> In article <9411081312.AA15640 at xtal220.harvard.edu> collins%xtal220 at HARVARD.HARVARD.EDU writes:
> >
> >Okay, I think we all agree and understand that the mechanisms for presenting
> >self or foreign peptides are interrelated and that macrophages are no
> >different in that respect than any other APC. The question has strayed from
> >that point I think. The question is: How do macrophages recognize a body to
> >be phagocytosed? While I agree that other systems can make it easy for the
> >macrophage (ie recognition by antibodies), this requires that the immune
> >system have previous knowledge of the foreign particle. Certainly it is true
> >that there will be cross-reactive antibodies around, but this is like the old
> >arguement about the chicken and the egg. To anthropomorphize a bit, don't y
> >believe that there must be a mechanism for the macrophage to make up its own
> >mind?
>
At least two potential mechanisms spring to mind, neither of which requires
the immune system to have any prior knowledge of the pathogen. Both of
these are generally referred to under the general heading of "innate
immunity".
In the first, the alternative pathway of complement activation -
essentially spontaneous activation of C3, which deposits on surfaces, binds
Factor B, etc - will lead to deposition of C3b on non-self surfaces and not
on self surfaces, which carry complement negative regulatory proteins (DAF,
MCP, Factor H) and do not bind the positive regulator, Factor P. C3b is
an opsonin and will encourage phagocytosis of the coated pathogen.
In the second, particularly relevant to cellular pathogens
(bacteria/yeast/fungi/protozoans) rather than noncellular
(viruses/injected or ingested toxins,venoms), binding of pathogen cell
surfaces to various macrophage receptors (LPS receptor/mannose receptor
etc) induce secretion of IL1 and IL6 which can in turn initiate acute phase
protein synthesis in the liver. Both mannose binding protein and
C-reactive protein bind to bacterial surfaces in preference to self
surfaces; they are opsonins in their own right and can also activate
complement and cause C3b deposition and further opsonisation.
Hope this helps.
Paul
--
Paul J Travers phone : +44-(0)71-631-6862 (office)
ICRF Structural Biology Unit " " " 6868 (lab)
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London WC1E 7HX email : p_travers at icrf.icnet.uk
England or : paul at histo.cryst.bbk.ac.uk
