Some Thoughts on the Response to Antigens that are Effector T‐Helper Independent (‘Thymus Independence’)[Note 1. This paper was written while the author was a ...]

The Self–Non‐Self discrimination is germline‐selected for defence mechanisms (‘innate immune systems’) whereas it is somatically learned for immune systems (‘adaptive immune systems’). It is proposed that immune systems evolved from defence mechanisms by adding large recognitive repertoires that, by aggregating with antigens, were able to trigger the already existent effector functions of defence mechanisms. Thus today there are two pathways to triggering each class of effector function (macrophage opsonization, complement lysis or natural killer/‐natural cytotoxic cell activity). The antigen–antibody complex and the T‐cell antigen–receptor interaction trigger the immune pathway; the receptors of the defence mechanism trigger the ‘alternate’ or ‘innate’ pathway. The evolutionary selection pressure on defence mechanisms was to increase the size of the recognitive repertoire, which in turn, necessitated the emergence of a somatically learned Self–Non‐Self discrimination. By contrast with defence mechanisms that are triggered effector T‐helper (eTh) independently by polymers (Signal[3]), immune systems can be activated by monomers, a pathway that requires associative recognition of monomer and the reading of two Signals, Signal[1] resulting from the binding of an epitope to the antigen–receptor complex, Signal[2] delivered by an eTh cell. The evolving immune system hijacked part of this eTh‐independent pathway (Signal[3]) into which Signal([1] + [2]) merged. A model of these relationships is proposed.