Mechanisms and Genes
Elucidation of the mechanistic and genetic basis of tolerance traits is of interest in its own right, not least in this age of extreme reductionism, when many in biomedicine simply do not believe something exists until the molecular pathways involved have been revealed.
Mechanisms of tolerance are likely to include increased investment in vulnerable tissues, both before and after attack.
Hosts with thicker gut linings will be less affected by grazing nematodes, and those able to more rapidly replace red cells will be less affected by severe malaria anaemia. Immunological mechanisms will also be involved. Tolerance may involve “anti-disease immunity” or “anti-toxin immunity,” where responses are not directed at the parasite itself, but rather at toxins and other harmful substances produced by the parasite.
Tolerance may also involve mechanisms which damp down inappropriate host responses and/or limit collateral damage (“immunopathology”) from otherwise well-directed immune responses [7].
Importantly, a particular mechanism may affect both resistance and tolerance. Thus, tolerance will almost certainly involve the great variety of mechanisms involved in resistance and many more besides.
Yet it is striking how little we know about tolerance mechanisms relative to resistance mechanisms—and indeed that the tolerance mechanisms we understand best are those that mitigate the side effects of resistance.