I was recently asked about the surveillance system present within immunity which operates to kill virally infected cells by lack of MHC expression, and why this same system doesn't destroy red blood cells (RBC), which lack MHC.
One function of Natural Killer (NK) cells is to destroy cells infected by viruses, which have a mechanism of evading T-cell killing by down-regulating MHC class I expression. MHC class I molecules are expressed on every cell in the body apart from RBCs; a lack of expression is detected by NK cells which act to destroy the cell. However, RBC remain unharmed.
V.S
Like everyone else I assumed the almighty google would provide me with the answer to my friends question, so I typed in my query and the only relevant link was to a 'yahoo answers' page, which answered a succinctly phrased question which I've used to entitle this blog entry. Unfortunately the answer just stated that 'NK cells don't kill RBC as they recognise them as self'. This is obviously the case as RBC exist in healthy individuals without any hassle from NK cells... but WHY???
So far, the only explanation I've come across from trauling the literature is the expression of a molecule known as CD47. The presence of this molecule allows RBCs to be recognised as self by NK cells through ligation of SIRP1alpha. This signalling provides an inhibitory kill signal to NK cells.
If anyone has any more knowledge on this subject, or the 'official' answer, please let me know!
One function of Natural Killer (NK) cells is to destroy cells infected by viruses, which have a mechanism of evading T-cell killing by down-regulating MHC class I expression. MHC class I molecules are expressed on every cell in the body apart from RBCs; a lack of expression is detected by NK cells which act to destroy the cell. However, RBC remain unharmed.
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| SEM of NK cells |
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| Red Blood Cells |
V.S
Like everyone else I assumed the almighty google would provide me with the answer to my friends question, so I typed in my query and the only relevant link was to a 'yahoo answers' page, which answered a succinctly phrased question which I've used to entitle this blog entry. Unfortunately the answer just stated that 'NK cells don't kill RBC as they recognise them as self'. This is obviously the case as RBC exist in healthy individuals without any hassle from NK cells... but WHY???
So far, the only explanation I've come across from trauling the literature is the expression of a molecule known as CD47. The presence of this molecule allows RBCs to be recognised as self by NK cells through ligation of SIRP1alpha. This signalling provides an inhibitory kill signal to NK cells.
If anyone has any more knowledge on this subject, or the 'official' answer, please let me know!
It does not happen as our red cells (unlike rabbits which is why we use them for alternate pathway CH50 testing) contain many membrane inhibitors or regulators of complement activation such as MCP, DAF or CD55 and most importantly CD 59 or homologous restriction factor. The last CD 59 inhibits C9 induced pore formation and protects us from hemolysis even when the RBC's are amidst CD8 and NK cells. The same CD 59 also inhibits perforin from attacking our RBC. In fact C9 and perforin are members of the innate immune system and are homologous. Thus, RBC and self proteins (such as vasculature, renal, synovium) are protected from C9 as well as perforin-granzyme complex. Granzyme-perforin mediated effects on RBC's by CD8 cells, which are class I restricted, are abrogated by similar mechanism
ReplyDeleteAs I think and believe that the NK have both inhibitory and activating receptors and as I believe also that the nucleated self-cells having an inhibitory ligand which is MHC1 while RBCs lack of it by the same way they lack an activation ligand.
ReplyDeleteBut I also believe on the presence of Cd47 as a self-marker.