sitn innate immunity complete

1. How to Spot a Virus
The origins of an immune response
Kevin Bonham
Sky Brubaker
Jillian Astarita

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
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
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
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?
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
Credit: CDC
Credit: NIAID
38. Viruses
Bacteria
Pattern Recognition Receptors Differentiate Pathogens
Credit: CDC
Credit: NIAID
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
Mattyman17: Wikimedia Commons

Viral Defense vs Bacterial Defense

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

Stops production of new virus 49. Detrimental to cells

X
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

Targeted cell killing 53. Uninfected cells are unharmed

X
X
X
X
X
X
X
X
X
X
X
X
X
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

Antiviral State 56. Recruit Cytotoxic cells 57. Neutralizing Antibodies

Questions?
58. Bacterial Defense
Phagocyte
Cytoplasm
Phagocytosis
Phagocyte
Nucleus
Cytokines
Phagocyte
Nucleus
Phagocyte Recruitment and Activation
Phagocyte
Cytoplasm
63. Bacteria Are Slippery
Credit: Phillip G. Allen http://www.biochemweb.org/neutrophil.shtml
Y
Opsonizing Antibody Production
Y
Y
Y
Phagocyte
Y
Cytoplasm

Phagocyte Recruitment 66. Phagocyte Activation 67. Opsonizing Antibody

Viral Defense vs Bacterial Defense

Phagocyte Recruitment 68. Antiviral State 69. Phagocyte Activation 70. Recruit Cytotoxic cells 71. Opsonizing Antibody 72. Neutralizing Antibodies

Responses to Different Pathogens

Viral Defense vs Bacterial Defense 73.Leprosy: A case of directing an inappropriate response

Leprosy: A Spectrum of Disease
Lepromatous
Tuberculoid

Few skin lesions 74. Numerous skin lesions 75. High number of bacteria 76. Low number of bacteria

24 year old man from Norway, suffering from leprosy.
77. Mycobacterium leprae: the causative agent of Leprosy
Nucleus
CDC Public Health Image Library: 2123
78. Immune Response Dictates Disease Outcome
Lepromatous
Tuberculoid

strong antibody response 79. Strong cytotoxic cell response

Y
Y
Y
Y
Y
cytotoxic cell
Nucleus
Y
24 year old man from Norway, suffering from leprosy.
Nucleus
80. Summary

Viral Defense vs Bacterial Defense 81.Leprosy: A case of directing an inappropriate response

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
?
?
Louis Pasteur discovers that repeatedly infecting chickens with cholera weakens the pathogen
1879
1796
1000
1855
MA passes first U.S. law mandating vaccination for school children
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
?
?
Louis Pasteur discovers that repeated passes through chickens weakens cholera
1879
1796
1000
1855
1890
Serum therapy for diptheria discovered by Kitasato and von Berhing
90. Generation of protective anti-toxins (antibodies)
?
Long-term (10-50 years) immunity
These vaccines workedand scientists were starting to figure out how
?
?
Inject protein from a pathogen (antigen)
No effect!
A. T. Glenny first used alum in diptheria vaccine to increase effectiveness
Louis Pasteur discovers that repeated passes through chickens weakens cholera
1920
1879
1796
1000
1950
1855
1890
Jonas Salk develops polio vaccine; approved for humans in 1955
Serum therapy for diptheria discovered by Kitasato and von Berhing
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!
?
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:

Seeing pathogens through pattern recognition receptors 98. Deciding what type of immune response should occur 99. Instructing other immune cells

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

sitn innate immunity complete

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