20th Annual John G. Wagner Lectureship in Pharmaceutical Sciences presented by Nobel Prize Laureate Dr. Rolf M. Zinkernagel

The Department of Pharmaceutical Sciences is pleased to announce the 20th Annual John G. Wagner Lectureship in Pharmaceutical Sciences on Tuesday, June 2, 2015 from 3:30 pm - 4:30 pm at the BSRB - Kahn Auditorium. This year’s lecture, "Immunology Taught by Viruses," will be presented by Dr. Rolf M. Zinkernagel.

This lecture is open to the public.

Dr. Zinkernagel received his MD degree from the University of Basel in 1970 and his PhD degree from the Australian National University in 1975. In addition to the Nobel Prize, he also won the Cloëtta Prize in 1981, the Cancer Research Institute William B. Coley Award in 1987 and the Albert Lasker Medical Research Award in 1995. He is a member of the Cancer Research Institute Scientific Advisory Council, The National Academy of Sciences, and The Academy of Cancer Immunology. Zinkernagel was elected as a Corresponding Fellow to the Australian Academy of Science also in 1996.

Title: Immunology Taught by Viruses

Abstract:  Immunology as a field of medical enquiry has drifted away often to turn purely academic, because the interest and appreciation of protective immunity in infectious disease medicine has been overtaken by ‘l’art pour l’art’ of so-called ‘basic immunology’. This development deprives much of immunological sciences of the biological basis and understanding that must be linked to co-evolution of infectious agents and hosts’ protective immunity. It is this co-evolutionary context that renders this field so different from studying yeast, bacteria, fibroblasts, lymphocytes or neuronal cells in splendid isolation in in vitro model situations, where everything is possible (and permitted or mistakes forgiven without repercussions) because the co-evolutionary context is ignored by too many.

With the help of vesicular stomatitis virus (VSV), I shall critically review the following parameters:1) Definition of specificity; by phenolic haptens or by protective antigenic sites against infections and explain why cross protective vaccines are an illusion. 2) The importance of antigen as the (major, only?) regulator of immunity versus the idea of regulatory T cells 3) Protective immunity by vaccines against the classical acute childhood infections (e.g. rabies, VSV or measles), by neutralising antibodies, whereas vaccines are not efficient against chronic persistent infections (e.g. TB, leprosy, HIV or malaria). 4) Affinity maturation of antibodies against poorly or cytolytic infections is too slow, and against noncytopathic agents so slow, that HIV or plasmodia escape by mutation. 5) So called immunological memory is an experimental artefact. It is the pre-existent level of protective (neutralizing) antibodies (or the number of pre-activated T cells) that determine protection. Re-stimulation of so called memory B cells to become antibody secreting plasma cells or T cells takes 2 - 5 days and therefore is generally too slow for rapid efficient protection. In summary I conclude that we cannot do better immunologically than co-evolution if we use the same tools as evolution has been using so far. But we certainly can do better if we use new tools not used by evolution such as antibiotics, antivirals, autoantibodies or education.

References:

• Kündig TM, Bachmann MF, DiPaolo C, Simard JJ, Battegay M, Lother H, Gessner A, Kuhlcke K, Ohashi PS and Hengartner H (1995) Fibroblasts as efficient antigen-presenting cells in lymphoid organs. Science 268:1343-1347

• Zinkernagel RM, Ehl S, Aichele P, Oehen S, Kundig T and Hengartner H (1997) Antigen localisation regulates immune responses in a dose- and time-dependent fashion: a geographical view of immune reactivity. Immunol Rev 156:199-209

• Zinkernagel RM (2002) On differences between immunity and immunological memory. Curr Opin Immunol 14:523-536

• Zinkernagel RM (2003) On natural and artificial vaccinations. Annu Rev Immunol 21:515-546

• Zinkernagel RM and Hengartner H (2004) On immunity against infections and vaccines: credo 2004. Scand J Immunol 60:9-13

• Zinkernagel RM (2007) On observing and analyzing disease versus signals. Nat Immunol 8:8-10

• Zinkernagel RM (2014) On plasma cell longevity or brevity. Expert Rev Vaccines. 2014 Jul;13(7):821-3. doi: 10.1586/14760584.2014.924402. Epub 2014 Jun 7.

• Zinkernagel RM (2014) On the role of dendritic cells versus other cells in inducing protective CD8+ T cell responses. Front. Immunol., 10 February 2014 | doi: 10.3389/fimmu.2014.00030