immunity to cancer Flashcards
what is cancer a disease caused by ?
an uncontrolled replication of the cell
what do oncogenic mutations in a cell result in ?
in activating the cell cycle and or inhibiting the normal processes that result in cell removal such as apoptosis.
give an example of how infections can cause cancer ?
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.
what does the gene E2 do ?
it is a negative regulator of the HPV oncogenes
what are the E6 and E7 genes for ?
they promote a malignant change in the host cell
how can cigarette smoking cause inflammation ?
it causes an imbalance in the cytokine secretion and inflammatory responses occur.
how does this inflammation lead to lung cancer ?
imbalance in cytokine secretion and inflammatory responses occur. This favours transformation of normal epithelial cells into malignant cells resulting in lung cancer.
what is the intrinsic pathway to cancer ?
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.
what is the extrinsic pathway to cancer ?
this is something outside the body that causes cancer
give an example of the extrinsic pathway to cancer ?
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
what innate cells are involved in the immune responses ?
macrophages
myeloid derived supressor cells
mast cells
eosinophils
what does the innate cells activation contribute towards ?
the reinforcement of the pro inflammatory milieu ( environment)
how can tumours evade immuno surveillance ?
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.
what does the cytotoxicity of the bodies own cell depend upon ?
induction of apoptosis and in the innate - NK cells and acquired this is cytotoxic T cells CD8+.
what does the MHC class I expression on the target cell cause ?
inhibition of the NK becoming activated
how are the granzymes /perforin released into the target cell and what do they cause ?
via the immunological synapse they punch holes in the membrane of the cell and leads to apoptosis
what does killing of the target cell depend on ?
the recognition of the ‘foreign antigen’ on the cancer cell through the T cell receptor
what is the difficulty in recognition ?
the identification of cancer specific antigens
how can the cancer cells avoid the protective immune response ?
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
are both the T helper and cytotoxic T cell involved in the response to cancer if so what does the helper T cell do ?
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.
what can the cytokines produced from the Th cell do ?
increase the production Tc cells directly by cytokines as they produce IFN gamma
they can act on dendritic cells to improve antigen presentation
what does T cell therapy Car T involve ?
the transfusion of autologous or allogenic tumour responsive T cells back into the patients body that have been modified to figh the cancer cells
why are the patients own body cells used ?
as they contain the correct MHC. If another persons cells they would contain a different MHC and it would be rejected
what is the recombinant receptor in Car T cells ?
they have a tumour antigen binding and T cell activating function
stages of Car T therapy ?
- collection of patients blood from periphery
- isolation of lymphocytes
- activation and amplification
- genetic Car / TCR engineering
- amplification and quality control
- transfusion of the Car T cell
what are the 1st generation Car T ?
only one intracellular signal component
2nd generation ?
this has an added co stimulatory molecule
3rd generation ?
another co stimulatory molecule has been added
4th generation ?
a downstream transcription factor has been added to induce cytokine production after recognition of the target antigen
5th generation ?
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.
why are minimum amount of Car T cells required used and not more ?
as this keeps the cost low
why can the Car T treatment cause pain ?
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
why can brain swelling occur ?
the inflammation in the brain draws fluid in
some of the healthy and non cancerous tissue can be damaged how can you avoid this ?
by adding suicide or elimation genes to the Car T that activate in sever toxicity and causes the Car T cells to deplete.
