1. BIOE 301
Lecture Eight

2. Review of Lecture 7 Science Engineering
“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. Roadmap of CS 1 Science Engineering Vaccines: From idea to product
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

5. 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

7. Neutrophil Lymphocyte Macrophage
White Blood Cells
Neutrophil Lymphocyte Macrophage

8. Pathogens
How They Cause Disease

9. Types of Pathogens Bacteria Viruses
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

10. Question:
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.

11. Bacteria

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

13. Virus

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

17. Pathophysiology of HIV/AIDS

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

19. Types of Immunity Three layers of immunity: Keep pathogens out
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 Innate Immune System
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. What happens when you get a splinter?
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
WBCs in action

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

30. Adaptive Immune System
Two main components
Fight pathogens outside of cells:
1) Antibodies
Fight pathogens inside of cells:
2) Killer T cells

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. Question: Which components of your kit are most like antibodies?
Arrange the components of the kit to demonstrate how these antibodies “bridge” a pathogen and the tool to kill it?

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

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. Question:
Using the components of the kit, demonstrate the two steps required for viral antigens to be presented on the MHC complexes on the surface of the blood cell.

40. Question:
Demonstrate how the T cell can identify a virus infected cell.
Why is this component of the adaptive immune system a significant advance over the innate immune system?

42. 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

45. Putting it all together

48. 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

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

50. Assignments Due Next Time
HW6