immunity to cancer

Question 1

what is cancer a disease caused by ?

Answer 1

an uncontrolled replication of the cell

Question 2

what do oncogenic mutations in a cell result in ?

Answer 2

in activating the cell cycle and or inhibiting the normal processes that result in cell removal such as apoptosis.

Question 3

give an example of how infections can cause cancer ?

Answer 3

human papilloma virus (HPV) is an infection driven inflammation.
integration of HPV DNA into the genome of the infected cell leads to the deletion of host genes e.g. E2 E6 and E7.

Question 4

what does the gene E2 do ?

Answer 4

it is a negative regulator of the HPV oncogenes

Question 5

what are the E6 and E7 genes for ?

Answer 5

they promote a malignant change in the host cell

Question 6

how can cigarette smoking cause inflammation ?

Answer 6

it causes an imbalance in the cytokine secretion and inflammatory responses occur.

Question 7

how does this inflammation lead to lung cancer ?

Answer 7

imbalance in cytokine secretion and inflammatory responses occur. This favours transformation of normal epithelial cells into malignant cells resulting in lung cancer.

Question 8

what is the intrinsic pathway to cancer ?

Answer 8

This is a series of genetic events e.g. activation of oncogenes, inactivation of tumour suppressor genes which causes neoplastic transformation such as breast cancer.

Question 9

what is the extrinsic pathway to cancer ?

Answer 9

this is something outside the body that causes cancer

Question 10

give an example of the extrinsic pathway to cancer ?

Answer 10

Inflammatory leukocytes (white blood cell) and soluble mediators maintain inflammation at a site and this inflammation increases the cancer risk e.g. colon, prostate, pancreas. The cells can form a mass called a tumour

Question 11

what innate cells are involved in the immune responses ?

Answer 11

macrophages
myeloid derived supressor cells
mast cells
eosinophils

Question 12

what does the innate cells activation contribute towards ?

Answer 12

the reinforcement of the pro inflammatory milieu ( environment)

Question 13

how can tumours evade immuno surveillance ?

Answer 13

cancer cells can present different antigens so the body no longer recognises the cancer cell. or cancer cells can release molecules that suppresses the T cell responses. They can recruit the immune cells such as Treg cells that supress the immune response.

Question 14

what does the cytotoxicity of the bodies own cell depend upon ?

Answer 14

induction of apoptosis and in the innate - NK cells and acquired this is cytotoxic T cells CD8+.

Question 15

what does the MHC class I expression on the target cell cause ?

Answer 15

inhibition of the NK becoming activated

Question 16

how are the granzymes /perforin released into the target cell and what do they cause ?

Answer 16

via the immunological synapse they punch holes in the membrane of the cell and leads to apoptosis

Question 17

what does killing of the target cell depend on ?

Answer 17

the recognition of the ‘foreign antigen’ on the cancer cell through the T cell receptor

Question 18

what is the difficulty in recognition ?

Answer 18

the identification of cancer specific antigens

Question 19

how can the cancer cells avoid the protective immune response ?

Answer 19

they can not express MHC or have low amounts , therefore they avoid the recognition through T cells

release immunosuppressive cytokines

induce apoptosis in the T cell

express antigens which have poor immunogenic epitopes

Question 20

are both the T helper and cytotoxic T cell involved in the response to cancer if so what does the helper T cell do ?

Answer 20

yes it causes IFN gamma to be released and this causes the NK cells to be actiavted and recruited also help dendritic cells activated CD8+ cells.

Question 21

what can the cytokines produced from the Th cell do ?

Answer 21

increase the production Tc cells directly by cytokines as they produce IFN gamma

they can act on dendritic cells to improve antigen presentation

Question 22

what does T cell therapy Car T involve ?

Answer 22

the transfusion of autologous or allogenic tumour responsive T cells back into the patients body that have been modified to figh the cancer cells

Question 23

why are the patients own body cells used ?

Answer 23

as they contain the correct MHC. If another persons cells they would contain a different MHC and it would be rejected

Question 24

what is the recombinant receptor in Car T cells ?

Answer 24

they have a tumour antigen binding and T cell activating function

Question 25

stages of Car T therapy ?

Answer 25

1. collection of patients blood from periphery
2. isolation of lymphocytes
3. activation and amplification
4. genetic Car / TCR engineering
5. amplification and quality control
6. transfusion of the Car T cell

Question 26

what are the 1st generation Car T ?

Answer 26

only one intracellular signal component

Question 27

2nd generation ?

Answer 27

this has an added co stimulatory molecule

Question 28

3rd generation ?

Answer 28

another co stimulatory molecule has been added

Question 29

4th generation ?

Answer 29

a downstream transcription factor has been added to induce cytokine production after recognition of the target antigen

Question 30

5th generation ?

Answer 30

this involves gene editing to inactivate the TRAC gene and this causes removal of the TCR alpha and beta chains of the T receptor so it can be modified to fight against the cancer antigen.

Question 31

why are minimum amount of Car T cells required used and not more ?

Answer 31

as this keeps the cost low

Question 32

why can the Car T treatment cause pain ?

Answer 32

as it induces a cytokine release storm ( CRS) as there is a large production in the number of inflammatory molecules from the Car T cells

Question 33

why can brain swelling occur ?

Answer 33

the inflammation in the brain draws fluid in

Question 34

some of the healthy and non cancerous tissue can be damaged how can you avoid this ?

Answer 34

by adding suicide or elimation genes to the Car T that activate in sever toxicity and causes the Car T cells to deplete.