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Chapter 43

Chapter 43. The Body’s Defenses (The Immune System). Reconnaissance , Recognition, and Response. The immune system recognizes foreign bodies and responds with the production of immune cells and proteins.

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Chapter 43

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  1. Chapter 43 The Body’s Defenses (The Immune System)

  2. Reconnaissance, Recognition, and Response • The immune system recognizes foreign bodies and responds with the production of immune cells and proteins

  3. Innate immunity- is present before any exposure to pathogens and is a nonspecific responses to pathogens and consists of external barriers plus internal cellular and chemical defenses

  4. Acquired immunity- develops after exposure to agents such as microbes, toxins, or other foreign substances. It involves a very specific response to pathogens

  5. 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

  6. Innate Immunity-Barrier Defenses • Include the skin and mucous membranes of the respiratory, urinary, and reproductive tracts • Mucus traps and allows for the removal of microbes • The low pH of skin and the digestive system prevents growth of microbes

  7. Innate Immunity-Cellular Innate Defenses • White blood cells (leukocytes) engulf pathogens in the body • A white blood cell engulfs a microbe, then fuses with a lysosome to destroy the microbe • Macrophages are part of the lymphatic system and are found throughout the body

  8. Types of white blood cells: • Neutrophil • Eosinophil • Basophil • Lymphocyte(natural-killer cells, T cells, B cells) • Monocytes • Macrophages • Dendritic cells

  9. Interstitial fluid Adenoid Tonsil Blood capillary Lymph nodes Spleen Lymphatic vessel Tissue cells Peyer’s patches (small intestine) Appendix Lymphatic vessels Lymph node Masses of defensive cells

  10. Innate Immunity-Antimicrobial Proteins • Attack microbes directly or impede their reproduction • Interferon proteinsprovide defense against viruses and helps activate macrophages

  11. Innate Immunity-Inflammatory Responses • Following an injury, mast cells release histamine,which promotes changes in blood vessels; this is part of the inflammatory response Pathogen Splinter Chemical signals Macrophage Mast cell Capillary Red blood cells Phagocytic cell

  12. Innate Immunity-Inflammatory Responses • Increases local blood supply and allow more phagocytes and antimicrobial proteins to enter tissues Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Red blood cells Phagocytic cell

  13. Innate Immunity-Inflammatory Responses • Pus- a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Phagocytosis Red blood cells Phagocytic cell

  14. Innate Immunity-Natural Killer Cells • All cells in the body (except red blood cells) have a class 1 MHC (major histocompatibility) protein on their surface • Cancerous or infected cells no longer express this protein; natural killer (NK) cells attack these damaged cells, causing them to lyse

  15. Innate Immune System Evasion by Pathogens • Some pathogens avoid destruction by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis • Example: Tuberculosis (TB), kills more than a million people a year

  16. Acquired immunity, lymphocyte receptors provide pathogen-specific recognition • White blood cells (lymphocytes) recognize and respond to antigens, foreign molecules • Lymphocytes that mature in the thymus are called T cells,and those that mature in bone marrow are called B cells

  17. Lymphocytes have an enhanced response to a foreign molecule encountered previously • B cells and T cells have receptor proteins that can bind to foreign molecules • Each individual lymphocyte is specialized to recognize a specific type of molecule

  18. Cytokines are secreted by macrophages and dendritic cells to recruit and activate lymphocytes

  19. Antigen Recognition by Lymphocytes • A single B cell or T cell has about 100,000 identical antigen receptors 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

  20. 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

  21. 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

  22. All antigen receptors on a single lymphocyte recognize the same epitope, or antigenic determinant, on an antigen Antigen- binding sites Epitopes (antigenic determinants) Antigen-binding sites Antigen Antibody A Antibody C V V V V C C C C Antibody B

  23. B cells give rise to plasma cells,which secrete proteins called antibodies or immunoglobulins Antigen- binding sites Epitopes (antigenic determinants) Antigen-binding sites Antigen Antibody A Antibody C V V V V C C C C Antibody B

  24. Antigen- binding site Antigen- binding site • B cell receptors bind to specific, intact antigens 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

  25. Antigen- binding site Antigen- binding site • Secreted antibodies (immunoglobulins) are free floating B cell receptors 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

  26. Antigen- binding site • T cells can bind to an antigen that is free or on the surface of a pathogen molecules 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

  27. Antigen- binding site • T cells bind to antigen fragments presented on a host cell-surface proteins- MHC 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

  28. The Role of the MHC • In infected cells, MHC molecules bind and transport antigen fragments 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

  29. Class I MHC molecules- display peptide antigens to cytotoxic T cells Top view: binding surface exposed to antigen receptors Antigen Class I MHC molecule Antigen Plasma membrane of infected cell

  30. Class II MHC molecules- located on dendritic cells, macrophages, and B cells. These are antigen-presenting cells that display antigens to cytotoxic T cells and helper T cells 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

  31. Lymphocyte Development Origin of Self-Tolerance • As lymphocytes mature in bone marrow or the thymus, they are tested for self-reactivity and destroyed if they test positive Amplifying Lymphocytes by Clonal Selection • The binding of a lymphocyte to an antigen induces the lymphocyte to divide rapidly- clonal selection • Two types of clones are produced: short-lived activated effector cells and long-lived memory cells

  32. Antigen molecules B cells that differ in antigen specificity Antigen receptor Antibody molecules Clone of memory cells Clone of plasma cells

  33. Primary vs Secondary immune response • The first exposure to a specific antigen represents the primary immune response • During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms • In the secondary immune response, memory cells facilitate a faster, more efficient response Animation: Role of B Cells

  34. Primary immune response to antigen A produces antibodies to A. Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B. 104 103 Antibody concentration (arbitrary units) Antibodies to A Antibodies to B 102 101 100 0 7 14 21 28 35 42 49 56 Exposure to antigen A Exposure to antigens A and B Time (days)

  35. Acquired immunity defends against infection of body cells and fluids • Humoral immune response (extracellular pathogens) involves activation and clonal selection of B cells, resulting in production of secreted antibodies • Cell-mediated immune response (intercellular pathogens and cancer) involves activation and clonal selection of cytotoxic T cells • Helper T cells aid both responses

  36. 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.

  37. 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

  38. 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

  39. Cytotoxic T Cells: A Response to Infected Cells • Cytotoxic T cells are the effector cells in cell-mediated immune response • 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 Animation: Cytotoxic T Cells

  40. Released cytotoxic T cell Cytotoxic T cell Perforin Granzymes CD8 TCR Dying target cell Class I MHC molecule Pore Target cell Peptide antigen

  41. B Cells: A Response to Extracellular Pathogens • The humoral response is characterized by secretion of antibodies by B cells • 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

  42. Bacterium Antigen-presenting cell Peptide antigen B cell Class II MHC molecule Clone of plasma cells Secreted antibody molecules + TCR CD4 Cytokines Endoplasmic reticulum of plasma cell Activated helper T cell Helper T cell Clone of memory B cells 2 µm

  43. 5 Antibody Classes • Polyclonal antibodies are the products of many different clones of B cells following exposure to a microbial antigen • Monoclonal antibodies are prepared from a single clone of B cells grown in culture

  44. Class of Immuno- globulin (Antibody) Distribution Function First Ig class produced after initial exposure to antigen; then its concentration in the blood declines Promotes neutraliza- tion and cross- linking of antigens; very effective in complement system activation IgM (pentamer) J chain

  45. Class of Immuno- globulin (Antibody) Distribution Function IgG (monomer) Most abundant Ig class in blood; also present in tissue fluids Promotes opsoniza- tion, neutralization, and cross-linking of antigens; less effec- tive in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus

  46. Class of Immuno- globulin (Antibody) Distribution Function IgA (dimer) Present in secretions such as tears, saliva, mucus, and breast milk Provides localized defense of mucous membranes by cross-linking and neutralization of antigens J chain Presence in breast milk confers passive immunity on nursing infant Secretory component

  47. Class of Immuno- globulin (Antibody) Distribution Function IgE (monomer) Present in blood at low concen- trations Triggers release from mast cells and basophils of hista- mine and other chemicals that cause allergic reactions

  48. Class of Immuno- globulin (Antibody) Distribution Function IgD (monomer) Present primarily on surface of B cells that have not been exposed to antigens Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection) Trans- membrane region

  49. The Role of Antibodies in Immunity • Neutralization- a pathogen can no longer infect a host because it is bound to an antibody • Agglutination- clumping of bound antibodies to antigens increase phagocytosis • Complement system- antibodies and proteins generate a membrane attack to lyse a cell Animation: Antibodies

  50. Viral neutralization Virus

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