Not seeing the wood for the trees.

This well known idiom is generally considered to mean that an overall perspective is overlooked because we become bogged down in detail. However, the double meaning of wood (ie, either "wood" as a group of trees or "wood" as in timber) allows us to see that we could miss the significance of both microscopic observations or grand scale observations by focusing just on the immediate apparance of what should really constitute a grand system, ranging from a quantal to a universal scale.

So it is with immunology. Metchnikoff started it off brilliantly with the realisation that, at base, it was dominantly orientated around phagocytes and the maintenance of order. But, very soon, the obvious (the trees) began to dominate. The majority of immunologists began to concentrate on complement and then antibodies. The "immune system" was obviously mobilised in infections and, soon, the identification, attack on and elimination of micro-organisms was seen to be the obvious role of the immune system. Once the function and importance of lymphocytes was realised, the immunology community decided to elevate these to acting as the commanders of all other immune system troops. Innate immunity took on an "also ran" – vestigial, left over, more primitive – importance in immunity (assumed to be a bug detection and killing system). Charlie Janeway is credited with precipitating the realisation that innate immunity was far more important and central than the community were acknowledging. However, if we had listened carefully to Metchnikoff, none of this diversion would have been necessary.

Then came Medawar and Burnet. They realised that thymic conditioning in utero (and in the first few days after birth) were a period in which tolerance was established. The obvious assumption was that this had purpose and was how an animal developed a definition of "self". But here, immunologists went for the apparently obvious (the trees). The classification into tidy (apoptotic) disposal of debris versus the disposal of untidy debris (catastrophic, rupturing, cell death) was missed.

On the "timber" side the involvement of immune cells in virtually any pathological condition you chose to examine under a microscope was ignored. "It's not part of the trees". Inflammation, the virtually universal response to any disruption, was somehow seen as a side show not belonging to the wood (as in forest). Innate immune memory has recently become an in vogue research interest; but I still see no one touting the idea that the adaptive immune system acts as a sophisticated memory for inflammation. The lymphocentric view of immunity persists for many; however, I'll wager that the immune system will soon be acknowledged to be "inflammocentric". The advantage of this perspective is that immune cells are now seen to be also involved in the regenerative/restitutive arm of the inflammatory response.

In the last few years, there has been a burgeoning interest in innate immune memory. BUT, what is the adaptive immune system? I contend that it's a "cunning" evolutionary development where cells, clearly derived and descended from the myelo-monocytic lineage, evolve a mechanism to develop a memory of innate immune encounters; with this they amplify and accelerate the inflammatory and innate immune disposal of compromised cells and tissues. So, why is the research arena so resistent to acknowledging this principle? I guess it is because the innate immune system is still regarded as a distinct and adjunctive system of immunity, where the adaptive immune system is seen as a powerful "new" evolutionary development that runs, in a dominant but independent fasshion, alongside the innate immune system (rather than being intricately integral). If the adaptive immune system is viewed as having no other function than to act as a memory for previous innate immune encounters, then the integral and seemless nature of the combined innate and adaptive systems sweeps away all prior conceptual divisions. The "immune" (or morphostastic) system has been testing out mechanisms to generate innate immune memory throughout the evolution of metazoans. The biggest breakthrough sems to have come with the advent and emergence of jawless vertebrates (chordates).

I could go on with this theme (probably will do given time and more thought). However, suffice it to say that the parochial, "trees only", view of the immune system has been hiding a panoply of inteconnected and expansive features that – by and large – might well be encompassed within the terse metaphor of "morphostasis". And, we may have only scraped the surface of this exploding perspective