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Hi, you've said all transplants will fail. Does this mean all transplant patients have chronic rejection?

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Hi Sarah,
Why does the host APC become activated in the first instance? is the antigen it is presenting to the donor T cell not self?

The APC is behaving as expected- it reacts to the incoming donor T cells, non-self antigens from the donor will be involved- that is correct. Thank you for your question.

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Hi Sarah,
are defined antigens and tumour specific antigens the same thing? and are undefined antigen and tumour associated antigen the same thing? If not, what is the difference?
Thanks

Sarah- The bottom line is that defined just means we actually know the identity of the antigen and this can be either on normal or tumour cells. Tumour-specific means its associated with the tumour. In other words- you can have a defined antigen on a non-transformed (non-tumour) cell.

In a similar fashion- we do not know the identity of an undefined antigen and this may or may not be specific to the tumour.

Please get back in touch if needed.

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Would it be useful to know some examples of undefined antigens given as vaccine/immunotherapy?

Sarah-Yes- that would be great. All additional reading is worthwhile. Thank you for getting in touch.

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Is telomerase an oncofetal protein and therefor its peptide derivatives be oncofetal antigen?

Sarah- Yes- telomerase is considered to be a tumor antigen, this is relevant towards cancer vaccines (please see the following for details PMID: 18767939). Thank you for getting in touch.

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Is MHCII deficiency, Bare lymphocyte syndrome?

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Is MHCII deficiency, Bare lymphocyte syndrome?

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It says in the lecture that the thymus and all APC's lacks MHCII, is this due to a gene deletion and lack of expression?

Alison- bare lymphocyte syndrome and MHCII deficiency are the same. It is caused by mutations in transcription factors associated with transcription of MHCII genes and therefore MHCII proteins are not expressed on the cell surface. It is a primary immune deficiency with autosomal recessive inheritance.

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Hi, a question for Alison,
Do we need to be able to describe the life cycle and therefore disease progression of HIV?

Alison- You do not need to know the full HIV lifecycle other than how the virus targets CD4 cells. The focus should be on the effects on the immune system and the affected individual rather than the virus itself.

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Hi Sarah,
Regarding tumour antigens, why would we use 'tissue specific differentiation antigens' in immunotherapy if they would be recognised as self by the immune system?

Sarah- That is correct. The advantages and disadvantages are summarised in the following article  in table 1 (PMID: 26589749). It is easy to develop 'off the shelf treatments' but yes- it would potentially be a shared antigen.

Also why would we use undefined antigens in therapy if we have better alternatives i.e. defined antigens?

Sarah- We don't always have full characterisation of the antigens. Undefined antigens are discussed in the literature extensively.

Finally how do we know immunotherapy will work in a patient if the immune system has not been successful in removing the primary tumour in the first instance? are these antigens cultured in a specific manner to ensure thively.ey are immunogenic?

Sarah- The T cells can be manipulated ex vivo- this is the principle of adoptive T-Cell therapy.

sorry for the list of questions!
thanks

Sarah- It is a pleasure- thank you :-)

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Hi Sarah,

Is there any literature you recommend for extra reading on the subject?

Absolutely! I have included references in the lecture. Start with Dunn et al., 2004. I'll chat more about this in the revision session tomorrow :-)

Another good review bursting with evidence (PMID: 27764780)

This YouTube video published by Nature is a good overview about tumour immunology:

https://www.youtube.com/watch?v=K09xzIQ8zsg

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Hi Sarah is there any difference between bone marrow transplant and haematopoietic stem cell transplant?

Sarah- A great question! As bone marrow is the source of hematopoietic stem cells - it is essentially the same in one respect. Strictly speaking there is a technical difference regarding the donation procedures.

In a bone marrow transplant, stem cells are collected from a donor’s bone marrow. General anaesthesia will allow the donor’s bone marrow to be harvested directly from the hip bones through a large needle.

In a  peripheral blood stem cell transplant, stem cells are harvested by apheresis. Donors also receive a medication for five days that increases stem cell production. As you harvest stem cells from the bloodstream, this is very similar to routine a blood donation.

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Evidence for immune response to tumours 

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Evidence for immune response to tumours 

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Hi Sarah,

I have looked at the recommended reading around this subject but still don't seem to understand some of the key points. I have watched the video and other YouTube videos, but i can't seem to find specific studies linking with each point in particular to the first point, the infiltrate of lymphocytes/macrophages for a better prognosis. Is there any literature where all the 7 points are explained more in detail. Kind regards

Sarah- These key points are documented throughout the literature.  My advice is to type each one into google scholar if you are struggling and you should find the relevant papers that you need. For example- I have just found a papers about lymphocytes relating to prognosis in NSCLC.

Please see the following:

DOI: 10.1158/1078-0432.CCR-08-0133

Good luck with your preparations

with best wishes- Sarah

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Hi Sarah, when referring to the HLA in the exam, does it matter if we use HLA or MHC, for example I am confident in explaining the difference between MHCI and MHCII, do this directly correspond to HLAI and HLAII? many thanks

Sarah-That's correct- it is the same machinery- just think of them as having different names. MHC molecules are found in invertebrates. HLA is only present in humans. It's important to know and recognise this distinction :-)

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Just regarding the autoimmune lecture, does molecular mimicry represent a survival strategy that pathogens have evolved to promote further infection and inflammation by the host inflicting autoimmune  damage?
or is it just a matter of chance due to somatic hypermutation of lymphocytes?

Alison- Hello, the way that molecular mimicry leads to autoimmune responses is not fully understood but seems to be by chance. Recognition of self epitopes similar to those on pathogens that have triggered an immune response lead to damage of host tissues as tolerance is broken.

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Hi Sarah,
I've written down that the danger signals are important when launching a pro-inflammatory response against cancer cells, but I can't remember if this is part of the natural immune response or if this is required for tumour immunotherapy?

Sarah- Thank you for getting in touch. The answer is both. A pro-inflammatory response would be useful  as part of the immuno-editing process- but also would benefit the established anti-tumour response.