immunity 3 - avoiding immune destruction Flashcards
how do tumour cells avoid being recognised? (3)
loose MHC, interfere with the process involved in making peptides, loose the antigen
escape mechanisms - increased mutation rate
mutations in the cancer cell results in loss of the epitope (antigen) that T cells recognise or cause a defect in the mechanism that causes MHC-peptides to be presented. Therefore the tumour is no longer recognised
mutations effect on the peptide in MHC groove
if the peptide is mutated it does not bind to the groove in MHC so there is a loss of recognition
escape mechanisms - downregulation of MHC
lack of MHC causes killing of cells by NK cells, in cancer it is downregulated so but there is still some MHC so NK activity is still stopped but there is not enough MHC to trigger T cells
how does the downregulation of MHC molecules occur
in a process similar to darwinian selection - too much MHC means death from T cells and too little means death from NK so having a little prevents both
escape mechanisms - Tumours produce mediators that inhibit immune cell function
tumours express TGF-beta whilst also downreguation TGF-beta receptors on its surface. The tumour creates space for itself by killing cells around it
what does TGF-beta do
induces apoptosis in surrounding cells and encourage formation of new blood vessels
the effect of tumours expressing TGF-beta on other cells
it directly effects T cells and APCs , phagocytic cells become immunosuppressive
what are MDSCs
myeloid derived supressor cells - phagocytic cells that become immunosuppressive
escape mechanisms - recruitment of regulatory T cells
cancer recruits T reg and form a immunosuppressive environment so normal T cells can’t target tumour cells
what do regulatory T cells do (T reg)
control an overenthusiastic immune response, actively suppressing it
how are natural T regs identified
by FoxP3 expression in CD4 cells
how are inducible T regs characterised
by the production of interleukin (IL-10) or TGF-beta
escape mechanisms - metabolic exhaustion of environment
they upregulate glycolysis in the hypoxic microenvironment and take nutrients away from immune cells and lower surrounding pH levels.
what does lower pH levels do to the immune system
stops maturation of T cells and MHC expression, including upregulation of enzymes (CD39 and CD73) on the cell surface that convert ATP into adenosine which inhibits T cell function
