Immunity ≠ Immunological Memory

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Immunity ≠ Immunological Memory Rolf Zinkernagel University of Zurich IMI Stakeholder Forum - 13 May 2013 - Brussels • Protective vaccines imitate co-evolution of infectious agents and hosts. • We cannot do better than evolution by using the same tools, only when introducing ‘new’ tools (antibiotics, antivirals, autoantibodies, behavioural changes) • Vaccines against solid tumours (carcinomas, sarcomas) and chronic persistent infections are theoretically not impossible but practically highly unlikely! Vaccines Not successful available Polio 1, 2, 3 TB bact. toxins Leprosy measles HIV Haem. infl. malaria (cholera) Neutr. / effector T cells opsonising antibodies antibodies igG (IgA) IMMUNITY • "innate resistance" > 95 % • Ab in eggs • protective memory via Ab (vaccines) • TB: no vaccine • autoimmunity > 30 y, female > male 5 : 1 • tumors > 30 years • Is what we measure biologically important ? (e.g. acad. memory: earlier + greater) CTL ELISA nAb Immunity Immunology Protection • ‚Memory‘ • Small pox • quicker - higher • Poliomeningitis • Measles • HIV, malaria - • Tuberculosis ± Antibody Memory after immunization with VSV a) neutralizing antibodies b) ELISA 12 12 ) 10 ) 10 2 3 8 8 40 log 10 log 6 - - 6 NP binding NP - 4 IND neutralizing 4 - IgG ( IgG ( 2 VSV 2 VSV 0 0 0 20 100 200 300 0 20 100 200 300 days after immunization days after immunization Why immunological Memory ? Protection (immunity) counts ! • Earlier + better • If first infection survived no need for memory • If first infection kills no need for memory • All vaccines that function protect via preex. neutr. antibodies? (autoantibodies ?) • Protection is antigen dependent Theoretical vaccines Theoretical HIV Theoretical Influenza (or TB) vaccine vaccine • persistence at low • combination of levels for T cell all possible activation (TB) hemagglutinins 4 • combination of 10 3 – 107 GP variants, ~ 10 variants? or mutating vaccine • repeat • low-no vaccinations immunopatholgy (TB) • crossprotective vaccine not • anti-virals, possible antibiotics, wait until HIV-1 ~ HIV-2? Conclusions • „Memory“, a nice idea, but is a laboratory artefact • Protection depends on preinfect. nAb titers and / or activated T cells (variability: HIV, malaria) • Both are antigen-driven (reencounter, persistence in host, antigen-antibody complexes on FDC) H. Hengartner A. Althage A. Ochsenbein M. Bachmann B. Odermatt A. Ciurea M. Pericin St. Freigang D. Pinschewer L. Hunziker M. Recher U. Karrer HP. Roost Th. Kündig Th. Rülicke B. Ludewig C. de la Torre M. Martinic M. Whitt Thank you! IMI Stakeholder Forum - 13 May 2013 - Brussels .

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View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by RERO DOC Digital Library Cell. Mol. Life Sci. (2012) 69:1635–1640 DOI 10.1007/s00018-012-0972-y Cellular and Molecular Life Sciences MULTI-AUTHOR REVIEW Immunological memory = protective immunity Rolf M. Zinkernagel Received: 10 March 2012 / Revised: 13 March 2012 / Accepted: 13 March 2012 / Published online: 6 April 2012 Ó Springer Basel AG 2012 Abstract So-called ‘immunological memory’ is, in my Introduction view, a typical example where a ﬁeld of enquiry, i.e. to understand long-term protection to survive reexposure to In the beginning was the fact that, once recovered from an infection, has been overtaken by ‘l’art pour l’art’ of ‘basic infection, the patient was resistant for life to disease by immunology’. The aim of this critical review is to point out the same infection. This, we call immunity. But since the some key differences between academic text book-deﬁned 1880s, with the beginning of modern immunology, the immunological memory and protective immunity as term immunological memory was borrowed from ‘con- viewed from a co-evolutionary point of view, both from the ventional’ (neurological) memory to seemingly explain this host and the infectious agents. A key conclusion is that fact. We still do not understand whether ‘conventional’ ‘immunological memory’ of course exists, but only in brain memory is due to once perceived or thought = particular experimental laboratory models measuring always remembered, versus repeatedly reencountered, ‘quicker and better’ responses after an earlier immuniza- recollected, or dreamed. This controversy is the subject of tion.
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