Further notes about the morphostasis concept – split files

(14) The backdrop for self/non–self

It is worth re–emphasising how the idea of self/non–self discrimination emerged; it was "born" as a simplistic concept based on the categorisation of epitopes into self or non–self (epitopes are roughly equivalent to antigens). For a very long time (and it continues for many) self and non–self was believed to be established epitope by epitope: each epitope is apportioned to either self or non–self.

Now if we abandon this simplistic assumption (reject it), we can now reform the whole concept on the basis of healthy–self/other–than–healthy–self whole–cells; this is a cell–identity based system. This means we have to abandon the idea that lymphocytes and antibodies classify epitopes into self and non–self; we will need an alternative explanation of what they are differentiating (for they do end up "differentiating" and it does tend to approximate to self/nonself epitopes). In this shift, every cell expresses an identity on the basis of its "I am OK" communication with its neighbours. This healthy–self identity could be simple or complex (e.g., one ligand–receptor interaction or multiple ligand–receptor interactions together with chemokine messages, unhealthy–self markers, cellular junctions and others). It is more likely that self/non–self recognition arose in this way because antibodies are late comers in phylogeny. Epitope by epitope would be a hopeless strategy in hydra. And, it also suggests a totally de novo emergence – not rooted in any pre–existing process (it is generally assumed that RAG genes are the things that allowed this).

The alternative explanation of antibody/T–cell reactivity is that it classifies epitopes (roughly) into inflammatory or non–inflammatory encounters: and these epitopes need not be expected to remain rigidly committed to one or other compartment (as they are with the self/non–self epitope concept).