 | First, I have not gone back and incorporated references to dendritic cells
in this series of articles. The story of these tissue resident antigen
presenting cells has evolved greatly over the last 8 or more years. The
wording of the Morphostasis papers does not need to be changed to incorporate
them in appropriate places. I have left this task to the readers. |
| Complement and gap junction insertion. Clearly, this does not happen in
the simplistic way envisaged. There is tantalising evidence that complement
and T2 tubules may be used by macrophages in their regenerative role and that
they may substitute for gap junctional intercellular channels. The original speculation
was that IgSF (immunoglobulin superfamily) CAMs (cell adhesion molecules)
somehow used their beta-2-microglobulin to spawn large numbers of gap
junctions with their LY permeable intercellular channels. It is not as simple
as this. |
| The origin of Ig (immunoglobulin) V genes and B-cells. It had seemed
likely that these evolved after Tc and Th1 cells. However, it may be that the
B-cell evolved as a "targeted macrophage" and the likely targets are particular
tissue antigens used to promote debris clearance during tissue remodelling in
embryo (eg, resorption of tadpole tail and finger webs amongst other things).
We could imagine that these primitive cells might use V genes alone (without D
and J splicing and without somatic hypermutation). [Gamma/delta
T cell receptors could have a special role in tissue resorption.] However, this change in
evolutionary sequence does not fatally upset the hypothesis - it may simply
prove to be
an ill conceived detail. |
| Complement Factor-B does not appear to promote GJs. Again, the speculation
has become too specific. |
| In formulating "the need for focal anergy" and attributing this entirely
to the severity of the inflammatory process, I have failed to include the
chronicity/persistence of inflammation in the equation. The persistence of
inflammation reflects an inability to close out and resolve the inflammatory
process that would normally lead to a regenerative resolution. Chronicity/persistence
of inflammation might
well prove to be just as important as its severity in leading to focal
anergy. Note the implied need for a continuing, stuttering attempt at
resolution (regeneration) and the increased temporal exposure to potential
faults in the regeneration process (? carcinogenesis ?). |
