lecture 14 Flashcards
(13 cards)
Define a tumour
tumour;
cells become altered so they grow uncontrollably
viruses, chemicals and other factors can cause tumour
proteins on the surface of a tumour maybe different from those found on normal cell
new or altered proteins may trigger an immune response
Define tumour antigen
Tumour ag
tumour cells either gain or lose membrane proteins
some tumours lose MHC I ag and can’t present ag to T cells
tumours induced by virus may express viral non-structural ag
tumours induced by single chemical may express unrelated ag
Define tumour antigens and tumour rejection antigens
-tumour ag can be classified according to the type of immune response, they elicit; humoral, cellular, CD4T (T helper) or CD8+ cytotoxic T lymphocytes response
-tumour rejection ag are specific to individual tumours
a point mutation in a self protein allows binding of a new peptide to MHC molecules
or a point mutation in a self peptide creates a new epitope for recognition by T cells
For immune surveillance explain the different phases
- elimination phase
- equilibrium phase
- escape phase
Immune surveillance of tumours includes 3 phase;
- elimination phase- when tumour arises in tissue, no. of immune cells can recognise and eliminate them.
- equilibrium phase- mutation that aid survival as a result of selection pressure, tumour cells can become resistance
- escape phase- accumulate sufficient mutation to elude the attention of immune system, so then cells escape the killing mechanism and grow without being annoyed by the immune system
List the immune response to tumour antigen
immune responses to tumour ag -tumour ag may cause an immune response -tumour cell destruction involve NK cells -other mechanism involve ab cytotoxic T cells activated macrophages
For NK cells list what they are functions type of killing antibody-independent killing
Natural killer cells
they are large lymphocyte with obvious granules
they bind to and kill target cells
NK cell killing is by ab dependent and ab
independent processes
For NK cells-antibody independent killing explain the activation of NK cells
- ligation of fas ligand
- IFN-y
NK cells-antibody independent killing
NK cells are activated by cytokines -> activated NK cells release proteolytic (breakdown proteins) enzymes, granzyme A and B, performs which induce tumour cell death ->ligation of Fas to Fas/CD95 receptor together with the binding of TNF alpha to death receptors induce apoptosis of tumour cell
NK cells secrete cytokines TNF alpha and IFN-y
IFN enhances NK acitvit by promoting differentiation of pre-NK cells and activates macrophages
How to ab contribute to the immune response to tumours
Antibody mediated immunity to tumours
ab are involved in anti tumour immunity
ab will help activate or differentiate NK cells and macrophages and then will secrete a cytokine
NK cell CD16 recognises an fc constant which will result in the secretion of cytokines and there is NK cell mediated ab dependent cellular toxicity
ab will induce all this suff
How do NK cells kill tumour cells
There is an ab response to the tumour, the NK cell will bind to the FC end and gives off a positive signal and this will cause the killing of the cell through a mediated ab response
For T cell mediated immunity discuss the importance cross presentation what occurs to tumour cells/ag function of costimulators what occurs after the activation of CLTs
- T cell very important for tumour destruction
- specific tumour ag sometime need cross-presentation (APC will take a ag with MHC I to CD8 T (cytotoxic T cells) cells) of tumour ag bu professional APC (dendritic cells)
- tumours or ag can be ingested by APC, they are processed inside, peptides derived form these ag are displayed bound to MHC I for the recognition by CD8 T cells
- APC express costimulators which proved signal needed for differentiation of CD8 T cells into anti-tumour CLTs (cytotoxic T lymphocytes)
- once CTLs are generated they can be recognised and kill tumour cells without the need for costimulation
Discuss the role of macrophages in immunity to tumours
role of macrophages in immunity to tumours
destroy tumour cells
activated cells produce iL-1 (which reduces the growth of tumours) and TNF -alpha
may tumours are inhibit the activation and therefore the function of macrophages
For the avoidance of immune recognition explain the following
- low immunogenicity
- tumor treated as self antigen
- antigenic modulation
- tumour induced immune suppression
- tumour- induced privileged site
-Low immunogenicity
no peptide: MHC ligand
No adhesion molecules
No co-stimulatory molecules
-Tumour treated at self ag
tumour ag taken up and presented by APC in absences of co-stimulator tolerance T cell
-antigenic modulation
T cells may eliminate tumours expressing immunogenic ag but not tumours which have lost such ag
-tumour induced immune suppression; factors (IL-10) secreted by tumour cells inhibit T cells directly. Expression of PD-L1 by tumour
-tumour-induced privileged site; factors secrete by tumour cells create a physical barrier to the immune system
List some immunotherapy fo tumours
tumour immunotherapy;
vaccination against tumour producing viruses
immune stimulation (adjuvants)
active immunisation against tumour ag (tumour vaccines)
ab therapy (increase ab mediated immune responses, can have hybrid ab which are specific for tumour ag)
cytokine therapy
NK and T cell therapies
