"David R. Johnson" <johnson at biomed.med.yale.edu> wrote:
snip
> There seem to be two issues here:
>1.) Although it is well established that CD4 cells need "professional" APC for
>priming, what is the evidence that CD8 cells do not respond to "amateur" APC
>(e.g. virally infected normal cells)?
Although this is a "muddy" area, most of the "real world" studies I recall
suggest that in the absence of good help one does not get get good CTL based
immunity. A virgin CTL will probably kill any virally infected cell it
encounters but this apparently is not sufficient to induce clonal expansion. On
the other hand there are experiments in "artificial" systems (knockouts for
example) which suggest that CTL expansion isn't dependent on CD4+ cells. I tend
to favor the real world studies myself.
>2.) Antigen specific B cells concentrate antigen by binding it with their
>membrane bound immunoglobulin (antibody). These antigen specific B cells then
>efficiently present the antigen to CD4 cells, and are in turn helped to mature
>by the CD4 cell. There does not seem to be any similar "logic" behind antigen
>presentation by macrophages. CD8 cells may be in an analogous position.
>Since IFN-gamma is uniquely capable of inducing MHC class II molecules on
>constitutively MHC class II-negative cells, could it be that the IFN-gamma
>produced by the CD8 cell induces Class II molecules and allows the infected
>cells to act as APC for CD4 cells?
Macrophages acquire antigen via opsonization. In the "naive" situation
complement probably plays a major role here (alternate pathway and mannose
binding lectin activation). This fits very nicely with Polly Matzingers
"danger" theory - the more damage something causes the more inflammation one
will see and the more complement activation is likely to occur.
I like the idea of autocrine stimulation of class II expression by CTL's, but it
still doesn't explain the apparent requirement for help in those "real world"
situations.
>pardon the lack of references (always much more effort than simply typing
>half-baked thoughts!)
References? What the heck are those? ;^)
Bob S.
