1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint Lectures for Biology: Concepts and Connections, Fifth Edition – Campbell, Reece, Taylor, and Simon Lectures by Chris Romero Chapter 24 The Immune System

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings An AIDS Uproar Acquired immune deficiency syndrome (AIDS) is epidemic throughout much of the world HIV, the virus that causes AIDS, attacks the immune system, destroying the body's ability to fight infection Drug trials in developing nations revealed the complex interconnectedness of science, politics, and ethics The ravaging effects of AIDS demonstrates how dependent we are on our body's built-in defenses

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 40 million people living with AIDS 3 million died in 2003 5 million newly infected in 2003 500,000 children under the age of 15 who died in 2003

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings INNATE DEFENSES AGAINST INFECTION 24.1 Innate defenses against infection include the skin and mucous membranes, phagocytic cells, and antimicrobial proteins Innate immunity is the body’s first line of defense against all invaders – Skin provides tough barrier and general chemical defenses – Mucous membranes – Stomach acid – Hairs, cilia

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Microbes that breach the body's external defenses are confronted by innate defensive cells – Found in blood and interstitial fluid – Macrophages are large phagocytic cells – Natural killer cells release chemicals – Specific proteins attack microbes or impede their reproduction Interferons help cells resist viruses The complement system – Initiated by microbes, can lead to lysis of invaders

7. LE 24-1a Bacteria Colorized SEM 3,800 

8. LE 24-1b VirusViral nucleic acid New viruses Interferon genes turned on DNA mRNA Interferon molecules Host cell 1 Makes interferon; is killed by virus Host cell 2 Protected against virus by interferon from cell 1 Interferon stimulates cell to turn on genes for antiviral proteins Antiviral proteins block viral reproduction

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.2 The inflammatory response mobilizes nonspecific defense forces Tissue damage triggers the inflammatory response – Can disinfect tissues and limit further infection Steps of the inflammatory response 1.Tissue injury releases chemical signals such as histamine 2.Local blood vessels dilate and leakiness increases; phagocytes migrate to the area

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3.Phagocytes consume bacteria and cell debris; tissue heals The inflammatory response may be widespread as well as localized – White blood cells may increase – Fever may stimulate phagocytosis – Septic shock Overwhelming systemic inflammatory response May cause death

11. LE 24-2 Pin Skin surface Bacteria Chemical signals White blood cell Blood vessel Tissue injury; release of chemical signals such as histamine 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 Phagocytes and fluid move into area Swelling Phagocytes

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.3 The lymphatic system becomes a crucial battleground during infection The lymphatic system is involved in both innate and acquired immunity – Branching network of lymphatic vessels – Lymph nodes packed with macrophages and white blood cells – Tonsils and adenoids – Appendix – Spleen – Bone marrow and thymus – Lymph, similar to interstitial fluid

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Main functions of the lymphatic system – Return tissue fluid to circulatory system Lymphatic vessels take up fluid from tissue spaces Lymph reenters circulatory system through two large lymphatic vessels – Fight infection Microbes picked up from infection sites travel in lymph through lymphatic organs packed with white blood cells

14. LE 24-3 Adenoid Tonsil Lymph nodes Right lymphatic duct, entering vein Thoracic duct, entering vein Thymus Thoracic duct Appendix Spleen Bone marrow Lymphatic vessels Lymphatic capillary Interstitial fluid Tissue cells Blood capillary Lymphatic vessel Valve Masses of lymphocytes and macrophages Lymph node

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings ACQUIRED IMMUNITY 24.4 The immune response counters specific invaders The immune system recognizes and defends against invading microbes and cancer cells – Can distinguish one infectious agent from another Acquired immunity develops only after exposure to a specific foreign substance (antigen) – System produces a specific type of antibody that helps counter the antigen's effects – Primed system remembers the antigen and reacts to it in the future

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Immunity is usually acquired by natural exposure to antigens but may be achieved by vaccination – Active immunity Person's own immune system actively produces antibodies – Passive immunity Person receives premade antibodies, as a fetus does from its mother Immunity lasts only as long as the antibodies do

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.5 Lymphocytes mount a dual defense Lymphocytes originate from stem cells in the bone marrow Humoral immunity – B cells secrete antibodies that circulate in blood and lymph to sites of infection – Defends primarily against bacteria and viruses present in body fluids

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell-mediated immunity – In the thymus, immature lymphocytes specialize into T cells – T cells attack cells infected with pathogens, fungi and protozoans, cancer cells – T cells also promote phagocytosis and production of antibodies

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Functioning of B and T cells – Certain genes in the cell are turned on – Cell synthesizes specific protein molecules, which are incorporated into the plasma membrane – Antigen receptors sticking up from cell surface recognize specific antigens and mount a defense Millions of diverse B and T cells stand ready to recognize and bind virtually every possible antigen

21. LE 24-5a Bone marrow Stem cell Immature lymphocyte Via blood Thymus Antigen receptors B cell Humoral immunity Via blood T cell Cell-mediated immunity Final maturation of B and T cells in lymphatic organ Lymph nodes, spleen, and other lymphatic organs Other parts of the lymphatic system

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.6 Antigens have specific regions where antibodies bind to them Antigens are usually molecules on the surface of viruses or foreign cells Antigenic determinants are the specific regions on an antigen to which antibodies bind – Antigens may have several different determinants – Immune system may direct several distinct antibodies against one antigen

24. LE 24-6 Antibody A molecules Antigen- binding sites Antigen molecule Antigenic determinants Antibody B molecule

25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.7 Clonal selection musters defensive forces against specific antigens Primary immune response: lymphocytes exposed to antigen for the first time – Antigen activates a small subset of lymphocytes (B cells) bearing complementary receptors – The selected B cells multiply into clones of effector and memory cells

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Effector (plasma) cells – Combat the antigen – Secrete antibody molecules that circulate in blood and contribute to humoral immunity – Last only 4 or 5 days Memory cells – Remain in lymph nodes – May last for decades, sometimes confer lifetime immunity

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Secondary immune response – Memory cells exposed to same antigen a second time – Second round of clonal selection ensues – Secondary response is faster and stronger; produces very high levels of antibodies Animation: Role of B Cells Animation: Role of B Cells

28. LE 24-7a Primary immune response Antigen receptor (antibody on cell surface) Antigen molecules First exposure to antigen Endoplasmic reticulum Memory cells Plasma (effector) cells secreting antibodies Memory cells Plasma (effector) cells secreting antibodies Antigen molecules Second exposure to same antigen Antibody molecules Endoplasmic reticulum Antibody molecules Secondary immune response

29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Comparison of primary and secondary immune response – Primary response Takes several days to occur, during which the individual may become ill Antibody level peaks in about two weeks, effector cells die out – Secondary response Occurs quickly Is of greater magnitude and is more prolonged

30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Acquired immunity is specific: the body's response to a second antigen is not influenced by its response to the first one

31. LE 24-7b Second exposure to antigen X, first exposure to antigen Y Secondary immune response to antigen X Primary immune response to antigen X Primary immune response to antigen Y First exposure to antigen X Antibodies to X Antibodies to Y Antibody concentration 0714212835424956 Time (days)

32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.8 Antibodies are the weapons of humoral immunity Antibody molecules are secreted by plasma (effector) B cells Antibody molecule structure – Y shaped, made of two identical "heavy" and two identical "light" polypeptide chains – A C (constant) and a V (variable) region on each chain – Antigen-binding sites specific to the antigenic determinants that elicited its secretion

33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Antibody functions in humoral immunity – Binds its antigen at the antigen-binding site – Assists in elimination of the antigen, at the C region of the heavy chains

35. LE 24-8b Antigen-binding sites V V C CC C V V Light chain Heavy chain

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.9 Antibodies mark antigens for elimination Effector mechanisms involve a specific recognition-and-attack phase followed by a nonspecific destruction phase Antibodies mark invaders by forming antigen- antibody complexes Binding triggers mechanisms to eliminate the invader – Neutralization – Agglutination of microbes – Precipitation of dissolved antigens – Activation of complement system

37. LE 24-9 Binding of antibodies to antigens inactivates antigens by Neutralization (blocks viral binding sites; coats bacteria) Agglutination of microbes Virus Bacterium Bacteria Precipitation of dissolved antigens Antigen molecules Activation of complement system Complement molecule Hole Foreign cell Cell lysisPhagocytosis Enhances Macrophage Leads to

38. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Animation: Anitbodies Animation: Anitbodies Animation: Antibodies Animation: Antibodies

39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings CONNECTION 24.10 Monoclonal antibodies are powerful tools in the lab and clinic Antibodies are used in clinical diagnosis, treatment, and research Monoclonal antibodies – All cells producing the antibodies are descendants of a single cell – Harvested from cell cultures rather than from animals

40. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Production of monoclonal antibodies – Animal injected with antigen that stimulates its B cells to make specific antibodies – B cells fused with tumor cells – Hybrid cells make antibodies specific for the desired antigenic determinant Can multiply indefinitely in culture

41. LE 24-10a Antigen injected into mouse B cells (from spleen) Tumor cells grown in culture Tumor cells Cells fused to generate hybrid cells Single hybrid cell grown in culture Antibody Hybrid cell culture, producing monoclonal antibodies

43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.11 Helper T cells stimulate humoral and cell- mediated immunity Cell-mediated immunity produced by T cells battles pathogens that have entered body cells T cells respond only to antigens present on the surface of the body's own cells – Cytotoxic T cells attack infected cells – Helper T cells Help activate T cells, B cells, and macrophages Interact with antigen-presenting cells

44. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Precise interaction of antigen-presenting cells and helper T cells – Antigen-presenting cell self protein binds antigen nonself molecules and displays them on the cell surface – Helper T cells recognize and bind to the self-nonself complex Depends on highly specific receptors in the T cell's plasma membrane – Binding activates helper T cells Enhanced by other signals

45. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Activated helper T cells promote the immune response, particularly secretion of stimulatory proteins – Make helper T cells grow and divide, producing memory cells and additional helper T cells – Help activate B cells, stimulating humoral immunity – Stimulate activity of cytotoxic T cells Animation: Helper T Cells Animation: Helper T Cells

46. LE 24-11 Microbe Macrophage Self-nonself complex Antigen from microbe (nonself molecule) Self protein Antigen-presenting cell T cell receptor Interleukin-1 stimulates helper T cell Binding site for antigen Binding site for self protein Helper T cell Interleukin-2 stimulates cell division B cell Interleukin-2 activates other B cells and T cells Cell-mediated immunity (attack on infected cells) Cytotoxic T cell Humoral immunity (secretion of antibodies by plasma cells)

47. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings CONNECTION 24.12 HIV destroys helper T cells, compromising the body's defenses HIV (human immunodeficiency virus) causes AIDS – Most often attacks helper T cells – Destruction of humoral and cell-mediated immunity compromises body's ability to fight infections Animation: HIV Reproductive Cycle Animation: HIV Reproductive Cycle

49. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mechanism of HIV action – Transmitted through body fluids – Inside the body, HIV binds to and enters helper T cells – RNA genome of HIV is reverse-transcribed inside the T cells – Newly produced DNA is integrated into host T cell's genome, able to direct the production of new viruses – HIV in the bloodstream may infect and kill other helper T cells

50. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Immune system impairment makes patients with AIDS susceptible to opportunistic infections and cancer So far, AIDS is incurable – Certain drugs slow HIV reproduction and the progress of AIDS – Best way to stop AIDS is to prevent spread of HIV

51. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.13 Cytotoxic T cells destroy infected body cells Like helper T cells, cytotoxic T cells recognize and bind with self-nonself complexes on infected cells Mechanism of cytotoxic T cell action – Binding to infected cell stimulates cytotoxic T cell to synthesize perforin – Perforin makes holes in infected cell's membrane, and T cell enzymes enter – Infected cell is destroyed

52. LE 24-13 Cytotoxic T cell binds to infected cell Self-nonself complex Perforin molecule Cytotoxic T cell Enzyme that can promote apoptosis Hole forming Perforin makes holes in infected cell’s membrane and enzyme enters Foreign antigen Infected cell is destroyed Infected cell

53. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Video: T Cell Receptors Video: T Cell Receptors Animation: Cytotoxic T Cells Animation: Cytotoxic T Cells

54. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.14 Cytotoxic T cells may help prevent cancer Genetic changes leading to cancer can result in new proteins displayed on cell surfaces T cells identify these tumor antigens as foreign and destroy the affected cells

56. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 24.15 The immune system depends on our molecular fingerprints Each person's cells have particular self protein "fingerprints" that mark them as off limits to attack by lymphocytes Self proteins are coded for by MHC (major histocompatibility complex) genes – Except for identical twins, two individuals cannot have identical self proteins Transplanted organs may be rejected because their cells lack the unique fingerprint of the recipient's self proteins

57. DISORDERS OF THE IMMUNE SYSTEM CONNECTION 24.16 Malfunction or failure of the immune system causes disease In autoimmune diseases, the immune system turns against some of the body's own molecules In immunodeficiency diseases, immune system components are lacking, and infections occur frequently Physical and emotional stress may weaken the immune system Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

58. CONNECTION 24.17 Allergies are overreactions to certain environmental antigens Allergies are abnormal sensitivities to antigens (allergens) in the surroundings Allergic reactions occur in two stages – Sensitization: initial exposure to allergen Allergen enters bloodstream B cells make antibodies Antibodies attach to mast cells that produce histamines and trigger the inflammatory response

59. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings – Later exposure to same allergen Allergen binds to antibodies on mast cell Histamine is released, causing allergy symptoms Anaphylactic shock is a severe allergic reaction – Causes severe drop in blood pressure – Potentially fatal

60. LE 24-17 B cell (plasma cell) Mast cell Antigenic determinant Allergen (pollen grain) enters blood stream B cells make antibodies Histamine Antibodies attach to mast cell Sensitization: Initial exposure to allergen Allergen binds to antibodies on mast cell Histamine is released, causing allergy symptoms Later exposure to same allergen