Immunologyoverview
Dendritic cellA hairy person (or someone whodoesn’t mind being hairy)
Dendritic cell• Hairy projections• Eats bugs• Presents antigens
Natural killer cellAn indiscriminate bully
Natural killer cell (top) killing infected cell (bottom)Natural killer cell• A brute• Indiscriminate killer• Part of innat...
Helper T cellA person who is always helpful
Helper T cell• Helps other cells dotheir jobs• Recognizes MHC II• Part of adaptiveimmunity
Cytotoxic T cellA highly trained, expert killer
Cytotoxic T cell• Deadly, accurate killer• Recognizes MHC I• Part of adaptive immunesystem
B cellAn extremely productive person
B cell• Turns into plasma cell• Makes antibodies• Part of adaptive immunesystem
MacrophageSomeone who likes to eat
Macrophage• Eats bugs• Presents antigen• Part of adaptive immunesystem
NeutrophilSomeone filled with toxic chemicals
Neutrophil• Eats stuff• Releases toxic stuff• Part of adaptive immunesystem
Infected cellA sick person
Infected cell• Virus laden• Expresses MHC I• Gets killed by cytotoxic Tcell
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immu...
Immunology Overview• Definitions
Definitions• Immunity = protection against infections• Immune system = collection of cells and moleculesthat defend us aga...
Innate (Natural) Immunity• Always present (innate); doesn’t change over time• First line of defense when bugs come• Major ...
Adaptive (Acquired) Immunity• Second line of defense• More specific (adaptive) and powerful than innate• Major components:...
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells
White Blood Cell Development
White blood cells
Immunology Overview• Definitions• Cells• Lymphocytes
Lymphocytes• Present in lymphoid organs and in blood• Groups• T-lymphocytes (grow up in thymus)• B-lymphocytes (grow up in...
Lymphocyte (could be B cell or T cell!)
Lymphoid tissues• Lymphocytes grow up in primary organs, thentravel to secondary organs, searching forantigens.• Primary o...
Lymph nodeInterfollicular area (brown)Follicle
T-Lymphocytes• Live in blood, bone marrow, lymphoid tissues• Two basic functions:• kill stuff• help other cells do their j...
The T-Cell Receptor
The T-Cell Receptor Bound to AntigenAntigen-presenting cellT cell
T-Lymphocytes• Helper T cells• CD4+ (and CD8-)• help B cells make antibodies• help macrophages eat bugs• Cytotoxic T cells...
Helper T cell Cytotoxic T cell
Cytotoxic T cells surrounding tumor cell
MHC• Collection of genes on chromosome 6• Three regions: class I, class II, class III• Highly polymorphic!• Gene products:...
class I MHC moleculeclass II MHC moleculeclass II MHC genes class I MHC genesclass III MHC genes
MHC• Encoded by three loci: HLA-A, HLA-B, HLA-C• Display antigens from within the cell(e.g., viral antigens) to CD8+ T cel...
MHC• Encoded by three loci: HLA-DP, HLA-DQ, HLA-DR• Display extracellular antigens (e.g., bacterialantigens the cell has e...
B-Lymphocytes• Live in blood, bone marrow, lymphoid tissues• Basic function: make antibodies (immunoglobulins)• B-cell rec...
The B-Cell Receptor
The B-Cell Receptor Bound to AntigenB cell
Natural Killer Cells• Belong to innate immunity arm• No highly variable receptors like T and B cells• Main job: recognize ...
Natural killer cell
Natural killer cell (top) killing infected cell (bottom)
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells
Antigen-presenting cells• Main job: catch antigens and display them to lymphocytes• Dendritic cells• Have fine cytoplasmic...
Dendritic cell surrounded by lymphocytes
Dendritic cell (right) talking to lymphocyte (left)
Dendritic cell (orange) talking to T lymphocytes (green)
MacrophageMonocyte
Macrophage reaching for bacterium
Macrophage gorging on bacteria
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells
Effector cells• These guys carry out the ultimate immunesystem task: eliminate infection• Types of effector cells• NK cell...
Plasma cell
Neutrophil
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immu...
The Innate Immune Response• Main bug barriers: skin, mucosa• If bugs make it through epithelium, theyencounter innate immu...
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immu...
Capturing and displaying antigens• Dendritic cells in epithelium capture bug antigens,transport them to lymph nodes• APCs ...
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immu...
Cell-Mediated ImmunityHumoral Immunity
Cell-Mediated ImmunityHumoral Immunity
Cell-mediated immunity• Naïve T cells are activated by antigen andcostimulators in lymph nodes…• …then they proliferate an...
Cell-mediated immunity• Polypeptides that do lots of different things:• help leukocytes grow and differentiate• activate T...
Cell-mediated immunity• CD4+ T cells differentiate into two kinds of effector cells:• TH1 cells (activate macrophages, cau...
Cell-Mediated Immunity
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immu...
Cell-Mediated ImmunityHumoral Immunity
• B cells get activated by exposure to antigens(sometimes with the help of CD4+ T cells)• B cells differentiate into plasm...
• Y-shaped glycoprotein• 2 light chains (κ or λ)• 2 heavy chains (α, γ, δ, ε, or μ)• Constant regions of heavy chain form ...
• Bind to – and “neutralize” – bugs, so they can’tinfect cells.• Coat (“opsonize”) bugs, making them yummy tomacrophages a...
What is complement?Just give me the bottom line.Humoral immunity• It’s a bunch of proteins that poke holes in cells.
Okay, give me a little more information.Humoral immunity• Consists of about 20 plasma proteins (C1, C2, etc.)• Can be acti...
Complement, ridiculously oversimplified
Humoral Immunity
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immu...
Immunologic memory• Most effector lymphocytes die after killing the bug.• A few memory cells live on for years.• expanded ...
Summary of the Adaptive Immune Response
Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immu...
Innate immunity1. Dendritic cell eats bugs
Innate immunity1. Dendritic cell eats bugs• Displays antigen to naïve T cells (which MHC?)
Innate immunity1. Dendritic cell eats bugs• Displays antigen to naïve T cells (which MHC?)• T cells mature (put on costume...
Innate immunity1. Dendritic cell eats bugs• Displays antigen to naïve T cells (which MHC?)• T cells mature (put on costume...
Innate immunity1. Dendritic cell eats bugs• Displays antigen to naïve T cells (which MHC?)• T cells mature (put on costume...
Adaptive immunity: Cell-mediated1. Helper T cell does stuff
Adaptive immunity: Cell-mediated1. Helper T cell does stuff• Tells macrophage to eat bugs
Adaptive immunity: Cell-mediated1. Helper T cell does stuff• Tells macrophage to eat bugs• Tells B cell to make antibodies
Adaptive immunity: Cell-mediated1. Helper T cell does stuff• Tells macrophage to eat bugs• Tells B cell to make antibodies...
Adaptive immunity: Cell-mediated1. Helper T cell does stuff• Tells macrophage to eat bugs• Tells B cell to make antibodies...
Adaptive immunity: Humoral1. B cell makes antibodies, which coat bugs• “Neutralizes” bugs• Opsonizes bugs (yummy for who?)
Immunology overview
Immunology overview
Immunology overview
Immunology overview
Immunology overview
Immunology overview
Immunology overview
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Immunology overview

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Immunology overview

  1. 1. Immunologyoverview
  2. 2. Dendritic cellA hairy person (or someone whodoesn’t mind being hairy)
  3. 3. Dendritic cell• Hairy projections• Eats bugs• Presents antigens
  4. 4. Natural killer cellAn indiscriminate bully
  5. 5. Natural killer cell (top) killing infected cell (bottom)Natural killer cell• A brute• Indiscriminate killer• Part of innate immunesystem
  6. 6. Helper T cellA person who is always helpful
  7. 7. Helper T cell• Helps other cells dotheir jobs• Recognizes MHC II• Part of adaptiveimmunity
  8. 8. Cytotoxic T cellA highly trained, expert killer
  9. 9. Cytotoxic T cell• Deadly, accurate killer• Recognizes MHC I• Part of adaptive immunesystem
  10. 10. B cellAn extremely productive person
  11. 11. B cell• Turns into plasma cell• Makes antibodies• Part of adaptive immunesystem
  12. 12. MacrophageSomeone who likes to eat
  13. 13. Macrophage• Eats bugs• Presents antigen• Part of adaptive immunesystem
  14. 14. NeutrophilSomeone filled with toxic chemicals
  15. 15. Neutrophil• Eats stuff• Releases toxic stuff• Part of adaptive immunesystem
  16. 16. Infected cellA sick person
  17. 17. Infected cell• Virus laden• Expresses MHC I• Gets killed by cytotoxic Tcell
  18. 18. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory
  19. 19. Immunology Overview• Definitions
  20. 20. Definitions• Immunity = protection against infections• Immune system = collection of cells and moleculesthat defend us against microbes• Immune deficiencies → infections• Immune excesses → autoimmune diseases
  21. 21. Innate (Natural) Immunity• Always present (innate); doesn’t change over time• First line of defense when bugs come• Major components:• Epithelial barriers (skin, GI, respiratory)• NK cells• Complement
  22. 22. Adaptive (Acquired) Immunity• Second line of defense• More specific (adaptive) and powerful than innate• Major components:• Lymphocytes• Lymphocyte products• Two types of adaptive immunity:• Humoral immunity (mediated by antibodies)• Cellular immunity (mediated by T cells)
  23. 23. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells
  24. 24. White Blood Cell Development
  25. 25. White blood cells
  26. 26. Immunology Overview• Definitions• Cells• Lymphocytes
  27. 27. Lymphocytes• Present in lymphoid organs and in blood• Groups• T-lymphocytes (grow up in thymus)• B-lymphocytes (grow up in bone marrow)• Each one has receptors for a specific antigen• Recognize millions of different antigens!• Diversity generated by:• rearrangement of antigen receptor genes• different joining of the gene segments• Gene rearrangement studies
  28. 28. Lymphocyte (could be B cell or T cell!)
  29. 29. Lymphoid tissues• Lymphocytes grow up in primary organs, thentravel to secondary organs, searching forantigens.• Primary organs• thymus• bone marrow• Secondary organs• lymph nodes• spleen• mucosal and cutaneous lymphoid tissues
  30. 30. Lymph nodeInterfollicular area (brown)Follicle
  31. 31. T-Lymphocytes• Live in blood, bone marrow, lymphoid tissues• Two basic functions:• kill stuff• help other cells do their jobs• T-cell receptor (TCR) complex recognizes antigens• binds antigen• sends signals to the T cell• Antigens must be:• displayed by other cells…• …AND bound to an MHC receptor
  32. 32. The T-Cell Receptor
  33. 33. The T-Cell Receptor Bound to AntigenAntigen-presenting cellT cell
  34. 34. T-Lymphocytes• Helper T cells• CD4+ (and CD8-)• help B cells make antibodies• help macrophages eat bugs• Cytotoxic T cells• CD8+ (and CD4-)• kill virus-infected cells and tumor cells
  35. 35. Helper T cell Cytotoxic T cell
  36. 36. Cytotoxic T cells surrounding tumor cell
  37. 37. MHC• Collection of genes on chromosome 6• Three regions: class I, class II, class III• Highly polymorphic!• Gene products:• class I molecules• class II molecules• class III molecules (and other stuff)Major histocompatibility (MHC) complex
  38. 38. class I MHC moleculeclass II MHC moleculeclass II MHC genes class I MHC genesclass III MHC genes
  39. 39. MHC• Encoded by three loci: HLA-A, HLA-B, HLA-C• Display antigens from within the cell(e.g., viral antigens) to CD8+ T cells.• Present on all nucleated cells! (Good idea.)Class I MHC molecules
  40. 40. MHC• Encoded by three loci: HLA-DP, HLA-DQ, HLA-DR• Display extracellular antigens (e.g., bacterialantigens the cell has eaten) to CD4+ T cells• Present mainly on antigen presenting cells, likemacrophages! (Makes sense.)Class II MHC molecules
  41. 41. B-Lymphocytes• Live in blood, bone marrow, lymphoid tissues• Basic function: make antibodies (immunoglobulins)• B-cell receptor complex recognizes antigens• binds antigen• sends signals to T cells• Antigens can be free and circulating (don’t have tobe bound to MHCs or displayed by other cells to berecognized!)
  42. 42. The B-Cell Receptor
  43. 43. The B-Cell Receptor Bound to AntigenB cell
  44. 44. Natural Killer Cells• Belong to innate immunity arm• No highly variable receptors like T and B cells• Main job: recognize and kill damaged or infected cells• Antigens can be free and circulating (don’t have to bebound to MHCs or displayed by other cells to berecognized!)
  45. 45. Natural killer cell
  46. 46. Natural killer cell (top) killing infected cell (bottom)
  47. 47. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells
  48. 48. Antigen-presenting cells• Main job: catch antigens and display them to lymphocytes• Dendritic cells• Have fine cytoplasmic projections• Present all over body: skin, lymph nodes, organs• Capture bug antigens, display to B and T cells• Other APCs• Macrophages eat bugs and present antigens toT cells, which tell macrophages to kill bugs• B cells present antigens to helper T cells, which tellB cells to make antibodies
  49. 49. Dendritic cell surrounded by lymphocytes
  50. 50. Dendritic cell (right) talking to lymphocyte (left)
  51. 51. Dendritic cell (orange) talking to T lymphocytes (green)
  52. 52. MacrophageMonocyte
  53. 53. Macrophage reaching for bacterium
  54. 54. Macrophage gorging on bacteria
  55. 55. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells
  56. 56. Effector cells• These guys carry out the ultimate immunesystem task: eliminate infection• Types of effector cells• NK cells• Plasma cells• T cells (both CD4+ and CD8+)• Macrophages• Other leukocytes (e.g., neutrophils)
  57. 57. Plasma cell
  58. 58. Neutrophil
  59. 59. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immune response
  60. 60. The Innate Immune Response• Main bug barriers: skin, mucosa• If bugs make it through epithelium, theyencounter innate immune system• What happens in the innate immune system?• Phagocytes eat bugs, kill them• Cytokines are released• Complement is activated• The adaptive immune system is activated
  61. 61. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immune response• Capturing and displaying antigens
  62. 62. Capturing and displaying antigens• Dendritic cells in epithelium capture bug antigens,transport them to lymph nodes• APCs in lymph nodes eat antigens, display them(using their MHC receptors) to T cells• B cells in lymph nodes also recognize antigens• Antigens and molecules produced during innateimmune response trigger proliferation anddifferentiation of B and T cells
  63. 63. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity
  64. 64. Cell-Mediated ImmunityHumoral Immunity
  65. 65. Cell-Mediated ImmunityHumoral Immunity
  66. 66. Cell-mediated immunity• Naïve T cells are activated by antigen andcostimulators in lymph nodes…• …then they proliferate and differentiate intoeffector cells that go find the antigen.• CD4+ T cells help macrophages eat bugs• CD8+ T cells kill infected cells directly• All these steps are dependent upon cytokinesHow does the process work?
  67. 67. Cell-mediated immunity• Polypeptides that do lots of different things:• help leukocytes grow and differentiate• activate T cells, B cells and macrophages• help leukocytes communicate• recruit neutrophils• Made by lymphocytes and macrophages• Examples: TNF, the interleukins, interferon γWhat are cytokines?
  68. 68. Cell-mediated immunity• CD4+ T cells differentiate into two kinds of effector cells:• TH1 cells (activate macrophages, cause B cells to secrete Ab)• TH2 cells (activate eosinophils, cause B cells to secrete IgE)• These guys go to the site of infection, and with thehelp of macrophages and cytokines, do their thing.• CD8+ T cells differentiate into cytotoxic T cells• These guys kill cells that have microbes in their cytoplasm.• They are like little assassins.What kinds of effector T cells are there?
  69. 69. Cell-Mediated Immunity
  70. 70. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity
  71. 71. Cell-Mediated ImmunityHumoral Immunity
  72. 72. • B cells get activated by exposure to antigens(sometimes with the help of CD4+ T cells)• B cells differentiate into plasma cells (that makeantibodies)• The antibodies do nasty things to bugsHow does the process work?Humoral immunity
  73. 73. • Y-shaped glycoprotein• 2 light chains (κ or λ)• 2 heavy chains (α, γ, δ, ε, or μ)• Constant regions of heavy chain form the Fc fragment• binds to APCs• defines isotype (immunoglobulin class: IgA, IgE, etc.)• Variable regions of both chains form the Fab fragments• binds to antigen• defines idiotypeWhat is an antibody again?Humoral immunity
  74. 74. • Bind to – and “neutralize” – bugs, so they can’tinfect cells.• Coat (“opsonize”) bugs, making them yummy tomacrophages and neutrophils (which havereceptors for the Fc portion of IgG! Howhandy!).• Activate complement.What do antibodies do?Humoral immunity
  75. 75. What is complement?Just give me the bottom line.Humoral immunity• It’s a bunch of proteins that poke holes in cells.
  76. 76. Okay, give me a little more information.Humoral immunity• Consists of about 20 plasma proteins (C1, C2, etc.)• Can be activated in a few different ways• by antigen-antibody complexes• by bacterial LPS• by bugs that have mannan on their surfaces• Activation proceeds in a cascade fashion• End results:• cell lysis• chemotaxis• opsonization
  77. 77. Complement, ridiculously oversimplified
  78. 78. Humoral Immunity
  79. 79. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory
  80. 80. Immunologic memory• Most effector lymphocytes die after killing the bug.• A few memory cells live on for years.• expanded pool of antigen-specific lymphocytes• respond faster, better than naïve cells• vaccines depend on these guys
  81. 81. Summary of the Adaptive Immune Response
  82. 82. Immunology Overview• Definitions• Cells• Lymphocytes• Antigen-presenting cells• Effector cells• Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory
  83. 83. Innate immunity1. Dendritic cell eats bugs
  84. 84. Innate immunity1. Dendritic cell eats bugs• Displays antigen to naïve T cells (which MHC?)
  85. 85. Innate immunity1. Dendritic cell eats bugs• Displays antigen to naïve T cells (which MHC?)• T cells mature (put on costumes, and getready to do their jobs)
  86. 86. Innate immunity1. Dendritic cell eats bugs• Displays antigen to naïve T cells (which MHC?)• T cells mature (put on costumes, and getready to do their jobs)2. Neutrophil eats bugs; kills with toxic chemicals
  87. 87. Innate immunity1. Dendritic cell eats bugs• Displays antigen to naïve T cells (which MHC?)• T cells mature (put on costumes, and getready to do their jobs)2. Neutrophil eats bugs; kills with toxic chemicals3. NK cell kills bugs
  88. 88. Adaptive immunity: Cell-mediated1. Helper T cell does stuff
  89. 89. Adaptive immunity: Cell-mediated1. Helper T cell does stuff• Tells macrophage to eat bugs
  90. 90. Adaptive immunity: Cell-mediated1. Helper T cell does stuff• Tells macrophage to eat bugs• Tells B cell to make antibodies
  91. 91. Adaptive immunity: Cell-mediated1. Helper T cell does stuff• Tells macrophage to eat bugs• Tells B cell to make antibodies2. Cytotoxic T cell does stuff
  92. 92. Adaptive immunity: Cell-mediated1. Helper T cell does stuff• Tells macrophage to eat bugs• Tells B cell to make antibodies2. Cytotoxic T cell does stuff• Finds and kills infected cell (how?)
  93. 93. Adaptive immunity: Humoral1. B cell makes antibodies, which coat bugs• “Neutralizes” bugs• Opsonizes bugs (yummy for who?)
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