Ch16 Lymphatic System and Immunity.docx

CHAPTER 16: LYMPHATIC SYSTEM AND IMMUNITY OBJECTIVES: 1. Name the organs that compose the lymphatic system and give three general functions performed by this system. 2. Trace the flow of lymph from interstitial tissues to the bloodstream. 3. Discuss the function of anchoring filaments that surround lymphatic capillaries. 4. Name four tissues that do not contain lymphatic capillaries. 5. Give the special name for lymphatic capillaries within the wall of the small intestine. 6. Distinguish between an afferent and efferent lymphatic vessel. 7. Explain how lymphatic vessels are similar to veins. 8. List the six primary body regions drained by lymphatic trunks. 9. Name the two lymphatic collecting ducts and indicate the portion of the body that is drained by each. 10. Name the vein that each of the two collecting ducts deposit their lymph. 11. Discuss the composition of interstitial fluid and lymph. 12. List the functions of lymph, noting its major function. 13. Explain the forces involved in the movement of lymph. 14. Name the condition that occurs when lymphatic flow is obstructed. 15. Discuss the structure, location, and major function of lymph nodes. 16. Discuss the structure, location, and major function of the spleen. 17. Distinguish between the body fluids filtered by lymph nodes and those filtered by the spleen. 18. Name the cell responsible for the filtering action of the lymph node and spleen. 19. Discuss the structure, location, and major function of the thymus. 20. Name the hormone secreted by the thymus that causes maturation of lymphocytes that have migrated to other tissues. 21. Describe what happens to the thymus as one ages. 22. Define the term pathogen. 23. Distinguish between the body's two types of defense mechanisms against infections. 24. Define the term nonspecific resistance and discuss the body's six major mechanisms. 25. Name the antibacterial enzyme present in tears. 26. Discuss how interferons, defensins, and collectins aid in fighting infection. 27. List the cardinal signs of inflammation. 28. List the steps involved in the inflammatory process. 29. Discuss the importance of phagocytosis, and indicate the origin of phagocytic cells. 30. Define the term specific resistance/ immunity. 31. Define the term antigen, and discuss how antigens cause immune responses to occur. 32. Discuss the origin and maturation of lymphocytes. 33. Discuss the process by which an immune response occurs, beginning with the “antigen-presenting cell”. 34. Distinguish between T cells and B cells. 35. Distinguish between Cell-Mediated Immunity (CMI) and Antibody-Mediated (or humoral) Immunity (AMI). 36. Discuss the general structure of an antibody (immunoglobulin [Ig]). 37. Name the five major classes of immunoglobulins and list the major characteristics of each. 38. Name the most abundant Ig. 39. Name the only Ig that can cross the placenta. 40. Name the Ig produced during a primary immune response (IR). 41. Name the Ig produced in abnormal amounts during allergic reactions. 42. Discuss the many actions of antibodies. 43. Distinguish between agglutination, precipitation, neutralization, and lysis. 44. Name the positive feedback mechanism that is activated by antibodies and list its effects. 45. Compare and contrast a primary IR vs. a secondary IR. 46. Discuss the four practical classifications of immunity. 47. Explain how immediate-type allergic reactions occur and proceed. 48. Name the four types of transplants performed. 49. Discuss the major problem that occurs in autoimmune disorders, and list some possible causes of autoimmunity. 50. Explain the theory of “microchimerism”, as it relates to autoimmunity. I. INTRODUCTION The lymphatic system is closely associated with the cardiovascular system. The primary organs of the lymphatic system are the bone marrow and thymus gland, and the secondary lymphatic organs include the lymph nodes and spleen. These organs work together to transport excess tissue (interstitial) fluid to the blood stream, transport dietary fat, and help defend the body against diseasecausing agents. II. LYMPHATIC PATHWAYS Lymphatic pathways begin as lymphatic capillaries, which come together to form afferent lymphatic vessels, which lead to lymph nodes. The vessels that leave the lymph nodes are called efferent lymphatic vessels, which come together to form lymphatic trunks, which lead to two collecting ducts, which finally join the subclavian veins, where the lymph enters the cardiovascular system. See General Overview Figure 16.1, page 609 and Fig 16.7, page 611. A. Lymphatic capillaries: See Fig 16.2, page 609 and Fig 16.8, page 611. 1. are microscopic closedended tubes that extend into interstitial spaces; 2. receive lymph through their thin walls; 3. are associated with anchoring filaments, which serve an important function during edema (discussed later); 4. are located throughout the body, except in: a. avascular tissues; b. CNS; c. splenic pulp; bone marrow. 5. include lacteals that are lymphatic capillaries within villi of the small intestine. B. Lymphatic vessels (LV): See Fig 16.3, page 609, 16.4 & 16.5, page 610. 1. are formed by the merging of lymphatic capillaries; 2. have walls similar to veins and possess valves that prevent backflow of lymph; 3. lead to lymph nodes as "afferent" LVs, leave lymph nodes as "efferent" LVs, and then merge into lymphatic trunks. II. LYMPHATIC PATHWAYS C. Lymphatic trunks: See Fig 16.4, page 610. 1. drain lymph from relatively large body regions; 2. Principal lymphatic trunks include the following: a. lumbar; b. intestinal; c. bronchomediastinal; d. subclavian; e. jugular; f. intercostal. 3. pass their lymph into venous blood by joining one of two collecting ducts. D. Collecting ducts: See Fig 16.6, page 610. 1. Two within the thoracic cavity: a. right lymphatic duct drains the right upper body (25% of total body); b. thoracic (left lymphatic) duct drains the remaining 75% of the body's lymph; 2. join the subclavian veins. See the above figures to study the relationship of lymphatic system to cardiovascular system. See Summary Figure 16.7, page 611. III. TISSUE FLUID AND LYMPH Tissue Fluid Formation Tissue fluid is blood plasma that has passed through cardiovascular capillary walls into interstitial spaces, minus large plasma proteins. Recall the constituents of plasma from Chapter 14: primarily water dissolved substances including small plasma proteins, nutrients, wastes, gases, electrolytes, enzymes and hormones. Lymph Formation As protein concentration in interstitial spaces increases, its pressure increases. Increasing pressure forces tissue fluid into lymphatic capillaries. This fluid is now called lymph. Lymph formation prevents accumulation of excess tissue fluid (i.e. prevents edema). C. Lymph Function 1. returns small leaked plasma proteins back to the blood stream. 2. transports foreign particles to the lymph nodes. transports lipids and lipid-soluble vitamins absorbed in GI tract to bloodstream. D. Lymph Movement 1. Lymph Flow a. Lymph is under low pressure and may not flow readily without aid from external forces (similar to venous return). The squeezing action of skeletal muscles aids movement. The low pressure in the thoracic cavity created by breathing movements, moves lymph up from abdominal to thoracic region. Recall the presence of one-way valves. 2. Obstruction of lymph movement a. Any condition that interferes with the flow of lymph results in edema. Edema = accumulation of excess interstitial fluid leading to swelling of tissues. Tissue swelling pulls on anchoring filaments making openings between cells even larger so that more fluid can move into the lymphatic capillary (i.e. reducing swelling). See Fig 16.8, p. 611. The surgical removal of lymph nodes causes obstruction and results in edema (i.e. accompanying mastectomy). IV. LYMPHATIC TISSUES A. Introduction Lymphatic tissue occurs in the body in various forms. 1. When it is not encapsulated, it is called diffuse lymphatic tissue (i.e. found in submucosa of mucous lining). 2. When it is aggregated into a solitary, oval-shaped mass, it is called a lymphatic nodule (i.e. tonsils, and recall the lymphatic nodule in the small intestine model). 3. Primary lymphatic organs are the sites of production of immunocompetent cells, B cells and T cells. These cells can carry out an immune response. a. bone marrow (red) b. thymus. 4. Secondary lymphatic organs are the sites where most immune responses occur. a. lymph nodes b. spleen. B. Lymph Nodes 1. Structure of a lymph node (See Fig 16.9, page 612.) a. Overview: Lymph nodes are located along lymphatic pathways, contain lymphocytes and macrophages, which destroy invading microorganisms. b. Size is usually less than 2.5 cm, and shape is bean-like, with blood vessels, nerves, and efferent lymphatic vessels attached to the indented region (hilum); Afferent lymphatic vessels enter at points on the convex surface. c. Node is enclosed in a dense CT capsule that extends into the node and subdivides it into nodules. d. Outer region = cortex; contains germinal centers of densely packed B cells (+ macrophages) in spaces called lymphatic nodules (or follicles). e. Inner region = medulla; contains T cells (+ macrophages and plasma cells) arranged as medullary cords (spaces through which lymph flows). IV. LYMPHATIC TISSUES B. Lymph Nodes (continued) Flow of Lymph through Lymph Node: See Fig 16.9, page 612 and Fig 16.10, page 613. a. One-way direction only. b. Lymph enters the node through one of several afferent lymphatic vessels on convex surface, c. flows inward through sinuses (between medullary cords), and d. exits the node via one of two efferent lymphatic vessels at the hilum. Locations of lymph nodes (See Fig 16.11, page 613.) a. Lymph nodes generally occur in groups or chains along the paths of larger lymphatic vessels. b. They occur primarily in the following regions: cervical axillary inguinal. c. They also occur within the following body cavities: pelvic abdominal thoracic. 4. Functions of lymph nodes a. Removal and destruction of potentially harmful foreign particles from lymph. Accomplished through phagocytosis by macrophages. b. Centers for the production of lymphocytes that act against foreign particles. IV. LYMPHATIC TISSUES C. Thymus See Fig 16.12 page 615. 1. soft, bilobed organ located within the mediastinum. 2. decreases in size (atrophy) after puberty. 3. composed of lymphatic tissue that is subdivided into lobules. 4. Each lobule contains an outer (dark-staining) cortex filled with densely packed lymphocytes around a central medulla (light staining) filled with swirled epithelial cells (called Hassall's Corpuscles). See Fig 16.12b, p615. 5. Functions: a. immature T cells migrate from the bone marrow to the thymus (via) the blood. ?The thymus is the site of maturation of T cells (which will leave the thymus and provide immunity) b. The epithelial cells secrete a hormone called thymosin, which stimulates further maturation of T cells after they leave the thymus and migrate to other lymphatic tissues. D. Spleen See Figure 16.14 page 616. 1. is located in the upper left portion of the abdominal cavity (behind stomach). 2. resembles a large lymph node that is encapsulated and subdivided into lobules by connective tissue. 3. contains two types of tissue. See Fig 16.14b, page 616. a. white pulp = lymphocytes arranged around central arteries. b. red pulp = blood filled sinuses (venous blood that also serves as blood reservoir). 4. Functions: a. Removal and destruction of foreign particles and worn blood cells from blood. Macrophages remove and destroy bacteria and damaged or worn red blood cells and platelets through phagocytosis. b. stores and releases blood during hemorrhage. c. in immunity as a site of B cell proliferation into plasma cells. * See summary Table 16.1, page 617, which summarizes the locations and major functions of lymph nodes, thymus, and spleen. V. BODY DEFENSES AGAINST INFECTION A. Introduction: Infection is caused by the presence and multiplication of pathogens. Pathogens are viruses and microorganisms (bacteria, fungi, protozoans, parasites) that cause disease. The body is equipped with two types of defense mechanisms to fight infection: innate (nonspecific) resistance, the 1st and 2nd lines of defense adaptive (specific) resistance (immunity), the 3rd line of defense. B. Innate (Nonspecific) Defenses = protection against a wide range of pathogens. Mechanisms include species resistance, mechanical barriers, chemical barriers, fever, inflammation and phagocytosis. 1. Species resistance Each species of organism is resistant to certain diseases that may affect other species, but susceptible to diseases that other species may be able to resist. (See cryptosporidiosis, blue box page 617). 2. Mechanical barriers (First Line of Defense) a. include the skin and mucous membranes. b. As long as mechanical barriers remain unbroken, they prevent the entrance of some pathogens. 3. Chemical Barriers (First and Second Line of Defense) a. Enzymes The enzyme in gastric juice (i.e. pepsin) is lethal to many pathogens. The enzyme in tears (i.e. lysozyme) has antibacterial action. b. Acid Low pH in stomach (hydrochloric acid) prevents growth of some bacteria. c. Salt High salt concentration in perspiration kills some bacteria. d. Interferons Interferon is a group of hormone-like peptides produced by certain uninfected cells in response to the presence of viruses. These antiviral proteins interfere with the proliferation of viruses, stimulate phagocytosis, and enhance the activity of cells that help resist infections and the growth of tumors. e. Defensins Destroy bacteria by making holes in their cell walls and/or membranes. f. Collectins Protect by attaching themselves to a variety of microbes. Provide broad protection against them. V. BODY DEFENSES AGAINST INFECTION B. Innate (Nonspecific) Defenses 4. Fever a. Infection (by bacteria and viruses) causes some lymphocytes to produce Interleukin I, which increases body temperature. b. Other factors can also increase body temperature, including exposure to heat, UV light, acids, and bases. c. Increased body temperature decreases blood iron levels, which increases phagocytic activity. 5. Natural Killer Cells (NK cells) a. special lymphocytes b. attack foreign material; microbes, cancer cells, other abnormal cells c. use perforins to rupture cell membranes d. enhance inflammation 6. Inflammation: Second Line Of Defense See Table 16.2, page 618. a. Inflammation is a tissue response to damage, injury, or infection. b. Blood vessels dilate, increasing capillary permeability. The response includes localized tissue redness (rubor), swelling (tumor), heat (calor), and pain (dolor). c. Chemicals released by damaged tissues attract various white blood cells to the site of injury. Pus may form as WBC’s, bacterial cells, and debris accumulate. d. Tissue fluid leaks into area. A clot (fibrin) may form in affected tissues. e. Fibroblasts arrive. A fibrous connective tissue sac may form around the injured tissue and thus prevent the spread of pathogens. 7. Phagocytosis: Second Line of Defense a. Definition: Phagocytosis is the process by which specialized cells engulf and ingest foreign particles in order to destroy them. Recall function of lysosomes. b. The most active phagocytes in the blood are neutrophils and monocytes. c. Monocytes give rise to macrophages (through diapedesis, Chap 14) that migrate to various body tissues. d. Phagocytic cells associated with the linings of blood vessels in the bone marrow, liver, spleen, and lymph nodes constitute the reticuloendothelial tissue. e. Phagocytes remove and destroy foreign particles from tissues and body fluids. * See Summary Table 16.3, page 619 to review nonspecific resistance mechanisms. V. BODY DEFENSES AGAINST INFECTION C. Adaptive (Specific) Defenses or Immunity is protection against particular disease-causing agents. It is our third line of defense against infection. Antigens (Ag's) a. Definition: An antigen is a substance (usually a protein) that causes the formation of an antibody and reacts specifically with that antibody. b. How does this process occur? Before birth, body cells inventory the proteins and other large molecules present in the body (i.e. “self” proteins). After the inventory, lymphocytes develop receptors that allow them to differentiate between foreign (non-self) antigens and self-antigens. When non-self or foreign antigens (Ag's) enter human tissues, they combine with T cell and B cell surface receptors, and stimulate these cells to cause an immune response/reaction (IR) against them. 2. Lymphocyte Origins: See Fig 16.16, page 620. a. Lymphocytes originate in red bone marrow and are released into the blood before they become differentiated. b. About half of these undifferentiated lymphocytes reach the thymus where they are processed into T cells. c. Some undifferentiated lymphocytes are (probably) processed in the bone marrow and become B cells. d. Both T cells (70%-80% of circulating lymphocytes) and B (20%-30%) cells are transported through the blood to the lymphatic organs (lymph nodes, spleen, thymus) where they reside and act in immune responses against foreign antigens. e. See SEM of circulating lymphocyte in Fig 16.15, page 619. 3. Lymphocyte Function a. Antigen-Presenting Cells Begin the Immune Response b. A macrophage is typically the first cell to respond to an antigen. It then alerts lymphocytes to the invader. c. After digestion of the antigen (by the macrophage), a self-protein attaches a copy of the foreign antigen to the cell membrane of the macrophage. A gene of the major histocompatibility complex (MHC) codes for this self-protein. d. A lymphocyte now recognizes and binds to the antigen-presenting cell. T cells and B cells are activated and begin a chain of reactions that ultimately destroy/neutralize the invading antigen. V. BODY DEFENSES AGAINST INFECTION C. Adaptive (Specific) Defenses or Immunity T cells provide cell-mediated immunity (CMI): T cells respond to antigens directly (by cell-to-cell contact). T cells secrete cytokines (lymphokines) to enhance other immune responses to antigens. See Table 16.4, page 621. Colony stimulating factors stimulate bone marrow to produce lymphocytes. Interferons block viral replication, stimulate macrophages to engulf viruses, stimulate B cells to produce antibodies, attack cancer cells. Interleukins control lymphocyte differentiation. Tumor necrosis factor stops tumor growth, etc. Types of T cells: Helper T cells (CD4) become activated when they encounter a displayed antigen (on macrophage) for which it is specialized to react (see 3.c. above) Once activated, helper T cells stimulate B cells to produce antibodies (see B. 5. below). CD4 Helper T cells stimulate Antibody Mediated Immunity (AMI) and secrete cytokines (CMI). The HIV virus cripples these cells. Memory T cells are produced upon initial exposure to an antigen. They allow for immediate response against subsequent exposure(s) to the same antigen. Cytotoxic T cells (CD8) recognize foreign antigens on tumor cells and virus-infected cells. Stimulated cytotoxic T cells proliferate into a large clone of cells that secrete perforin to destroy target cells. Natural Killer Cells also use perforins to destroy tumor cells. Both cytotoxic T cells and natural killer cells can lyse antigens in other ways also. V. BODY DEFENSES AGAINST INFECTION C. Adaptive (Specific) Defenses or Immunity B cells provide Antibody-mediated immunity (or humoral) (AMI): a. B cells interact with antigenbearing agents indirectly, by secreting proteins called antibodies. b. B Cell Activation B Cell becomes activated when it binds to an activated T cell. Once activated, a B cell proliferates, enlarging into its clone. Activated B cells specialize into plasma cells that secrete antibodies. Antibodies react against the specific antigen-bearing agent that stimulated its production. A diverse population of B cells defends one against a large number of pathogens. See Fig 16.17, page 622, Fig 16.18, page 623, and Fig 16.19, page 626 to see the complex cascade of CMI and AMI events involved in an immune response. c. Antibody molecules: See Figure 16.20, page 627. Antibodies are proteins called immunoglobulins. They constitute the gamma globulin fraction of plasma. Each immunoglobulin molecule consists of four chains of amino acids linked together. Two heavy chains. Two light chains. Variable regions at the ends of these chains are specialized to react with antigens. Comprise antigen-binding sites. V. BODY DEFENSES AGAINST INFECTION C. Adaptive (Specific) Defenses or Immunity 5. B cells provide Antibody-mediated immunity (or humoral) (AMI): d. Types of immunoglobulins: See Table 16.7, page 627. The five major types of immunoglobulins are IgG, IgA, IgM, IgD, and IgE. IgG most abundant circulating antibody (80% of total) occurs in plasma and tissue fluids defends against bacterial cells, viruses & toxins activates complement only antibody to cross placenta. IgA about 13% of circulating antibodies occurs in exocrine gland secretions (i.e. tears, saliva, breast milk, etc.) defends against bacterial cells and viruses levels decrease during stress, lowering resistance to infection. IgM about 6 % of circulating antibodies first antibodies to be secreted after initial exposure to an antigen occurs in plasma produced in blood transfusions activates complement. IgD < 1% of antibodies occurs on the surface of most B cells involved in activation of B-cells. IgE < 0.1 % of antibodies occurs in exocrine gland secretions. promotes inflammation and allergic reactions because they cause the release of histamine from mast cells (basophils). V. BODY DEFENSES AGAINST INFECTION C. Adaptive (Specific) Defenses or Immunity 5. B cells provide Antibody-mediated immunity (or humoral) (AMI): e. Antibody Action: See Table 16.8, page 628. Antibodies attack antigens directly, activate complement, and stimulate local tissue changes that hinder antigen-bearing agents. Direct attachment involves the following: agglutination precipitation neutralization. Activation of complement (a positive feedback mechanism) involves the following: See Table 16.8, p 628. opsonization chemotaxis inflammation lysis. See Table 16.6, page 624, which summarizes the steps in antibody production and compares T & B cell activity. 6. Immune responses (IR): See Fig 16.21, page 628. a. When B cells or T cells first encounter an antigen for which they are specialized to react, the reaction is called a primary IR. During this response, antibodies are produced for several weeks (IgM). Some B cells and T cells remain dormant as memory cells. b. A secondary IR occurs rapidly if the same antigen is encountered at a later time (IgG). 7. Practical Classification of Immunity See Table 16.9, page 630. a. A person who encounters a live pathogen, which stimulates a primary IR, and suffers symptoms of a disease, develops naturally acquired active immunity. b. A person who receives a vaccine containing a dead or weakened pathogen. However, stimulation of the IR causes the person to develop artificially acquired active immunity. c. A person who receives an injection of gamma globulin that contains readymade antibodies has artificially acquired passive immunity. In this instance, the patient does not have time to develop active immunity (i.e. hepatitis), no IR occurs, and the immunity provided is only short-term. d. When antibodies (IgG) pass through a placental membrane from a pregnant woman to her fetus, the fetus develops naturally acquired passive immunity. This provides short-term immunity without development of an IR. VI. Disorders/Homeostatic Imbalances of the Immune System A. Allergic or Hypersensitivity Reactions (IR gone awry) Allergic reactions involve antigens combining with antibodies (IgE); The resulting IR is likely to be excessive or violent and may cause tissue damage. 2. Types of allergic reactions: Delayedreaction allergy (type IV), which can occur in anyone and can cause inflammation of the skin, results from repeated exposure to antigenic substances (i.e. household detergents, cosmetics). Antibody-dependent cytotoxic allergic reactions (type III) occur when blood transfusions are mismatched (review incompatible donors from Chapter 14). Immune complex allergic reactions (type II) involve autoimmunity, which is an IR against self-antigens (see VI. C. below). Immediatereaction allergy (type I), which is inherited, causes the production of an abnormally large amount of IgE (animal dander, pollen, etc.). See Fig 16.22, page 631 that summarizes steps involved. Allergic reactions result from mast cells (recall from Chap 14 that mast cells are basophils that have traveled from the blood into tissues) bursting and releasing allergy mediators, such as histamine and serotonin. In anaphylactic shock, these allergy mediators are responsible for the symptoms of the allergic reaction, including decreased blood pressure (vasodilation) and difficulty breathing (bronchoconstriction). Suppressor cells that inhibit the production of IgE usually terminate an allergic reaction. VI. Disorders/Homeostatic Imbalances of the Immune System Transplantation and Tissue Rejection There are four types of tissue transplants: See Table 16.10, page 632. Isografts occur between identical twins. i.e. A bone marrow transplant from a healthy twin to one with leukemia. Autografts are “self” grafts. i.e. a skin graft from one part of the body to another. Allografts occur between individuals of the same species. i.e. kidney transplant from a relative Xenografts occur between individuals of different species. i.e. A pig heart valve into a human. A transplant recipient’s immune system may react with donated (non-self) tissue in a tissue rejection reaction. Matching cell surface molecules of donor and recipient tissues (MHC) and using immunosuppressive drugs can minimize tissue rejection. Immunosuppressive drugs increase the recipient’s susceptibility to infection (decreases resistance). Autoimmunity In autoimmune disorders, the body produces antibodies against “self” antigens, resulting in an attack on one’s own tissues. The cause of autoimmune disorders is unknown, but researchers feel that they may be caused by: a previous viral infection, faulty T cell development, reaction to a self antigen that is close in structure to a non-self antigen, by persistent fetal cells, where fetal cells persist in the female’s circulation as an adult. For some unknown reason, these “hiding” fetal cells in tissues such as skin, emerge stimulating antibody production. This mechanism called “microchimerism” may explain why so many more females are stricken with autoimmune disorders than males. In scleroderma, which means “hard skin”, patients are typically diagnosed between ages 45-55. Symptoms include fatigue, swollen joints (See Fig 16.23, page 634), stiff fingers and mask-like face. Hardening may also affect blood vessels, lungs, and esophagus. VI. Disorders/Homeostatic Imbalances of the Immune System C. Autoimmunity (continued) Some autoimmune diseases are presented in Table 16.11, page 633. Glomerulonephritis where antibodies attack kidney cells that resemble streptococcal antigens. See Clinical Application 20.2, page 780. Grave’s Disease where antibodies attack thyroid gland. See Fig 13.22, page 488. Type I Diabetes (IDDM) where antibodies attack beta cells of Islets of Langerhans of pancreas. See CA 13.4, page 499. Hemolytic anemia where antibodies attack erythrocytes. Myasthenia Gravis where antibodies attack acetylcholine receptors in skeletal muscle. See Clinical Application 9.1, page 284. Pernicious Anemia where antibodies attack the vitamin B binding sites in gastric mucosa. See box on page 516. Rheumatic Fever where antibodies attack heart valves that resemble streptococcal antigens. Rheumatoid arthritis where antibodies attack synovial membranes. See Clinical Application 8.2, page 272. Systemic Lupus Erythematosus (SLE) where antibodies attack DNA, neurons, and blood cells. Ulcerative Colitis where antibodies attack colon cells. See Clinical Application 17.5, page 684. D. Other Disorders/Homeostatic Imbalances of the Immune System Severe Combined Immune Deficiency (SCID), page 629. Chronic Fatigue Syndrome, page 634. Immunity Breakdown: AIDS. Clinical Application 16.1, pp. 635. VII. LIFE SPAN CHANGES A. The immune system declines early in life, partially due to the decreasing size of the thymus. B. The activity level of T cells and B cells declines as we age. C. The proportions of the five types of immunoglobulins shift as we age. VIII. Other interesting Topics A. Immunotherapy. See pages 624-625 B. Vaccines, page 629. C. Tuberculin skin test, page 632. IX. Innerconnections of the Lymphatic System. See page 636. X. Clinical Terms Related to the Lymphatic System and Immunity. See page 637 Chapter 16 Lymphatic System and Immunity Explain how the lymphatic system is related to the cardiovascular system. The lymphatic and cardiovascular systems include a network of capillaries and vessels that assist in circulating the body fluids. The lymphatic vessels transport excess fluid away from the interstitial spaces of tissues and return it to the bloodstream. The walls of both vessels are alike. For instance, they both contain a single layer of epithelial cells that allows fluids and substances to cross into them. Trace the general pathway of lymph from the interstitial spaces to the bloodstream. The lymphatic capillary system is found next to the systemic and pulmonary capillary networks. It then travels through lymph vessels into lymph nodes. It returns to lymph vessels and then is returned into the bloodstream at various points. Identify and describe the locations of the major lymphatic trunks and collecting ducts. The lymphatic trunks are named for the regions they serve. The locations can be found in fig. 16.4, on page 623. The collecting ducts are: Thoracic duct—It begins in the abdomen. It passes upward medially through the diaphragm to the left subclavian, where it empties. Right lymphatic duct—It begins as the union of the right jugular, right subclavian, and right bronchomediastinal trunks. It empties into the right subclavian vein. Distinguish between tissue fluid and lymph. Lymph is tissue fluid that has entered into a lymphatic capillary. Describe the primary functions of lymph. The primary functions of lymph are to return the proteins to the bloodstream that have leaked out of the blood capillaries and to transport bacteria and other foreign particles to the lymph nodes. Explain why physical exercise promotes lymphatic circulation. The contractions of the skeletal muscles, pressure changes due to the actions of breathing muscles, and smooth muscle contractions of the larger lymphatic trunks all aid in the movement of lymph through the body. Explain how a lymphatic obstruction leads to edema. Continuous movement of fluid from the interstitial spaces into the lymphatic system stabilizes the volume of fluids in these spaces. When an obstruction occurs, the tissue fluid builds up and causes edema. Describe the structure of a lymph node, and list its major functions. Each lymph node is enclosed in a capsule of fibrous connective tissue and subdivides into compartments. The compartments contain dense masses of lymphocytes and macrophages. These masses, called nodules, are the structural units of a lymph node. Lymph nodes function in lymphocyte production and phagocytosis of foreign substances, damaged cells, and cellular debris. Locate the major body regions occupied by lymph nodes. The major body regions include: cervical region, axillary region, inguinal region, pelvic cavity, abdominal cavity, thoracic cavity, and supratrochlear region. Describe the structure and functions of the thymus. The thymus is a soft, bilobed structure whose lobes are surrounded by a capsule of connective tissue. It is composed of lymphatic tissue, which is subdivided into lobules by connective tissues. The lobules contain many lymphocytes. It functions to produce T-lymphocytes that help in the immune response. It also secretes thymosin, which is thought to stimulate the maturation of T-lymphocytes after they leave the thymus. Describe the structure and functions of the spleen. The spleen is the largest lymphatic organ. It resembles a large lymph node and is subdivided into chambers or lobules. The spaces within the chambers are filled with blood instead of lymph. There are two types of tissues within the lobules of the spleen. They include: White pulp - distributed throughout the spleen in tiny islands, composed of splenic nodules, and containing large numbers of lymphocytes. Red pulp - surrounds the venous sinuses and contains many red blood cells along with numerous lymphocytes and macrophages. The spleen functions to filter the blood. Distinguish between innate (nonspecific) and adaptive (specific) body defenses against infection. Nonspecific body defenses include species resistance, mechanical barriers such as the skin and mucous membranes, and chemical barriers such as enzymes, interferon, inflammation, and phagocytosis. Specific body defenses include immune mechanisms, where certain cells recognize the presence of particular foreign substances and act against them. Lymphocytes and macrophages achieve this. Explain species resistance. Species resistance is referring to the fact that a given kind of organism or species develops diseases that are unique to it. A species may be resistant to diseases that affect other species, because its tissues somehow fail to provide the temperature or chemical environment needed by a particular pathogen. Name two mechanical barriers to infection. The skin and the mucous membranes are two mechanical barriers to infection. Describe how enzymatic actions function as defense mechanisms against pathogens. Enzymes provide a chemical barrier to pathogens. By splitting components of the pathogen or decreasing the pH, the enzyme can have lethal effects on pathogens. Distinguish among the chemical barriers (interferons, defensins, and collectins), and give examples of their different actions. Interferons stimulate uninfected cells to synthesize antiviral proteins that block proliferation of viruses; stimulate phagocytosis; and enhance activity of cells that help resist infections and stifle tumor growth. Defensins make holes in bacterial cell walls and membranes. Collectins provide broad protection against a wide variety of microbes by grabbing onto them. List possible causes of fever, and explain the benefits of fever. Viral or bacterial infection stimulates certain lymphocytes to secrete IL-1, which temporarily raises body temperature. Physical factors, such as heat or ultraviolet light, or chemical factors, such as acids or bases, can cause fever. Elevated body temperature and the resulting decrease in blood iron level and increased phagocytic activity hamper infection. Describe Natural Killer (NK) Cells and their action. NK cells are a small population of lymphocytes. NK cells defend the body against various viruses and cancer by secreting cytolytic substances called perforins. List the major effects of inflammation, and explain why each occurs. Localized rednessresult of blood vessel dilation and the increase in blood volume of affected tissues. Swellingresult of increased blood volume and increased permeability of nearby capillaries. Heatdue to the presence of blood from deeper body parts, which is generally warmer than that near the surface. Painresults from the stimulation of nearby pain receptors. Identify the major phagocytic cells in the blood and other tissues. The most active phagocytic cells of the blood are neutrophils and monocytes. Macrophages are fixed phagocytic cells found in lymph nodes, spleen, liver, and lungs. This constitutes reticuloendothelial tissue. Distinguish between an antigen and a hapten. An antigen is a foreign substance, such as a protein, polysaccharide or a glycolipid, to which lymphocytes respond. A hapten is a molecule that by itself cannot stimulate the immune response. It must combine with a larger molecule. Review the origin of T cells and B cells. T cells originate in the thymus. B cells are those processed in another part of the body, probably the fetal liver. Explain the immune response. The lysosomal digestive process of phagocytosis of an invading bacterium releases antigens. They are moved to the macrophage's surface membrane. They are then displayed on the membrane with major histocompatibility complex. If the antigen then fits the helper T cell, it becomes activated. At this point, the helper T cell seeks out the appropriate T cell and by attaching to it, activates the T cell into a response. Cell-mediated immunity (CMI) is when a T cell, for example, attaches itself to antigen-bearing cells and interacts with the foreign cells directly. Define cytokine. Cytokines (lymphokines) are a variety of polypeptides that are synthesized and secreted by T cells and macrophages. These enhance various cellular responses to antigens. They stimulate the synthesis of lymphokines from other T cells, help activate resting T cells, cause T cells to proliferate, stimulate the production of leukocytes in the red bone marrow, cause growth and maturation of B cells, and activate macrophages. List three types of T cells and describe the function of each in the immune response. Helper T cells—mobilize the immune system to stop a bacterial infection through a series of complex steps. Memory T cells—provide for no delay in the response to future exposures to an antigen. Cytoxic T cells—recognize non-self antigens that cancerous or virally infected cells display on their surfaces. Define clone of lymphocytes. Clone of lymphocytes refers to cells that are derived from one early cell that are capable of responding to a certain antigen. As there are many differing antigens, there are also many differing varieties of clones. Explain humoral immunity. A B cell is activated when it binds to an activated T cell. An activated B cell proliferates, enlarging its clone. Some activated B cells specialize into antibody-producing plasma cells. Antibodies react against the antigen-bearing agent that stimulated their production. An individual’s diverse B cells defend against a very large number of pathogens. Explain how a B cell is activated. B cells become activated when they encounter an antigen whose molecular shape fits the shape of the B cell's antigen receptors. As a result of this combination, the B-cells proliferate by mitosis and its clone is enlarged. This mechanism for activation is similar to the lock and key model used by enzymes and substrates. Explain the function of plasma cells. Plasma cells are some of the newly formed members of the activated B cell's clone. They make use of their DNA information and protein-synthesizing mechanism to produce antibody molecules. Describe an immunoglobulin molecule. An immunoglobulin molecule consists of two identical light changes of amino acids and two identical heavy chains of amino acids. See figure 16.20, page 637. Distinguish between the variable region and the constant region of an immunoglobulin molecule. Variable regions are the portion of one end of each of the heavy and light chains consists of variable sequences of amino acids making them specific for specific antigen molecules. Constant regions are the remaining portions of the chains whose amino acid sequences are very similar from molecule to molecule. List the major types of immunoglobulins, and describe their main functions. Immunoglobulin G (IgG)—occurs in plasma and tissue fluids. Immunoglobulin A (IgA)—occurs in milk, tears, nasal fluid, gastric juice, intestinal juice, bile, and urine. Immunoglobulin M (IgM)—develops in blood plasma. Immunoglobulin D (IgD)—is important in activating B cells. Immunoglobulin E (IgE)—occurs in exocrine secretions and is associated with allergic reactions. Describe three ways in which antibody attack on a direct antigen helps in the removal of antigen. Agglutination—antibodies combine with antigens and clumping results. Precipitation—antibodies combine with antigens and insoluble substance forms. Neutralization—antibodies cover the toxic portions of antigen molecules and neutralize their effects. Lysis—antibodies cause the cell membranes to rupture. Explain the function of complement. It is a group of inactive enzymes that become activated when certain IgG or IgM antibodies combine with antigens and the reactive sites become exposed. The activated enzymes produce chemotaxis, agglutination, opsonization, and lysis. It can also promote the inflammation reaction. Distinguish between a primary and a secondary immune response. A primary immune response occurs when B cells or T cells become activated after first encountering the antigens to which they are specifically reactant. A secondary immune response happens when memory cells are activated and increased in size, so they can respond rapidly to the antigen to which they were previously sensitized. Distinguish between active and passive immunity. Active immunity can be either naturally acquired or artificially acquired. Naturally acquired active immunity is stimulated as a result of exposure to live pathogens. Artificially acquired active immunity is stimulated by exposure to a vaccine containing weakened or dead pathogens. Passive immunity can also be either naturally acquired or artificially acquired. Naturally the antibodies passed to a fetus from a mother with active immunity stimulate acquired passive immunity. Artificially acquired passive immunity is stimulated by an injection of gamma globulin that contains antibodies. Define vaccine. A vaccine is a substance that contains an antigen that can stimulate a primary immune response against a particular disease-causing agent, but does not cause severe disease symptoms. Explain how a vaccine produces its effect. A vaccine contains bacteria or viruses that have been killed or weakened so they cannot cause a serious infection; or it may contain a toxin of an infectious organism that has been chemically altered to destroy its toxic effects. The antigens present still retain the characteristics needed to simulate a primary immune response. Describe how a fetus may obtain antibodies from the maternal blood. Receptor-mediated endocytosis utilizing receptor sites on cells of the fetal yolk sac transfers IgG molecules to the fetus. Explain the relationship between an allergic reaction and an immune response. Allergic reactions are closely related to immune responses in that both may involve the sensitizing of lymphocytes or the combining of antigens with antibodies. Allergic reactions are likely to be excessive and to cause tissue damage. Distinguish between an antigen and an allergen. An antigen is a substance that stimulates cells to produce antibodies. An allergen is a foreign substance capable of stimulating an allergic reaction. Describe how an immediate-reaction allergic response may occur. In an immediate-reaction allergy, the individuals have an inherited ability to synthesize abnormally large quantities of antibodies in response to certain antigens. In this instance, the allergic reaction involves the activation of B-cells. List the major events leading to a delayed-reaction allergic response. It results from repeated exposure of the skin to certain chemical substances. As a consequence of these repeated contacts, the foreign substance and a large number of T cells collect in the skin and eventually activate the T cells. Their actions and the actions of macrophages they attract cause the release of various chemical factors. This causes eruptions and inflammation of the skin. It is called delayed since it takes about forty-eight hours to occur. Explain the relationship between a tissue rejection and an immune response. Tissue rejection is when the immune system sees transplanted tissue as foreign and starts the immune response to try to rid the body of it. Describe two methods used to reduce the severity of a tissue rejection reaction. Matching the donor and recipient tissues may reduce it. It can also involve giving drugs that suppress the immune system. How do immunosuppressant drugs increase the likelihood of success of a transplant, yet place the patient at a higher rise of developing infections? An immunosuppressive drug interferes with the recipient’s immune response by suppressing formation of antibodies or production of T cells. This will ultimately leave the recipient relatively unprotected against infection. Explain the relationship between autoimmunity and an immune response. Autoimmunity occurs when the immune system does not distinguish between self and nonself and manufactures autoantibodies that attack the body's own cells. For whatever reason, the autoantibodies treat a certain cell type in the body as a foreign object and signal the immune system to defend against the perceived invader. Describe the causes for a decline in the strength of the immune response in the elderly. The immune system begins to decline early in life, in part due to the decreasing size of the thymus. Numbers of T cells and B cells do not change significantly, but activity levels do. Proportions of the different antibody classes shift. Chapter 16: Lymphatic System and Immunity I. Introduction A. The lymphatic system is closely associated with B. Lymphatic vessels transport and return it to the C. Lacteals are _____________________ and function to D. The organs of the lymphatic system also defend II. Lymphatic Pathways A. Lymphatic Capillaries 1. Lymphatic capillaries are that extend into 2. The walls of lymphatic capillaries are similar to 3. The thin walls of capillaries make it possible for 4. Lymph is B. Lymphatic Vessels 1. The walls of lymphatic vessels are similar to those of 2. Lymphatic vessels have which prevents backflow of lymph. 3. Larger lymphatic vessels lead to 4. After leaving nodes, lymphatic vessels merge together to form C. Lymphatic Trunks and Collecting Ducts 1. Lymphatic trunks drain and are named for 2. Examples of lymphatic trunks are 3. Lymphatic trunks join 4. The two collecting ducts are 5. The thoracic duct is located _________________________ and empties into 6. The thoracic duct drains 7. The right lymphatic duct is located ________________________ and empties into 8. The right lymphatic duct drains 9. After leaving the two collecting ducts, lymph enters and becomes part of III. Tissue Fluid and Lymph A. Introduction 1. Lymph is 2. Lymph formation depends on B. Tissue Fluid Formation 1. Capillary blood pressure filters and the resulting fluid consists of 2. Water is drawn back into capillaries because C. Lymph Formation 1. Filtration from the plasma normally exceeds , leading to 2. Tissue fluid moves into lymphatic capillaries because 3. Lymph formation prevents D. Lymph Function 1. Lymphatic vessels in the small intestine play a major role in 2. Lymph returns to the bloodstream. 3. Lymph transports to lymph nodes. 4. Lymphatic capillaries can receive proteins and foreign particles that blood capillaries cannot because 5. The lumen of a lymphatic capillary remains open because IV. Lymph Movement A. Introduction 1. The _______________ pressure of tissue fluid drives lymph into 2. largely influences movement of lymph through lymphatic vessels. B. Lymph Flow 1. Lymph is under pressure. 2. Contracting compress lymphatic vessels. 3. Lymph does not flow back because 4. Breathing aids lymph circulation by C. Obstruction of Lymph Movement 1. Conditions that interfere with lymph movement causes 2. The continuous movement of lymph from stabilizes the volume of fluid in interstitial spaces. V. Lymph Nodes A. Introduction 1. Lymph nodes are located 2. Lymph nodes contain , which fight B. Structure of a Lymph Node 1. The hilum of a lymph node is 2. Afferent lymphatic vessels are 3. Efferent lymphatic vessels are 4. Lymph nodules are 5. Germinal centers contain 6. Tonsils are composed of 7. Peyer’s patches are located and are composed of 8. Lymph sinuses are C. Locations of Lymph Nodes 1. Lymph nodes generally occur in along the paths of but are absent 2. Major locations of lymph nodes are 3. Lymph nodes of the cervical region are associated with lymphatic vessels that drain 4. Lymph nodes of the axillary region are associated with lymphatic vessels that drain 5. Lymph nodes of the inguinal region are associated with lymphatic vessels that drain 6. Lymph nodes of the pelvic cavity are associated with lymphatic vessels that drain 7. Lymph nodes of the abdominal cavity are associated with lymphatic vessels that drain 8. Lymph nodes of the thoracic cavity are associated with lymphatic vessels that drain 9. Lymph nodes of the supratrochlear region are associated with lymphatic vessels that drain D. Functions of Lymph Nodes 1. The two primary functions of lymph nodes are 2. Along with , lymph nodes are centers for lymphocyte production. 3. Lymphocytes attack 4. The functions of macrophages are VI. Thymus and Spleen A. Thymus 1. The thymus is composed of and is located 2. After puberty, the thymus 3. Most cells of the thymus gland are 4. The hormones secreted by the thymus gland are called 5. Thymosins function to B. Spleen 1. The largest lymphatic organ is 2. The spleen is located 3. The spleen resembles 4. White pulp contains 5. Red pulp contains 6. The functions of the spleen are VII. Body Defenses Against Infection A. A pathogen is B. An infection is C. Examples of pathogens are D. Innate defenses are and include E. Adaptive defenses are and are carried out by VIII. Innate Defenses A. Species Resistance 1. Species resistance refers to 2. A species may be resistant to diseases that affect other species because B. Mechanical Barriers 1. Mechanical barriers prevent 2. Examples of mechanical barriers are 3. The first line of defense is 4. The second line of defense is C. Chemical Barriers 1. Chemical barriers are 2. Examples of chemical barriers are 3. Interferon is produced by and its functions include 4. Defensins are produced by 5. The functions of defensins are 6. Collectins are and their functions include D. Fever 1. A fever begins when 2. The functions of fever are E. Natural Killer Cells 1. Natural killer cells are 2. Functions of natural killer cells are 3. Perforins are F. Inflammation 1. Inflammation produces 2. Redness of inflammation is the result of 3. Swelling of inflammation is the result of 4. Heat of inflammation is the result of 5. Pain of inflammation is the result of 6. Cells that commonly migrate to areas of inflammation are 7. Pus is the result of 8. The functions of inflammation are G. Phagocytosis 1. Phagocytosis removes 2. Examples of phagocytic cells are 3. The mononuclear phagocytic system is IX. Adaptive Defenses or Immunity A. Introduction 1. Immunity is 2. An immune response is based on 3. Antigens are 4. carry out immune responses. B. Antigens 1. Receptors on lymphocyte surfaces enable cells to recognize 2. Antigens may be 3. The antigens most effective in eliciting an immune response is 4. A hapten is 5. Examples of haptens are C. Lymphocyte Origins 1. T cells are derived from 2. B cells are derived from 3. The blood distributes cells. 4. B cells and T cells are abundant in D. Lymphocyte Functions 1. The cellular immune response is 2. Cytokines are produces by 3. Examples of cytokines are 4. Functions of cytokines are 5. T cells may also secrete toxins that , growth-inhibiting factors that , or interferon that 6. B cells differentiate into 7. Plasma cells produce 8. The humoral immune response is 9. A clone is 10. Different varieties of T cells and B cells have a particular type of on their cell membranes that E. T Cells and the Cellular Immune Response 1. A lymphocyte must be before it can respond to an antigen. 2. T cell activation requires 3. Antigen-presenting cells are 4. T cell activation begins when 5. The major histocompatibility complex is 6. MHC antigens help 7. Class I MHC antigens are located 8. Class II MHC antigens are located 9. The functions of helper T cells are 10. The functions of cytotoxic T cells are 11. The functions of memory T cells are F. B Cells and the Humoral Immune Response 1. Introduction a. B cells may become activated when b. Upon activation, B cells c. T cells help B cells by d. The functions of memory B cells are e. The functions of plasma cells are f. An immune response may include several types of antibodies manufactured against a single microbe because g. A polyclonal response is 2. Antibody Molecules a. Antibodies are b. Each antibody is composed of c. The light chains are d. The heavy chains are e. The five major types of antibodies are distinguished by f. The variable region is g. Variable regions are specialized to h. Antigen-binding sites are i. Idiotypes are j. Constant regions are 3. Types of Immunoglobulins a. The five major types of immunoglobulins are b. The three types of immunoglobulins that make up the bulk of circulating antibodies are c. IgG is found in d. The functions of IgG are e. IgA is found in f. The functions of IgA are g. IgM is found in h. The functions of IgM are i. IgD is found in j. The functions of IgD are k. IgE is located l. The functions of IgE are 4. Antibody Actions a. The three ways antibodies react to antigens are b. In a direct attack, antibodies combine with and cause them to c. Phagocytic cells can engulf antigens more readily when d. Antibodies can also cover and neutralize e. Complement is f. Complement is activated by g. Functions of complement are h. IgE antibodies are usually attached to membranes of i. Mast cells release their biochemicals when G. Immune Responses 1. The primary immune response occurs when 2. Following a primary immune response, some B cells produce 3. The secondary immune response occurs when H. Practical Classification of Immunity 1. Naturally acquired active immunity develops when 2. Artificially acquired active immunity develops when ` 3. A vaccine is 4. Artificially acquired passive immunity occurs when 5. Naturally acquired passive immunity occurs when I. Allergic Reactions 1. An allergic reaction is 2. Allergens are 3. An immediate-reaction allergy occurs when 4. Anaphylactic shock is 5. Antibody-dependent cytotoxic reactions occur when 6. Immune complex reactions occur when 7. Autoimmunity refers to 8. A delayed-reaction allergy occurs when J. Transplantation and Tissue Rejection 1. Transplanted tissues and organs include 2. A tissue rejection reaction is 3. Tissues are rejected because 4. Isografts are 5. Autografts are 6. Allografts are 7. Xenografts are 8. Immunosuppressive drugs are used to K. Autoimmunity 1. Autoantibodies are 2. Reasons people develop autoimmunities are 3. Scleroderma is X. Life-Span Changes A. The immune system begins to decline B. By age 70, the thymus C. Elderly people have a higher risk of developing cancer and infections because D. AIDS is more difficult to diagnose in older people because E. Elderly people may not be candidates for certain medical treatments because