1. BIOLOGY CONCEPTS & CONNECTIONS Fourth Edition Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Neil A. Campbell Jane B. Reece Lawrence G. Mitchell Martha R. Taylor From PowerPoint ® Lectures for Biology: Concepts & Connections CHAPTER 24 The Immune System Modules 24.1 – 24.2

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3. Acquired immune deficiency syndrome (AIDS) is epidemic throughout much of the world 14,000 people are infected with the AIDS virus every day –HIV is the virus that causes AIDS –HIV is transmitted mainly in blood and semen –Former L.A. Laker Magic Johnson is one of 900,000 Americans who are HIV-positive The Continuing Problem of HIV

4. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Our immune system is a specific defense system –It backs up several mechanisms of nonspecific resistance HIV attacks the immune system –It eventually destroys the body’s ability to fight infection

5. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Basic Mechanisms of Defense There are three basic lines of defense against disease Vertebrate have all three lines of defense

6. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Basic Mechanisms of Defense The 1st line of defense: nonspecific external barriers –Prevent microbes from entering the body –Examples: skin and mucous membranes

7. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Basic Mechanisms of Defense The 2nd line of defense: nonspecific internal barriers –Occurs when microbes breach nonspecific external barriers –Broad internal responses to microbe infection –Examples: phagocytic white blood cells, inflammation, fever

8. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Basic Mechanisms of Defense The 3rd line of defense: specific immune response –Immune cells selectively destroy specific invading microbes and toxins –Invaders are “remembered,” allowing for a rapid future response to invasion

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13. The body’s first lines of defense against infection are nonspecific –They do not distinguish one infectious microbe from another 24.1 Nonspecific defenses against infection include the skin and mucous membranes, phagocytic cells, and antimicrobial proteins NONSPECIFIC DEFENSES AGAINST INFECTION

14. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Skin and Mucous Membranes The skin is important in blocking microbe entry and suppressing microbe growth –Skin is a barrier to microbes –Skin is continually shed, removing microbes that gain a foothold on skin –Many skin secretions contain natural antibiotics

15. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Skin and Mucous Membranes Mucous membranes have effective microbe defense mechanisms –Mucous membrane secretions contain antibacterial enzymes (example: lysozymes) –Mucus traps microbes entering the nose or mouth –Respiratory tract cilia sweep mucus and microbes away from lungs

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17. Nonspecific Internal Defenses Broad defenses that attack microbes that penetrate the skin Three major categories of nonspecific internal defenses –Phagocytic cells and natural killer cells –The inflammatory response –Fever

18. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Macrophages wander in the interstitial fluid –They “eat” any bacteria and virus-infected cells they encounter Figure 24.1A

19. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Natural Killer Cells A type of white blood cell Attack body cells that are cancerous or infected with virus –Secrete enzymes that poke holes in the cell membrane of virally-infected or cancerous cells

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21. Fever Helps combat large-scale infection by elevating body temperature

22. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Fever Some cells release cytokines in response to infection –Antibacterial cytokines Macrophages release endogenous pyrogens: elevate body temperature Other cytokines: decrease iron in the blood Both act to slow bacterial reproduction –Antiviral cytokines: Interferon, which helps cells resist viral attack

23. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Interferon and complement proteins are activated by infected cells Figure 24.1B 1 2 3 4 Interferon genes turned on Interferon molecules 5 Interferon stimulates cell to turn on genes for antiviral proteins HOST CELL 2 Protected against virus by interferon from cell 1 HOST CELL 1 Makes interferon; is killed by virus Antiviral proteins block viral reproduction VIRUS Viral nucleic acid mRNA New viruses 6

24. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Tissue damage triggers the inflammatory response 24.2 The inflammatory response mobilizes nonspecific defense forces Figure 24.2 Tissue injury; release of chemical signals such as histamine 1 23 Dilation and increased leakiness of local blood vessels; migration of phagocytes to the area Phagocytes (macrophages and neutrophils) consume bacteria and cell debris; tissue heals Pin Skin surface Bacteria Chemical signals White blood cell Swelling Phagocytes and fluid move into area Phagocytes

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26. The inflammatory response can –disinfect tissues –limit further infection

27. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The lymphatic system is a network of lymphatic vessels and organs –It returns tissue fluid to the circulatory system –It fights infections 24.3 The lymphatic system becomes a crucial battleground during infection

28. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 23.3 Right lymphatic duct, entering vein Thoracic duct Appendix Adenoid Tonsil Lymph nodes Thoracic duct, entering vein Thymus Spleen Bone marrow Lymphatic vessels LYMPHATIC VESSEL VALVE Blood capillary Tissue cells Interstitial fluid LYMPHATIC CAPILLARY Masses of lymphocytes and macrophages

29. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings This lymphatic vessel is taking up fluid from tissue spaces in the skin It will return it as lymph to the blood –Lymph contains less oxygen and fewer nutrients than interstitial fluid Figure 23.3B LYMPHATIC VESSEL VALVE Blood capillary Interstitial fluid LYMPHATIC CAPILLARY Tissue cells

30. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Lymph nodes are key sites for fighting infection –They are packed with lymphocytes and macrophages Figure 23.3C, D Masses of lymphocytes and macrophages Lymphocytes Macrophages Outer capsule of lymph node

31. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Our immune systems responds to foreign molecules called antigens Infection or vaccination triggers active immunity The immune system reacts to antigens and “remembers” an invader We can temporarily acquire passive immunity 24.4 The immune response counters specific invaders SPECIFIC IMMUNITY

32. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Key Characteristics The immune response involves specialized white blood cells called lymphocytes The immune system: lymphocytes, the chemicals they produce, and the organs that they live in

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34. Two kinds of lymphocytes carry out the specific immune response –B cells secrete antibodies that attack antigens –T cells attack cells infected with pathogens 24.5 Lymphocytes mount a dual defense Figure 24.5 BONE MARROW Stem cell Immature lymphocytes Via blood Antigen receptors B cell HUMORAL IMMUNITY CELL- MEDIATED IMMUNITY T cell THYMUS Via blood OTHER PARTS OF THE LYMPHATIC SYSTEM Lymph nodes, spleen, and other lymphatic organs Final maturation of B and T cells in lymphatic organ

35. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings An immune response has three steps –First: recognizing an invader –Second: launching an attack –Third: remembering specific invaders to ward off future infections

36. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Step 1: Recognizing an Invader Foreign invaders exhibit characteristic antigens –Foreign molecules that are particular to an invading microbe or toxin –Immune cells respond to the presence of antigens

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38. Antibodies and T-cell Receptors Antibodies and T-cell receptors recognize and bind to foreign antigens

39. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Antibodies Antibodies are proteins that can be attached to B cells or free-floating in the blood

40. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Antibodies –Y-shaped molecules made of light peptide chains and heavy peptide chains –Both chains have constant and variable regions that form highly specific antigen binding sites –Each type of antibody is unique to the B cell that makes them

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42. An antibody molecule 24.10 Antibodies are the weapons of humoral immunity Figure 24.10A

43. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Antibodies There are five different classes of antibodies, which perform various functions –Inactivate their antigens by binding them and causing them to clump together –Assist white blood cells to engulf microbes –Activate natural killer cells –Bind to blood proteins of the complement system…

44. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Antibodies –Some classes of antibodies can cross the placenta and provide immunity to a developing child –Another class is secreted in breast milk –Both help the newborn, whose immune system is not fully developed

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47. Antigenic determinants (epitopes) are the molecules to which antibodies bind 24.6 Antigens have specific regions where antibodies bind to them Figure 24.6 Antibody A molecules Antigen Antibody B molecule Antigenic determinants Antigen- binding sites

48. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Immune Cells Launch an Attack Once an invading antigen has been detected, two forms of attack occur –Humoral immunity –Cell-mediated immunity

49. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings When an antigen enters the body, it activates only lymphocytes with complementary receptors –B and T cells multiply into clones of specialized effector cells that defend against the triggering antigen –This is called clonal selection 24.7 Clonal selection musters defensive forces against specific antigens

50. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Humoral Immunity Provided by B cells and circulating antibodies Attack antigens circulating in the bloodstream and lymph Each B cell has a unique antibody attached to its surface that will only bind with properly shaped antigens

51. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Humoral Immunity The mechanism of humoral immunity occurs in the following series of steps 1.Attached B cell antibodies bind to an invading antigen in the blood 2.Bound B cell divides rapidly forming many identical copies (clonal selection) 3.B cell clones differentiate to form memory B cells and plasma cells

52. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 24.7 Antigen molecules Variety of B cells in a lymph node Cell growth division, and differentiation Clone of many effector cells secreting antibodies Antibody molecules Antigen receptor (antibody on cell surface) Endoplasmic reticulum

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54. Humoral Immunity Memory B cells: saved to fight future infection Plasma cells: mass-produce the specific antibody into the blood

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56. Antibodies may –block harmful antigens on microbes –clump bacteria or viruses together –precipitate dissolved antigens –activate complement proteins 24.11 Antibodies mark antigens for elimination

57. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 24.11 Binding of antibodies to antigens inactivates antigens by Neutralization (blocks viral binding sites; coats bacterial toxins) Agglutination of microbes Precipitation of dissolved antigens Activation of complement Virus Bacterium Bacteria Antigen molecules Complement molecule Foreign cell Hole Enhances Phagocytosis Macrophage Cell lysis Leads to

58. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings In the primary immune response, clonal selection produces memory cells –These cells may confer lifelong immunity 24.8 The initial immune response results in a type of “memory” Figure 24.8A

59. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings When memory cells are activated by subsequent exposure to an antigen, they mount a more rapid and massive secondary immune response Figure 24.8B Unstimulated lymphocyte First exposure to antigen FIRST CLONE Memory cells Effector cellsSecond exposure to antigen SECOND CLONE More memory cells New effector cells

60. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Triggered by a specific antigen, a B cell differentiates into an effector cell –The effector cell is called a plasma cell –The plasma cell secretes antibodies 24.9 Overview: B cells are the main warriors of humoral immunity

61. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 24.9 PRIMARY RESPONSE (initial encounter with antigen) Antigen Antigen receptor on a B cell Antigen binding to a B cell Memory B cell Antibody molecules Plasma cell Cell growth, division, and differentiation SECONDARY RESPONSE (can be years later) Cell growth, division, and further differentiation Larger clone of cells Plasma cell Antibody molecules Later exposure to same antigen Memory B cell Clone of cells

62. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings These molecules are produced by fusing B cells specific for a single antigenic determinant with easy-to-grow tumor cells 24.12 Connection: Monoclonal antibodies are powerful tools in the lab and clinic Figure 24.12A Antigen injected into mouse Tumor cells grown in culture B cells (from spleen) Tumor cells Cells fused to generate hybrid cells Single hybrid cell grown in culture Antibody Hybrid cell culture, producing monoclonal antibodies

63. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings These cells are useful in medical diagnosis –Example: home pregnancy tests They are also useful in the treatment of certain cancers Figure 24.12B

64. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Provided by T cells, which attack cancer cells and cells that have been invaded by viruses Three types of T cells are involved –Helper T cells –Cytotoxic T cells –Memory T cells 24.13 T cells mount the cell-mediated defense and aid humoral immunity

65. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Cell-Mediated Immunity Helper T cells –Bind to antigens “presented” by a macrophage that consumed them

66. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Cell-mediated immunity –An antigen- presenting cell (APC) first displays a foreign antigen and one of the body’s own self proteins to a helper T cell Figure 24.13A 1 2 3 4 Microbe Macrophage (will become APC) Antigen from microbe (nonself molecule) Self protein displaying antigen T cell receptor Binding site for self protein Helper T cell Binding site for antigen APC

67. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Cell-Mediated Immunity Helper T cells –Produce cytokines that stimulate T cell division and differentiation Will form memory T cells and cytotoxic T cells Will also stimulate division of B cells (humoral response) that are bound to an antigen

68. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The helper T cell’s receptors recognize the self- nonself complexes on the APC –The interaction activates the helper T cells –The helper T cell can then activate cytotoxic T cells with the same receptors Figure 24.13B Self protein displaying an antigen T cell receptor Interleukin-2 stimulates cell division Cytotoxic T cell Interleukin-2 activates other T cells and B cells Cell-mediated immunity (attack on infected cells) Humoral immunity (secretion of antibodies by plasma cells) B cell Helper T cell APC Interleukin-1 activates helper T cell

69. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Cytotoxic T cells –Bind directly to cancerous or virally-infected cells –Release proteins that poke holes in cancer/infected cell membrane, killing the cell

70. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Cytotoxic T cells bind to infected body cells and destroy them Figure 24.13C Cytotoxic T cell binds to infected cell 12 3 Perforin makes holes in infected cell’s membrane Infected cell is destroyed INFECTED CELL Perforin molecule Cytotoxic T cell Foreign antigen Hole forming Cell-Mediated Immunity

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72. Cell-Mediated Immunity Memory T cells –Dormant helper T cells that fight future infection by the antigen that produced it

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74. Cytotoxic T cells may attack cancer cells –The surface molecules of cancer cells are altered by the disease 24.14 Cytotoxic T cells may help prevent cancer Figure 24.14

75. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The immune system normally reacts only against nonself substances –It generally rejects transplanted organs –The cells of transplanted organs lack the recipient’s unique “fingerprint” of self proteins 24.15 The immune system depends on our molecular fingerprints

76. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Autoimmune diseases –The system turns against the body’s own molecules Immunodeficiency diseases –Immune components are lacking, and infections recur Physical and emotional stress may weaken the immune system 24.16 Connection: Malfunction or failure of the immune system causes disease DISORDERS OF THE IMMUNE SYSTEM

77. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Allergies are abnormal sensitivities to allergens in the surroundings 24.17 Connection: Allergies are overreactions to certain environmental antigens Figure 24.17 Allergen (pollen grain) B cells make antibodies Antigenic determinant SENSITIZATION: Initial exposure to allergen Antibodies attach to mast cell B cell (plasma cell) Histamine Mast cell Allergen binds to antibodies on mast cell Histamine is released, causing allergy symptoms LATER EXPOSURE TO SAME ALLERGEN

78. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The AIDS virus attacks helper T Cells –This cripples both cell-mediated and humoral immunity So far, AIDS is incurable –Drugs and vaccines offer hope for the future Practicing safer sex could save many lives 24.18 Connection: AIDS leaves the body defenseless