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
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
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
34. Cells With Pattern Recognition Receptors Instruct B-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
79. Strong cytotoxic cell response 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
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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 worked…but scientists didn’t 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 worked…and 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 worked…and 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 worked…and scientists figured out how! Inject weakened pathogen ? Immune cells see pathogen through innate receptors, instruct adaptive cells
93. Problems with the old methods Don’t work for every pathogen Largely result in antibodies Sometimes need different responses
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
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
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
