Conceptions vs Preceptions

When we consider the process that we have named "the immune system", it is probably important to detach our current conceptions from prior preceptions. The main preception has been that the immune system is, far and away, predominantly driven by the adaptive [cognate] immune system (lymphocytes, antibodies and the specific recognition of antigenic determinants) and that it hunts and kills "pathogens".

There are, to my mind, probably two overriding "activities" that drive the immune system in health:

  1. A primordial amoebocytic capacity to find, chase and assimilate "food". The recognition and response to food/fuel are primordial capabilities handed down from the free living amoebocytes that were our ancestors. Organic debris and living micro-organisms are the preferred diet of unicellular (amoebocytic) organisms. Macrophages retain this amoebocytic capacity and probably use evolutionarily primordial molecular machinery to carry out this task.
  2. Morphostasis: we can divide this into intracellular cytoplasmic homeostasis and organ tissue homeostasis. Autophagy is critical in intracellular homeostasis; and apoptosis is critical in organ homeostasis (organ is used here to denote any structure built up of multiple zygote derived cells). Morphostasis follows a biphasic sequence: debridement then regeneration.

Tissue homeostasis is disrupted in disease (infections, injuries, degenerations etc). This disruption triggers various alert systems, the major outcome of which is an inflammatory ingess of innate immune cells of the phagocytic lineage (though other innate immune cells can also participate). In relying upon this primordial feeding mechanism to clear debris, the system is limited by the satiety that affects the participating phagocytes. These cells cannot continue to gorge themselves forever on over-copious organic debris. Once they have reached a point of satiety, they will prefer to pass on their surplus nutrients. The ingested debris has to be digested, assimilated and can be passed on to regenerating tissues so that these can effect repair and resolution. This is probably reflected in the shift from M1 (aggressive/debriding) to M2 macrophages (tolerating/pro-resolving).