As far as I understand, in complement system C3b gets deposited on pathogen surface but it can also be deposited on host cells. Host cells have some negative regulatory system such as membrane cofactor of proteolysis MCP, decay associating factor DAF etc which either removes C3b or cleave it using factor I to iC3b which can not form a C3 convertase or C5 convertase so no production of membrane attack complex on host cells.

However, phagocytes contain complement receptors CR2, CR3 etc that specifically recognise iC3b and engulfs the cells bearing it. While it is very useful for pathogens bearing iC3b (In those cases where pathogens contain sialic acid residue which attracts factor I and prevents forming MAC on those pathogens) wouldn't it be very dangerous for host cells?

So if there is receptors against iC3b on phagocytes then what is the point of host cells converting C3b into iC3b, they get killed one way or another anyway


There's a relatively new concept of self-associated molecular patterns (SAMPs), which much like DAMPs and PAMPs, help immune cells make a decision in a slurry of signals. There's at least a fair article on SAMPs here, and to go even further, the suggestion that tumor-associated SAMPs can dampen immune clearance of cancer cells.

In my head a few things are going on:

(1) The opsonins are potentially binding to everything. Of course, there are surfaces like ECM that don't have any receptors or patterns that you don't want getting damaged, and there's at least some evidence that complement clearance by factors I and H (paywall) may contribute to ablating that effect.

(2) The actual targets for the immune system are expressing patterns that specialized pattern recognition receptors on your phagocytes and so forth can recognize.

(3) Self cells are expressing receptors and patterns that tell the very same cells there's no threat, either through direct inhibition or degradation of kill signals.

Remember that when self cells are damaged, the expression of DAMPs help macrophages and the like come clear them away, so there's obviously a way for self cells to control that effect.


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