1. BME 301 Lecture Eight

2. Review of Lecture 7 Science “Science is the human activity of seeking natural explanations for what we observe in the world around us.” Engineering Systematic design, production and operation of technical systems to meet practical human needs under specified constraints Six steps of the engineering design method

3. Q3: How can technology solve health care problems? CS1: Prevention of infectious disease

4. Outline Pathogens: How They Cause Disease The Immune System: How We Fight Disease How Vaccines Work The Power of Vaccines: Childhood Illnesses Designing a New Vaccine: HIV/AIDS

5. Roadmap of CS 1 Science Organisms that cause disease Immunity Engineering How to make a vaccine Vaccines: From idea to product Societal Impact Health and economics Ethics of clinical trials Developed world/Developing world

6. Connections: First Day of Class Blood Plasma Cells Red blood cells White blood cells Platelets Cells made in bone marrow from pluripotent hematopoeitic stem cells http://www.nursing.ucla.edu/Userpages/mwoo/cbc/ima ges/norm1.jpg

7. http://cwx.prenhall.com/bookbind/pubboo ks/silverthorn2/medialib/Image_Bank/CH1 6/FG16_03.jpg

8. White Blood Cells NeutrophilLymphocyteMacrophage http://altmed.creighton.edu/pel vic2/images/lymphocyte.jpg http://www.thecrookstoncollection.com/Collect ion/medslides/Slides/Macrophage-01.jpg http://medlib.med.utah.edu/WebPat h/jpeg5/HEME001.jpg

9. Pathogens How They Cause Disease

10. Types of Pathogens Bacteria Cells with membrane and cell wall (usually) Can survive outside host Can reproduce without a host Can be killed or inhibited by antibiotics Viruses Nucleic acid core with protein envelope Use host intracellular machinery to reproduce Cannot be killed with antibiotics >50 different viruses that can infect humans

11. Bacteria http://www.earthlife.net/prokaryotes/images/bacteria1.gif http://www.up.ac.za/academic/electron/bacteria.jpg

12. How do Bacteria Cause Disease? Invade host Reproduce Produce toxins which disturb function of normal cells

13. Virus http://www.qub.ac.uk/afs/vs/vsd3.jpg http://www.theuniversityhospital.com/healthlink/winter2003 /images/article/anitbiotics/virus.jpg

14. How do Viruses Cause Disease? Virus invades host cell Binds to cell membrane receptors Endocytosis brings virus into cell Virus takes over cell Use viral nucleic acid and host cell resources to make new viral nucleic acid and proteins More virus is released from host cell Virus causes host cell to lyse OR Viral particles bud from host cell surface

16. Pathophysiology of HIV/AIDS http://health.howstuffworks.com/aids3.htm

17. Pathophysiology of HIV/AIDS http://www.roche.com/pages/facets/4/hiv_life_cycle2.jpg

18. The Immune System How Are We Protected Against Pathogens?

19. Types of Immunity Three layers of immunity: Physical Barriers Innate Immune System All animals possess Adaptive Immune System Vertebrates possess Keep pathogens out Kill them if they get in

20. Types of Immunity Physical Barriers Skin (2 square meters) Mucous Membranes (400 square meters) Innate Immune System Produces general inflammatory response when pathogens penetrate physical barriers Adaptive Immune System Can adapt to defend against any invader Important when innate immune system cannot defend against attack Provides immune system with “memory”

21. Physical Barriers

22. What happens when you get a splinter?

23. Pathogen makes it past a physical barrier Symptoms? Red, swollen, hot, pus What causes these symptoms? Innate immune system is kicking into gear Usually innate immune system can take care of it

24. What happens when you get a splinter? Macrophages eat bacteria on splinter Phagocytosis Produce chemicals which: Increase local blood flow Redness Heat Increase permeability of blood vessels Swelling Recruit other phagocytes to site of infection Pus

25. What happens when you get a splinter? Phagocytosis http://www.cellsalive.com/mac.htm WBCs in action http://cbr.med.harvard.edu/investigator s/springer/lab/lab_goodies/lab_goodies. html http://cbr.med.harvard.edu/investigator s/springer/lab/lab_goodies/lab_goodies. html

27. Innate Immune System Primarily effective against pathogens outside of cells Two main weapons: 1) Professional phagocytes Cells that eat stuff 2) The complement system Proteins that tag stuff for destruction

28. Components of Innate Immune System 1) Macrophages: Sentinels that patrol periphery If they find an invader, they become “activated” If activated, they: Send signals to recruit other immune system cells (Neutrophils) Become vicious killers Present antigen to adaptive immune system (more on this later)

29. Components of Innate Immune System 2) Complement proteins Present in tissues & blood Attach to surfaces of bacteria and viruses Target them for destruction by phagocytes Form Membrane Attack Complexes Recruit other immune cells from blood http://www.bmb.psu. edu/courses/bisci004 a/immune/attack.jpg

30. Adaptive Immune System Two main components Fight pathogens outside of cells: 1) Antibodies Fight pathogens inside of cells: 2) Killer T cells http://cwx.pren hall.com/bookbi nd/pubbooks/sil verthorn2/medi alib/Image_Ban k/CH22/FG22_1 2.jpg

31. What is an antibody? Bridge between: Pathogen Tool to kill it Antibodies have two important regions: Fab region: Binds antigen Binds surface of virus infected cell Fc region: Binds macrophages and neutrophils, induces phagocytosis Binds natural killer cell, induces killing

32. http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/ medialib/Image_Bank/CH22/FG22_06b.jpg

33. http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/ medialib/Image_Bank/CH22/FG22_14.jpg

34. Antibodies How are antibodies made? B cells Lymphocytes that make antibodies Have B cell receptors on surface 100 million different types of B cells, each with different surface receptors B cell receptors are so diverse they can recognize every organic molecule When a B cell binds antigen: Proliferates - In one week, clone of 20,000 identical B cells Secretes antibody

35. http://cwx.prenhall.com/bookbind/pubbo oks/silverthorn2/medialib/Image_Bank/C H22/FG22_09.jpg http://cwx.prenhall.com/bookbind/pubbooks/ silverthorn2/medialib/Image_Bank/CH22/FG2 2_10.jpg

36. Adaptive Immune System How do we kill virus once inside the cell? Antibodies cannot get to it Need T cells T Cells Recognize protein antigens When bind antigen, undergo clonal selection Three types of T Cells: Killer T Cells (Cytotoxic T Lymphocytes – CTLs) Helper T Cells Regulatory T Cells

37. How do T Cells ID Virus Infected Cells? Antigen Presentation All cells have MHC molecules on surface When virus invades cell, fragments of viral protein are loaded onto MHC proteins T Cells inspect MHC proteins and use this as a signal to identify infected cells

38. http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/ medialib/Image_Bank/CH22/FG22_05.jpg

40. Immunologic Memory First time adaptive immune system is activated by an antigen: Build up a clone of B cells and T cells Takes about a week After infection is over, most die off Some remain – memory cells Second time adaptive immune system is activated by that antigen: Memory cells are easier to activate Response is much faster – no symptoms

42. http://cwx.prenhall.com/bookbind/pubbooks/ silverthorn2/medialib/Image_Bank/CH22/FG2 2_11.jpg

43. Putting it all together

44. http://cwx.prenhall.com/bookbi nd/pubbooks/silverthorn2/medi alib/Image_Bank/CH22/FG22_1 3.jpg

45. http://cwx.prenhall.com/boo kbind/pubbooks/silverthorn2 /medialib/Image_Bank/CH22 /FG22_18.jpg

46. Summary of Lecture 8 Pathogens: Bacteria and Virus Levels of Immunity: Barriers  First line of defense Innate  Inflammation Phagocytes Complement Adaptive  Immunologic memory Antibody mediated immunity Cell mediated immunity  Pathogens within cells Diversity to recognize 100 million antigens

47. Next Time Two examples of viral infections: Influenza HIV Vaccine The most cost-effective medical intervention known to prevent death or disease Vaccine Video

48. Assignments Due Next Time Two reading assignments: http://www.immunizationinfo.org/ parents/vaccine_effectiveness.cfm http://www.immunizationinfo.org/ parents/vaccine_effectiveness.cfm http://www.immunizationinfo.org/ parents/howVaccines_work.cfm http://www.immunizationinfo.org/ parents/howVaccines_work.cfm