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2. Outline for the Evening
Kevin Bonham The eyes of the immune system
Sky Brubaker Different Responses for different disease causing
organisms
Jillian Astarita Instructing the immune system to make better
vaccines
3. The Eyes of the Immune System
What does the immune system need to see?
How does a cell see?
The many eyes of the immune system
4. A Cell is the Basic Unit of Life
Plasma Membrane
Nucleus
Cytoplasm
5. Cells are Organized Into Tissues and Organs
Intestine
6. Cells Need to Change Behavior Based on External Cues
Intestine
7. The Eyes of the Immune System
What does the immune system need to see?
How does a cell see?
The many eyes of the immune system
8. There are Many Types of Organisms that Cause Disease
Viruses
Bacteria
Single-celled parasites
Multicellular parasites
Pathogens
Credit: CDC
Credit: NIAID
Jasper Lawrence, wikimedia commons
9. Pathogens Cause Disease in Different Ways
Bacteria
Intestine
Sven Manguard : Wikimedia Commons
10. Pathogens Cause Disease in Different Ways
Worm
Intestine
Sven Manguard : Wikimedia Commons
11. The Eyes of the Immune System
What does the immune system need to see?
How does a cell see?
The many eyes of the immune system
12. Cells Need to Change Behavior Based on External Cues
What Determines Cell Behavior?
13. Proteins are Molecular Machines
http://en.wikipedia.org/wiki/Hemoglobin
Fotoosvanrobin Flickr http://flic.kr/p/4EyhUv
14. A Cells Behavior is Determined by Which Proteins are Made
Translation
Transcription
Nucleus
Cytoplasm
15. Cells Need to Change Behavior Based on External Cues
Signal
Nucleus
Cytoplasm
16. Receptors Allow Cells to See the Outside World
Receptor
Nucleus
Cytoplasm
17. Ligand
Binding
site
Receptor
Different Receptors See Different Signals
18. Quick Recap
The immune system has to change its behavior depending on what type
of pathogen it encounters
This behavior is altered by changing which proteins are being
produced
A cell can get different signals by using different receptors that
bind to different ligands
Questions?
19. The Eyes of the Immune System
What does the immune system need to see?
How does a cell see?
The many eyes of the immune system
20. Pathogens Can Evolve Faster Than We Can
Flickr user AREALFAKE http://flic.kr/p/4LB8tn
Flickr User Ngislew http://flic.kr/p/3d335r
21. There Are Patterns to Pathogens of a Particular Type
Pattern Recognition Receptors
Flickr user AREALFAKE http://flic.kr/p/4LB8tn
Flickr User Ngislew http://flic.kr/p/3d335r
22. Pattern Recognition Receptors See Shapes Common to Large Groups
of Pathogens
Bacteria
Flagellum
23. Pattern Recognition Receptors See Shapes Common to Large Groups
of Pathogens
24. Pattern Recognition Receptors Can Tell the Difference Between
Different Pathogens
Ligand
Innate Immunity
Binding
site
Virus!
Worm!
Bacteria!
25. Our Immune System Needs to See Shapes That Can Change Too
26. Pathogens Can Change Some Proteins Without Eliminating Their
Function
27. A Receptor for One Shape May Not Be Able to See Another
28. Some Specialized Immune Cells Have Receptors That Can See Many
Shapes
Binding sites
B-cell
29. B-cell Receptors Are Highly Variable
B-cells
30. B-cell Receptors Can Potentially See Almost Any Shape
31. Most B-cells Wont See Any Given Infection
B-cells
32. But Some Can
33. B-cell Receptors Dont Know What Type of Pathogen They Can
See
I see it!
34. Cells With Pattern Recognition Receptors InstructB-cells
Adaptive Immunity
Bacteria!
I see it!
Bacteria!
Got it!
Now what?
B-cells
Innate immune
Cell
35. Summary
The immune system recognizes pathogens through specialized
receptors
Innate immune receptors recognize patterns associated with
pathogens and can tell the difference between large groups of
pathogens
Adaptive immune cells can see almost any shape, but need
instruction from the innate immune system
36. Different Pathogens, Different Responses
Up Next: Sky Brubaker
37. Viruses
Bacteria
Different Pathogens, Different Responses
Single-celled parasites
Multicellular parasites
Credit: CDC
Credit: NIAID
Jasper Lawrence, wikimedia commons
38. Viruses
Bacteria
Pattern Recognition Receptors Differentiate Pathogens
Single-celled parasites
Multicellular parasites
Credit: CDC
Credit: NIAID
Jasper Lawrence, wikimedia commons
39. Different Pathogens, Different Responses
Why use different responses?
40. Directing the Appropriate Response
Holger.Ellgaard: Wikimedia Commons
FieldMarine: Wikimedia Commons
Luis FernndezGarca : Wikimedia Commons
41. Directing the Appropriate Response
Holger.Ellgaard: Wikimedia Commons
FieldMarine: Wikimedia Commons
Mattyman17: Wikimedia Commons
42. Different Pathogens, Different Responses
Why use different responses?
Viral Defense
Cytoplasm
43. Viral Defense
Virus
Nucleus
Cytoplasm
44. Viral Defense
Cytokines
Virus
Nucleus
Cytoplasm
45. Viral Defense
Antiviral State
Cytoplasm
46. Viral Defense
Virus
Nucleus
47. Viral Defense
Antiviral State
Stops All Protein Production
X
X
48. Viral Defense
Antiviral State
Virus
Stops All Protein Production
X
FieldMarine: Wikimedia Commons
X
X
50. Viral Defense
Antiviral State
X
X
X
X
X
X
X
X
X
X
X
X
X
Sam: Wikimedia Commons
Cytoplasm
51. Viral Defense
Recruit cytotoxic cells
X
X
X
X
X
X
X
X
X
X
X
X
X
Cytoplasm
52. Viral Defense
Recruit cytotoxic cells
X
X
X
X
X
X
X
X
X
X
X
X
X
Sam: Wikimedia Commons
Cytoplasm
54. Viral Defense
Y
Production of Neutralizing Antibodies
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
B-cell
X
X
X
X
X
X
X
X
X
X
X
X
Cytoplasm
55. Viral Defense
Questions?
58. Bacterial Defense
Phagocyte
Cytoplasm
59. Bacterial Defense
Phagocytosis
60. Bacterial Defense
Phagocyte
Nucleus
61. Bacterial Defense
Cytokines
Phagocyte
Nucleus
62. Bacterial Defense
Phagocyte Recruitment and Activation
Phagocyte
Cytoplasm
63. Bacteria Are Slippery
Credit: Phillip G. Allen
http://www.biochemweb.org/neutrophil.shtml
64. Bacterial Defense
Y
Opsonizing Antibody Production
Y
Y
Y
Phagocyte
Y
Cytoplasm
65. Bacterial Defense
Viral Defense vs Bacterial Defense
Responses to Different Pathogens
Why use different responses?
Leprosy: A Spectrum of Disease
Lepromatous
Tuberculoid
24 year old man from Norway, suffering from leprosy.
Sam: Wikimedia Commons
77. Mycobacterium leprae: the causative agent of Leprosy
Nucleus
CDC Public Health Image Library: 2123
78. Immune Response Dictates Disease Outcome
Lepromatous
Tuberculoid
Y
Y
Y
Y
Y
cytotoxic cell
Nucleus
Y
24 year old man from Norway, suffering from leprosy.
Nucleus
Sam: Wikimedia Commons
Sven Manguard : Wikimedia Commons
80. Summary
Why use different responses?
After the break.
Jillian Astarita
Instructing the innate immune system to make better vaccines
82. How to Spot a Virus
The origins of an immune response
Kevin Bonham
Sky Brubaker
Jillian Astarita
83. Quick recap
Many types of pathogens exist
Immune cells have different receptors to see these pathogens
Innate immune cells instruct adaptive immune cells
Different immune responses are required to effectively kill
different pathogens
84. How can we instruct the immune system to make better
vaccines?
History lesson: how did scientists develop vaccines?
Why old vaccines do not always work
What we need to learn to make them better
New techniques/promising clinical trials
85. A brief history of vaccination
Edward Jenner infects 8 yr old boy with cowpox and confers smallpox
protection
1796
1000
Son of a Chinese statesman inhaled dried smallpox scabs to confer
protection
Thehistoryofvaccines.org
86. Long-term (10-50 years) immunity
These vaccines workedbut scientists didnt know how
Inject (not very harmful) pathogen
?
?
87. A brief history of vaccination
Edward Jenner infects 8 yr old boy with cowpox and confers smallpox
protection
Louis Pasteur discovers that repeatedly infecting chickens with
cholera weakens the pathogen
1879
1796
1000
1855
Son of a Chinese statesman inhaled dried smallpox scabs to confer
protection
MA passes first U.S. law mandating vaccination for school
children
Thehistoryofvaccines.org
88. Long-term (10-50 years) immunity
These vaccines workedand scientists were starting to figure out
how
Inject (not very harmful) pathogen
Inject weakened pathogen
?
?
89. A brief history of vaccination
Louis Pasteur discovers that repeated passes through chickens
weakens cholera
Edward Jenner infects 8 yr old boy with cowpox and confers smallpox
protection
1879
1796
1000
1855
1890
Son of a Chinese statesman inhaled dried smallpox scabs to confer
protection
MA passes first U.S. law mandating vaccination for school
children
Serum therapy for diptheria discovered by Kitasato and von
Berhing
Thehistoryofvaccines.org
90. Generation of protective anti-toxins (antibodies)
?
Long-term (10-50 years) immunity
These vaccines workedand scientists were starting to figure out
how
?
Inject weakened pathogen
?
Inject protein from a pathogen (antigen)
No effect!
91. A brief history of vaccination
A. T. Glenny first used alum in diptheria vaccine to increase
effectiveness
Louis Pasteur discovers that repeated passes through chickens
weakens cholera
Edward Jenner infects 8 yr old boy with cowpox and confers smallpox
protection
1920
1879
1796
1000
1950
1855
1890
Son of a Chinese statesman inhaled dried smallpox scabs to confer
protection
Jonas Salk develops polio vaccine; approved for humans in
1955
MA passes first U.S. law mandating vaccination for school
children
Serum therapy for diptheria discovered by Kitasato and von
Berhing
Thehistoryofvaccines.org
92. Generation of protective anti-toxins (antibodies)
Long-term (10-50 years) immunity
or
Inject protein from a pathogen (antigen) + an adjuvant
These vaccines workedand scientists figured out how!
Inject weakened pathogen
?
Immune cells see pathogen through innate receptors, instruct
adaptive cells
93. Problems with the old methods
Dont work for every pathogen
Largely result in antibodies
Sometimes need different responses
94. Limitations of antibody protection
Influenza binding sites
HIV binding sites
HIV
Flu
95. What do we need to learn to make better vaccines?
What type of immune response will be most effective?
Which pattern recognition receptors should be targeted?
Which cells should antigen and adjuvants be delivered to?
96. 1. What type of immune response will be most effective?
Bacteria
Receptor
Nucleus
Cytoplasm
Virus
97. Dendritic cells are specialized phagocytes
Dendritic cells are very good at:
Dendritic cell
100. 2. Which receptors should an adjuvant target?
Cytokines released
Type of immune response
Dendritic cell
101. 3. Which dendritic cells should be targeted?
102. Recent advances in vaccines
Directly targeting antigens to dendritic cells
Collecting dendritic cells and modulating them outside the
body
103. There are many types of DCs in different areas of the
body
Small intestine
104. vaccine
?
K
?
?
Old vaccine technology provides full body protection
105. Vaccines can be targeted to specific DCs
106. Recent advances in targeted antigen delivery
Directly targeting pathogenic antigens to Dendritic Cells
Collecting Dendritic Cells and modulating them outside the
body
107. Cancer and the immune system
Current cancer treatments (chemotherapy) are non-specific and very
harmful to healthy cells
Immune system can fight cancer cells
But, it is hard to see them because they look similar to our own
cells in many ways
We can use vaccine technology to help the immune system
108. Preventative vaccines
vs.
Treatment vaccines
109. Inject Dendritic Cells back into patient
Cytokines
Cancer antigens
Grow large numbers of dendritic cells
Dendritic cells can be removed from the body and educated to
recognize antigens
Blood collected from patient
http://www.dendritic.info/index.html
110. Dendritic cells therapy has some drawbacks
Costly and time consuming
Need more knowledge of cancer antigens
Need more knowledge about how to best train dendritic cells
111. but shows great promise for several diseases
Has been largely safe for patients
Prostate cancer - first FDA-approved cancer vaccine for men with
metastatic prostate cancer
Melanoma
HIV
112. Summary of part 3
Many successful vaccines confer protection through antibodies
For some diseases, different types of protective responses are
needed
Scientists need to learn more about immune responses to make better
vaccines
113. How to spot a virus: take home messages
There are many different types of pathogens the immune system needs
to see and defend the body against
The immune system needs to direct an appropriate response against
different pathogens
Understanding how to direct these responses will allow us to make
better vaccines
114. Thank you!
SITN would like to acknowledge the following organizations for
their generous support.
Harvard Medical School
Office of Communications and External Relations
Division of Medical Sciences
The Harvard Graduate School of Arts and Sciences (GSAS)
The Harvard Biomedical Graduate Students Organization (BGSO)
The Harvard/MIT COOP
Restaurant Associates