Avoiding immune destruction

Question 1

what mouse model was evidence that tumours can be repressed by the immune system?

Answer 1

tumour transplantation models.
immunity was only seen in prophylactic immunization and not therapeutic
once a mouse had been implanted with the tumour, immunization with irradiated cancer cells did nothing to stop tumour growth

Question 2

what does this mouse model support the existence of?

Answer 2

tumour associated antigens

immunosurveillance theory where carcinomas are constantly eradicated from the immune system

Question 3

TF: macrophages are only anti tumour

Answer 3

false can be either depending on signals

Question 4

how can macrophages be anti-tumour?

Answer 4

present the antigen to the T helper cell and trigger tumour cell killing by antibodies

Question 5

which 2 signals can activate macrophages in a anti tumour way?

Answer 5

bacteria lipopolysaccharide

interferon gamma

Question 6

what can trigger macrophages in a pro tumour way?

Answer 6

hypoxia and other physiological signals released by tumours.

Question 7

macrophage subtype M__ promotes immune attack on tumours and the subtype M__ promotes tumour progression

Answer 7

M1

M2

Question 8

what initiates the process of phagocytosis and destruction of infected cells by the immune system?

Answer 8

coating of mammalian cells by antibody molecules due to the cell presenting target antigens

Question 9

what do natural killer cells do once the mammalian cell is covered by antibodies. what does this activate?

Answer 9

natural killer cells uses its Fc cell surface receptor to bind to the constant regions of the antibody molecules
this activates the NK cell which then destroys the target cell by releasing cytotoxic granules

Question 10

what is antibody dependent cell mediated cytotoxicity

Answer 10

the way NK cells kill cells using cytotoxic granules, Due to antibodies being present on the surface of cells presenting antigens

Question 11

which cells tend to notably present antigens?

Answer 11

dendritic cells

Question 12

where do langerhans reside?

Answer 12

in the skin

Question 13

what do langerhans do?

Answer 13

take up antigens by phagocytosis and takes them to the lymph nodes
here they mature to dendritic cells and present the antigen to T cells triggering an immune response against this antigen.

Question 14

dendritic cells activate which cells?

Answer 14

Th and Tc

Question 15

what happens when a dendritic cell finds a T helper cell which recognises the antigens it (the dendrite) is presenting

Answer 15

the T helper cell becomes activated which leaves to find B-cells also displaying this surface antigen

Question 16

once the T helper cell finds a B cell presenting the antigen which the dentrite has presented to the T cell, what happens?

Answer 16

the B cell proliferates and differentiates into plasma cells which release antibody molecules

Question 17

what is the interaction between dendritic cells and cytotoxic T cell precursors called? what effect does this have on the cytotoxic T cell precursors?

Answer 17

cross presentation

helps the precursors mature into active cytotoxic T cells

Question 18

what do cytotoxic granules from Tc contain?

Answer 18

perforin and granzyme B

Question 19

5 Mechanisms by which tumours escape immune recognition?

Answer 19

1. low immunogenicity
2. tumour treated as self antigen
3. antigenic modulation
4. tumour induced immune suppression
5. tumour induced privileged site

Question 20

explain how low immunogenicity can help the tumour

Answer 20

low expression of adhesion molecules or MHC’s so appear normal to the immune system

Question 21

explain how the tumour is treated as a self antigen to evade immune response

Answer 21

APCs present the tumour antigens in the absence of co-stimulatory signals- this makes the T cells tolerative of them so they dont attack

Question 22

explain how antigenic modulation helps a tumour evade the immune response

Answer 22

tumour initially express antigens which the immune system response to but can lose them by: ‘antibody induced internalisation’ or ‘antigenic variation’

Question 23

2 ways tumours can lose their antigens to evade the immune system?

Answer 23

antibody induced internalisation

antigenic variation

Question 24

what products can tumour cells make to suppress the immune system?

Answer 24

TGF-b

Question 25

explain a tumour induced privileged site to avoid immune destruction

Answer 25

factors produced by tumour cells to create a physical barrier to the immune system

Question 26

examples of factors produced by tumour cells to create a physical barrier to the immune system? what does this prevent?

Answer 26

collagen

lymphocyte access

Question 27

Tregs cells are _____ in number in tumour tissues than in normal

Answer 27

higher

Question 28

why are Tregs at higher number in tumour cells?

Answer 28

probably because the regulatory T cells are activated by a large number of self antigens which tumour cells secrete

Question 29

how are T regulatory cells attracted to a tumour? what do tumour cells produce to attract?

Answer 29

tumour cells produce CCL 22 chemokine which bind to their receptor on T regs and attracts them to the tumour

Question 30

what effect does tumour growth factor beta released by tumour cells have on Tregs

Answer 30

critical for the expression of transcription factors which regulate Tregs cell differentiation

Question 31

once Tregs are recruited to the tumour what do they inhibit? EFFECT?

Answer 31

CD4 Thelper cells
CD8 cytotoxic T cells
CRIPPLE HOST ADAPTIVE RESPONSE TO TUMOUR

Question 32

so T-regs in the tumour ME is _____ for the tumour

Answer 32

GOOD stops immune response by inhibiting Tcells

Question 33

how do dendrites work?

Answer 33

bind antigens from viruses or bacteria and present them to T cells for the initial immune response

Question 34

how can we target dendrites in therapy?

Answer 34

scientists fuse a cytokine to a tumour antigen, hope this will send a strong antigenic signal
then they grow the patient dendritic cells in an incubator and allow them to take up the fused cytokine tumour antigens
then revive these dendrites to the patient to let them present the antigen to the immune system and make the T cells mount an attack on the cancer cells

Question 35

2 things that can be introduced to redirect T cells to have tumour specificity

Answer 35

1. transgenic T cell receptors

2. chimeric antigen receptor proteins

Question 36

what are chimeric antigen receptor proteins?

Answer 36

fusion proteins composed of an extracellular portion derived from an antibody
an intracellular signalling molecules derived from T cell signalling proteins

Question 37

what can we target for a PROPHYLACTIC vaccine against human papilloma viruses?

Answer 37

capsid proteins L1 and L2 which interact with the surface molecules of epithelial cells to gain entry to the cells
As this is present during the initial infection they’re ideal targets prophylactically

Question 38

what to target for a therapeutic vaccine against HPV

Answer 38

the E6 and E7 oncoprotein are expressed during viral infection
they are the primary targets in HPV vaccines.

Question 39

what do the E6 and E7 oncoproteins do in a HPV infection

Answer 39

produced during the infection

bind the p53 and the retinoblastoma TSGs

Question 40

Gemtuzumab mechanism of action?

Answer 40

anti CD-33 antibody
coupled with a toxin to treat AML
Toxin gets internalised and damages DNA

Question 41

immunotherapy advantages?

Answer 41

• purity of the antigenic preparation hence sensitive and effective
• defined antigens that are simple to isolate from each patient
• minimal possibility for auto immune reactions

Question 42

immunotherapy disadvantages?

Answer 42

• can only be used in a small number of cancers
• unclear which antigens are the best choice to mount an effective anti-tumour response in vivo
• patient specific antigens aren’t shared between patients even with the same cancer type
• need alot of tumour tissue to purify the antigen