Immunotherapy 1 Flashcards
What causes spontaneous regression (tumour regression)?
When the immune system attacks a tumour and prevents it growing further
Why are HIV sufferers more cancer prone?
They are immunocompromised and therefore there is less immune surveillance
Why are TILS evidence for tumour surveillance?
(tumour infiltrating lymphocytes) - associated with better prognosis
What are the 5 initial pieces of evidence for tumour surveillance by the immune system?
1) Spontaneous regression
2) Immunocompromised individuals more cancer prone
3) TILS = better prognosis
4) Nude mice more cancer prone
5) Tumours with TSA (immunogenic tumours) attract immune system
Give example of primary lymphoid tissues?
BM, thymus
Give example of secondary lymphoid tissues?
lymph nodes, spleen, tonsils, MALT
Give examples of cells in innate immunity?
gamma-delta-t cells, NK cells, NKT cells, APCs, macrophages
- recognise cellular stress markers and use ADCC and phagocytosis
What does ADCC stand for?
antibody dependant cell mediated cytotoxicity
Give examples of cells in adaptive immunity?
Tc cells, B cells, Treg, Th1/Th2
- activated by cytokine and chemokines
Upon recognition of a tumour cells what does a macrophage release?
IFN-gamma and IL-12
IFN-gamma causess what in other cells?
Production of IFN-gamma and activates T cells
What makes DC and MPs APCs?
They present antigen to T/B cells and activate them
What cytokines are NK cells activated by (from MPs)?
IL-2, IL-12, IL-15, IL-21, IFN-alpha
How do NK cells kill infected/tumour cells?
Release cytotoxic granules (containing perforin to form pores) to activate caspase pathway
What cytokines do NK cells release to activate T cells?
IFN-gamma and TNF-alpha
What two mechanism do NK cells use to activate T cells?
Missing self - down regulation of MHC1
Induced self - balance between inhibitory and excitatory signals in the NK cell (too many excitatory ligands on the target cell).
What NK cell receptor bind Fc?
CD16
What is the function of NKG2D?
costimulatory to CD8 in T cells
only excitatory receptor on NK cells (activated too much in induced self)
Do normal cells express ligand for NKG2D?
No
What causes expression of NKG2D ligands?
DNA damage - upregulates MICA and MICB (ligands for NKG2D) - lead to cell death
What are the costimulatory receptors of TCRs?
NKG2D, CD28
What does TCR costimulatory receptor bind?
B7.1 ligand
What causes generation of TSA?
Mutations in tumour cells
What is a shared antigen?
Expressed by many independent tumours
What is unique antigen?
Expressed by 1 tumours or very few
What are TAAs?
Self proteins that re over expressed or only expressed during development e.g. PSA
What are viral anitgens?
No self proteins coded by viral genome expressed by infected cells
What are the 3 E’s of cancer?
Elimination
Equilibrium
Escape
Describe elimination.
Tumours expressed TSAs and apoptotic receptors (FAS/TRAIL) - so are killed by immune system cells.
Describe equilibrium.
There are a few mutant tumour cells left after elimination phase, but are controlled by immune system (secretion of anti-cancer and tumour promoting cytokines).
Which cytokines are tumour promoting?
IL-10 and IL-23
Which cytokines are anti-cancer?
IL-12 and IFN-gamma
