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Tumour immunology
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in depth immunology notes, made using synchronous, asynchronous and extra reading material
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Tumour immunology. Tumour mass in the body is developed using your own cells.
There may not be any markers on that tumour to define it as foreign.
Tumour antigens.
Neoplastic cells are self-cells:subject to tolerance mechanisms and normal aim is to
avoid autoimmunity.
Tumours can express novel or inappropriate antigens: perceived as non-self.
Generates an immune response.
Neoplastic cells: these are cells where the tolerance mechanism becomes overly
productive so we cannot recognise a tumour cell.
Or we can get modification of the proteins by cancer cells that are expressed in the
tumour surface and sometimes the immune system will see them, but they are
generally good at hiding from the immune system or suppressing our own immune
system, so those cells are not targeted and removed.
Tumour antigens arise normally by standard methods:
Presented by MHC class 1. Recognised by cytotoxic C8 T cells.
They are changes to RNA, DNA leading to changes in the protein structure. The
protein is then processed internally and expressed if you are a member on MHC class
1. If the immune system recognises that antigen as foreign the CD8 T cell will kill the
infected cell.
Tumours have evolved ways so that our CD8 T cells no longer recognise the
cancerous epitope.
Or they are suppressed, and they are inhibited from killing that cancer and allowing
removal of that altered cell.
Oncovirus antigens.
HPV- cervical cancer link
HBV- Hepatocellular carcinoma.
SV40- Mesothelioma.
Viral antigens are directly associated with changes to our own cells, making them
cancerous and forming a tumour mass.
HPV vaccine-
This is one of the first clinically approved cancer vaccine that we have against HPV.
It is not strictly a cancer vaccine against this particular form of cancer because it does
not protect you against all forms of the virus it only protects you against the
papilloma virus. Does not vaccinate against all forms of HPV.
Cancer-testis antigens.
A protein that is restricted to its expression in the testes.
This is a site of immune privilege. Our T cells and B cells should normally never see
this particular antigen because it is in this restricted area of immune privilege and it
is isolated from our own immune cells.
, Research found that this particular antigen has been released from the site of
immune privilege and you can find it throughout the body.
It is often associated with multiple different kinds of cancers.
If you have a protein that is not normally seen by the immune system, you will
activate your immune response, you will drive inflammation.
Mutated antigens: BCRA-1?2
There are key proteins in our body which are tumour suppressors.
These are proteins that we have evolved to help dampen down the induction of
mutations causing cancerous cells.
They are often genes which are involved with DNA damage repair.
And if you lose, you’re function of these you will increase your risk of developing
cancers.
Immune response to cancer.
There are cell intrinsic processes, key proteins which prevent tumours forming by
making sure that we repair our DNA properly.
There are also cell extrinsic properties that our immune cells should be able to
recognise cancer cells and remove them.
As the cancerous cells develop, they induce mutations in their own proteins and they
are often expressed on the surface of the cells and the real question is why they do
not get removed before a tumour is developed.
Evidence for immunosurveillance.
Compromised immunity increases the risk of cancer onset.
In certain conditions where you have reduced immune function through loss of one
particular cell population, you can increase you’re risk of developing cancer.
E.g. People with AIDS have low CD4 T cells-
People who are immunosuppressed transplant recipients are highly susceptible to
developing cancers as a result of dampening down our immune system, we can no
longer servile for the cancer cells and kill them.
Involves innate and adaptive immunity
Requires innate and adaptive immune response to be healthy and functional to
identify cancer cells and remove them before they can take hold, proliferate and
form a tumour.
We have multiple ways we can kill tumours: the T cells can kill them directly; we can
use our innate system to try and clear the infection as soon as possible using our
natural killer cells, NK cells are constantly patrolling looking for cells that are virally
infected. There are also other soluble factors that the system will release to try and
prevent angiogenesis, tumour cells like lots of blood supply so that they can continue
to rapidly divide, if we can inhibit the blood supply to them then we can inhibit the
tumour formation.
It requires multiple aspects of our immune response to be functional to try and
prevent this from happening.
M1 macrophages.
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