The warts, the misconceptions, the errors
– – noticed so far
So what is misconceived or not quite on the ball.
- 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 markers (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 ?).