Aug 16, 2013 - H8. H9. H10. H11. H12. H13. H14. H15. H16. Influenza A. Virus Host. Range. Species that maintain the viru
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The Killer Defence Peter C. Doherty, University of Melbourne, and St Jude Children’s Research Hospital , Memphis TN.
Influenza is incredibly infectious
http://www.rit.edu/~andpph/photofile-c/sneeze-k-17.jpg
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H1
Influenza A Virus Host Range
H2 H3 H4 H5
Species that maintain the virus in nature
H6
Also infects seals, whales, cats, leopards, stone martens, racing greyhounds etc
H10
H7 H8 H9 H11 H12 H13 H14 H15 H16
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IMMUNITY: A complex defence system
IMMUNE IMMUNIS EXEMPT WITHOUT TAX?? Has evolved to minimize the tax of infection, the process whereby simpler life forms, like viruses, live in, or on, us. Immunity has to deal constantly with novel challenges
Immunity is basically a function of the white blood cells, or white corpuscles First described in 1843 by G Andral and W. Addison (Hadju,SI J Clin Lab Sci 33:237, 2003) The thinking at that time was that they might be involved in nutrition. Then Rudolf Virchow argued that the white corpuscles in blood were the same as the “pus corpuscles” in inflammation The whole field moved forward in 1879 when Paul Ehrlich used vital dyes to stain blood smears.
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By the early 20th century, Eli Metchnikoff had identified the macrophage, and Rudolf Virchow pointed to its role in inflammation But it was not till the 1960’s that the experiments of Jim Gowans, Av Mitchison and others told us that the lymphocytes that are so prominent in blood are immune cells that recirculate from lymph node, to blood, to tissue and so on Then Jacques Miller identified the key role of the thymus, and we realised that there are separate lineages of T and B lymphocytes
INNATE IMMUNITY gives rapid, partial protection of limited specificity. It is very old in the evolutionary senses, and may both provide and suggest useful targets for therapeutic intervention. ADAPTIVE IMMUNITY is “young” (400 million years) in evolutionary terms, has a high level of specificity and is characterized by the long-term memory targeted by the vaccinologists.
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ADAPTIVE IMMUNITY Since 350x106+ years Only those who had recovered from the plague could nurse the sick because they could not catch the disease a second time …..this altered state is specific. Thucidides -2425 years
The Persistence of Memory, S. Dali
THE BASIS OF VACCINATION IS IMMUNE MEMORY
Antibodies work well against systemic infections.
We have no vaccine for HIV/AIDS or for hepatitis C virus, and we need a better vaccine against influenza
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The CD8+ “killer” T cell is the “legionnaire” of the immune system that operates at short range to eliminate “damaged and dangerous” self using multiple effector molecules.
Pilium
Gladius
We work on the CD8+ “Killer” T cells, the “hit-men” of immunity
V
NK T cell
Movie by Misty Jenkins, NHMRC CJ Martin Fellow with GillianGriffith, Cambridge, then Joe Trapani,PeterMac, Melbourne
V
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Virus-specific CD8+ “killer T cells: the “hit men” of immunity T cell killing of allogeneic cells was first reported by Rosenau and Moon in 1961, then greatly developed through the 1970’s by Jean Charles Cerrottini and Teddy Brunner.
Induced apoptotic “suicide”of cell virus“factories”
Cells that “hit” other cells must be precisely targeted.
The same basic mechanisms can operate to control some forms of cancer. A great deal of current research is aimed at making preventive or therapeutic cancer vaccines. The papilloma virus vaccine is showing great promise in cervical carcinoma.
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This cell-surface targeting/surveillance function works via the MHC class I glycoproteins TCR
Epitope
Graft rejection is an epiphenomenon of surveillance of self. The MHC-I genes are encoded at 3 loci and are very polymorphic. The CD8 T cell response is highly INDIVIDUALIZED
Co-crystallization of TCR/pMHCI shows that the TCR dominates peptide contact for DbPA224 β-chain TRBV29/BJ2-7
α-chain TRAV21/AJ53*01
CDR1β V CDR3α
CDR2β
PA peptide CDR1α
CDR3β
H2Db CDR2α V
m2m
Day, EB et al PNAS 108: 9536-41, 2011
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CD8+ T Cell Recognition: 1974 “biology” version.
The discovery of MHC restriction told us that cytotoxic T lymphocytes (CTLs) are targeted to eliminate pathogen-modified cells rather than the pathogens themselves
Though science may advance by the type of “paradigm shift” that sometimes wins Nobel prizes, every discovery depends to some extent on what goes before. C.C. Little, started the Jackson Lab Miss Abbie Lathrop, former school teacher and ornamental mouse breeder who provided seed stock for the Roscoe B. Jackson Laboratories at Bar Harbor ME, Miss Abbie George Snell shared is the “mother of mouse genetics” the 1980 Nobel Prize
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Stage of Stockholm Concert Hall, December 10, 1996
Science celebrity has about the same resonance in the broader community as being a minor character in a coffee commercial
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There are no more Prizes after the Nobel, but other things happen like having stuff named after you
Serial killers
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SCIENCE COMMUNICATION IS FOR ALL OF US It’s particularly Important to interest school children in the idea that science can solve problems 2007 2005/6 Aug 2012/ Sept 2013
W H AT EV E RY O N E N EE D S T O KN O W
PETER DOHERTY
Sept 2013
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