Acquired Immunity and Immunological Memory

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. lt 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.The key role of protective antibody levels is their transferability from mother to immune incompetent offspring. With the help of infectious virus, 1 shall critically review the following parameters:

1) Definition of specificity; by very small phenolic haptens or by protective antigenic sites against infections and explain efficient serotypically defined vs.less efficient cross protective vaccines.

2) The importance of antigen as the (major, only?) regulator of immunity versus the idea of regulatory T cells suppression,networks etc.

3) Protective immunity by vaccines against the classical acute childhood infections (e.g. rabies or measles), by neutralising antibodies, whereas vaccines are often 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. lt is the pre­existent level of protective (neutralizing) antibodies (or the number of pre­activated T cells) that determine protection.Re-stimulation,-of so called memory B cells to become antibody secreting plasma cells or T cells take about 5 days and therefore is generally too slow for rapid efficient protection.

In summary, 1 conclude that we cannot do better immunologically than co-evolution if we use the same tools as evolution has been using so far(including vaccines). However, we certainly can do better if we use new tools not used by evolution such as antibiotics, antivirals, induced or manufactured monoclonal autoantibodies and ,very important, education.

References:

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• Zinkernagel RM, Eh1 S, Aicheie P, Oehen S, Kundig Tand Hengartner H (1997) Antigen localisation regulates immune responses in a dose- and time-dependent fashion: a geographical view of immune reactivity. Immunei Rev 156: 199-209
  
  
• Zinkernagel RM (2002) On differences between immunity and immunological memory. Curr Opin lmmunol 14:523-536
  
  
• Zinkernagel RM (2003) On natural and artificial vaccinations. Annu Rev Immunei 21 :515-546
  
  
• Zinkernagel RM and Hengartner H (2004) On immunity against infections and vaccines: credo 2004. Scand J lmmunol 60:9-13
  
  
• Zinkernagel RM (2007) On observing and analyzing disease versus signals. Nat Immunei 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. Immunei., 10 February 2014 1 doi: 10.3389/fimmu.2014.00030