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The Lymphatic System and Immunity

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1 The Lymphatic System and Immunity
13 The Lymphatic System and Immunity

2 Chapter 13 Learning Outcomes
Section 1: Anatomy of the Lymphatic System 13.1 Describe the structure and function of important lymphatic vessels, their relationship to blood vessels, and how lymph flows in the body. 13.2 Describe the lymph collecting vessels, identify the structures returning lymph to the venous system, and explain lymphedema. 13.3 Define lymphopoiesis, and discuss the classes of lymphocytes, their importance, and their distribution in the body. 13.4 Identify and describe lymphoid tissues and lymphoid organs, and trace the pathway of lymph flow through a lymph node. © 2013 Pearson Education, Inc.

3 Chapter 13 Learning Outcomes
Section 2: Nonspecific Immunity 13.5 Explain how physical barriers and phagocytes play a role in nonspecific defenses. 13.6 Explain the significance of inflammation and fever as mechanisms of nonspecific defenses, and summarize nonspecific defenses. Section 3: Specific Immunity 13.7 Explain how antigens trigger specific defenses and the immune response. © 2013 Pearson Education, Inc.

4 Chapter 13 Learning Outcomes
13.8 Discuss the structure of an antibody and the types of antibodies in body fluids, and explain the primary and secondary responses to antigen exposure. 13.9 Explain the mechanisms used by antibodies to destroy target antigens. 13.10 CLINICAL MODULE Define allergies and anaphylaxis and describe the role of antibodies in causing allergic and anaphylactic responses. 13.11 CLINICAL MODULE Describe autoimmune disorders, graft rejection, allergies, immunodeficiency diseases, and age-related changes with respect to excessive or misdirected immune responses or inadequate immune responses. © 2013 Pearson Education, Inc.

5 The Lymphatic System (Section 1)
Includes cells, tissues, and organs that defend the body against environmental hazards and internal threats Cells are lymphocytes Vessels are lymphatic vessels (or lymphatics) Lymphoid tissues and organs are scattered throughout the body © 2013 Pearson Education, Inc.

6 The Lymphatic System (Section 1)
Lymphocytes Primary cells of lymphatic system that respond to: Invading pathogens Abnormal body cells Foreign proteins Most produced and stored within lymphoid tissues and organs Also produced in red bone marrow Surrounded by lymph Liquid that resembles interstitial fluid © 2013 Pearson Education, Inc.

7 An overview of the lymphatic system
Lymphatic Vessels and Lymph Nodes Cervical lymph nodes Thoracic duct Right lymphatic duct Lymphoid Tissues and Organs Axillary lymph nodes Tonsil Thymus Cisterna chyli Spleen Mucosa-associated lymphoid tissue (MALT) in digestive, respiratory, urinary, and reproductive tracts Appendix Inguinal lymph nodes Module 13 Section 1 Anatomy of the Lymphatic System Figure 13 Section 1-2 2 © 2013 Pearson Education, Inc.

8 Fluid Flow (13.1) Lymphatic vessels
Carry lymph from peripheral tissues to venous system Begin with lymphatic capillaries Found in almost every tissue and organ Closely associated with blood capillaries Interstitial fluid flows into lymphatic capillaries Fluid inside lymphatic capillaries is called lymph © 2013 Pearson Education, Inc.

9 Lymphatic capillaries
Arteriole Endothelial cells Lymphatic capillary Blood capillaries Module 13.1 Interstitial fluid flows into lymphatic capillaries to become lymph within lymphatic vessels Loose connective tissue Venule Interstitial fluid Lymph flow Figure 1 © 2013 Pearson Education, Inc.

10 Lymphatic Capillaries (13.1)
Lined by endothelial cells Incomplete or missing basement membrane Differ from blood capillaries Originate as pockets instead of forming continuous tubes Have larger diameters Have thinner walls Look flattened or irregular in sectional view © 2013 Pearson Education, Inc.

11 One-Way Flow (13.1) Overlapping endothelial cells in lymphatic capillaries Act as one-way valve Permit entry of fluids and solutes Prevent return to intercellular spaces © 2013 Pearson Education, Inc.

12 Sectional view of lymphatic and blood capillaries
Although lymphatic capillaries are lined by endothelial cells, the basement membrane is incomplete or missing entirely. Lymphocyte Loose connective tissue Lymph flow To larger lymphatics Overlapping endothelial cells act as one-way valve Interstitial fluid Interstitial fluid Loose connective tissue Module 13.1 Interstitial fluid flows into lymphatic capillaries to become lymph within lymphatic vessels Lymphatic capillary Blood capillary Sectional view Figure 2 © 2013 Pearson Education, Inc.

13 Lymphatic Flow (13.1) Lymph flows from lymphatic capillaries
Into larger lymphatic vessels Toward body's trunk Larger lymphatic vessels contain valves Valves close together Vessels bulge at each valve Series of bulges make vessels resemble string of beads Low pressure in lymphatic vessels Valves prevent backflow © 2013 Pearson Education, Inc.

14 Lymphatic vessels and valves
Artery Vein Lymphatic vessel Vein Artery Lymphatic vessel To larger lymphatic vessels that deliver lymph to the venous system Lymphatic valve From lymphatic capillaries Module 13.1 Interstitial fluid flows into lymphatic capillaries to become lymph within lymphatic vessels Lymphatic valve Lymphatic vessel Valve in lymphatic vessel LM x 65 Figure 3 4 © 2013 Pearson Education, Inc.

15 Lymphatic Capillary Locations (13.1)
Areas without blood supply have no lymphatic capillaries Cornea of eye Other areas without lymphatic capillaries Red bone marrow Central nervous system © 2013 Pearson Education, Inc.

16 Module 13.1 Review What is the function of lymphatic vessels?
What is lymph? What is the function of overlapping endothelial cells in lymphatic capillaries? © 2013 Pearson Education, Inc.

17 Extracellular Fluid Circulation (13.2)
Blood confined to vessels of cardiovascular system Water and solutes move from plasma into surrounding interstitial fluid Lymph contained in lymphatic vessels Forms as interstitial fluid drains into lymphatic vessels © 2013 Pearson Education, Inc.

18 Fluid Homeostasis (13.2) Continuous recirculation of interstitial fluid Helps eliminate local differences in levels of nutrients, wastes, and toxins Maintains blood volume Alerts immune system to infections in peripheral tissues © 2013 Pearson Education, Inc.

19 The circulation of extracellular fluid
2 Capillaries are the smallest and most delicate blood vessels. All exchange between the blood and interstitial fluid occurs at capillaries. The Circulation of Extracellular Fluid Start 1 3 Arteries carry blood away from the heart and into the tissues of the body. At capillary networks, blood pressure forces water and small solutes out of the bloodstream and into the surrounding interstitial fluid. Water and solutes from bloodstream Heart 4 Lymph forms as interstitial fluid enters lymphatic vessels. 5 6 Module 13.2 Small lymphatic vessels merge to form lymphatic ducts that empty lymph into subclavian veins Veins carry blood from capillary beds to the heart. Lymphatic vessels form a network that returns lymph to large subclavian veins near the heart. Figure 1 © 2013 Pearson Education, Inc.

20 Lymphatic Drainage (13.2) Superficial and deep lymphatics converge to form: Larger vessels, lymphatic trunks, which empty into: Collecting vessels Thoracic duct Right lymphatic duct Cisterna chyli is expanded chamber at base of thoracic duct Receives lymph from inferior part of abdomen, pelvis, lower limbs via: Right and left lumbar trunks Intestinal trunk © 2013 Pearson Education, Inc.

21 Pattern of lymphatic fluid drainage in the body
Drainage of thoracic duct Drainage of right lymphatic duct Module 13.2 Small lymphatic vessels merge to form lymphatic ducts that empty lymph into subclavian veins Figure 2 © 2013 Pearson Education, Inc.

22 Lymphatic Ducts (13.2) Thoracic duct Right lymphatic duct
Collects lymph from: Body inferior to diaphragm Left side of body superior to diaphragm Empties into the left subclavian vein Right lymphatic duct Right side of body superior to diaphragm Empties into right subclavian vein © 2013 Pearson Education, Inc.

23 Relationship between lymphatic ducts and the venous system
Right internal jugular vein Brachiocephalic veins Left internal jugular vein Right Lymphatic Duct Thoracic Duct Left jugular trunk Left subclavian trunk Right subclavian vein Thoracic duct entering left subclavian vein Left bronchomediastinal trunk Superior vena cava (cut) Rib (cut) Thoracic duct Azygos vein Thoracic lymph nodes Module 13.2 Small lymphatic vessels merge to form lymphatic ducts that empty lymph into subclavian veins Parietal pleura (cut) Diaphragm Intestinal trunk Inferior vena cava (cut) Cisterna chyli Right lumbar trunk Left lumbar trunk Figure 3 © 2013 Pearson Education, Inc.

24 Lymphedema (13.2) Caused by blocked lymphatic drainage
Interstitial fluid accumulates Causes swollen and distended areas Usually affects limbs; can affect other areas Swelling may become permanent Connective tissue loses elasticity Stagnant interstitial fluids may accumulate toxins and pathogens Local immune defenses overwhelmed © 2013 Pearson Education, Inc.

25 Lymphedema Module 13.2 Small lymphatic vessels merge to form lymphatic ducts that empty lymph into subclavian veins Figure 4 © 2013 Pearson Education, Inc.

26 Module 13.2 Review Name the two large lymphatic ducts into which the lymphatic trunks empty. Describe the drainage of the right lymphatic duct and the thoracic duct. Explain lymphedema. © 2013 Pearson Education, Inc.

27 Lymphocytes (13.3) Account for 20–40 percent of circulating leukocytes
Circulating lymphocytes are a small fraction of total lymphocyte population Three classes of lymphocytes T cells B cells NK cells © 2013 Pearson Education, Inc.

28 Antigens (13.3) All classes of lymphocytes are sensitive to antigens
Pathogens, parts or products of pathogens, or other foreign substances Most are proteins Some are lipids, polysaccharides, and nucleic acids Stimulate an immune response © 2013 Pearson Education, Inc.

29 T Cells (13.3) 80 percent of circulating lymphocytes
Three major categories of T cells Cytotoxic T cells Attack foreign cells or body cells infected by viruses Primary cells involved in cell-mediated immunity Helper T cells Stimulate activation and function of T cells and B cells Suppressor T cells Inhibit activation and function of T cells and B cells With helper T cells, involved in sensitivity of immune response © 2013 Pearson Education, Inc.

30 B Cells (13.3) 10–15 percent of circulating lymphocytes
Differentiate into plasma cells when stimulated Produce and secrete antibodies Responsible for antibody-mediated immunity Some B cells become memory B cells instead of plasma cells Remain in reserve to fight subsequent infections by same antigen © 2013 Pearson Education, Inc.

31 NK Cells (13.3) NK (natural killer) cells
5–10 percent of circulating lymphocytes Attack Foreign cells Body cells infected with viruses Cancer cells in normal tissues Continuously monitor peripheral tissues Immunological surveillance © 2013 Pearson Education, Inc.

32 Classes of lymphocytes
T Cells B Cells NK Cells Cytotoxic T Cells Helper T Cells Suppressor T Cells Plasma Cells Module 13.3 Lymphocytes are responsible for the immune functions of the lymphatic system Cytotoxic T cell Foreign or infected cell Figure 1 © 2013 Pearson Education, Inc.

33 Lymphopoiesis (13.3) Lymphocyte production Involves:
Red bone marrow Thymus Peripheral lymphoid tissues Red bone marrow primary in maintaining normal lymphocyte population © 2013 Pearson Education, Inc.

34 Lymphopoiesis in Red Bone Marrow (13.3)
Hemocytoblasts generate lymphoid stem cells One group of lymphoid stem cells migrates to thymus Second group stays in red bone marrow and divides to produce: B cells Mature and move into lymph nodes, spleen, other lymphoid tissue NK cells Mature and migrate throughout body, patrolling peripheral tissues © 2013 Pearson Education, Inc.

35 Lymphopoiesis in Thymus (13.3)
Blood-thymus barrier Isolates stem cells from general circulation Thymic hormones Stimulate lymphoid stem cells to divide, producing T cells T cells Produced and differentiate in thymus Reenter bloodstream when near mature and travel to: Red bone marrow Peripheral tissues © 2013 Pearson Education, Inc.

36 The derivation and distribution of lymphocytes
Red Bone Marrow Lymphoid stem cells Thymus Lymphoid stem cells divide, producing various kinds of T cells Migrates to thymus Stays in red bone marrow and divides Production and differentiation of immature T cells Mature T cell B cells NK cells Module 13.3 Lymphocytes are responsible for the immune functions of the lymphatic system When they are almost mature, T cells reenter the bloodstream and either return to the red bone marrow or travel to peripheral lymphoid tissues and organs. As they mature, B cells and NK cells enter the bloodstream and migrate to peripheral tissues. Peripheral Tissues Cell-mediated immunity Antibody-mediated immunity Immunological surveillance Figure 2 © 2013 Pearson Education, Inc.

37 Lymphocyte Reproduction (13.3)
Stem cells in red bone marrow Migrated B cells and T cells maintain ability to divide Produce daughter cells of same type Crucial to success of immune response © 2013 Pearson Education, Inc.

38 Module 13.3 Review Identify the three main classes of lymphocytes.
Which cells are responsible for antibody-mediated immunity? Which tissues are involved in lymphopoiesis? © 2013 Pearson Education, Inc.

39 Lymphoid Tissue (13.4) Connective tissue dominated by lymphocytes
Lymphoid nodules Spherical masses of lymphoid tissue Lymphoid organs Lymph nodes, thymus, spleen Separated from surrounding tissues by fibrous connective tissue © 2013 Pearson Education, Inc.

40 Lymphoid Nodules (13.4) Clusters of lymphoid tissues
Found in tracts opening to exterior environment Deep to epithelia lining passages As a group, called mucosa-associated lymphoid tissue (MALT) © 2013 Pearson Education, Inc.

41 The Tonsils (13.4) Three locations of large lymphoid nodules in walls of pharynx Pharyngeal tonsil (or adenoid) Located on posterior, superior wall of nasopharynx Palatine tonsils Located in posterior, inferior margin of oral cavity along boundary of pharynx Lingual tonsils Deep to epithelium covering base of tongue Tonsillitis Swollen tonsils from infection © 2013 Pearson Education, Inc.

42 Lymphoid tissue in the body
MALT in large intestine Module 13.4 Lymphocytes within lymphoid tissues and lymphoid organs protect the body from pathogens and toxins Pharyngeal tonsil Hard palate Palatine tonsil Lingual tonsil Figure 1 2 © 2013 Pearson Education, Inc.

43 Lymph Nodes (13.4) Small, lymphoid organs shaped like a kidney bean
Function like a water filter Purifies lymph before reaching venous circulation Removes 99 percent of antigens from lymph Immune response stimulated as needed Afferent lymphatics bring lymph into lymph node Lymph flows through network of fibers and dendritic cells Involved in initiation of immune response Regions in lymph nodes contain B cells and plasma cells Efferent lymphatics carry lymph out of node toward veins © 2013 Pearson Education, Inc.

44 Lymph node Lymphatic vessel Lymph nodes Afferent lymphatics
Lymph node structure Lymph node Lymphatic vessel Lymph nodes Afferent lymphatics Dendritic cells Regions containing B cells and plasma cells Module 13.4 Lymphocytes within lymphoid tissues and lymphoid organs protect the body from pathogens and toxins Lymph node artery and vein Efferent lymphatics Figure 3 © 2013 Pearson Education, Inc.

45 The Thymus (13.4) Produces hormones important to development of functional T cells Several complementary hormones known as thymosins Size and secretory abilities decline with age Correlated with increased susceptibility to disease © 2013 Pearson Education, Inc.

46 Thyroid gland Trachea Thymus Right Left lung lung Heart Diaphragm
The thymus Thyroid gland Trachea Thymus Right lung Left lung Heart Module 13.4 Lymphocytes within lymphoid tissues and lymphoid organs protect the body from pathogens and toxins Diaphragm Figure 4 © 2013 Pearson Education, Inc.

47 The Spleen (13.4) Contains largest mass of lymphoid tissue in body
Same function for blood that lymph nodes perform for lymph Removes abnormal red blood cells by phagocytosis Stores iron recycled from red blood cells Initiates immune response by B cells and T cells © 2013 Pearson Education, Inc.

48 Diaphragm Stomach Gastrosplenic ligament Rib Liver Gastric area
The spleen Diaphragm Stomach Gastrosplenic ligament Rib Liver Gastric area Pancreas Spleen Inferior vena cava Hilum Aorta Spleen Kidneys Lateral surface of spleen Renal area Module 13.4 Lymphocytes within lymphoid tissues and lymphoid organs protect the body from pathogens and toxins Lateral surface of the spleen Figure 5 © 2013 Pearson Education, Inc.

49 Module 13.4 Review Name the lymphoid tissue that protects epithelia lining the digestive, respiratory, urinary, and reproductive tracts. Define tonsils, and name the three types of tonsils. Describe the functions of the spleen. © 2013 Pearson Education, Inc.

50 Immunity (Section 2) Ability to resist infection and disease
Two forms that work independently and together Nonspecific (innate) immunity Does not distinguish one type of pathogen from another Response is the same regardless of invading agent Present at birth (innate) Provide nonspecific resistance Specific (adaptive) immunity © 2013 Pearson Education, Inc.

51 Nonspecific Defenses (Section 2)
Physical barriers Phagocytes Immunological surveillance Interferons Complement system Inflammatory response Fever © 2013 Pearson Education, Inc.

52 Specific Defenses (Section 2)
Protect against particular pathogen Depend on activities of specific lymphocytes Produce state of protection known as specific resistance © 2013 Pearson Education, Inc.

53 Module 13 Section 2 Nonspecific Immunity
Overview of immunity Immunity Nonspecific (Innate) Defenses Specific (Adaptive) Defenses Physical barriers Phagocytes Immunological surveillance Destruction of abnormal cells Module 13 Section 2 Nonspecific Immunity Interferons The complement system The inflammatory response Inflammation Fever Figure 13 Section 2 © 2013 Pearson Education, Inc.

54 The Integumentary System (13.5)
Provides major physical barrier to invasion by pathogens Glands Sebaceous and sweat gland secretions flush surface Wash away microorganisms and chemical agents May contain bactericidal chemicals, destructive enzymes, and antibodies Hair Protects against mechanical abrasion Often prevents hazardous material or insects from contact with skin Epithelial covering Multiple layers Keratinized cells in outer layers Network of desmosomes locks adjacent cells together © 2013 Pearson Education, Inc.

55 Integumentary system as a physical barrier to the external environment
Hair Secretion Duct of sweat gland Epithelium Keratinized cells Sebaceous gland Desmosomes Module 13.5 Physical barriers and phagocytes play a role in nonspecific defenses Figure 1 © 2013 Pearson Education, Inc.

56 Epithelial Barriers (13.5)
Line "tracts" (digestive, respiratory, urinary, and reproductive) Provide physical barrier Secretions contain enzymes, antibodies, or acid Acid in stomach destroys many pathogens Mucus in respiratory tract traps pathogens Urine flushes urinary passageways Glandular secretions in reproductive tract flush tract MALT provides nonspecific defense © 2013 Pearson Education, Inc.

57 Mucous membranes as a nonspecific defense barrier
Mucus Tight junctions Mucous cell Basement membrane Epithelial cell Module 13.5 Physical barriers and phagocytes play a role in nonspecific defenses Epithelial cells tied together by tight junctions Figure 2 © 2013 Pearson Education, Inc.

58 Phagocytes (13.5) "First line of cellular defense"
Found in peripheral tissues Remove cellular debris Respond to invasion by foreign compounds or pathogens Can attack and remove microorganisms before lymphocytes detect presence Different types target different threats All function in same basic way © 2013 Pearson Education, Inc.

59 Micrograph of phagocyte engulfing bacteria
Module 13.5 Physical barriers and phagocytes play a role in nonspecific defenses Phagocyte (yellow) engulfing bacteria (orange) SEM x 2900 Figure 4 © 2013 Pearson Education, Inc.

60 Types of Phagocytes (13.5) Neutrophils Eosinophils
Abundant, mobile, fast-acting Phagocytize cellular debris or invading bacteria Eosinophils Less abundant than neutrophils Phagocytize foreign compounds or pathogens that have been coated with antibodies Monocyte–macrophage system Macrophages derived from monocytes Fixed macrophages scattered among connective tissue Free macrophages travel throughout body © 2013 Pearson Education, Inc.

61 Monocyte–macrophage system
Types of phagocytes Types of Phagocytes 12 µm 8–10 µm Monocyte–macrophage system Neutrophils Eosinophils Module 13.5 Physical barriers and phagocytes play a role in nonspecific defenses Fixed macrophages Free macrophages Figure 3 © 2013 Pearson Education, Inc.

62 Functional Characteristics of Phagocytes (13.5)
Can leave capillaries by squeezing between adjacent endothelial cells Process called diapedesis May be attracted to or repelled by chemicals in surrounding fluids Phenomenon called chemotaxis Particularly sensitive to chemicals released by body cells or pathogens Receptors on plasma membrane of phagocyte bind to surface of target First step in phagocytosis After attaching, phagocyte either destroys target itself or promotes its destruction by activating specific defenses © 2013 Pearson Education, Inc.

63 Module 13.5 Review How does the integumentary system protect the body?
Identify the types of phagocytes in the body, and differentiate between fixed macrophages and free macrophages. Define chemotaxis. © 2013 Pearson Education, Inc.

64 Inflammation (13.6) Localized tissue response to injury
Produces swelling, redness, heat, and pain Caused by various stimuli that kill cells, damage connective tissue fibers, or injure tissue Result is altered chemical composition of interstitial fluid Prostaglandins, proteins, potassium ions released Foreign proteins or pathogens introduced Changes trigger inflammation process © 2013 Pearson Education, Inc.

65 Inflammation and the steps in tissue repair
Damage Slide 1 Chemical change in interstitial fluid Module 13.6 Inflammation is a localized tissue response to injury; fever is a generalized response to tissue damage and infection Figure 1 © 2013 Pearson Education, Inc.

66 Inflammation and the steps in tissue repair
Damage Slide 2 Chemical change in interstitial fluid Mast Cell Activation Mast cells release histamine and heparin Module 13.6 Inflammation is a localized tissue response to injury; fever is a generalized response to tissue damage and infection Figure 1 © 2013 Pearson Education, Inc.

67 Inflammation and the steps in tissue repair
Damage Slide 3 Chemical change in interstitial fluid Mast Cell Activation Mast cells release histamine and heparin Redness, Swelling, Heat, and Pain Phagocyte Attraction Phagocytes, especially neutrophils, are attracted to area Blood vessels dilate, blood flow increas- es, vessel be- comes more permeable Clot forms (temporary repair) Module 13.6 Inflammation is a localized tissue response to injury; fever is a generalized response to tissue damage and infection Figure 1 © 2013 Pearson Education, Inc.

68 Inflammation and the steps in tissue repair
Damage Slide 4 Chemical change in interstitial fluid Mast Cell Activation Mast cells release histamine and heparin Redness, Swelling, Heat, and Pain Phagocyte Attraction Phagocytes, especially neutrophils, are attracted to area Blood vessels dilate, blood flow increas- es, vessel be- comes more permeable Release of cytokines (chemical messengers affecting immune defenses) Clot forms (temporary repair) Module 13.6 Inflammation is a localized tissue response to injury; fever is a generalized response to tissue damage and infection Neutrophils and macrophages remove debris; fibroblasts are stimulated Specific defenses are activated Figure 1 © 2013 Pearson Education, Inc.

69 Inflammation and the steps in tissue repair
Damage Slide 5 Chemical change in interstitial fluid Mast Cell Activation Mast cells release histamine and heparin Redness, Swelling, Heat, and Pain Phagocyte Attraction Phagocytes, especially neutrophils, are attracted to area Blood vessels dilate, blood flow increas- es, vessel be- comes more permeable Release of cytokines (chemical messengers affecting immune defenses) Clot forms (temporary repair) Module 13.6 Inflammation is a localized tissue response to injury; fever is a generalized response to tissue damage and infection Neutrophils and macrophages remove debris; fibroblasts are stimulated Specific defenses are activated Tissue Repair Pathogens are removed, clot erodes, scar tissue forms Figure 1 © 2013 Pearson Education, Inc.

70 Fever (13.6) Rise in body core temperature above 37.2ºC
Pyrogens (circulating proteins) reset temperature thermostat in hypothalamus Can be beneficial within limits Inhibits some viruses and bacteria Increases body metabolism Quicker mobilization of tissue defenses Accelerated repair process © 2013 Pearson Education, Inc.

71 Summary of Nonspecific Defenses (13.6)
Physical barriers Keep hazardous organisms and materials outside body Phagocytes Engulf pathogens and cellular debris Immune surveillance by NK cells Monitor peripheral tissues Release perforins that destroy abnormal cell's membrane Interferons Released by lymphocytes, macrophages, or virus-infected cells Trigger production of antiviral proteins Stimulate macrophages and NK cells © 2013 Pearson Education, Inc.

72 Summary of Nonspecific Defenses (13.6)
Complement system Group of circulating proteins that help antibodies destroy pathogens Inflammation (inflammatory response) Localized, tissue-level response to limit spread of injury or infection Fever Accelerates body metabolism and defense activity © 2013 Pearson Education, Inc.

73 Summary of Nonspecific Immunity
Physical Barriers Secretions Prevent approach of and deny access to pathogens Epithelium Duct of sweat gland Hair Phagocytes Remove debris and pathogens Free macrophage Fixed macrophage Neutrophil Eosinophil Monocyte Immune Surveillance by NK cells Continuously monitor normal tissues and destroy abnormal cells Natural killer cell Lysed abnormal cell Interferons Increase resistance of cells to viral infection; slow the spread of disease Complement System Module 13.6 Inflammation is a localized tissue response to injury; fever is a generalized response to tissue damage and infection When activated, attacks and breaks down the surfaces of cells, bacteria, and viruses; attracts phagocytes; stimulates inflammation Lysed pathogen Complement Inflammation (Inflammatory Response) • Blood flow increased • Phagocytes activated • Damaged area isolated by clotting reaction • Capillary permeability increased • Complement activated • Regional temperature increased • Specific defenses activated Multiple effects make nonspecific and specific defenses more effective Mast cell Fever 100 80 Mobilizes defenses; accelerates repairs; inhibits pathogens 60 40 20 Body temperature rises above 37.2°C in response to pyrogens Figure 3 © 2013 Pearson Education, Inc.

74 Module 13.6 Review What is the result of mast cell activation?
Summarize the body's nonspecific defenses. A rise in the level of interferons in the body suggests what kind of infection? © 2013 Pearson Education, Inc.

75 Specific Immunity (Section 3)
Protects against specific pathogens Coordinated activity of T cells and B cells provides specific defenses T cells primarily responsible for cell-mediated immunity Defends against abnormal cells and pathogens inside cells B cells provide antibody-mediated immunity Defends against antigens and pathogens in body fluids © 2013 Pearson Education, Inc.

76 Types of Specific Immunity (Section 3)
Active immunity When body develops antibodies in response to antigen Passive immunity When receive antibodies from another source Both can be naturally acquired or artificially acquired © 2013 Pearson Education, Inc.

77 Immunity Forms of immunity Module 13 Section 3 Specific Immunity
The ability to resist infection and disease Specific (Adaptive) Immunity Nonspecific (Innate) Immunity Specific immunity is not present at birth; you acquire immunity to a specific antigen only when you have been exposed to that antigen or receive antibodies from another source. Present at birth— anatomical and other defense mechanisms Active Immunity Passive Immunity Develops in response to antigen exposure Produced by trans- ferring antibodies from another source Naturally acquired active immunity Artificially induced active immunity Module 13 Section 3 Specific Immunity Naturally acquired passive immunity Artificially induced passive immunity Develops after exposure to antigens in environment Develops after administering an antigen to prevent disease (as in a vaccine) Conferred by transferring maternal antibod- ies across placenta or in breast milk Conferred by admin- istering antibodies to combat infection Figure 13 Section 3-1 1 © 2013 Pearson Education, Inc.

78 Specific Properties of Specific Immunity (13.7)
Specificity Each T cell or B cell has receptors that bind to one specific antigen, but ignore all others Response of activated T cell or B cell specific only to that antigen Versatility Millions of different lymphocyte populations, each sensitive to different antigen When activated, appropriate lymphocyte divides, producing more of same lymphocyte type All cells produced by the division of activated lymphocyte constitute a clone © 2013 Pearson Education, Inc.

79 Specific Properties of Specific Immunity (13.7)
Immunological memory Activated lymphocytes produce two groups of cells Group that attacks invader immediately Group that remains inactive unless exposed to same antigen later Memory cells that enable immune system to "remember" antigens and launch faster, stronger, longer-lasting counterattack when exposed again Tolerance Immune response ignores "self" but targets abnormal and foreign ("non-self") Can develop over time in response to chronic exposure to antigen © 2013 Pearson Education, Inc.

80 Specific Defenses – Triggers (13.7)
Exposure to antigen activates phagocytes, which stimulate: Cell-mediated defenses involving attacks by T cells Antibody-mediated defenses First step is antigen presentation © 2013 Pearson Education, Inc.

81 Overview of the immune response
1 Cell-Mediated Immunity Direct Physical and Chemical Attack Activated T cells find the pathogens and attack them through phagocy- tosis or the release of chemi- cal toxins. Specific Defenses Antigen presenta- tion triggers spe- cific defenses, or an immune response. Phagocytes activated T cells activated Communication and feedback Destroy antigens 2 Attack by Circulating Antibodies Antibody-Mediated Immunity Virus Module 13.7 Specific defenses are triggered by exposure to antigenic fragments Activated B cells give rise to cells that pro- duce anti- bodies. Bacterium Figure 1 © 2013 Pearson Education, Inc.

82 Antigen-Presenting Cells (13.7)
Specialized cells Monocytes, macrophages, and dendritic cells Engulf a pathogen Digest pathogen to produce antigenic fragments Bind those fragments to proteins Display antigenic fragments on plasma membrane © 2013 Pearson Education, Inc.

83 Antigen-presenting cells
5 Plasma membrane Antigenic fragments are displayed on the plasma membrane. 1 Phagocytic APCs engulf an extracel- lular pathogen. 4 Antigenic fragments are bound to these proteins. Phagocytic cell 3 2 The rough endoplasmic reticulum produces proteins that will be incorporated into the phagocytic cell’s plasma membrane. Lysosomal action produces antigenic fragments. Module 13.7 Specific defenses are triggered by exposure to antigenic fragments Nucleus Lysosome Endoplasmic reticulum Figure 2 © 2013 Pearson Education, Inc.

84 Defenses against Pathogens (13.7)
Defenses against bacterial pathogens Usually initiated by active macrophages Followed by antigen presentation by macrophage Defenses against viruses involve: Direct contact with virus-infected cells Antigen presentation by antigen-presenting cells (APCs) Release of interferons © 2013 Pearson Education, Inc.

85 Defenses against bacterial and viral pathogens
VIRUSES Macrophage activation Infection of tissue cells Infection of or uptake by APCs Antigen presentation Release of interferons Appearance of antigen in plasma membrane Antigen presentation Contact with active APCs activates cytotoxic T cells. Activated T cells divide to produce more cytotoxic T cells and inactive memory TC cells. Contact with the surface of an active APC activates helper T cells. These cells divide to produce additional activated helper T cells and memory TH cells. Increased resistance to viral infection and spread Contact with surfaces of infected cells stimulates NK cells. Activation of cytotoxic T cells Contact with the surface of an active APC activates helper T cells. These cells divide to produce additional activated helper T cells and memory TH cells. Module 13.7 Specific defenses are triggered by exposure to antigenic fragments Contact with activated helper T cells activates B cells. Activated B cells divide to produce active plasma cells and inactive memory B cells. Destroy infected cells Contact with activated helper T cells activates B cells. Activated B cells divide to produce active plasma cells and inactive memory B cells. Destroy viruses or prevent viruses from entering into cells Destroy bacteria by cell lysis or phagocytosis Plasma cells produce antibodies Plasma cells produce antibodies Figure 3 4 © 2013 Pearson Education, Inc.

86 Memory Cells (13.7) No role in initial infection
Dramatically reduce response time for subsequent infection by same pathogen Upon secondary exposure, differentiate into: Cytotoxic T cells (memory TC cells) Helper T cells (memory TH cells) Plasma cells (memory B cells) Rapid and effective response © 2013 Pearson Education, Inc.

87 Module 13.7 Review Describe antigen presentation.
Which cells can be activated by direct contact with virus-infected cells? Which cells produce antibodies? © 2013 Pearson Education, Inc.

88 Antibodies (13.8) Antibody molecule composed of:
Two parallel pairs of polypeptide chains One pair heavy chains One pair light chains Each chain has: Constant segments Variable segments Constant segments of heavy chains form base of molecule © 2013 Pearson Education, Inc.

89 Antigen Binding Sites (13.8)
Free tips of two variable segments Can interact with antigen similar to enzyme interaction with substrate Differences in variable segment structure affect shape of binding site Antibodies specific for different antigens Variation occurs during production, division, and differentiation of B cells © 2013 Pearson Education, Inc.

90 Antibody structure Antigen binding sites Heavy chain Antigen binding site Variable segment Disulfide bond Light chain Binding sites that can activate the complement system are covered when the antibody is secreted but become exposed when the antibody binds to an antigen. Constant segments of light and heavy chains Module 13.8 Antibodies are small soluble proteins that bindto specifi c antigens; they may inactivate theantigens or trigger another defensive process Binding sites may also be present that attach the secreted antibody to the surfaces of macrophages, basophils, or mast cells. Figure 1 © 2013 Pearson Education, Inc.

91 Antigenic Determinant Sites (13.8)
Antibody binds to antigen to form antigen-antibody complex Binding between antibody and antigenic determinant sites Specific portions of exposed antigen surface Bacteria may contain millions of antigenic determinant sites © 2013 Pearson Education, Inc.

92 Types of Antigens (13.8) Complete antigen Partial antigen (or hapten)
At least two antigenic determinant sites Partial antigen (or hapten) Does not ordinarily activate B cells Can attach to carrier molecules and function as complete antigen Antibodies will attack hapten and carrier molecule If carrier molecule is normally found in tissues: Antibodies may attack normal cells Basis for drug reactions like allergy to penicillin © 2013 Pearson Education, Inc.

93 Formation of antigen-antibody complex
1 Antigenic determinant sites Carrier molecule Antibody Partial antigen (hapten) Antigen-antibody complex Module 13.8 Antibodies are small soluble proteins that bindto specific antigens; they may inactivate theantigens or trigger another defensive process Antibody 2 3 Complete antigen Partial antigen Figure 2 © 2013 Pearson Education, Inc.

94 Antibodies bind to antigenic determinant sites
Module 13.8 Antibodies are small soluble proteins that bindto specific antigens; they may inactivate theantigens or trigger another defensive process Antigenic determinant sites Antibodies Figure 3 © 2013 Pearson Education, Inc.

95 Classes of Antibodies (13.8)
Five classes of antibodies or immunoglobulins (Igs) Determined by differences in structure of heavy-chain constant segments IgG IgE IgD IgM IgA © 2013 Pearson Education, Inc.

96 IgG antibodies are responsible for resis-
tance against many viruses, bacteria, and bacterial toxins. They account for 80 percent of all antibodies. IgE attaches to basophils and mast cells, releasing histamine and speeding up inflammation. IgD is an individual molecule on the surfaces of B cells, where it can bind antigens in the extra- cellular fluid. This binding can play a role in sensitizing the B cell. IgM is the first class of antibody secreted after an antigen is encountered. IgM concentration declines as IgG production accelerates. The anti-A and anti-B antibodies responsible for the agglutination of incom-patible blood types are IgM antibodies. IgA is found primarily in glandular secretions such as mucus, tears, saliva, and semen. These antibodies attack patho-gens before they gain access to internal tissues. Module 13.8 Antibodies are small soluble proteins that bindto specific antigens; they may inactivate theantigens or trigger another defensive process Figure 4 © 2013 Pearson Education, Inc.

97 Primary Response to Antigen Exposure (13.8)
Primary response is initial response to exposure Takes time to develop Antigen activates B cells Differentiate into plasma cells Secrete antibodies Antibody titer (concentration) peaks one to two weeks after exposure then declines if no longer exposed to antigen © 2013 Pearson Education, Inc.

98 Secondary Response to Antigen Exposure (13.8)
Secondary response triggered when antigen encountered again More extensive and lasts longer than primary Antibody titer increases rapidly and to much higher levels Result of immediate response by memory B cells Appears even if second exposure is years after first Memory cells survive 20 years or more © 2013 Pearson Education, Inc.

99 The primary and secondary responses in antibody-mediated immunity
Primary response Secondary response IgG Antibody titer in plasma IgG IgM IgM 1 2 3 4 1 2 3 4 Module 13.8 Antibodies are small soluble proteins that bind to specific antigens; they may inactivate theantigens or trigger another defensive process Time (weeks) Time (weeks) Figure 5 6 © 2013 Pearson Education, Inc.

100 Module 13.8 Review Define antigenic determinant site.
Describe the structure of an antibody. Name the five classes of immunoglobulins and cite a function of each. © 2013 Pearson Education, Inc.

101 Antibody Mechanisms (13.9)
Seven different mechanisms for eliminating antigens Neutralization Prevention of pathogen adhesion Activation of complement Opsonization Attraction of phagocytes Stimulation of inflammation Agglutination © 2013 Pearson Education, Inc.

102 Antibody Mechanisms (13.9)
Neutralization Bacteria and viruses must bind to plasma membrane of body cells before they can enter cells Antibodies attach to binding sites on bacteria or toxins Neutralizes binding ability of bacteria and toxins No binding sites available now for attachment to body cells Prevention of pathogen adhesion Antibodies part of saliva, mucus, tears, and perspiration Coating of antibodies creates barrier Difficult for pathogens to adhere to body surfaces © 2013 Pearson Education, Inc.

103 Antibody Mechanisms (13.9)
Activation of complement Binding to antigen changes antibody molecule shape Exposed area binds to complement proteins, activating complement system Opsonization Coating of antibodies and complement makes surfaces of bacteria less slick Phagocytes can bind more easily Attraction of phagocytes Neutrophils, eosinophils, and macrophages attracted to antigens coated with antibodies © 2013 Pearson Education, Inc.

104 Antibody Mechanisms (13.9)
Stimulation of inflammation Antibodies stimulate release of heparin and histamine from basophils and mast cells Promotes inflammatory response Agglutination Antibodies can bind to antigenic determinant sites on adjacent antigens Large numbers of antigens together create immune complex Formation of immune complex from surface antigens called agglutination For example, clumping of erythrocytes in transfusion reaction © 2013 Pearson Education, Inc.

105 Mechanisms antibodies use to destroy target antigens
Prevention of Pathogen Adhesion Activation of Complement Neutralization Opsonization Agglutination Antigenic determinant sites Module 13.9 Antibodies use many diff erentmechanisms to destroy target antigens Immune Complex Stimulation of Inflammation Attraction of Phagocytes Figure 13.9 © 2013 Pearson Education, Inc.

106 Module 13.9 Review Describe the ways that antigen-antibody complexes can destroy target antigens. Define opsonization. Which cells are involved in inflammation? © 2013 Pearson Education, Inc.

107 Antibody Overreactions (13.10)
Allergies Inappropriate or excessive immune responses to antigens Sudden increase in cellular activity and antibody titers Neutrophils or cytotoxic T cells may destroy normal cells in addition to antigen Antigen-antibody complex may trigger inflammation Antigens triggering allergic reactions called allergens © 2013 Pearson Education, Inc.

108 Allergic Responses (13.10) Initial exposure to allergen
Causes sensitization Production of large quantities IgE Immediate hypersensitivity Rapid, severe response to antigen Example is allergic rhinitis (includes hay fever) Inflammation of nasal membrane Hypersensitivity reaction May be limited to body surface or can be systemic © 2013 Pearson Education, Inc.

109 Module 13.10 Antibody responses can causeallergies and anaphylaxis
Seasonal allergies Module Antibody responses can causeallergies and anaphylaxis Figure 13.10 © 2013 Pearson Education, Inc.

110 Anaphylactic Shock (13.10) Allergen can trigger systemic response
Anaphylaxis Circulating allergen stimulates histamine release from mast cells throughout body Can cause extensive peripheral vasodilation Extreme drop in blood pressure leading to circulatory collapse Anaphylactic shock © 2013 Pearson Education, Inc.

111 Mechanism of anaphylaxis
First Exposure Allergen fragment Allergens Macrophage TH cell activation B cell sensitization and activation Plasma cell IgE antibodies Subsequent Exposure IgE Allergen Granules Sensitization of mast cells and basophils Massive stimulation of mast cells and basophils Module Antibody responses can cause allergies and anaphylaxis Release of histamines and other chemicals that cause pain and inflammation Localized Allergic Reactions Systemic Allergic Reactions If the allergen is at the body surface: localized inflamma- tion, pain, and itching Example: allergic rhinitis If the allergen is in the bloodstream: itching, swelling, and difficulty breathing (due to constricted airway) Example: anaphylaxis Figure 13.10 © 2013 Pearson Education, Inc.

112 Module 13.10 Review Define allergy and allergen. What is anaphylaxis?
Which chemicals do mast cells and basophils release when stimulated in an allergic reaction? © 2013 Pearson Education, Inc.

113 Immune Disorders (13.11) Can be excessive or misdirected immune response Autoimmune disorders Graft rejection Allergies Can be inadequate immune response Immunodeficiency diseases Age-related reductions in immune activity © 2013 Pearson Education, Inc.

114 Autoimmune Disorder Process (13.11)
Immune system attacks body's own tissue Malfunction of "self" antigen recognition system produces autoantibodies Affects about 5 percent of adults in North America and Europe Many caused by similarities in proteins Protein associated with measles, Epstein–Barr, influenza, and other viruses has the same amino acid sequence as myelin proteins Antibodies targeting these pathogens may also attack myelin sheaths Likely mechanism responsible for multiple sclerosis © 2013 Pearson Education, Inc.

115 Autoimmune Disorders (13.11)
Thyroiditis Inflammation from release of autoantibodies against thyroglobulin Rheumatoid arthritis Autoantibodies attack connective tissue in joints Cause inflammation and destruction of joints Type I diabetes Autoantibodies attack insulin-producing cells in pancreatic islets © 2013 Pearson Education, Inc.

116 Autoimmune disorders Module Immune disorders involving bothoveractivity and underactivity can be harmful Figure 13.11 © 2013 Pearson Education, Inc.

117 Graft Rejection (13.11) Occurs after organ transplant
Recipient's T cells activated by donated tissue attack and destroy foreign cells Transplant success improved by immunosuppression Reducing sensitivity of immune system Cyclosporin A (CsA) Suppresses immune response by inhibiting helper T cells while not affecting suppressor T cells © 2013 Pearson Education, Inc.

118 Inadequate Immune Response (13.11)
Immunodeficiency diseases Result from: Embryological development problems with lymphoid organs and tissues Infection with virus that depresses immune function Treatment with or exposure to immunosuppressive agents Age-related reductions in immune activity © 2013 Pearson Education, Inc.

119 Immunodeficiency Diseases (13.11)
Acquired immune deficiency syndrome (AIDS) Most common immunodeficiency disease Caused by human immunodeficiency virus (HIV) Virus binds to CD4 proteins and infects helper T cells Infected cells synthesize and release new viral proteins Infected helper T cells destroyed by virus or immune defenses Impairs cell-mediated and antibody-mediated responses Suppressor T cells not affected by virus Body vulnerable to microbial invaders, opportunistic infections, cancer Spread by contact with body fluids (blood, semen, vaginal secretions) Infects 33 million people worldwide with 2 million deaths each year © 2013 Pearson Education, Inc.

120 Immunodeficiency diseases
Module Immune disorders involving bothoveractivity and underactivity can be harmful HIV (green) budding from an infected TH cell SEM x 40,000 Figure 13.11 © 2013 Pearson Education, Inc.

121 Age-Related Reductions in Immune Activity (13.11)
Immune system is less effective with age Thymus shrinks and thymic hormones decrease Increased susceptibility to viral and bacterial infections T cells less responsive to antigens Fewer cytotoxic T cells respond to infection Number of helper T cells reduced B cells less responsive Antibody levels slower to rise after antigen exposure Vaccinations (flu, pneumonia) strongly recommended Increased incidence of cancer Declining immune surveillance and elimination of tumor cells © 2013 Pearson Education, Inc.

122 Age-related reductions in immune activity
Module Immune disorders involving bothoveractivity and underactivity can be harmful Figure 13.11 © 2013 Pearson Education, Inc.

123 Module 13.11 Review Define autoimmune disorders.
Describe immunosuppression. Provide a plausible explanation for the increased incidence of cancer in the elderly. © 2013 Pearson Education, Inc.


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