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Pathogens and the immune system Veronica Leautaud, Ph.D. vl2@ rice.edu Keck Hall 224 / 232-lab Lecture 8 BIOE 301-Bioengin...
<ul><li>Science </li></ul><ul><ul><li>“ Science  is the human activity of seeking natural explanations for what we observe...
<ul><li>Infectious diseases: a global health problem </li></ul>(From Morens, D., et al , 2004)
<ul><li>Infectious diseases: a global health problem </li></ul>(MRSA)
<ul><li>Infectious diseases: a global health problem </li></ul>
<ul><li>Infectious diseases: a global health problem </li></ul>
<ul><li>1. Understanding biology: pathogens & disease </li></ul><ul><li>  immune system </li></ul><ul><li>2. Developing va...
Lecture map 1. The players: Types of pathogens  Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B. ...
Lecture map 1. The players: Types of pathogens   Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B....
<ul><li>Bacteria </li></ul>Types of pathogens Mycobacterium tuberculosis  Staphylococus aureus Escherichia coli O147:H7 Vi...
<ul><li>- Cells with membrane and cell wall (usually) </li></ul><ul><li>- Can survive & reproduce outside host </li></ul><...
How do bacteria cause disease? <ul><li>Invade host </li></ul><ul><li>Reproduce </li></ul><ul><li>Produce toxins which dist...
How do bacteria cause disease? MRSA: Methycillin Resistant Staphylococcus aureus http://www.npr.org/templates/story/story....
Viruses <ul><li>Nucleic acid core surrounded by protein capsid, and for some viruses an envelope </li></ul><ul><li>Use hos...
<ul><li>Virus invades host cell </li></ul><ul><ul><li>- Binds to cell membrane receptors </li></ul></ul><ul><ul><li>- Endo...
How do viruses cause disease?
The Human Immunodeficiency virus (HIV) Viral components: -nucleic acid core  (DNA/RNA) -protein capsid -envelope -Glycopro...
The Human Immunodeficiency virus (HIV)
How are we protected against pathogens?
Lecture map 1. The players: Types of pathogens   Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B....
Cells of the immune system Bone marrow Blood = plasma + cells
Cells of the immune system Bone marrow Blood = plasma + cells O 2  & CO 2  transport Clotting White Blood Cells (WBC) (T/B...
Cells of the immune system Bone marrow Blood = plasma + cells Phagocytosis- ‘eating pathogens’ Innate Immunity Macrophages...
Cells of the immune system Neutrophil  Macrophage  Lymphocyte Phagocytosis- killing B-lymphocytes T lymphocytes NK cells
Question: <ul><li>Based on your understanding of the  characteristics of bacteria, viruses, and blood cells, identify whic...
Lecture map 1. The players: Types of pathogens   Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B....
Types of Immunity <ul><li>Physical Barriers   </li></ul><ul><li>- skin   (2 square meters!) </li></ul><ul><li>- mucose mem...
What happens when you get a splinter?
What happens when you get a splinter? <ul><li>Pathogen makes it past a physical barrier </li></ul><ul><li>Symptoms? </li><...
The Innate Immune System:  3 main weapons <ul><li>- Activated Macrophages   </li></ul>Phagocyte (‘eat’) invading pathogens...
What happens when you get a splinter?
Macrophage attacking  E.coli  SEM x 8,800  © Denis Kunkel
Question: <ul><li>Based on your understanding of the  innate immune system, represent a macrophage during phagocytosis </l...
Lecture map 1. The players: Types of pathogens   Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B....
The Adaptive Immune System <ul><li>Humoral immunity   </li></ul><ul><li>- Relies on  Antibodies  produced by  B -lymphocyt...
<ul><li>Bridge between: </li></ul><ul><ul><li>Pathogen  </li></ul></ul><ul><ul><li>Tool to kill it </li></ul></ul><ul><li>...
<ul><li>1. Neutralization : Blocking the biological activity of toxin or pathogen  ie. Blocking access </li></ul><ul><li>2...
The Adaptive Immune response:  humoral immunity 1. Neutralization 2. Bridge: pathogen-phagocyte Target cell Target cell Ma...
Question: <ul><li>Which components of your kit are most like antibodies? </li></ul><ul><li>Arrange the components of the k...
The Adaptive Immune response:  humoral immunity <ul><li>How are antibodies made?  </li></ul><ul><ul><li>B cells </li></ul>...
Clonal selection and proliferation (proliferation) B cells
The Adaptive Immune response:  cell-mediated immunity <ul><li>How do we kill virus once inside the cell? </li></ul><ul><ul...
How do T Cells recognize Virus-Infected Cells?  <ul><li>All cells have  M ajor  H istocompatibility  C omplex  (MHC) molec...
Antigen presentation and  cellular immunity T Helper Cell (CD4+) Macrophage Strengthen antibody response Killer T-cell (CD...
Question: <ul><li>Demonstrate how the T cell can identify a virus infected cell: antigen presentation </li></ul><ul><li>Wh...
Immunologic Memory <ul><li>First time  adaptive immune system is activated by an antigen: </li></ul><ul><ul><li>Build up a...
Immunologic Memory
The adaptive Immune Response Putting it together…
The Adaptive immune response B cell: antibodies (neutralize & bridge) T-helper cell Killer T cell Antigen presentation Ant...
Summary of lecture 8 <ul><li>Pathogens: Bacteria and Virus </li></ul><ul><li>Levels of Immunity: </li></ul><ul><ul><li>Bar...
Next time <ul><li>How do vaccines work? </li></ul><ul><li>Vaccine development: </li></ul><ul><ul><ul><li>Design </li></ul>...
Assignments Due Next Time <ul><li>Homework 5 </li></ul><ul><ul><li>- Reading: ‘Polio: an end in sight’. Toby Reynolds  </l...
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  • Andrew SPEAKER FLEW TO EUROPE FOR HIS WEDDING AND HONEYMOON AFTER BEING ADVISED BY HEALTH OFFICIALS NOT TO MAKE THE TRIP BECAUSE HE HAD TB. THEN, WHILE HE WAS IN ROME, U.S. HEALTH OFFICIALS TOLD HIM TO STAY PUT BECAUSE FURTHER TESTS SHOWED HE HAD AN EVEN MORE DANGEROUS, DRUG-RESISTANT TYPE OF TB THAN PREVIOUSLY THOUGHT. THE 31-YEAR-OLD NEWLYWED DISREGARDED THOSE INSTRUCTIONS, TAKING COMMERCIAL JETS TO PRAGUE AND THEN MONTREAL IN AN ATTEMPT TO SNEAK BACK INTO THE UNITED STATES. IN AN INTERVIEW EARLIER THIS WEEK WITH THE ATLANTA JOURNAL-CONSTITUTION, SPEAKER SAID HE DECLINED TO REPORT TO ITALIAN HEALTH OFFICIALS BECAUSE HE BELIEVED THE ONLY LIFESAVING CARE FOR HIS CONDITION WAS AVAILABLE IN THE U.S.
  • Transcript of "VL 08lecture2008.ppt"

    1. 1. Pathogens and the immune system Veronica Leautaud, Ph.D. vl2@ rice.edu Keck Hall 224 / 232-lab Lecture 8 BIOE 301-Bioengineering and World Health
    2. 2. <ul><li>Science </li></ul><ul><ul><li>“ Science is the human activity of seeking natural explanations for what we observe in the world around us.” </li></ul></ul><ul><li>Engineering </li></ul><ul><ul><li>Systematic design, production and operation of technical systems to meet practical human needs under specified constraints </li></ul></ul><ul><ul><li>Six steps of the engineering design method </li></ul></ul>Review of lecture 7
    3. 3. <ul><li>Infectious diseases: a global health problem </li></ul>(From Morens, D., et al , 2004)
    4. 4. <ul><li>Infectious diseases: a global health problem </li></ul>(MRSA)
    5. 5. <ul><li>Infectious diseases: a global health problem </li></ul>
    6. 6. <ul><li>Infectious diseases: a global health problem </li></ul>
    7. 7. <ul><li>1. Understanding biology: pathogens & disease </li></ul><ul><li> immune system </li></ul><ul><li>2. Developing vaccines: from idea to product </li></ul><ul><li>- vaccine design </li></ul><ul><li> - production </li></ul><ul><li>- testing safety & effectiveness </li></ul><ul><li>3. Addressing challenges for vaccine development: </li></ul><ul><li> - Developed vs. developing countries </li></ul><ul><li>- The AIDS vaccine challenge </li></ul>How can technology help? Science Engineering
    8. 8. Lecture map 1. The players: Types of pathogens Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B. Innate Immunity 2C. Adaptive Immunity Macrophages Neutrophils Complement proteins B-lymphocytes: ANTIBODIES T-lymphocytes: Cell-mediated Immunologic MEMORY Splinter example
    9. 9. Lecture map 1. The players: Types of pathogens Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B. Innate Immunity 2C. Adaptive Immunity Macrophages Neutrophils Complement proteins B-lymphocytes: ANTIBODIES T-lymphocytes: Cell-mediated Immunologic MEMORY Splinter example
    10. 10. <ul><li>Bacteria </li></ul>Types of pathogens Mycobacterium tuberculosis Staphylococus aureus Escherichia coli O147:H7 Vibrio cholera Bordetella pertussis (whooping cough) Viruses SARS- Severe Acute Respiratory Syndrome Influenza (Flu) HIV (AIDS) Hepatitis C virus Ebola/ Marburg viruses Parasites Plasmodium sp. (Malaria) Cryptospridium Candida albicans Fungi
    11. 11. <ul><li>- Cells with membrane and cell wall (usually) </li></ul><ul><li>- Can survive & reproduce outside host </li></ul><ul><li>- Can be killed or inhibited by antibiotics </li></ul><ul><li>- Responsible for >90% of hospital infections </li></ul>Bacteria Size ~ 1 μ m DNA
    12. 12. How do bacteria cause disease? <ul><li>Invade host </li></ul><ul><li>Reproduce </li></ul><ul><li>Produce toxins which disturb function of normal cells </li></ul>Paralyze cilia & inhibit clearance of respiratory secretions = whooping cough pertussis
    13. 13. How do bacteria cause disease? MRSA: Methycillin Resistant Staphylococcus aureus http://www.npr.org/templates/story/story.php?storyId=15453093
    14. 14. Viruses <ul><li>Nucleic acid core surrounded by protein capsid, and for some viruses an envelope </li></ul><ul><li>Use host intracellular machinery to reproduce </li></ul><ul><li>They cannot be killed with antibiotics, but antivirals may inhibit different stages of their life cycle in the host </li></ul><ul><li>>50 viruses that can infect humans </li></ul>Size ~ 0.1 μ m = 100nm
    15. 15. <ul><li>Virus invades host cell </li></ul><ul><ul><li>- Binds to cell membrane receptors </li></ul></ul><ul><ul><li>- Endocytosis brings virus into cell </li></ul></ul><ul><li>Virus takes over cell </li></ul><ul><ul><li>- Use viral nucleic acid and host cell resources to make new viral nucleic acid and proteins </li></ul></ul><ul><li>More virus is released from host cell </li></ul><ul><ul><li>- Virus causes host cell to lyse OR </li></ul></ul><ul><ul><li>- Viral particles bud from host cell surface </li></ul></ul>How do viruses cause disease?
    16. 16. How do viruses cause disease?
    17. 17. The Human Immunodeficiency virus (HIV) Viral components: -nucleic acid core (DNA/RNA) -protein capsid -envelope -Glycoproteins Spikes
    18. 18. The Human Immunodeficiency virus (HIV)
    19. 19. How are we protected against pathogens?
    20. 20. Lecture map 1. The players: Types of pathogens Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B. Innate Immunity 2C. Adaptive Immunity Macrophages Neutrophils Complement proteins B-lymphocytes: ANTIBODIES T-lymphocytes: Cell-mediated Immunologic MEMORY Splinter example
    21. 21. Cells of the immune system Bone marrow Blood = plasma + cells
    22. 22. Cells of the immune system Bone marrow Blood = plasma + cells O 2 & CO 2 transport Clotting White Blood Cells (WBC) (T/B) Macrophages
    23. 23. Cells of the immune system Bone marrow Blood = plasma + cells Phagocytosis- ‘eating pathogens’ Innate Immunity Macrophages Defense vs. parasites Allergic reactions B-lymphoctes T-lymphocytes Natural Killer Cells Antibody production Pathogen killing Adaptive Immunity
    24. 24. Cells of the immune system Neutrophil Macrophage Lymphocyte Phagocytosis- killing B-lymphocytes T lymphocytes NK cells
    25. 25. Question: <ul><li>Based on your understanding of the characteristics of bacteria, viruses, and blood cells, identify which item best represents a bacterium, a virus and a blood cell and be able to explain why you chose each. </li></ul>
    26. 26. Lecture map 1. The players: Types of pathogens Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B. Innate Immunity 2C. Adaptive Immunity Macrophages Neutrophils Complement proteins B-lymphocytes: ANTIBODIES T-lymphocytes: Cell-mediated Immunologic MEMORY Splinter example
    27. 27. Types of Immunity <ul><li>Physical Barriers </li></ul><ul><li>- skin (2 square meters!) </li></ul><ul><li>- mucose membranes (400 square meters!) </li></ul><ul><li>Innate Immune System </li></ul><ul><ul><li>- General inflammatory response against pathogens outside of the cell </li></ul></ul><ul><li>Adaptive Immune System </li></ul><ul><li>- Can adapt to defend against any specific invader inside or outside of the cell </li></ul><ul><li>- Important when innate immunity cannot defend against the attack </li></ul><ul><li>-Provides ‘Immune Memory’ </li></ul>
    28. 28. What happens when you get a splinter?
    29. 29. What happens when you get a splinter? <ul><li>Pathogen makes it past a physical barrier </li></ul><ul><li>Symptoms? </li></ul><ul><ul><li>Red, swollen, hot, pus </li></ul></ul><ul><li>What causes these symptoms? </li></ul><ul><ul><li>The Innate immune system is kicking into gear! </li></ul></ul><ul><li>Usually innate immune system can take care of it </li></ul>
    30. 30. The Innate Immune System: 3 main weapons <ul><li>- Activated Macrophages </li></ul>Phagocyte (‘eat’) invading pathogens Produce chemicals that: - increase blood flow (redness & heat) - cause ‘fuild leaking’ (swelling) - recruit neutrophils (pus) Present antigen to adaptive immune system - Complement proteins Present in tissue and blood Attach to surface of bacteria and viruses targeting them for phagocytosis Recruit other immune cells from blood
    31. 31. What happens when you get a splinter?
    32. 32. Macrophage attacking E.coli SEM x 8,800 © Denis Kunkel
    33. 33. Question: <ul><li>Based on your understanding of the innate immune system, represent a macrophage during phagocytosis </li></ul>
    34. 34. Lecture map 1. The players: Types of pathogens Cells of the Immune system 2. Types of Immunity 2A. Physical barriers 2B. Innate Immunity 2C. Adaptive Immunity Macrophages Neutrophils Complement proteins B-lymphocytes: ANTIBODIES T-lymphocytes: Cell-mediated Immunologic MEMORY Splinter example
    35. 35. The Adaptive Immune System <ul><li>Humoral immunity </li></ul><ul><li>- Relies on Antibodies produced by B -lymphocytes </li></ul><ul><li>- Fights pathogens outside of cells </li></ul><ul><li>Recognizes antigens (molecular signatures) specific for each pathogen </li></ul><ul><li>Effective against both intra- and extracellular pathogens </li></ul><ul><li>Two main components: </li></ul>Cell-mediated Immunity - Relies on specific receptors on the surface of T -lymphocytes - Fights pathogens inside of cells
    36. 36. <ul><li>Bridge between: </li></ul><ul><ul><li>Pathogen </li></ul></ul><ul><ul><li>Tool to kill it </li></ul></ul><ul><li>Antibodies have two important regions: </li></ul><ul><ul><li>Fab region: </li></ul></ul><ul><ul><ul><li>Binds antigen </li></ul></ul></ul><ul><ul><ul><li>Binds surface of virus infected cell </li></ul></ul></ul><ul><ul><li>Fc region: </li></ul></ul><ul><ul><ul><li>Binds macrophages and neutrophils, induces phagocytosis </li></ul></ul></ul><ul><ul><ul><li>Binds natural killer cell, induces killing </li></ul></ul></ul>What is an antibody?
    37. 37. <ul><li>1. Neutralization : Blocking the biological activity of toxin or pathogen ie. Blocking access </li></ul><ul><li>2. Bridge: Bringing together pathogens and phagocytes </li></ul>The Adaptive Immune response: humoral immunity How do antibodies work?
    38. 38. The Adaptive Immune response: humoral immunity 1. Neutralization 2. Bridge: pathogen-phagocyte Target cell Target cell Macrophage
    39. 39. Question: <ul><li>Which components of your kit are most like antibodies? </li></ul><ul><li>Arrange the components of the kit to demonstrate how these antibodies “bridge” a pathogen and the tool to kill it? </li></ul>
    40. 40. The Adaptive Immune response: humoral immunity <ul><li>How are antibodies made? </li></ul><ul><ul><li>B cells </li></ul></ul><ul><ul><ul><li>Lymphocytes that make antibodies </li></ul></ul></ul><ul><ul><ul><li>Have B cell receptors on surface </li></ul></ul></ul><ul><ul><ul><li>100 million different types of B cells, each with different surface receptors </li></ul></ul></ul><ul><ul><ul><li>B cell receptors are so diverse they can recognize every organic molecule </li></ul></ul></ul><ul><ul><li>When a B cell binds antigen : </li></ul></ul><ul><ul><ul><li>Proliferates - In one week, clone of 20,000 identical B cells </li></ul></ul></ul><ul><ul><ul><li>Secretes antibody </li></ul></ul></ul>
    41. 41. Clonal selection and proliferation (proliferation) B cells
    42. 42. The Adaptive Immune response: cell-mediated immunity <ul><li>How do we kill virus once inside the cell? </li></ul><ul><ul><li>Antibodies cannot get to it </li></ul></ul><ul><ul><li>Need T cells </li></ul></ul><ul><li>T Cells </li></ul><ul><ul><li>Recognize protein antigens </li></ul></ul><ul><ul><li>When bind antigen, undergo clonal selection </li></ul></ul><ul><ul><li>Three types of T Cells: </li></ul></ul><ul><ul><ul><li>Killer T Cells (Cytotoxic T Lymphocytes – CTLs) </li></ul></ul></ul><ul><ul><ul><li>Helper T Cells (orchestrate adaptive immune response) </li></ul></ul></ul><ul><ul><ul><li>Regulatory T Cells </li></ul></ul></ul>
    43. 43. How do T Cells recognize Virus-Infected Cells? <ul><li>All cells have M ajor H istocompatibility C omplex (MHC) molecules on surface </li></ul><ul><li>When virus invades target cell, fragments of viral protein are loaded onto MHC proteins </li></ul><ul><li>‘ Profesional’ Antigen Presentation Cells (APCs= phagocytes of innate immunity) </li></ul><ul><li>T Cells inspect MHC proteins and use this as a signal to identify infected cells </li></ul><ul><li>Antigens (bits of pathogens) get loaded into MHC molecules: </li></ul>
    44. 44. Antigen presentation and cellular immunity T Helper Cell (CD4+) Macrophage Strengthen antibody response Killer T-cell (CD8+) Strengthen Killer T cell response MHC TCR Infected cell MHC TCR Macrophage Infected cell
    45. 45. Question: <ul><li>Demonstrate how the T cell can identify a virus infected cell: antigen presentation </li></ul><ul><li>Why is this component of the adaptive immune system a significant advance over the innate immune system? </li></ul>
    46. 46. Immunologic Memory <ul><li>First time adaptive immune system is activated by an antigen: </li></ul><ul><ul><li>Build up a clone of B cells and T cells </li></ul></ul><ul><ul><li>Takes about a week </li></ul></ul><ul><ul><li>After infection is over, most die off </li></ul></ul><ul><ul><li>Some remain – memory cells </li></ul></ul><ul><li>Second time adaptive immune system is activated by that antigen: </li></ul><ul><ul><li>Memory cells are easier to activate </li></ul></ul><ul><ul><li>Response is much faster – no symptoms </li></ul></ul>
    47. 47. Immunologic Memory
    48. 48. The adaptive Immune Response Putting it together…
    49. 49. The Adaptive immune response B cell: antibodies (neutralize & bridge) T-helper cell Killer T cell Antigen presentation Antigen presentation macrophage macrophage infected cell 1. Cellular Immunity: 2. Humoral Immunity:
    50. 50. Summary of lecture 8 <ul><li>Pathogens: Bacteria and Virus </li></ul><ul><li>Levels of Immunity: </li></ul><ul><ul><li>Barriers  First line of defense </li></ul></ul><ul><ul><li>Innate  Inflammation </li></ul></ul><ul><ul><ul><li>Phagocytes </li></ul></ul></ul><ul><ul><ul><li>Complement </li></ul></ul></ul><ul><ul><li>Adaptive  Immunologic memory </li></ul></ul><ul><ul><ul><li>Antibody mediated immunity </li></ul></ul></ul><ul><ul><ul><li>Cell mediated immunity  Pathogens within cells </li></ul></ul></ul><ul><ul><ul><li>Diversity to recognize 100 million antigens </li></ul></ul></ul>
    51. 51. Next time <ul><li>How do vaccines work? </li></ul><ul><li>Vaccine development: </li></ul><ul><ul><ul><li>Design </li></ul></ul></ul><ul><ul><ul><li>Production </li></ul></ul></ul><ul><ul><ul><li>Testing safety & efficacy </li></ul></ul></ul><ul><li>Challenges of vaccine development </li></ul>
    52. 52. Assignments Due Next Time <ul><li>Homework 5 </li></ul><ul><ul><li>- Reading: ‘Polio: an end in sight’. Toby Reynolds </li></ul></ul><ul><ul><li>- Questions 1-3 </li></ul></ul>
    53. 53. The end.
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