into the subclavian veins. In this manner they are returned to the blood. Now they embark on still another long journey—through blood, tissue spaces, and lymph and then back to the bloodstream. This recirculation and widespread distribution of lymphocytes allows these cells to search out, recognize, and destroy foreign invaders anywhere in the body.
Take a moment to re-read the information in Box 19-2 before you continue.
16. What is adaptive immunity?
17. What cells are involved in antibody-mediated immunity?
18. Why is the CD system so important to diseases such as AIDS?
FIGURE 19-15 Two strategies of adaptive immunity. Simplified summary of antibody-mediated (humoral) immunity and cell-mediated (cellular) immunity.
FIGURE 19-16 Clinical progression of HIV/AIDS. Changing numbers of CD4 T cells as an HIV infection progresses to AIDS.
B Cells and Antibody-Mediated Immunity
Development and Activation of B Cells
B-cell lymphocytes develop in two stages (Figure 19-17). By the time a human infant is a few months old, its pre-B cells have completed the first stage of their development. At this stage they are known as naïve B cells. These cells synthesize antibody molecules, but secrete few if any of them. Instead, the Naïve B cells insert as many as 100,000 of the same antibody molecules on the surface of their plasma membranes. These molecules serve as receptors should a specific antigen come by.
After Naïve B cells are released from the bone marrow, they circulate to the lymph nodes, spleen, and other lymphoid structures.
The second major stage of development occurs when the Naïve B cells become activated. This can only happen when a Naïve B cell actually encounters the antigen (e.g., from a virus) to the type of antibody it already has produced. This means that the antigen must fit into the combining sites of that specific antibody on the B-cell membrane. Now, the stimulated cells undergo rapid mitotic divisions, producing a clone (“family”) of identical B cells. Some of these cells differentiate to form plasma cells. Others do not differentiate completely and remain in the lymphatic tissue as the so-called memory B cells.
Plasma cells synthesize and secrete huge amounts of antibody molecules—up to 2,000 a second during the few days that they live! All the cells in a clone of plasma cells secrete identical antibodies because they have all descended from the same B cell. Memory B cells do not secrete antibodies. However, if they are later exposed to the antigen that triggered their formation, memory B cells will rapidly divide to produce more plasma cells and memory cells. The newly formed plasma cells then quickly secrete antibodies. As before, these antibodies can combine with the initiating antigen to combat the invading microorganism. In a way, the ultimate function of B cells is to serve as future producers of antibody-secreting plasma cells.
Structure of Antibody Molecules
Antibodies are actually proteins called immunoglobulins (Igs). Like all proteins, antibodies are macromolecules composed of chains of amino acids. Each immunoglobulin is actually composed of four polypeptide chains—chains of amino acids strung together. Two of these chains are called heavy chains and the other two are called light chains. Each polypeptide chain is intricately folded to form globular regions joined together so that the resulting immunoglobulin molecule is shaped like a Y.
Take a moment now to look at Figure 19-18, A. The twisted strands of red spheres (amino acids) represent the light chains. The two twisted strands of blue spheres (also amino
FIGURE 19-17 B cell development. B cell development takes place in two stages. First stage: Shortly before and after birth, stem cells develop into naïve B cells. Second stage (occurs only if naïve B cell contacts its specific antigen): Naïve B cell develops into activated B cell, which divides rapidly and repeatedly to form a clone of plasma cells and a clone of memory cells. Plasma cells secrete antibodies capable of combining with specific antigens that cause Naïve B cells to develop into active B cells. Stem cells maintain a constant population of newly differentiating cells.
FIGURE 19-18 Structure of the antibody molecule. A, In this molecular model of a typical antibody molecule, the light chains are represented by strands of red spheres (each represents an individual amino acid). Heavy chains are represented by strands of blue spheres. Notice that the heavy chains can join with a carbohydrate chain. B, This simplified diagram shows the variable regions, highlighted by colored bars, that represent amino acid sequences unique to that molecule. Constant regions of the heavy and light chains are marked with the letter C. The inset shows that the variable regions at the end of each arm of the molecule form a cleft that serves as an antigen-binding site.
acids) represent the heavy chains. Heavy chains are about twice as long and weigh about twice as much as light chains, hence their name.
The regions with colored bars seen in Figure 19-18, B, represent variable regions. This means that the amino acid sequence in these regions can vary between different antibody molecules. Because the sequence of amino acids varies in these regions, so does the final shape of the binding sites in these areas. At the end of each “arm” of the Y-shaped antibody molecule, the unique shapes of the variable regions form a molecular opening or cleft. This cleft serves as the antibody’s binding site for antigens. It is this incredible structural feature that enables our antibodies to recognize and combine with specific antigens. This is the first crucial step in our body’s defense against invading microorganisms and other foreign cells.
In addition to its variable region, each light chain of an antibody also has a constant region. The constant region comprises an amino acid sequence that is identical in all antibody molecules. Each heavy chain of an antibody molecule consists of three constant regions in addition to its one variable region. Note in Figure 19-18, B, the location of two complement-binding sites on the antibody molecule (one on each heavy chain).
Diversity of Antibodies
Every normal baby is born with an enormous number of different clones of B cells. Populations of these cells are found in the bone marrow, lymph nodes, and spleen. All the cells of each clone are already committed to synthesizing a specific antibody. The sequence of amino acids in the variable regions of a specific antibody is different from the sequence in all the countless clones of B cells in the baby’s body. This enormous variability may be due to the way the genes encode for the antibodies. In a way, the system acts like a genetic lottery, producing millions of unique genes by combining different gene segments to produce the unique polypeptides.
Classes of Antibodies
There are five classes of immunoglobulin antibodies, identified by letter names as immunoglobulins M, G, A, E, and D (Figure 19-19). Immunoglobulin M (written IgM) is the antibody that immature B cells synthesize and insert into their plasma membranes. It is also the predominant class of antibody produced after initial contact with an antigen. However, the most abundant circulating antibody, making up about 75% of all antibodies in your blood, is IgG. Production of IgG increases after later contacts with a given antigen. The IgG antibodies are also those that cross the placental barrier during pregnancy. This is how natural passive immunity is given to the baby (Box 19-3).
BOX 19-3 FLI
Without direct access to external antigens, it is no wonder that the immune system is not very capable (on its own) of a vigorous defense during its maturation process before birth (prenatal development). However, as part A of the figure shows, certain antibodies from the mother (maternal antibodies) can be actively transported across the maternal-fetal blood barrier (trophoblast). Only IgG antibodies in the mother’s blood can bind to the receptors. This binding then triggers endocytosis and transports each IgG antibody across to the fetal bloodstream. This mechanism provides passive natural immunity before and shortly after birth.
Part B of the figure shows that, at birth, the newborn has adult levels of IgG—but nearly all of it came from the mother (maternal IgG, blue line). Shortly after birth, the maternal IgG is broken down (blue line) and replaced with new IgG made by the newborn’s own immune system (red line).
Note also in part B of the figure that the concentration of IgM (broken blue line) is only about 20% of the adult level at birth but steadily increases after birth. IgM reaches adult levels in about 2 years. IgA, an important component of the mucosal immune system, also begins to rise at birth. IgA reaches adult levels in just a few months. All three types of antibody are also found in breast milk, providing another avenue of passive immunity after birth.
A, Transport of antibodies across the placenta. B, Antibody concentrations before and after birth.
There are three other types of immunoglobulins: IgA, IgE, and IgD. IgA is the major class of antibody in the mucous membranes of the body. It is also found in saliva and in tears. IgE, although present in very small amounts, can produce the major symptoms of allergies. IgD is also present in our blood, but in very small amounts. We don’t yet know its function. As Figure 19-19 shows, some immunoglobulin
FIGURE 19-19 Classes of antibodies. Antibodies are classified into five major groups: immunoglobulin M (IgM), immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin E (IgE), and immunoglobulin D (IgD). Notice that each IgM molecule has five Y-shaped basic antibody units, IgA has two basic antibody units, and the others have a single basic antibody unit.
molecules are created by the joining of several basic antibody units.
Functions of Antibodies
The function of antibody molecules—some 100 million trillion of them—is to produce antibody-mediated immunity. Antibodies fight disease organisms by first recognizing substances that are foreign or abnormal. In effect, they distinguish nonself-antigens from selfantigens. A small region, the epitope, on an antigen fits into and binds with the antigen-binding site of an antibody. This binding of the antigen to the antibody creates an antigen-antibody complex.
This creation of antigen-antibody complexes may produce several effects. For example, it can transform antigens that are toxins into harmless substances. In other cases, antibodies bind to antigens on the surface of microorganisms. This makes the organisms stick together in clumps (agglutinate). The agglutination of the invaders (whether they are toxins or microorganisms) allows macrophages and other phagocytes to dispose of them rapidly as a sticky group, rather than one at a time. The binding of antigens to antibodies often produces still another effect. It alters the shape of the antibody molecule, not very much, but enough to expose the molecule’s previously hidden complement-binding sites. This may seem like a small effect, but it is not, as we will see below. In fact, this action initiates an incredible series of reactions that culminate in the destruction of microorganisms and other foreign cells (Figure 19-20).
Complement is a component of blood plasma that consists of about 20 inactive enzyme compounds. They are activated in a sequence and together catalyze a series of intricately linked reactions.
Here’s how it works. The binding of an antibody to an antigen located on the surface of a cell alters the shape of the antibody molecule. By doing so, the complement-binding site is exposed. Through a complex series of reactions—a complement cascade—other series of events, such as inflammation, take place (see Figure 19-20). One of the more spectacular results of the complement cascade is the creation of membrane attack complexes (MACs). Molecules formed
FIGURE 19-20 Actions of antibodies. Antibodies act on antigens by inactivating and bending them together to facilitate phagocytosis, and by initiating inflammation and activating the complement cascade.
in this complement cascade assemble themselves on the enemy cell’s surface in the form of a doughnut with a hole in it. Ions and water then rush into the foreign cell through the hole created by the MAC. As a result, the foreign cell swells and bursts (cytolysis).
Other complement cascades serve other functions. Some attract neutrophils to the site of infection and help with phagocytosis. The complement cascade can also be initiated by innate immune mechanisms, causing lysis (rupture) of the foreign cells.
Primary and Secondary Responses
As you can see in Figure 19-21, the first encounter with a specific antigen produces a primary response. This response increases antibody production in a few days. As
FIGURE 19-21 Antibody response times. The initial encounter with a specific antigen (primary stimulus) produces a primary response (increased production of IgM and IgG) in a few days. A later encounter (secondary stimulus) produces a secondary response in much less time. Note that both IgM production and IgG production occur more quickly in the secondary response—and IgG production also increases in the total amount of antibody produced.
the antigen is bound up and destroyed, the antibody levels decrease to their normal levels. However, memory B cells have been produced during this initial phase, in wait for future attack by the same antigen. If there is a later encounter with the same antigen, the dormant memory B cells become active and produce a secondary response in much less time. The memory B cells quickly divide to form more memory cells as well as a large number of plasma cells that produce antibodies against the antigen. As a result, the second response is typically faster and stronger than the first response. The strength of the secondary response can be used to boost the effectiveness of immunizations (Box 19-4).
BOX 19-4 Health Matters
Active immunity can be established artificially by using a technique called vaccination. The first vaccine was a live cowpox virus that was injected into healthy people to cause a mild cowpox infection. The term vaccine literally means “cow substance.” Because the cowpox virus is similar to the deadly smallpox virus, vaccinated individuals developed antibodies that imparted immunity against both cowpox and smallpox viruses.
Modern vaccines work on a similar principle: Substances that trigger the formation of antibodies against specific pathogens are introduced orally or by injection. Some of these vaccines are killed pathogens or “live,” attenuated (weakened) pathogens. Such pathogens still have their specific antigens intact, so they can trigger formation of the proper antibodies, but they are no longer virulent (able to cause disease). Although rarely, these vaccines sometimes backfire and actually cause an infection. Many of the newer vaccines avoid this potential problem by using only the part of the pathogen that contains antigens. Because the disease-causing portion is missing, such vaccines cannot cause infection.
The amount of antibodies in a person’s blood produced in response to vaccination or an actual infection is called the antibody titer. As you can see in the figure, the initial injection of vaccine triggers a rise in the antibody titer that gradually diminishes. Often, a booster shot, or second injection, is given to keep the antibody titer high or to raise it to a level that is more likely to prevent infection. The secondary response is more intense than the primary response because memory B cells are ready to produce a large number of antibodies at a moment’s notice. A later accidental exposure to the pathogen will trigger an even more intense response—thus preventing infection.
Toxoids are similar to vaccines but use an altered form of a bacterial toxin to stimulate production of antibodies. Injection of toxoids imparts protection against toxins, whereas administration of vaccines imparts protection against pathogenic organisms and viruses.
Changes in blood antibody titers following primary and secondary (booster) vaccinations.
Techniques that permit biologists to produce and isolate large quantities of pure and very specific antibodies called monoclonal antibodies (MAbs) and tiny antibody fragments called nanobodies have resulted in dramatic advances in medicine. Learn how this works in Monoclonal Antibodies and Nanobodies online at A&P Connect.
19. What is the difference between a plasma cell and a memory B cell?
20. What are immunoglobulin antibodies?
21. What is the significance of constant regions and variable regions in antibodies?
22. How does immunization work?
T Cells and Cell-Mediated Immunity
Development of T Cells
By definition, T cells are lymphocytes that have passed through the thymus gland before migrating to the lymph nodes and spleen. During their stay in the thymus, pre-T cells develop into thymocytes. These cells proliferate rapidly, dividing up to three times each day! Thymocytes then leave the thymus and pass into the blood, finding a new home in the lymph nodes and spleen. They are now called T cells.
Activation and Function of T Cells
Each T cell (like each B cell) has antigen receptors on its surface membrane. These receptors are not immunoglobulins, but proteins similar to them. When an antigen (presented by phagocytes) encounters a Naïve T cell, the antigen binds to the T cell’s receptors, but only if the surface receptors fit the antigen’s epitope (see earlier discussion above).
Here is where we see one of several differences between antibody-mediated immunity and cell-mediated immunity. Antibodies can react to antigens dissolved in the plasma, but T cells can only react to protein fragments presented on the surface of antigen-presenting cells (APCs). Thus T cells react to cells that are already infected—or have engulfed the antigen. B cells, in contrast, react primarily to antigens that are in the plasma.
The “presentation” of an antigen by an antigenpresenting cell activates or sensitizes the T cell. The T cell then divides repeatedly to form a clone of identical sensitized T cells that form effector T cells and memory T cells. Effector T cells include cytotoxic T cells (killer T cells) and helper T cells. Memory T cells ultimately produce additional active T cells. We’ve summarized the process of T-cell development and activation for you in Figure 19-22.
The effector T cells then travel to the site where the antigens originally entered the body. There, in the inflamed tissue, the sensitized T cells bind to antigens of the same kind that led to their formation. However, T cells bind to their specific antigen only if the antigen is presented by an APC such as a macrophage or dendritic cell (DC).
As we saw earlier, the chemical messengers released by T cells are called cytokines (sometimes called lymphokines when secreted by lymphocytes). These messengers perform a variety of immune functions. For example, cytokines such as lymphotoxins quickly kill any cell they attack, including cancer cells. Cytokines also serve as signals that trigger additional immune responses. Cytokines released from helper T cells help activate both cytotoxic T cells and B cells when they are presented with antigens.
The general function of T cells is to produce cell-mediated immunity. These cells search out, recognize, and bind to appropriate antigens located on the surfaces of cancerous cells or cells that have been invaded by viruses. This action kills the cells—the ultimate function of killer T cells. Foreign cells—from transplanted tissue, for example—may also be attacked unless the killer T cells are suppressed. T cells also serve as overall regulators of adaptive immune mechanisms.
23. From what structure do T cells derive their name?
24. What is the difference between effector T cells and memory T cells?
Types of Adaptive Immunity
Remember that innate immunity occurs when nonspecific immune mechanisms are formed before birth—during the early stages of human development in the uterus. However, adaptive immunity is a specific kind of resistance that develops after birth. Adaptive immunity is, therefore, acquired immunity. Acquired immunity may be further classified as either natural immunity or artificial immunity, depending on how the body is exposed to a specific antigen (Table 19-1).
FIGURE 19-22 T-cell development. The first stage occurs in the thymus gland shortly before and after birth. Stem cells maintain a constant population of newly differentiating cells as they are needed. The second stage occurs only if a T cell is presented an antigen, which combines with certain proteins on the T cell’s surface.
TABLE 19-1 Types of Adaptive Immunity
DESCRIPTION OR EXAMPLE
Exposure to the causative agent is not deliberate.
A child develops measles and acquires an immunity to a subsequent infection.
A fetus receives protection from the mother through the placenta, or an infant receives protection through the mother’s milk.
Exposure to the causative agent is deliberate.
Injection of the causative agent, such as a vaccination against polio, confers immunity.
Injection of protective material (antibodies) that was developed by another individual’s immune system confers immunity
Natural exposure to pathogens is not deliberate, but unfortunately it takes place every day of our lives. That is, we are naturally exposed to many disease-causing agents whether we like it or not. Artificial, or deliberate, exposure to potentially harmful antigens is called immunization.
Natural and artificial immunity may be “active” or “passive.” Active immunity results when an individual’s own immune system responds to a harmful agent—regardless of how it was encountered. Passive immunity results when immunity to a disease that has developed in another individual is transferred to an individual who was not previously immune. For example, antibodies in a mother’s milk impart passive immunity to her nursing infant (see Box 19-3). Active immunity generally lasts longer than
FIGURE 19-23 Summary of adaptive immunity. Flowchart summarizing an example of adaptive immune response when exposed to a microbial pathogen.
passive immunity. Passive immunity, although temporary, provides immediate protection.
Summary of Adaptive Immunity
Adaptive immunity is specific immunity—that is, it targets specific antigens. Two special types of lymphocytes play a major role in immunity: B cells and T cells. B cells recognize specific antigens and produce specific antibodies (immunoglobulins) to destroy the antigen. This is antibody-mediated immunity. T cells recognize antigens presented on cell surfaces to attack infected and abnormal cells in several ways. This is cell-mediated immunity.
Adaptive immunity progresses along a pathway of stages. First, B cells and T cells recognize a specific antigen. Next, the B and T cells are activated. They expand their population (a clone) and thus produce effector cells and memory cells. Then, the effector cells attack the source or sources of the antigen. When there are no longer enough antigens to continue stimulating these immune responses, the effector B and effector T cells die (apoptosis). This represents a return to a homeostatic balance. However, a number of memory cells remain—ready to quickly engage the antigen should it reappear later (Figure 19-23).
25. Describe the basic process of acquired immunity.
26. What is the difference between natural and artificial immunity?
27. What is the difference between active and passive immunity?
A & P CONNECT
The mucosal immune system is a set of innate and adaptive mechanisms that defend our body at the mucous membrane barriers to the outside world. Understanding this unique system has led to new strategies of immunization. Learn why this is so in Mucosal Immunity online at A&P Connect.
Cycle of LIFE
Most of the organs containing masses of developing lymphocytes appear before birth and continue growing through most of childhood. At puberty, this growth typically slows dramatically. After puberty, the lymphoid organs typically begin to slowly atrophy and are much reduced in size by adulthood. These organs—including the thymus, lymph nodes, tonsils, and other lymphoid structures—shrink in size and become fatty or fibrous. The notable exception is the spleen, which develops early in life and remains intact until very late adulthood.
As we’ve seen, the overall function of the immune system is maintained throughout maturity. However, deficiency of the immune system creates a greater risk of infections and cancer. Likewise, hypersensitivity of the immune system may make autoimmune conditions more likely to occur.
The BIG Picture
You can think of the lymphatic system as a vast, systemic filtration system that drains away excess lymph from the vascular system. The treatment sites in this filtration system are the lymph nodes. Contaminants are removed from lymph and the recycled fluid is eventually returned to the bloodstream. The lymphatic system not only prevents dangerous fluid buildup in our tissues, it also is vital in the production of lymphocytes to fight infections. During our later years, deficiency of the immune system permits a much greater risk from infection and cancer.
The agents of the immune system—antibodies, lymphocytes, and other substances and cells—are everywhere in the body. Without the constant defensive activity of the immune system, our internal homeostasis would be constantly challenged by cancer, infections, and even minor injuries.
We’ve seen some of the basic intricacies of the immune system, yet this is just the beginning. Recent research suggests that our immune system is regulated to some degree by the nervous and endocrine systems. A new field, neuroimmunology, is emerging. This is more evidence that all systems in our bodies are highly integrated. The agents of the immune system are not a separate, distinct group of cells and substances. They include blood cells, skin cells, mucosal cells, brain cells, liver cells, and many other types of cells and their secretions. Thus the immune system is more like a self-defense force made up of ordinary citizens who work shoulder-to-shoulder—with military specialists!
MECHANISMS OF DISEASE
We are afflicted with a variety of disorders and diseases of the lymphatic and immune systems, many of which can be life threatening. For example, there are disorders such as lymphedema associated with lymphatic vessels as well as diseases that cause acute inflammation of the lymphatic vessels. There are also a number of disorders associated with lymph nodes and the lymphatic organs, including the well-known ones such as tonsillitis and several types of lymphomas such as Hodgkin disease.
Disorders of the immune system include a variety of allergies and autoimmune conditions, such as systemic lupus erythematosus. Other conditions involve autoimmunity, an inappropriate and excessive response to self-antigens, and deficiencies of the immune system such as those seen in congenital immune deficiency and acquired immune deficiency.
Find out more about these disorders and diseases of the lymphatic and immune systems online at Mechanisms of Disease: Lymphatic and Immune Systems.
To download an MP3 version of the chapter summary for use with your iPod or other portable media player, access the Audio Chapter Summaries online at http://evolve.elsevier.com.
Scan this summary after reading the chapter to help you reinforce the key concepts. Later, use the summary as a quick review before your class or before a test.
COMPONENTS OF THE LYMPHATIC AND IMMUNE SYSTEMS
A. The lymphatic system has at least three different functions:
1. Serves to maintain the fluid balance of our internal body environment
2. Serves as part of our immune system
3. Helps regulate the absorption of lipids from digested food in the small intestines and their transport to the large systemic veins
B. The immune system serves as an internal “security force” to deal with abnormal cells
1. Repels and destroys microorganisms
2. Defends us from our own abnormal cells that can cause cancer
A. Overview of the lymphatic system (Figure 19-1)
1. The lymphatic system solves the problem of fluid retention in tissues
a. Acts as a drainage system
b. Collects excess tissue fluid and returns it to the venous blood just before it reaches the heart
2. Lymphatic system is a part of the circulatory system
a. Consists of moving fluid derived from the blood and tissue fluid as well as a group of vessels that return the lymph to the blood
3. In addition to lymph and lymphatic vessels, the system includes various structures that contain lymphoid tissue (Figure 19-2)
4. Lymphatic system provides a unique transport function
a. Returns tissue fluid, proteins, fats, and other substances to the general circulatory system
5. Lymphatic vessels do not form a closed system of vessels
a. They begin blindly in the intercellular spaces of the soft tissue of the body (Figure 19-1)
B. Lymph and interstitial fluid
1. Lymph—clear fluid found in the lymphatic vessels
2. Interstitial fluid—complex fluid that fills the spaces between the cells
3. Both fluids closely resemble blood plasma in composition
a. Difference is that lymph cannot clot like blood
C. Lymphatic vessels
1. Lymphatic vessels—microscopic blind-ended lymphatic capillaries; wall of each lymphatic capillary consists of a single layer of flattened endothelial cells
a. Networks of lymphatic capillaries branch and then rejoin repeatedly to form a network throughout the interstitial spaces of our bodies
b. Lymphatic capillaries merge to form larger and larger vessels until main lymphatic trunks are formed—right lymphatic duct and thoracic duct (Figure 19-2, B)
2. Structure of lymphatic vessels (Figure 19-3)
a. Walls of lymphatic capillaries
(1) Have numerous openings or clefts between the cells
(2) As lymph flows from the thin-walled capillaries into vessels with larger diameters, the walls become thicker
b. Eventually these larger vessels have the three layers typical of arteries and veins
c. One-way valves are abundant in lymphatic vessels of all sizes
3. Functions of lymphatic vessels
a. Permeability of the lymphatic capillary wall permits very large molecules and even small particles to be removed from the interstitial spaces
b. Lacteals in small intestines are important in the absorption of fats and other nutrients
c. Chyle is the milky lymph found in lacteals after digestion
D. Circulation of lymph
1. About 50% of the total blood protein leaks out of the capillaries into the interstitial fluid; ultimately returns to the blood by way of the lymphatic vessels (Figure 19-4)
2. The lymphatic pump
a. Lymph moves slowly and steadily along in its vessels into the general circulation at about 3 L/day
(1) Lymph flow is possible because of the large number of valves that permit fluid flow only in the general direction toward the heart
(2) Breathing movements and skeletal muscle contraction aid in this motion
E. Lymph nodes
1. Structure of lymph nodes (Figure 19-5)
a. Oval-shaped or bean-shaped structures; widely distributed throughout the body
b. Lymph nodes are linked together by the lymphatic vessels
c. Fibrous partitions or trabeculae extend from the covering capsule toward the center of a lymph node, creating compartments called cortical nodules
d. Center, or medulla, of a lymph node is composed of sinuses; separate medullary cords composed of plasma cells and B cells
2. Locations of lymph nodes
a. Most lymph nodes occur in groups, or clusters (Figure 19-2)
b. Approximately 500 to 600 lymph nodes are located in the body
3. Functions of lymph nodes
a. Defend our bodies from invading pathogens; sites of both biological and mechanical filtration
b. Provide sites for the maturation of some types of lymphocytes
F. Lymphatic drainage of the breast
1. Distribution of lymphatics in the breast
a. Mammary glands and surrounding tissues of the breast are drained by two sets of lymphatic vessels
(1) Some originate in and drain the surface area and skin over the breast
(2) Others originate in and drain the underlying tissue of the breast itself
2. Lymph nodes associated with the breast
a. Many anastomoses between the superficial lymphatics from both breasts
b. Breast infections (e.g., mastitis) are serious health concern, and can spread easily because of the lymphatic pathways of the breast
G. Structure and function of the tonsils
1. Tonsils—form a protective ring under the mucous membranes in the mouth and back of the throat (Figure 19-7)
a. Protects against bacteria that may invade tissue in the area around the openings between the nasal and oral cavities; first line of defense from the external environment
(1) Palatine—located on each side of the throat
(2) Pharyngeal (adenoids)—lie near the posterior opening of the nasal cavity
(3) Lingual—lie near the base of the tongue
H. Structure and function of aggregated lymphoid nodules
1. Also called Peyer patches—small oval patches or groups of lymph nodes that form protective layer in mucous membrane of the small intestine
a. Provide protection in a location that is potentially open to the external environment via the mouth
b. Macrophages and other cells prevent most bacteria from penetrating the gut wall
I. Structure and function of the thymus
1. Thymus—a primary organ of the lymphatic system
a. Consists of two pyramid-shaped lobes
b. Located in the mediastinum, extending up into the neck, close to the thyroid gland (Figure 19-8)
c. Thymus plays a critical part in the body’s defenses against infection
d. Soon after birth, the thymus begins secreting a group of hormones that enable lymphocytes to develop into mature T cells
J. Structure and function of the spleen
1. Spleen—located directly below the diaphragm, just above most of the left kidney and behind the fundus of the stomach (Figure 19-2)
a. Roughly oval in shape (Figure 19-9)
b. Spleen has variety of functions:
(3) Erythrocyte and platelet destruction
(4) Reservoir for blood
A. Organization of the immune system
1. Identification of cells and other particles
a. Antigens—cells, viruses, and other particles with unique molecules on their surfaces
(2) Nonself—molecules on the surface of foreign or abnormal cells or particles that serve as recognition markers for identification by our immune system
(3) Self-tolerance—ability of our immune system to attack abnormal or foreign cells while sparing our own cells
b. Two categories of defense mechanisms:
(1) Innate immunity
(2) Adaptive immunity
2. Innate (nonspecific) and adaptive (specific) immunity
a. Innate immunity—“in place” before you are exposed to a particular harmful particle or condition; nonspecific immunity
b. Adaptive immunity—involves mechanisms that program the body to recognize specific threatening agents; specific immunity
(1) Primary types of cells involved in innate immunity:
(a) Epithelial barrier cells
(b) Phagocytic cells
(c) Natural killer (NK) cells
(2) Primary types of cells involved in adaptive immunity:
(a) T cells
(b) B cells
(3) Cytokines—chemicals released from cells to trigger or regulate innate and adaptive immune responses
(a) Interleukins (ILs)
(c) Interferons (IFNs)
(4) Human immune systems are such that there is a type of “species resistance”; genomes of specific organisms may be resistant to particular pathogens
B. Overview of innate (nonspecific) immunity
1. Mechanical and chemical barriers—first line of defense
a. Internal environment is protected by a cutaneous membrane (skin) and mucous membranes (Figure 19-10)
b. Skin and mucous membranes provide additional immune mechanisms; sebum, mucus, enzymes, and hydrochloric acid produced by the stomach
2. Inflammatory response and fever—second line of defense
a. Inflammatory response—elicits a number of actions that promote returning your body to a normal state (Figure 19-11)
(1) Abnormal tissue damage triggers the release of various inflammation mediators
(2) Inflammation mediators—function to attract leukocytes to the area in a process called chemotaxis (Figure 19-12)
(3) Characteristic signs of inflammation are heat, redness, pain, and swelling
b. Fever—a state of elevated body temperature
(1) Results from a “reset” of the body’s thermostat in the hypothalamus
(2) Fever is thought to increase immune functions and inhibit the reproduction of some microbial pathogens
3. Phagocytosis and phagocytic cells
a. Phagocytosis—ingestion and destruction of microorganisms and other small particles by cells called phagocytes
b. Phagocytosis is classified as an innate defense; also play an important role in adaptive immunity
c. The most numerous type of phagocyte is the neutrophil; other types include macrophages.
d. Chemotactic factors cause neutrophils and other phagocytes to adhere to the endothelial lining of capillaries servicing the affected area (Figure 19-12)
(1) After this, phagocytic cells squeeze through the wall of a blood vessel to get to the site of the injury or infection; diapedesis
4. Natural killer cells—provide important innate defensive functions for our bodies
a. Kill many types of tumor cells and cells infected by different kinds of viruses
b. Produced in the red bone marrow and make up about 15% of the total lymphocyte number
c. Recognize markers on surface membrane of invading or defective cells
(1) Release chemicals called perforins that cause the cell’s membrane to rupture and disintegrate
5. Interferon—glycoprotein that interferes with the ability of viruses to replicate and cause disease in the host’s cells
a. Induces the activation of antiviral genes in neighboring cells
(1) Allows virus-infected cells to send out an “alarm” to nearby cells that protects the uninfected cells
b. Three major types of interferons have now been produced with gene-splicing techniques
6. Complement—name that applies to a group of about 20 inactive enzymes in the plasma and on cell membranes
a. Complement molecules are activated in a cascade of chemical reactions triggered by either adaptive or innate mechanisms
b. Complement also marks microbes for destruction by phagocytic cells; opsonization
C. Overview of adaptive (specific) immunity
1. Adaptive immunity—body’s third line of defense; provided by two different types of lymphocytes (Figure 19-13)
a. Two major classes of lymphocytes:
(1) B lymphocytes (B cells)
(2) T lymphocytes (T cells)
b. B cells produce molecules called antibodies that attack the pathogens or direct other cells, such as phagocytes, to attack them; antibody-mediated immunity
c. T cells attack pathogens more directly and thus operate as cell-mediated immunity (cellular immunity) (Figure 19-15)
d. Lymphocytes bear proteins on their cellular surfaces called surface markers
(1) International system for naming the surface markers on blood cells; CD system (CD stands for cluster of differentiation)
(2) Densest populations of lymphocytes occur in the bone marrow, thymus gland, spleen, and lymph nodes
D. B cells and antibody-mediated immunity
1. Development and activation of B cells
A. B-cell lymphocytes develop in two stages (Figure 19-17)
(1) Pre-B cells develop by a few months of age; Naïve B cells
(2) Second major stage of development then occurs when the Naïve B cells become activated
2. Antibodies (immunoglobulins)
3. Structure of antibody molecules—consist of two heavy and two light polypeptide chains; each molecule has two antigen-binding sites and two complement-binding sites (Figure 19-18)
4. Diversity of antibodies—every normal baby is born with an enormous number of different clones of B cells
A. Cells of each clone are already committed to synthesizing a specific antibody
5. Classes of antibodies—five classes of immunoglobulin antibodies; identified by letter names as immunoglobulins M, G, A, E, and D (Figure 19-19)
a. IgM—antibody that immature B cells synthesize and insert into their plasma membranes
b. IgG—most abundant circulating antibody; crosses placental barrier during pregnancy to give passive immunity to baby (Table 19-1 and Box 19-3)
c. IgA—major class of antibody in the mucous membranes of the body; also in saliva and tears
d. IgE—produces the major symptoms of allergies
e. IgD—small amount in blood; function unknown
6. Functions of antibodies
a. Antigen-antibody reactions—antibody molecules produce antibody-mediated immunity
(1) Antibodies first recognize substances that are foreign or abnormal
(2) Distinguish nonself-antigens from self-antigens
(3) Epitopes—bind to an antibody molecule’s antigen-binding sites; form an antigen-antibody complex
b. Complement—component of blood plasma that consists of about 20 inactive enzyme compounds
(1) They are activated in a complex sequence; catalyze a series of intricately linked reactions
(2) Complement cascade—series of reactions that take place as a result of the binding of an antibody to an antigen; membrane attack complexes (MACs) (Figure 19-20)
c. Primary and secondary responses (Figure 19-21)
(1) Primary response—initial encounter with a specific antigen triggers the formation and release of specific antibodies that reaches its peak in a few days
(2) Secondary response—later encounter with the same antigen triggers a much quicker response; memory B cells rapidly divide, producing more plasma cells and thus more antibodies
E. T cells and cell-mediated immunity
1. Development of T cells
a. T cells—lymphocytes that have passed through the thymus gland before migrating to the lymph nodes and spleen
(1) Pre-T cells develop into thymocytes while in thymus
(2) Thymocytes leave the thymus and pass into the blood, to lymph nodes and spleen; now called T cells
2. Activation and functions of T cells
a. T cells have antigen receptors on their surface membrane
b. The “presentation” of an antigen by an antigen-presenting cell activates or sensitizes the T cell
c. T cell then divides repeatedly; forms a clone of identical sensitized T cells that form effector T cells and memory T cells (Figure 19-22)
(1) Effector T cells—travel to the site where the antigens originally entered the body and begin their attack
(a) Cytotoxic (killer) T cells—destroy infected or cancerous cells
(b) Helper T cells—signal activation of cytotoxic T cells and B cells when presented with antigen
(2) Memory T cells—ultimately produce additional effector T cells
d. Cytokines—chemical messengers
(1) Perform a variety of immune functions
(2) Quickly kill any cell they attack, including cancer cells
(3) Trigger activation of other immune responses
F. Types of adaptive immunity (Table 19-1)
1. Innate immunity—occurs when nonspecific immune mechanisms are formed before birth
2. Adaptive immunity—specific kind of resistance that develops after birth
3. Acquired immunity—classified as either natural immunity or artificial immunity
a. Natural immunity—results from nondeliberate exposure to antigens
b. Artificial immunity—results from deliberate exposure to antigens; immunizations
4. Natural and artificial immunity may be “active” or “passive
a. Active immunity—results when an individual’s own immune system responds to a harmful agent, regardless of how it was encountered
b. Passive immunity—results when immunity to a disease that has developed in another individual is transferred to an individual who was not previously immune (Box 19-3)
G. Summary of adaptive immunity
1. Adaptive immunity is specific immunity; targets specific antigens
2. Two special types of lymphocytes play a major role in immunity:
a. B cells—antibody-mediated immunity
b. T cells—cell-mediated immunity
3. Adaptive immunity progresses along a pathway of stages
a. Recognition of antigen
b. Activation of lymphocytes
c. Effector phase (immune attack)
d. Decline of antigen causes lymphocyte death
e. Memory cells remain for later response if needed
Write out the answers to these questions after reading the chapter and reviewing the Chapter Summary. If you simply think through the answer without writing it down, you won’t retain much of your new learning.
1. List the anatomical components of the lymphatic system.
2. How do interstitial fluid and lymph differ from blood plasma?
3. How do lymphatic vessels originate?
4. Briefly describe the anatomy of the lymphatic capillary wall.
5. Lymph from what body areas enters the general circulation by way of the thoracic duct? By way of the right lymphatic duct?
6. Where does lymph enter the blood vascular system?
7. In general, lymphatics resemble veins in structure. List three exceptions to this general rule.
8. What are the unique lymphatic vessels that originate in the villi of the small intestine called?
9. Locate the thymus, and describe its appearance and size at birth, at maturity, and in old age.
10. Describe the location and functions of the spleen.
11. List several mechanisms of innate defense, and give a brief description of each one.
12. Identify the body’s first line of defense.
13. Activated B cells develop into clones of what two kinds of cells?
14. What cells synthesize and secrete copious amounts of antibodies?
15. Explain the function of memory cells.
16. Differentiate between the classifications of natural and artificial immunity.
17. Describe the process behind the functioning of natural and artificial immunity.
CRITICAL THINKING QUESTIONS
After finishing the Review Questions, write out the answers to these items to help you apply your new knowledge. Go back to sections of the chapter that relate to items that you find difficult.
1. Even though the lymphatic system is a component of the circulatory system, why is the term circulation not the most appropriate term to describe the flow of lymph?
2. Explain how lymph is formed.
3. Discuss the importance of valves in the lymphatic system.
4. Explain the role of the lymphatic system in the spread of breast cancer.
5. If a person had a mutation that prevented the formation of the complement proteins, what capabilities would be lessened in the immune system?
6. Why would you think the development of cancer can be seen as a failure of the immune system?
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