BIOE 301 Lecture Eight

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BIOE 301 Lecture Eight

• Amit Mistry
• Feb 6, 2007

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BIOE 301 Lecture 8

• WARM-UP
• Observation Global average near-surface
  atmospheric temperature rose 1.1
  0.4 Fahrenheit in the 20th century.
• What is the scientific approach to this?
• What is the engineering approach to it?

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Review of Lecture 7

• Science
• Science is the human activity of seeking natural
  explanations for what we observe in the world
  around us.
• Five steps of the scientific method

• Engineering
• Systematic design, production and operation of
  technical systems to meet practical human needs
  under specified constraints
• Six steps of the engineering design method

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Q3 How can technology solve health care
problems?

• CS1 Prevention of infectious disease

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Roadmap of CS 1

• Science
• Organisms that cause infectious 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

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Connections First day of class

• What caused the first bone marrow transplants to
  be rejected by recipients?

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Bone Marrow - Pluripotent Stem Cells

• Hematopoietic stem cells differentiate into
• White blood cells
• Red blood cells
• Platelets
• Mesenchymal stem cells differentiate into
• Bone, cartilage, muscle

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White Blood Cells
Neutrophil Lymphocyte Macrophage
The Defense The Good Guys
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Pathogens

• How They Cause Disease

The Offense The Bad Guys
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Types of Pathogens

• Bacteria
• Cells with membrane and cell wall (usually)
• Can survive outside host reproduce without 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
• gt50 different viruses that can infect humans

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Question

• Based on your understanding of the
  characteristics of bacteria, viruses, and blood
  cells, identify which item best represents each
  and be able to explain why you chose each.
• Bacterium
• Virus
• Blood cell

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Pathogens
Human hair 100,000,000 nm
Red blood cell 7,000 nm
E. coli bacteria 800 nm
Virus 100 nm
www.awcommunity.org www.its.caltech.edu/boozer
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Bacteria
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How do Bacteria Cause Disease?

• Invade host
• Reproduce
• Produce toxins ? disturb cell function
• Examples
• Escherichia Coli
• Bacillus Anthracis
• Microbacterium tuberculosis
• Streptococcus pneumoniae

http//www.cubanology.com/Articles/Virus_vs_Bacter
ia.htm
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Virus
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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

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Virus examples Influenza, HIV, West Nile,
Hepatitis Human Papillomavirus, Viriola Major
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Using Viruses for Good, not Evil

• Gene Therapy infect cells with beneficial DNA
• Diabetes
• SCID
• Cancer
• Sickle cell anemia
• MS
• Cystic fibrosis

www.nih.gov
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Pathophysiology of HIV/AIDS
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Pathophysiology of HIV/AIDS
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The Immune System

• How Are We Protected Against Pathogens?

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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

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Types of Immunity - Defense
Line of scrimmage
Physical Barriers Defensive Line
Innate Secondary Defense
Adaptive Coach
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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

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Physical Barriers
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What happens when you get a splinter?
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What happens when you get a splinter?

• Pathogens gets past physical barrier
• Macrophages eat bacteria on splinter
• Phagocytosis
• Activated macrophages produce chemicals which
• Increase local blood flow
• Increase permeability of
• blood vessels
• Recruit other phagocytes to site

Redness Heat
Swelling
Pus
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What happens when you get a splinter?

• Phagocytosis
• http//jcs.biologists.org/cgi/content/full/119/9/1
  903/DC1

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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

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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)

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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

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Adaptive Immune System

• Antibody-mediated
• Fight pathogens outside of cells
• Cell-mediated
• Fight pathogens inside of cells

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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

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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?

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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

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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 (targeted by HIV)
• Regulatory T Cells

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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

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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.

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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?

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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

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Putting it all together

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Putting it all together
Virus invades
Antibodies bind
Prevent virus function
Signal phagocytosis
Infects cells
Present antigen
Activates Killer T cells
Antigen presentation
Activates B cells
Kill infected cells!
Make more antibodies
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Antibody-mediated
Virus invades
Antibodies bind
Prevent virus function
Signal phagocytosis
Infects cells
Present antigen
Activates Killer T cells
Antigen presentation
Activates B cells
Kill infected cells!
Make more antibodies
Cell-mediated
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Summary of Lecture 8

• Pathogens Bacteria and Virus
• Levels of Immunity
• Barriers ? First line of defense
• Innate ? Inflammation
• Phagocytes
• Complement
• Adaptive ? Immunologic memory
• Cell mediated immunity ? Pathogens within cells
• Antibody mediated immunity
• Diversity to recognize 100 million antigens

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• Turn in HW 4 today
• Next Time
• Project Task 2 due on 2/8/07
• Influenza virus
• Vaccines
• The most cost-effective medical intervention
  known to prevent death or disease

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For more info

• National Bone Marrow Program http//www.marrow.or
  g/
• Baylor Center for Cell and Gene Therapy
• http//www.bcm.edu/genetherapy/
• Immunobiology BIOS 423 - Dr. Novotny