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Chapter 43: Internal Defense

Chapter 43: Internal Defense. Immune Response – fight antigens. Nonspecific (innate)– general Specific (adaptive or acquired) – tailor made Antibodies. Fig. 43-2. Pathogens (microorganisms and viruses). Barrier defenses: Skin Mucous membranes Secretions. INNATE IMMUNITY. •.

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Chapter 43: Internal Defense

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  1. Chapter 43: Internal Defense

  2. Immune Response – fight antigens • Nonspecific (innate)– general • Specific (adaptive or acquired) – tailor made • Antibodies

  3. Fig. 43-2 Pathogens (microorganisms and viruses) Barrier defenses: Skin Mucous membranes Secretions INNATE IMMUNITY • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells • Rapid response Humoral response: Antibodies defend against infection in body fluids. ACQUIRED IMMUNITY • Recognition of traits specific to particular pathogens, using a vast array of receptors Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells. • Slower response

  4. Nonspecific defense • Skin • Mucus membranes • Acid secretions / enzymes of stomach • Hairs in nose • Phagocytes

  5. Cytokines – signaling molecules • Interferons • Interleukins • Tumor necrosis factors

  6. Interferons • Secreted by cells infected with viruses, parasites • Produced by macrophages • Type I interferons • Inhibit viral replication • Viruses exposed to Type I interferon can’t infect other cells as well • Activate natural killer cells • Type II interferons • Specific immune system • Enhance activities of other immune cells • Stimulate macrophages to destroy tumor cells and virus-infected cells

  7. Interleukins • Secreted by macrophages and lymphocytes • Regulate actions between lymphocytes and other body cells • Interleukin-1 can reset body’s thermostat in hypothalamus resulting in fever

  8. Tumor necrosis factors (TNFs) • Secreted by macrophages and lymphocytes • Stimulate immune cells for inflammation • Kill tumor cells

  9. Complement system • Complements actions of other defenses • 20+ proteins in body fluids • Inactive until body exposed to antigen • Sometimes activated directly OR by binding of antigen to antibody • Nonspecific • 4 actions: • Lyse pathogen cell wall • Coat pathogen (phagocytes can work more easily) • Attract WBCs to infected site • Increase inflammation by stimulating release of histamine

  10. Phagocytosis • Nonspecific • Phagocytes = • neutrophils (~20 bacteria) • Macrophages (~100 bacteria) • Endocytosis

  11. Fig. 43-3 Microbes PHAGOCYTIC CELL Vacuole Lysosome containing enzymes

  12. Natural Killer (NK) Cells • Large, granular lymphocytes • Bone marrow • Nonspecific and specific • Release cytokines and enzymes to destroy target cells

  13. Inflammation • Heat, redness, edema, pain • Regulated by plasma proteins, cytokines, platelet substances, basophils, mast cells • Blood vessels dilate • Increase capillary permeability • Increase blood flow – lots neutrophils, phagocytes, platelets, basophils, mast cells to infected area • Mast cells release histamine, serotonin • Increase blood flow  skin warm, appears red • Phagocytes go out of capillaries to infected tissue (phagocytosis)

  14. Edema – fluid and antibodies leave circulation to enter tissues • Swelling = increased volume of fluid in area • Pain – from edema and action of enzymes in plasma

  15. Fig. 43-8-3 Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Phagocytosis Red blood cells Phagocytic cell

  16. Fever • Body’s thermostat in hypothalamus reset • Higher temp. interferes with growth and replication of some pathogens • Lysosomes break down, destroying cells infected by viruses • Increased temp. promotes T cell activity and production of antibodies • Increased phagocytosis

  17. Specific immune response • 2 types • Antibody-mediated immunity • Cell-mediated immunity

  18. Fig. 43-16 Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure) Stimulates Gives rise to + Engulfed by Antigen- presenting cell + + + B cell Helper T cell Cytotoxic T cell + + Memory Helper T cells + + + Antigen (2nd exposure) Memory Cytotoxic T cells Active Cytotoxic T cells + Plasma cells Memory B cells Secreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells.

  19. Lymphocytes • 3 types: • T cells • B Cells • NK cells

  20. Natural Killer cells • Kill virally infected and tumor cells

  21. B cells • Antibody-mediated immunity • Mature into plasma cells (produce specific antibodies) • Encode a receptor that binds to a specific antigen • B cell receptors bind to antigen  B cell activated • Divides rapidly  differentiate into plasma cells which produce antibody • Antibody binds to antigen that originally activated B cells

  22. Some become memory B cells • Continue to make small amounts of antibody after infection has been overcome

  23. Fig. 43-19-3 Bacterium Antigen-presenting cell Peptide antigen B cell Class II MHC molecule Secreted antibody molecules Clone of plasma cells + TCR CD4 Cytokines Activated helper T cell Helper T cell Clone of memory B cells

  24. Fig. 43-14 Antigen molecules B cells that differ in antigen specificity Antigen receptor Antibody molecules Clone of memory cells Clone of plasma cells

  25. Role of B Cells Animation

  26. T cells • Cell-mediated immunity • “T” = thymus-derived • Thymus make T cells immunocompetent • In thymus – cells divided many times, develop specific surface proteins with distinctive receptor sites • Attack body cells infected by invading pathogens, foreign cells, cancer cells

  27. T cell antigen receptor (TCR) • Distinguishes T cells • Allows T cells to recognize specific antigens • 2 main types • CD8 T cells (surface marker CD8) • Cytotoxic T cells (killer T cells) • Recognize/destroy foreign antigens • Targets virus-infected cells, cancer cells, foreign tissue grafts • Kill by releasing variety of cytokines and enzymes to lyse cells

  28. Fig. 43-18-3 Released cytotoxic T cell Cytotoxic T cell Perforin Granzymes CD8 TCR Dying target cell Class I MHC molecule Pore Target cell Peptide antigen

  29. CD4 T cells (surface marker CD4) • Helper T cells • Secrete substances that activate or enhance immune responses • 2 subsets • T helper 1 – cell-mediated • T helper 2 – antibody- mediated : stimulate B cells divided and produce antibodies

  30. Fig. 43-17 Antigen- presenting cell Peptide antigen Bacterium Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell + Cytokines Humoral immunity (secretion of antibodies by plasma cells) + Cell-mediated immunity (attack on infected cells) + + B cell Cytotoxic T cell

  31. Fig. 43-12 Microbe Antigen- presenting cell Infected cell Antigen associates with MHC molecule 1 Antigen fragment Antigen fragment 1 1 Class I MHC molecule Class II MHC molecule 2 2 T cell receptor T cell receptor 2 T cell recognizes combination (a) Cytotoxic T cell (b) Helper T cell

  32. Major Histocompatibility complex • MHC antigens – cell surface proteins • Help vertebrates distinguish self vs. nonself • Coded for by set of closely linked genes = Major histocompatibility complex (MHC) • Humans MHC = HLA (human leukocyte antigen) • Polymorphic • Many combination  not likely for people to have same combo (except identical twins)

  33. Antibody-mediated Immunity • (humoral immunity) • B cells responsible • Produce surface receptors • Bind to particular antigen • B cell activates

  34. Foreign antigen displayed on immune cell surface • Contacts helper T cell (has complementary receptors) • Macrophage secretes IL-1 – activated helper T cells • (T cells do not recognize an antigen presented alone) • Antibody receptor of B cell binds with complementary antigen

  35. Inside B cell – antigen degraded  peptide fragments • B cells display fragments on surface • Activated helper T binds with B cells • Activated helper T releases interleukins which, with antigen, activate B cell • B cell increases in size  mitosis • Each new cells makes antibodies specific to antigen from original B cell

  36. Some cells of B cell clone  plasma cells • Secrete antibody specific to antigen • Plasma cells do not leave lymph nodes • Antibodies can pass out of lymph tissue to infected area

  37. Some B cells  memory B cells • Live and make antibody after infection gone • Same pathogen enters later  circulating antibody targets it for destruction • Same time  memory cells divided  plasma cells

  38. Helper T Cell Activation

  39. Fig. 43-9 Antigen- binding site Antigen- binding site Antigen- binding site Disulfide bridge V V V V Variable regions V V C C Constant regions C C C C Light chain Transmembrane region Plasma membrane  chain  chain Heavy chains Disulfide bridge B cell Cytoplasm of B cell Cytoplasm of T cell T cell (a) B cell receptor (b) T cell receptor

  40. Fig. 43-9a Antigen- binding site Antigen- binding site Disulfide bridge V V V V Variable regions C C Constant regions C C Light chain Transmembrane region Plasma membrane Heavy chains B cell Cytoplasm of B cell (a) B cell receptor

  41. Fig. 43-9b Antigen- binding site Variable regions V V Constant regions C C Transmembrane region Plasma membrane  chain  chain Disulfide bridge Cytoplasm of T cell T cell (b) T cell receptor

  42. Antibodies • (immunoglobulin, Ig) • 2 main functions • Combines with antigen • Activate processes to destroy antigen • Labels antigen for destruction • Doesn’t destroy antigen directly

  43. Structure of Antibody • 4 polypeptide chains • 2 identical long chains  heavy chains • 2 identical short chains  light chains • Can bind with different affinities • During immune response, higher affinity antibodies are made

  44. Antigenic determinant • Give antigen specific shape to be recognized by antibody • Usually antigen has many different antigenic determinants • Many antibodies can bind to antigen

  45. Fig. 43-10 Antigen- binding sites Epitopes (antigenic determinants) Antigen-binding sites Antigen Antibody A Antibody C V V V V C C C C Antibody B

  46. 5 Classes of Antibodies • Unique AA sequences in heavy chain • 1. IgG – human ~ 75% • Gamma globulin fraction of plasma • Interact with macrophages, activate complement system • 2. IgM • Interact with macrophages, activate complement system • Defend against pathogens in blood

  47. 3. IgA • Mucus, tears, saliva, milk • Body openings • 4. IgD • Low concentration in plasma • Helps activate B cells after antigen binding • 5. IgE • Low concentration in plasma • Can bind to mast cells, cells with histamine (allergy) • Parasitic worms

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