Further notes about the morphostasis concept – split files

(29) Trying to usurp the hegemony of extant, perceived wisdom

I will progressively expand this section so these are early thoughts. Thomas Kuhn talked of "tautologies"; the emergence of perceptions that, in retrospect, become so obvious that it is hard to see they were ever regarded differently.

The greatest mis-conceptual skyscraper that I believe we need to topple is the conviction that the immune system is a pathogen hunting and killing system. The immune system – for many immunologists – hunts, identifies, chases and destroys invaders (pathogens). For example (a recent quote):

The exponents of this perspective generally see the word pathogen as a synonym for a potentially pathogenic micro–organism (potential here reflecting a tendency to cause disease in at least some of the multi-cellular creatures that are exposed to it). But, as the examples quoted in the introduction to "A proliferation of pathogens ..." article demonstrate, those that use this interpretation lose sight of the perspective that "pathogen-equates-to-damage" and start to use the word interchangeably with a "micro-organism-in-general". And they do so in a vacillating interpretation that they seem to remain unaware of.

There is no question, whatsoever in my mind, that a failing immune system does render us susceptible to infections. However, it is the failure to respond to and contain damage that leads to immune responses that we then interpret as specific adaptive responses against the infecting organisms. Epitopes of damaging micro-organisms will tend to be both novel (not previously tolerised following controlled-cell-shutdown then tidy-disposal) and exposed at the sites of cell damage. These epitopes will "favour" aggressive responses; but not because "they are foreigners and need to be zapped". Immune cells (inflammatory to adaptive) are rather like caretakers of a public building who will tolerate visitors provided they do not stray too much or start breaking up bits of the building. And these caretakers won't leave free lunches lying around that invite all and sundry to come along to enjoy the party. They will ensure that these visitors seek their sustenance elsewhere (except for those who are welcomed because they help).

The innate immune response is generally regarded as a rather primitive system that, on its own, can retain no significant memory of a past encounter with a specific "pathogen". This view is beginning to change as various papers surface suggesting that innate immune responses can be "trained" (for example look at Eur J Clin Invest 2013; 43 (8): 881-884 then locate it in PubMed for a list of related articles ). There are a few other articles describing invertebrate immunity where immune responses appear to be adaptive. This observation would have been regarded as heresy by past generations of immunologists. But, what all these articles fail to shout, from the rooftops, is that the adaptive arm of the vertebrate immune system is managed by the innate immune system (at both initiation and execution points) so that it acts as a memory for past pathogenic stimuli. The inflammatory response is thus quicker, more focused and more aggressive on re-encountering a similar pathogenic stimulus; and it can also be dampened down when not needed (tolerance). My guess is that the immune system has, throughout evolution, explored mechanisms for producing a "trained innate immunity". The so called "big bang" in immunity, set off by the incorporation of RAG genes, was probably a dramatic jump in this quest.