Immunotherapy 1

Question 1

What causes spontaneous regression (tumour regression)?

Answer 1

When the immune system attacks a tumour and prevents it growing further

Question 2

Why are HIV sufferers more cancer prone?

Answer 2

They are immunocompromised and therefore there is less immune surveillance

Question 3

Why are TILS evidence for tumour surveillance?

Answer 3

(tumour infiltrating lymphocytes) - associated with better prognosis

Question 4

What are the 5 initial pieces of evidence for tumour surveillance by the immune system?

Answer 4

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

Question 5

Give example of primary lymphoid tissues?

Answer 5

BM, thymus

Question 6

Give example of secondary lymphoid tissues?

Answer 6

lymph nodes, spleen, tonsils, MALT

Question 7

Give examples of cells in innate immunity?

Answer 7

gamma-delta-t cells, NK cells, NKT cells, APCs, macrophages

- recognise cellular stress markers and use ADCC and phagocytosis

Question 8

What does ADCC stand for?

Answer 8

antibody dependant cell mediated cytotoxicity

Question 9

Give examples of cells in adaptive immunity?

Answer 9

Tc cells, B cells, Treg, Th1/Th2

- activated by cytokine and chemokines

Question 10

Upon recognition of a tumour cells what does a macrophage release?

Answer 10

IFN-gamma and IL-12

Question 11

IFN-gamma causess what in other cells?

Answer 11

Production of IFN-gamma and activates T cells

Question 12

What makes DC and MPs APCs?

Answer 12

They present antigen to T/B cells and activate them

Question 13

What cytokines are NK cells activated by (from MPs)?

Answer 13

IL-2, IL-12, IL-15, IL-21, IFN-alpha

Question 14

How do NK cells kill infected/tumour cells?

Answer 14

Release cytotoxic granules (containing perforin to form pores) to activate caspase pathway

Question 15

What cytokines do NK cells release to activate T cells?

Answer 15

IFN-gamma and TNF-alpha

Question 16

What two mechanism do NK cells use to activate T cells?

Answer 16

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).

Question 17

What NK cell receptor bind Fc?

Answer 17

CD16

Question 18

What is the function of NKG2D?

Answer 18

costimulatory to CD8 in T cells

only excitatory receptor on NK cells (activated too much in induced self)

Question 19

Do normal cells express ligand for NKG2D?

Answer 19

No

Question 20

What causes expression of NKG2D ligands?

Answer 20

DNA damage - upregulates MICA and MICB (ligands for NKG2D) - lead to cell death

Question 21

What are the costimulatory receptors of TCRs?

Answer 21

NKG2D, CD28

Question 22

What does TCR costimulatory receptor bind?

Answer 22

B7.1 ligand

Question 23

What causes generation of TSA?

Answer 23

Mutations in tumour cells

Question 24

What is a shared antigen?

Answer 24

Expressed by many independent tumours

Question 25

What is unique antigen?

Answer 25

Expressed by 1 tumours or very few

Question 26

What are TAAs?

Answer 26

Self proteins that re over expressed or only expressed during development e.g. PSA

Question 27

What are viral anitgens?

Answer 27

No self proteins coded by viral genome expressed by infected cells

Question 28

What are the 3 E’s of cancer?

Answer 28

Elimination
Equilibrium
Escape

Question 29

Describe elimination.

Answer 29

Tumours expressed TSAs and apoptotic receptors (FAS/TRAIL) - so are killed by immune system cells.

Question 30

Describe equilibrium.

Answer 30

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).

Question 31

Which cytokines are tumour promoting?

Answer 31

IL-10 and IL-23

Question 32

Which cytokines are anti-cancer?

Answer 32

IL-12 and IFN-gamma