Search for notes by fellow students, in your own course and all over the country.
Browse our notes for titles which look like what you need, you can preview any of the notes via a sample of the contents. After you're happy these are the notes you're after simply pop them into your shopping cart.
Title: Cancer and the Immune System
Description: 2nd year university level Imperial College London - Immunology Module The mechanisms that cancers use to avoid the immune system.
Description: 2nd year university level Imperial College London - Immunology Module The mechanisms that cancers use to avoid the immune system.
Document Preview
Extracts from the notes are below, to see the PDF you'll receive please use the links above
Cancer and the Immune System
The response of the immune system is essential for cancer progression
...
A lot of our cells mutate and some are potentially cancerous
...
If cells are maintained within a fixed area the cancer is benign, once the cells become malignant they
have broken out of the area and are spreading
...
Benign
Malignant- break out of defined area, start to proliferate and metastasize to other cells
...
Leukaemic cells take up lots of space,
can interfere will red blood cell production
...
Secondary infections are
the main reason for death in leukaemia in children
...
So how does this happen? The immune response is very quick at responding to
threats, but responding to cancer may take time
...
• In some cases, transplantable tumours can be rejected by sygeneic hosts
(no differences in MHC)
•
spectrum of immunogenicity
•
T cell-dependent effect
•
Immune surveillance:
1
...
If #1 is not completely successful then Equilibrium phase (cancer
immunoediting- when you have a cancer which is not expanding but is maintained
at a certain level by the immune response)
3
...
Tumour rejection antigens are specific to individual tumours
If you immunize a mouse with irradiated tumour cells it means that they won’t
grow when injected in the mouse but is the mouse capable of mounting an
immune response to the irradiated cells?
If you then leave the mouse for a while and inject viable tumour cells of the
same tumour and the tumour does not develop, it means that the mouse
developed a unique response to that tumour
...
The
mouse has not developed tumour rejection antigens
...
In the process of becoming a cancer cell, that
cell has given signals that no longer make it a self-cell
...
In the
first phases it is NK cells which recognise
the tumour cells
...
But if a cell lacks MHCI
the NK cell will destroy it
...
When a cell becomes
tumours it is very often the case that
MHCI gets downregulated
...
This is used as
a strategy to avoid T cell recognition, but
NK cells do recognise it
...
If that happens during the
equilibrium phase, the tumour will escape cytotoxic effects on it
...
The tumour will now be able to spread, divide and invade
...
Melanoma, 1-2 year post-kidney transplant in recipients from same donor
Someone who had melanoma and recovered from it
...
2
...
Tumours use multiple mechanisms to avoid immune regulation
•
•
•
Spontaneous tumours may initially lack mutations that produce new tumour i
...
specific
antigens that elicit T cell responses
PD-L1 ligand for inhibitory receptor found on activated T cells
IDO = indoleamine 2,3 dioxygenase, catabolizes Trp ➔ Kynurenine, immunosuppressive
metabolite – negative effect on CTLs and T helper cells
...
The effect of cytotoxic T cells and NK cells
• Regression transplanted tumours due to CTLs
•
Tumour variant with low MHCI, less sensitive to
CTLs but more sensitive to NK cells
•
nude mice = no T cells, more NK cells than normal
•
Tumour rejection antigens = peptides of tumour
cell proteins presented on MHC
•
Target of tumour-specific response even though
present on normal tissues e
...
strategy to induce response
to melanoma antigen ➔ vitiligo
1) Normal mice will mount an immune response using
mostly CTL, while nude mice will not be so successful at
dealing with the tumour
...
3) Tumour lost MHCI, is supplied with an MHCI gene
we are back to original scenario
...
It is often random and some of these
proteins are not even cell surface antigens
...
- Proteins normally only expressed in male
germ cells, male germ cells do not express
MHC therefore these peptides not normally
presented to T cells
...
g
...
- Tumour immunotherapy tries to harness and
augment these responses
...
•
•
•
•
Monoclonal antibodies (mAbs) as therapeutic agents
Inefficient killing of cells after mAb binding
improved by linking mAb to immunotoxin e
...
ricin A chain
Inefficient penetration of mAb into tumour mass
improved by using small antibody fragments(fab fragments which are the antigen binging part
of the antibody)
...
If you just attach a drug to an antibody, it can cause damage to other cells
...
There is a molecule on NK cells CD16
which is very good at recognizing
antibodies when they are bound
...
The toxin only becomes
activated when it is
internalized and
cleaved
...
TRA = tumour rejection antigens
...
It is difficult to get enough GM-CSF into the body without
causing severe side effects is difficult
...
‘Virus-Like Particles’ with HPV-16 capsid protein L1
...
Poor outcome in treating established cervical cancer
...
Spontaneous tumours, peptides of TRAs may not be shared between patients & only presented
on particular MHC e
...
melanoma MAGE-1 only presented by HLA-A1 haplotype
Title: Cancer and the Immune System
Description: 2nd year university level Imperial College London - Immunology Module The mechanisms that cancers use to avoid the immune system.
Description: 2nd year university level Imperial College London - Immunology Module The mechanisms that cancers use to avoid the immune system.