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Chapter 15

Chapter 15. Immune System. 15-1. Chapter 15 Outline Innate Immunity Adaptive Immunity Complement System T Cells Histocompatibility Antigens Interactions Between Antigen-Presenting Cells & Lymphocytes Active Immunity Passive Immunity Immune System & Cancer

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Chapter 15

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  1. Chapter 15 Immune System 15-1

  2. Chapter 15 Outline • Innate Immunity • Adaptive Immunity • Complement System • T Cells • Histocompatibility Antigens • Interactions Between Antigen-Presenting Cells & Lymphocytes • Active Immunity • Passive Immunity • Immune System & Cancer • Diseases Caused By Immune System 15-2

  3. Defense Mechanisms • Against pathogens constitute the immune system • Can be grouped into 2 categories: • Innate (nonspecific) immunity is inherited as part of structure of each organism • Adaptive (specific) immunity is a function of lymphocytes & changes with exposure 15-3

  4. Innate Immunity 15-4

  5. Innate Immunity • Is 1st line of defense against invading pathogens • Includes epithelial barriers, high acidity of gastric juice, phagocytosis, & fever 15-5

  6. Phagocytosis • Is triggered in response to pathogen-associated molecular patterns (PAMPs) produced only by microorganisms • Best known are lipopolysaccharide (LPS) from gram-bacteria & peptidoglycan from gram+s 15-6

  7. Phagocytosis continued • Is performed by 3 classes of phagocytic cells: • Neutrophils - 1st to arrive at infection sites • Mononuclear phagocytes - macrophages & monocytes • Organ-specific phagocytes in liver, spleen, lymph nodes, lungs, & brain • Fixed phagocytes line sinusoids of liver, spleen, & lymph nodes & remove pathogens 15-7

  8. Phagocytosis continued • Connective tissue & blood contain mobile leukocytes (WBCs) • These are attracted to infection (chemotaxis) by chemokines • WBCs from blood exit capillaries by extravasation (diapedesis) & ingest pathogens Fig 15.1 15-8

  9. Phagocytosis continued • Pseudopods from phagocyte surround pathogen • Forming a vacuole • Vacuole fuses with lysosomes which digest pathogen Fig 15.2 15-9

  10. Fever • Appears to be component of innate immunity • Occurs when hypothalamic thermostat is reset upwards by IL1- & other cytokines (endogenous pyrogens) • Pyrogens are released by WBCs in response to endotoxin from gram– bacteria 15-10

  11. Interferons • Are polypeptides produced by cells infected with virus that provide short-acting, non-specific resistance to viral infection in nearby cells • 3 types: a, b, g, interferon 15-11

  12. Fig 15.3 15-12

  13. 15-13

  14. Adaptive Immunity 15-14

  15. Adaptive Immunity • Is acquired ability to defend against specific pathogens by prior exposure to those pathogens • Is mediated by production of specific antibodies by lymphocytes 15-15

  16. Antigens • Are molecules that elicit production of antibodies that specifically bind those antigens • Are usually large molecules that are foreign to the body • Immune system can distinguish “self” molecules from non-self antigens • Normally makes antibodies only against non-self antigens • Large, complex molecules can have a number of antigenic determinant sites (different sites that stimulate production of, & bind to, different antibodies) 15-16

  17. Haptens • Are small non-antigenic molecules that become antigens when bound to proteins (form an antigenic determinant site) • Useful for creating antibodies for research and diagnosis 15-17

  18. Immunoassays • Are tests that use specific antibodies to identify a particular antigen • The binding of antibody to antigen causes clumping (agglutination) which can be visualized Fig 15.4 15-18

  19. Lymphocytes • Are derived from stem cells in bone marrow • Which replace selves by cell division so are not depleted • Lymphocytes produced by this process seed thymus, spleen, & lymph nodes with self-replacing colonies 15-19

  20. T Lymphocytes (T cells) • Develop from lymphocytes that seed thymus • Do not secrete antibodies • Attack infected host cells, cancer cells, & foreign cells • Thus they provide cell-mediated immunity • Supply 65 – 85% of lymphocytes for blood & most of lymphocytes in germinal centers of lymph nodes & spleen 15-20

  21. B Lymphocytes (B cells) • Fight bacterial infections by secreting antibodies into blood & lymph • Thus provide humoral immunity 15-21

  22. Thymus • Is located below the thyroid gland • Grows during childhood, gradually regresses after puberty • Contains T cells that supply other tissues • T cells can be depleted, e.g. by AIDs or chemotherapy • These can only be replenished up to late childhood • After that, repopulation is accomplished by production in secondary lymphoid organs 15-22

  23. Secondary Lymphoid Organs • Consist of lymph nodes, spleen, tonsils, & Peyer’s patches • Located in areas where antigens could gain entry to blood or lymph • Lymphocytes migrate constantly through blood & lymph from one lymphoid organ to another • Enhances chance that antibody will encounter its antigen • Spleen filters blood; other lymphoid organs filter lymph 15-23

  24. Local Inflammation • Occurs when bacteria enter a break in the skin • Inflammatory reaction is initiated by nonspecific mechanisms of phagocytosis & complement activation • Complement activation attracts phagocytes to area 15-24

  25. Local Inflammation continued • As inflammation progresses, B cells produce antibodies against bacterial antigens • Attachment of antibodies to antigens amplifies nonspecific responses because of complement activation • & promotes phagocytic activity of neutrophils, macrophages, & monocytes (= opsinization) 15-25

  26. Local Inflammation continued • In inflamed area, leukocytes attach to surface of endothelial cells • Move by chemotaxis to inflamed site • Neutrophils arrive 1st, then monocytes, then T cells • Undergo extravasation Fig 15.6 15-26

  27. Local Inflammation continued Fig 15.5 • Mast cells secrete heparin, histamine, prostaglandins, leukotrienes, cytokines, & TNF-a • These produce redness, warmth, swelling, pus, & pain • Recruit more leukocytes • If infection continues, endogenous pyrogens are released 15-27

  28. B Lymphocytes (B cells) • Have antibodies on surface that are receptors for antigens • When bound to antigen, are stimulated to divide & secrete antibodies Fig 15.8 15-28

  29. B Lymphocytes (B cells) • When B cells divide, some progeny become memory cells • Some become plasma cells that produce about 2000 antibodies/sec that are specific for original antigen • This provides active immunity Fig 15.7 15-29

  30. B Lymphocytes (B cells) • Binding of B cells to antigen also triggers a cascade of reactions that activate complement proteins • Complement proteins can kill antigen-bearing cells & promote phagocytosis 15-30

  31. Antibodies • Are proteins called immunoglobulins • Part of gamma globulin class of plasma proteins • Antibodies have same basic structure but their differences provide for antibody specificity 15-31

  32. 15-32

  33. Antibody Structure • Is in shape of “Y” • 2 long heavy (H) chains are joined to 2 shorter light (L) chains • When cleaved, stalk of Y becomes crystallizable fragment (Fc) • Fc is constant among different antibodies • Arms of Y contain antigen-binding fragment (Fab) • Fab contains a variable region that confers antibody specifity Fig 15.10 15-33

  34. Antibody Diversity • Each person has about 1020 antibody molecules • With a few million different specificities • Likely there is an antibody specific for any antigen a person might encounter • 2 mechanisms might account for diversity • If a few hundred genes code for Hs & a few hundred for Ls, different combinations of these could lead to millions of different antibodies • Mutations could increase diversity, especially with age 15-34

  35. Complement System 15-35

  36. The Complement System • Is part of nonspecific defense system • Activity is triggered by binding of antibodies to antigens (classic pathway) & by bacterial coat polysaccharides (alternative pathway) • Binding of antibodies to antigens does not by itself destroy antigens or pathogens • Antibodies label targets for complement system attack & also stimulate opsonization 15-36

  37. T Cells 15-42

  38. Killer or Cytotoxic T Cells • Carry CD8 cell surface marker • Destroy body cells that possess foreign antigens • Usually from a pathogen, but can be from malignancy or self cells never seen by immune system • Kill by cell-mediated destruction • That is, must be in contact with victim cell • Kill by secreting perforins which create a pore in victim's membrane & cause lysis • Also secrete granzymes which cause destruction of victim's DNA 15-43

  39. Helper & Suppressor T Cells Fig 15.14 • Helper Ts carry CD4 surface marker • Indirectly participate by enhancing responses of both killer T cells & B cells • Suppressor Ts decrease responses of killer Ts & B cells 15-44

  40. Lymphokines • Are cytokines secreted by lymphocytes • Usually called interleukin-1, 2, 3 . . . or IL-1, IL-2 . . . 15-45

  41. T Cell Receptor Proteins • Only protein antigens are recognized by most T cells • T cell receptors cannot bind to free antigens • T cells respond to foreign antigens when they are presented on surface of antigen-presenting cells • Chief antigen presenting cells are macrophages & dendritic cells 15-46

  42. Histocompatibility Antigens 15-47

  43. Dendritic Cells • Originate in marrow, then migrate to most tissues • Prominent where pathogens might enter body • Engulf protein antigens, partially digest them, & display polypeptide fragments on surface for T cells to "see" 15-48

  44. Dendritic Cells continued • Fragments are associated on surface with histocompatibility antigens which are necessary to activate Ts • To increase chance of interacting with correct T cells, dendritics migrate to secondary lymphoid organs • Where secrete chemokines to attract Ts Fig 15.15 15-49

  45. Histocompatibility Antigens • Are on surface of all body's cells except mature RBCs • Also called human leukocyte antigens (HLAs) • Are coded for by group of 4 genes on chromosome 6 called major histocompatibility complex (MHC) • 4 genes have multiple alleles creating many possible MHC types 15-50

  46. MHC • MHC genes produce 2 types of cell surface molecules: class-1 & class-2 • Class-1s are made by all cells except RBCs • Class-2s are made only by antigen-presenting cells & B cells • These present class-2s together with foreign antigen to helper Ts • This is only way to activate helper Ts so they can promote B cell activity 15-51

  47. MHC continued • In order for killer & helper Ts to function they require co-presentation of antigen with a specific MHC marker • Killer Ts are activated to kill victim cell only by co-presentation of antigen & class-1 marker • Helper Ts require antigen & class-2 marker 15-52

  48. MHC continued • Co-presentation requirement comes from presence of different coreceptors on killer & helper T cells • Killer T coreceptor CD8 interacts only with class-1s • Helper T coreceptor CD4 interacts only with class-2s Fig 15.16 15-53

  49. Interactions Between Antigen Presenting Cells & Lymphocytes 15-54

  50. T Cell Response to a Virus • When virus infects body it is phagocytized by macrophage or dendritic cell • Its partially-digested polypeptide fragments are antigens that are displayed on surface • Form a complex with class-2 MHC molecules that macrophages present to helper T cells • Helper Ts bind & are activated • Can now promote B cell activity 15-55

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