Self and non-self

I have said very little about the metaphor of "self" and "non-self" for quite some time. Remember, this is a metaphor and, thus, simply a conceptualising tool. As of all metaphors, it won't turn out to be more than a manipulative device to get closer to the mirage of the "truth".

Let's think about the emergence of early multicellulates. What is quite evident is that those cells – that consitute simple metazoans – group together and co-operate with one another. These cells are usually (dominantly in actuality) the proliferative product of one "grandparent" cell that leads to a zygote-derived-colony. These colonies tend to attack or expulse interlopers – perhaps simply by ignoring them (there may be no cohesion to them as a colony moves around). They must employ some process by which they dock and co-operate with one another. Now, we can dub this a type of "self/nonself" discrimination; but we must remember the evolutionary roots of the process. We cannot, then, simply invent an alternative "self/nonself" discrimination based on self-epitope/non-self-epitope discrimination without first considering how and why this split should have occurred.

As metazoans evolve to become more complex, so the intricacies of identity discrimination also become more complex; now the colony has to have sub-identities for various tissues and employ even more complex identity mechanisms. Remember that "identity" itself is also a loose metaphor that covers intercellular junctions, various "docking" cell surface molecules (CAMs), mechanical forces, various long range (secreted) cytokines and, probably, many more mechanisms that are variously involved in multicellular co-operation.

[I will now use the abbreviation S/NS for self/non-self discrimination.]

I have just re-read Silverstein and Rose's article "On the mystique of the immunologigical self" ; . This has helped me to focus on these points:

• The glaring assumption has been that S/NS is based upon the categorisation of epitopes into S or NS.
• The "mystique of S/NS" is rooted in the vagueness of the term and its multiple interpretations.
• S/NS started as a useful metaphor but is in danger of becoming (has already become?) reified into a corrupt perspective.
• "Does the immune system, instead, distinguish beween noxious and innocuous stimuli" (ie, damaging stimuli – it is only by recording – "memorising" – a previous damaging stimulus that a danger quality can be attributed to the stimulus on its re-encounter; I contend that this is the purpose of adaptive immunity).
• Burnet took an early interest in identity.
• Metazoan existence depends upon cell lines co-operating with each other.
• The original horror autotoxicus definition focused on an aversion to "attacking" self epitopes. I suggest that the real horror autotoxicus is an aversion to attacking co-operating-healthy-self-whole-cells.
• The whole self-epitope/non-self-epitope concept of S/NS ignored innate lymphocytes (NK, Tnk, other innate lymphocytes and even gamma-delta T-cells). It is now obvious that alpha-beta T-cells are a fractional part of the immune response.
• The obfuscation created by regarding pathogens as obligate micro-organisms rather than as generic damaging agents.
• Zinkernagel and Doherty's realisation/discovery of antigen presentation in association with Mhc molecules brought a clear focus on identity ; .
• On the evolution of the vertebrate immune system; there are two things to note about common presumptions. First, they imply that self/non-self is dependant on antibodies and T-cell receptors (so invertebrates don't have "an immune system"). Second, they imply that invertebrates do not distinguish S from NS.
• Adjuvant induced autorejection to selected tissues is easily provoked. The stimulus just needs to be strong and persistent.
• Identity mechanisms in co-operating cell lines are found throughout the plant and animal kingdoms (and even in bacteria).
• Assumption: "infection is the prime driver of the immune system". But – this is only inasmuch as a bacterium (for example) needs to damage (metaphorically" pulverise") parts of its chosen host so that it can feed on the damaged host debris.