The all too slow evolution of eukaryotes to encode a new recognit

The all too slow evolution of eukaryotes to encode a new recognition became no match for the evolutionary potential of the prokaryotes to rapidly encode escape from that recognition. The only solution was to somatically generate a random recognitive repertoire that divided the antigenic universe into combinatorials of determinants referred Ku-0059436 to as epitopes. This somatically generated repertoire characterizes what is referred to as the adaptive immune system. While this made it very difficult for an infectious agent to escape recognition, a random somatically generated repertoire posed two new problems that demanded

concurrent solutions. First, the repertoire had to be sorted into those specificities which if expressed would debilitate the host [i.e. anti-self (S)] and those specificities which if not expressed would result in the debilitation of the host by infection [i.e. anti-nonself (NS)]. The anti-S had to be purged leaving as a residue the anti-NS to protect the host. This process is metaphorically referred to as ‘the S-NS discrimination’. Second, the sorted anti-NS repertoire had to be selectively coupled to largely

the same panoply of effector functions that were used by the recognitive repertoire click here of the innate system. These two problems need comment. It is the fact that the output is just as biodestructive Ureohydrolase and ridding for the host as it is for the pathogen that mandates a mechanism to sort the repertoire. The innate repertoire is sorted by germline selection over evolutionary time with the result

that it distinguishes the self-of-the-species from the pathogenic universe. On the one hand, any mutation in the innate repertoire that resulted in recognition of a self-component of the species would be lethal in the offspring of a mating between that mutant and an individual expressing that self-component. On the other hand, any mutation that resulted in the recognition of an antigenic determinant common to many pathogens would be distinctly advantageous. As a consequence, the innate repertoire is blind to the self-of-the-species and recognizes a limited number of epitopes shared by many pathogens. This can be easily seen as hosts without adaptive immune systems permit grafting without rejection between individuals of a species and in many cases between species. In the presence of the adaptive system, grafts between individuals of a randomly mating species are rejected. The adaptive system is individual-specific; the innate system is species-specific. Specificity of the epitope-recognitive receptors (paratopes) is evolutionarily driven by the necessity to make a S-NS discrimination. For the innate system, its specificity must be sufficient to distinguish the pathogen from the self-of-the-species.

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