simultaneously excluding pathogens, was the role of the immune system. Most
evolutionary biologists now believe that the adaptive immune system evolved in
parallel with this complex microbiota precisely because the innate immune system
could not do the job (Pancer and Cooper 2006; discussed in Rook et al. 2017). The
innate immune system relies on inherited germ line-encoded pattern recognition
receptors (PRR), but rapid bacterial evolution can give rise to pathogens with
structures not recognised by existing PRR. The innate immune system can try to
catch up by duplicating the gene for a PRR and selecting a modification of its
structure that is able to recognise the new pathogen, but clearly this process is too
slow, quite apart from the fact that the genome would eventually become cluttered
with massive numbers of duplicated PRR genes. The development of the adaptive
immune system in vertebrates provided a way to create a very large repertoire of
different receptors with a minimal increase in genetic complexity. This is achieved
by somatic hypermutation involving the genes encoding the receptors of B and T
lymphocytes. These random mutations create large numbers of distinct T and B
lymphocyte clones bearing a huge diversity of receptors, but this creates several
potential problems. For example, random mutation could result in vast numbers of
useless lymphocytes that recognise nothing and so waste metabolic resources and
space. Worse still, there might be lymphocytes that recognise the host’s tissues and
so mediate autoimmunity. However, the diversified receptors generated by mutation
are expressed clonally. Each lymphocyte clone expresses only one receptor, so that if
a receptor turns out to be useless or autoreactive, the relevant cell line can be
eliminated. The autoreactive cells are mostly eliminated in the thymus, where selfantigens are expressed. However, in order to decide which other lymphocyte clones
to keep for managing and tolerating the microbiota, while eliminating pathogens, the
adaptive immune system requires data from the microbiota that is picked up from
mother and family, and data from the environment. The subtlety of this arrangement
is that each new individual develops an immune repertoire that is matched to the
microbial world into which he or she is born.
Therefore, just like the brain, the adaptive immune system is a learning system,
and like the brain, it must receive appropriate data inputs, and these must be received
early in life, and then maintained and updated throughout life. These inputs come
from the microbiota of mother and family, and also from the natural environment.
Deprivation or corruption of these inputs, for example by depletion or distortion of
the microbiota, is now known to have widespread physiological consequences.
Thus, if we can determine which microbial data inputs are essential to our health,
and which lifestyle changes are disrupting these inputs, we can expect to identify
prophylactic and therapeutic strategies.
18.1.3 Evolution Turns the Inevitable into a Necessity
Which microbial data inputs are essential? The subtitle for this essay is “Evolution
turns the inevitable into a necessity”. For example, crucial functions can be
330
G. A. W. Rook
evolutionary biologists now believe that the adaptive immune system evolved in
parallel with this complex microbiota precisely because the innate immune system
could not do the job (Pancer and Cooper 2006; discussed in Rook et al. 2017). The
innate immune system relies on inherited germ line-encoded pattern recognition
receptors (PRR), but rapid bacterial evolution can give rise to pathogens with
structures not recognised by existing PRR. The innate immune system can try to
catch up by duplicating the gene for a PRR and selecting a modification of its
structure that is able to recognise the new pathogen, but clearly this process is too
slow, quite apart from the fact that the genome would eventually become cluttered
with massive numbers of duplicated PRR genes. The development of the adaptive
immune system in vertebrates provided a way to create a very large repertoire of
different receptors with a minimal increase in genetic complexity. This is achieved
by somatic hypermutation involving the genes encoding the receptors of B and T
lymphocytes. These random mutations create large numbers of distinct T and B
lymphocyte clones bearing a huge diversity of receptors, but this creates several
potential problems. For example, random mutation could result in vast numbers of
useless lymphocytes that recognise nothing and so waste metabolic resources and
space. Worse still, there might be lymphocytes that recognise the host’s tissues and
so mediate autoimmunity. However, the diversified receptors generated by mutation
are expressed clonally. Each lymphocyte clone expresses only one receptor, so that if
a receptor turns out to be useless or autoreactive, the relevant cell line can be
eliminated. The autoreactive cells are mostly eliminated in the thymus, where selfantigens are expressed. However, in order to decide which other lymphocyte clones
to keep for managing and tolerating the microbiota, while eliminating pathogens, the
adaptive immune system requires data from the microbiota that is picked up from
mother and family, and data from the environment. The subtlety of this arrangement
is that each new individual develops an immune repertoire that is matched to the
microbial world into which he or she is born.
Therefore, just like the brain, the adaptive immune system is a learning system,
and like the brain, it must receive appropriate data inputs, and these must be received
early in life, and then maintained and updated throughout life. These inputs come
from the microbiota of mother and family, and also from the natural environment.
Deprivation or corruption of these inputs, for example by depletion or distortion of
the microbiota, is now known to have widespread physiological consequences.
Thus, if we can determine which microbial data inputs are essential to our health,
and which lifestyle changes are disrupting these inputs, we can expect to identify
prophylactic and therapeutic strategies.
18.1.3 Evolution Turns the Inevitable into a Necessity
Which microbial data inputs are essential? The subtitle for this essay is “Evolution
turns the inevitable into a necessity”. For example, crucial functions can be
330
G. A. W. Rook