1 / 76

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

ondrea
Download Presentation

Chapter 15

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related