1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Chapter 43 The Immune System

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview: Reconnaissance, Recognition, and Response An animal must defend itself from the many dangerous pathogens it may encounter Two major kinds of defense have evolved: innate immunity and acquired immunity

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Innate immunity is present before any exposure to pathogens and is effective from the time of birth It involves nonspecific responses to pathogens Innate immunity consists of external barriers plus internal cellular and chemical defenses Key internal defenses are macrophages and other phagocytic cells

4. LE 43-1 3 µm

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Acquired immunity, or adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances It involves a very specific response to pathogens Recognition is by white blood cells called lymphocytes Some lymphocytes produce antibodies; others destroy infected cells, cancer cells, or foreign tissue

6. LE 43-2 Invading microbes (pathogens) External defenses Skin Mucous membranes Secretions INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes Internal defenses Phagocytic cells Inflammatory response Humoral response (antibodies) Antimicrobial proteins Natural killer cells Cell-mediated response (cytotoxic lymphocytes)

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 43.1: Innate immunity provides broad defenses against infection A pathogen that breaks through external defenses encounters innate cellular and chemical mechanisms that impede its attack

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings External Defenses Skin and mucous membranes are physical barriers to entry of microorganisms and viruses Mucous membrane cells produce mucus, a viscous fluid that traps microbes and other particles In the trachea, ciliated epithelial cells sweep mucus and any entrapped microbes upward, preventing microbes from entering the lungs

9. LE 43-3 10 µm

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Secretions of the skin and mucous membranes provide an environment hostile to microbes Secretions give the skin a pH between 3 and 5, acidic enough to prevent colonization of many microbes Skin secretions include proteins such as lysozyme, which digests bacterial cell walls

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Internal Cellular and Chemical Defenses Internal cellular defenses depend mainly on phagocytosis White blood cells called phagocytes ingest microorganisms and initiate inflammation

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Phagocytic Cells Phagocytes attach to prey via surface receptors and engulf them, forming a vacuole that fuses with a lysosome

13. LE 43-4 Pseudopodia Microbes MACROPHAGE Lysosome containing enzymes Vacuole

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Macrophages, a type of phagocyte, migrate through the body and are found in organs of the lymphatic system The lymphatic system defends against pathogens

15. LE 43-5 Adenoid Tonsil Lymph nodes Peyer’s patches (small intestine) Spleen Appendix Lymphatic vessels Lymph node Masses of lymphocytes and macrophages Lymphatic vessel Blood capillary Tissue cells Lymphatic capillary Interstitial fluid

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Antimicrobial Proteins Proteins function in innate defense by attacking microbes directly or impeding their reproduction About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation Interferons provide innate defense against viruses and help activate macrophages

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inflammatory Response In local inflammation, histamine and other chemicals released from injured cells promote changes in blood vessels These changes allow more fluid, phagocytes, and antimicrobial proteins to enter tissues

18. LE 43-6 Pathogen Pin Chemical signals Capillary Phagocytic cells Macrophage Red blood cell Blood clotting elements Blood clot Phagocytosis

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Natural Killer Cells Natural killer (NK) cells attack virus-infected body cells and cancer cells They trigger apoptosis in the cells they attack

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Invertebrate Immune Mechanisms Many invertebrates defend against infection by many of the same mechanisms in the vertebrate innate response

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 43.2: In acquired immunity, lymphocytes provide specific defenses against infection Acquired immunity is the body’s second major kind of defense An antigen is a foreign molecule that is recognized by lymphocytes and elicits a response from them A lymphocyte recognizes and binds to a small portion of the antigen called an epitope

22. LE 43-7 Antigen- binding sites Epitopes (antigenic determinants) Antibody A Antibody B Antibody C Antigen

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Antigen Recognition by Lymphocytes Two main types of lymphocytes circulate in the blood of vertebrates: B lymphocytes (B cells) and T lymphocytes (T cells) A single B cell or T cell has about 100,000 identical antigen receptors All antigen receptors on a single cell recognize the same epitope

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings B Cell Receptors for Antigens B cell receptors bind to specific, intact antigens Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane Video: T Cell Receptors Video: T Cell Receptors

25. LE 43-8 Antigen- binding site Disulfide bridge Light chain V V C C C C V V Antigen- binding site Variable regions Constant regions Transmembrane region Antigen- binding site C V C V Plasma membrane T cell  chain  chain Disulfide bridge Cytoplasm of T cell A T cell receptor consists of one  chain and one  chain linked by a disulfide bridge. A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges. Heavy chains Cytoplasm of B cellB cell

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings T Cell Receptors for Antigens and the Role of the MHC Each T cell receptor consists of two different polypeptide chains V V C C

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings T cells bind to antigen fragments that are bound to cell-surface proteins called MHC molecules MHC molecules are so named because they are encoded by a family of genes called the major histocompatibility complex

28. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Infected cells produce MHC molecules, which bind to antigen fragments and are transported to the cell surface, a process called antigen presentation A nearby T cell can then detect the antigen fragment displayed on the cell’s surface Depending on their source, peptide antigens are handled by different classes of MHC molecules

29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Class I MHC molecules are found on almost all nucleated cells of the body They display peptide antigens to cytotoxic T cells

30. LE 43-9 Antigen- presenting cell Antigen fragment Class II MHC molecule T cell receptor Helper T cell Antigen fragment Class I MHC molecule T cell receptor Cytotoxic T cell Infected cell Microbe

31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells They display antigens to helper T cells

32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Lymphocyte Development Lymphocytes arise from stem cells in bone marrow Newly formed lymphocytes are alike but later develop into B cells or T cells, depending on where they mature

33. LE 43-10 Lymphoid stem cell Bone marrow Thymus T cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others) B cell

34. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Generation of Lymphocyte Diversity by Gene Rearrangement Random, permanent gene rearrangement forms functional genes encoding the B or T cell antigen receptor chains

35. LE 43-11 DNA of undifferentiated B cell DNA of differentiated B cell pre-mRNA mRNA Cap Light-chain polypeptide Variable region Constant region B cell B cell receptor Translation Poly (A) RNA processing (removal of intron; addition of cap and poly (A) tail) Transcription of resulting permanently rearranged, functional gene Functional gene Deletion of DNA between a V segment and J segment and joining of the segments V 4 –V 39 V1V1 V2V2 V3V3 V 40 V1V1 V2V2 V3V3 J5J5 C Intron J5J5 C J4J4 J3J3 J2J2 J1J1 V3V3 J5J5 C V3V3 J5J5 C V C

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Testing and Removal of Self-Reactive Lymphocytes As B and T cells mature in the bone and thymus, their antigen receptors are tested for self-reactivity Lymphocytes with receptors for antigens that are already in the body are destroyed by apoptosis or rendered nonfunctional

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Clonal Selection of Lymphocytes In a primary immune response, binding of antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation This process is called clonal selection Clonal selection of B cells generates a clone of short-lived activated effector cells and a clone of long-lived memory cells Animation: Role of B Cells Animation: Role of B Cells

38. LE 43-12 B cells that differ in antigen specificity Antigen molecules Antigen receptor Antibody molecules Clone of memory cells Clone of plasma cells

39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In the secondary immune response, memory cells facilitate a faster, more efficient response

40. LE 43-13 Antibodies to A Antibodies to B Time (days) 56 49 42 35 28 21 14 7 0 10 4 10 3 10 2 10 1 10 0 Antibody concentration (arbitrary units)

41. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 43.3: Humoral and cell-mediated immunity defend against different types of threats Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells

42. LE 43-14_3 First exposure to antigen Antigens engulfed and displayed by dendritic cells Activate Humoral immune response Cell-mediated immune response Helper T cell Active and memory helper T cells Gives rise to Antigens displayed by infected cells Activate Cytotoxic T cell Memory cytotoxic T cells Gives rise to Secreted cytokines activate Active cytotoxic T cells Defend against infected cells, cancer cells, and transplanted tissues Activate Gives rise to Secrete antibodies that defend against pathogens and toxins in extracellular fluid Plasma cells Memory B cells Intact antigens

43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Helper T Cells: A Response to Nearly All Antigens A surface protein called CD4 binds the class II MHC molecule This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs Activated helper T cells secrete cytokines that stimulate other lymphocytes Animation: Helper T Cells Animation: Helper T Cells

44. LE 43-15 Dendritic cell Bacterium Peptide antigen Class II MHC molecule TCR CD4 Helper T cell B cell Cytokines Cytotoxic T cell Cell-mediated immunity (attack on infected cells) Humoral immunity (secretion of antibodies by plasma cells) Dendritic cell

45. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytotoxic T Cells: A Response to Infected Cells and Cancer Cells Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer The activated cytotoxic T cell secretes proteins that destroy the infected target cell

46. LE 43-16 Peptide antigen Target cell Class I MHC molecule TCR CD8 Granzymes Perforin Cytotoxic T cell Pore Apoptotic target cell Released cytotoxic T cell Cytotoxic T cell Cancer cell

47. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Animation: Cytotoxic T Cells Animation: Cytotoxic T Cells

48. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Antibody Classes The five major classes of antibodies, or immunoglobulins, differ in distribution and function

49. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings B Cells: A Response to Extracellular Pathogens Activation of B cells is aided by cytokines and antigen binding to helper T cells Clonal selection of B cells generates antibody- secreting plasma cells, the effector cells of humoral immunity

50. LE 43-17 Macrophage Class II MHC molecule Bacterium Peptide antigen CD4TCR Helper T cell Activated helper T cell Cytokines Clone of memory B cells Endoplasmic reticulum of plasma cell Clone of plasma cells Secreted antibody molecules B cell +

51. LE 43-18a J chain IgM (pentamer) Promotes neutralization and agglutination of antigens; very effective in complement activation (see Figure 43.19) First lg class produced after initial exposure to antigen; then its concentration in the blood declines

52. LE 43-18b IgG (monomer) Promotes opsonization, neutralization, and agglutination of antigens; less effective in complement activation than lgM (see Figure 43.19) Only lg class that crosses placenta, thus conferring passive immunity on fetus Most abundant lg class in blood; also present in tissue fluids

53. LE 43-18c IgA (dimer) Provides localized defense of mucous membranes by agglutination and neutralization of antigens (see Figure 43.19) J chain Secretory component Presence in breast milk confers passive immunity on nursing infant Present in secretions such as tears, saliva, mucus, and breast milk

54. LE 43-18d IgE (monomer) Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions (see Figure 43.20)

55. LE 43-18e IgD (monomer) Present primarily on surface of naive B cells that have not been exposed to antigens Transmembrane region Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection)

56. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Antibody-Mediated Disposal of Antigens The binding of antibodies to antigens is also the basis of antigen-disposal mechanisms Microbes are eliminated by phagocytosis and complement-mediated lysis Animation: Antibodies Animation: Antibodies

57. LE 43-19 Viral neutralization (blocks binding to host and opsonization increases phagocytosis) Agglutination of antigen-bearing particles, such as microbes Precipitation of soluble antigens Activation of complement system and pore formation Binding of antibodies to antigens inactivates antigens by Bacteria Soluble antigens MAC Complement proteins Foreign cell Pore Virus Bacterium Enhances Phagocytosis Macrophage Cell lysis Leads to

58. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Active and Passive Immunization Active immunity develops naturally in response to an infection It can also develop following immunization, also called vaccination In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory

59. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Passive immunity provides immediate, short-term protection It is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk It can be conferred artificially by injecting antibodies into a nonimmune person

60. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 43.4: The immune system’s ability to distinguish self from nonself limits tissue transplantation The immune system can wage war against cells from other individuals Transplanted tissues are usually destroyed by the recipient’s immune system

61. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Blood Groups and Transfusions Antigens on red blood cells determine whether a person has type A, B, AB, or O blood Antibodies to nonself blood types exist in the body Transfusion with incompatible blood leads to destruction of the transfused cells Recipient-donor combinations can be fatal or safe

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63. A red blood cell antigen called the Rh factor creates difficulties when an Rh-negative mother carries successive Rh-positive fetuses

64. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tissue and Organ Transplants MHC molecules stimulate rejection of tissue grafts and organ transplants

65. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chances of successful transplantation increase if donor and recipient MHC tissue types are well matched Immunosuppressive drugs facilitate transplantation Lymphocytes in bone marrow transplants may cause a graft versus host reaction in recipients

66. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 43.5: Exaggerated, self-directed, or diminished immune responses can cause disease If the delicate balance of the immune system is disrupted, effects range from minor to often fatal

67. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Allergies Allergies are exaggerated (hypersensitive) responses to antigens called allergens In localized allergies such as hay fever, IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells

68. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The next time the allergen enters the body, it binds to mast cell–associated IgE molecules Mast cells release histamine and other mediators that cause vascular changes leading to typical allergy symptoms An acute allergic response can lead to anaphylactic shock, a life-threatening reaction that can occur within seconds of allergen exposure

69. LE 43-20 IgE Allergen Granule Mast cell Histamine

70. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Autoimmune Diseases In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain molecules of the body Rheumatoid arthritis is an autoimmune disease leading to damage and inflammation of joints

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72. Other examples of autoimmune diseases: – Systemic lupus erythematosus – Multiple sclerosis – Insulin-dependent diabetes

73. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Immunodeficiency Diseases Inborn or primary immunodeficiency results from hereditary or congenital defects that prevent proper functioning of innate, humoral, and/or cell- mediated defenses Acquired or secondary immunodeficiency results from exposure to chemical and biological agents

74. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inborn (Primary) Immunodeficiencies In severe combined immunodeficiency (SCID), both the humoral and cell-mediated branches of acquired immunity fail to function

75. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Acquired (Secondary) Immunodeficiencies Acquired immunodeficiencies range from temporary states to chronic diseases

76. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Stress and the Immune System Growing evidence shows that physical and emotional stress can harm immunity

77. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Acquired Immunodeficiency Syndrome (AIDS) People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse Because AIDS arises from loss of helper T cells, it impairs both the humoral and cell-mediated immune responses The loss of helper T cells results from infection by the human immunodeficiency virus (HIV) Animation: HIV Reproductive Cycle Animation: HIV Reproductive Cycle

78. LE 43-22 1 µm

79. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The spread of HIV is a worldwide problem The best approach for slowing this spread is education about practices that transmit the virus