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Nk cell defiencies and herpes viruses

heapsreal

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There are a surprisingly large number of human natural killer (NK) cell deficiency states that provide insight into the role of NK cells in defense against human infectious disease. Many disorders associated with NK cell defects are caused by single gene mutations and, thus, give additional understanding concerning the function of specific molecules in NK cell development and activities. A resounding theme of NK cell deficiencies is susceptibility to herpesviruses, suggesting that unexplained severe herpesviral infection should raise the possibility of an NK cell deficit.

http://www.ncbi.nlm.nih.gov/pubmed/12505527
 

Enid

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No scientist heaps - this in the light of findings/suspects so far certainly makes sense to me.
 

allyb

Senior Member
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I am no scientist either, in my ignorance I often wonder 'chicken and egg' would you catch a virile strain of the herpes virus because you already had single gene mutations in your NK cells or would the virile strain of herpes that you had caught cause a single gene mutations in your NK cells?

As I am relatively new to PR I don't know if this has been posted and discussed before (should it be on a thread of its own?) My apologies if it has but I would love your opinion and that of others.
kind regards
allyb

Viral evasion gene reveals new targets for eliminating chronic infections
link

http://www.wehi.edu.au/site/latest_...ew_targets_for_eliminating_chronic_infections

Dr Gabrielle Belz's team has discovered how a key viral gene helps viruses evade early detection by the immune system.
Walter and Eliza Hall Institute researchers have discovered how a key viral gene helps viruses evade early detection by the immune system. Their finding is providing new insights into how viruses are able to establish chronic infections, leading scientists to re-evaluate their approaches to viral vaccine development.
Researchers from the institutes Immunology division together with collaborators at the University of Cambridge (UK) have been studying how the immune system responds to viruses that cause persistent or chronic infections and why the immune system is unable to eliminate these infections.
Dr Gabrielle Belz, Dr Adele Mount and colleagues are particularly interested in immune system cells called dendritic cells and their interaction with viruses that cause chronic infections.
Chronic infections are one of the greatest health challenges for the Western world, but currently we have very few ways of dealing with them, Dr Belz said. They require ongoing medical care and support due to an inability to treat infection effectively.
We are trying to understand how chronic infections sneak past the usually highly effective immune armoury and covertly establish disease. If we can stop these infections establishing then we can eliminate, or substantially reduce, that societal burden.
Dendritic cells, which are studied by Dr Belz, Dr Mount and colleagues, act as sentinels of the immune system; they are critical for the early detection of invading bacteria and viruses and are one of the first cells to trigger the immune response. Dendritic cells are called antigen presenting cells; they digest infectious agents into small fragments and shuttle these fragments to the outside of the cell where they are displayed to virus-specific killer T cells, helping to launch a full-blown immune response, Dr Belz said.
The team has been investigating a virus called gamma herpesvirus-68, which establishes chronic infections in mice and provides a model of the workings of the human gamma herpesvirus Epstein-Barr Virus, commonly known to cause infectious mononucleosis, or kissing disease. Their results, which have been published in the Journal of Immunology show that a viral gene called K3 rapidly disables the antigen-processing machinery normally used by dendritic cells to alert the immune system to infections.
This gene quickly helps the virus to hide from the immune system by subverting normal antigen presentation to T cells, which have the critical task of destroying virally-infected cells, Dr Belz said. The virus carries out a top-secret operation. It shuts down the normal mechanisms that allow the immune system to recognise an infection and then boards the antigen-presenting cells which ferry the virus through the blood and tissues, allowing it to spread throughout the body and establish system infection.

Dr Belz said the study could change conventional views on the best way to generate an immune response to combat chronic infections.
Our research shows that viral evasion of the immune system in chronic infections happens incredibly early, Dr Belz said. Dendritic cells are compromised long before they have the chance to interact with T cells for the next phase of the immune response, so the T cells are never really activated properly. If we want to make an effective vaccine, we need to look at these early escape points used by the virus as the first target for trying to generate a more efficient immune response that will contain the virus and prevent it establishing a systemic infection.
This work was supported by the National Health and Medical Research Council, the Wellcome Trust, the Swiss National Science Foundation, the Sylvia & Charles Viertel Charitable Foundation and the Howard Hughes Medical Institute.
 

heapsreal

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I did come accross a few links to a dysfunctional gene in nk cell defiency states, not sure but i think this type of defiency state is a lack of nk cells, where in cfs there can be normal amount of nk cells but they just dont work?? But u would think that all the co-infection that go with it would be the same??
good link allby.
 

searcher

Senior Member
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SF Bay Area
I am no scientist either, in my ignorance I often wonder 'chicken and egg' would you catch a virile strain of the herpes virus because you already had single gene mutations in your NK cells or would the virile strain of herpes that you had caught cause a single gene mutations in your NK cells?

Hi allyb- That's a good question. I am not a scientist but have a biology background, so hopefully someone will correct me if I make a mistake. A single gene mutation is something you are born with and is passed down from your parents. So the deficient states talked about in heapsreal's link are not caused by herpes viruses. But our situations could be different, since as far as we know CFS patients weren't born with deficient NK cells (although I suspect we don't know that for sure.) The only researcher I have discussed this with thinks that the low NK cell function is the reason for herpes viruses going crazy, and that there is another underlying cause for the NK cell dysfunction. I think figuring out the cause of the NK cell dysfunction will be they key to this illness.
 

floydguy

Senior Member
Messages
650
Hi allyb- That's a good question. I am not a scientist but have a biology background, so hopefully someone will correct me if I make a mistake. A single gene mutation is something you are born with and is passed down from your parents. So the deficient states talked about in heapsreal's link are not caused by herpes viruses. But our situations could be different, since as far as we know CFS patients weren't born with deficient NK cells (although I suspect we don't know that for sure.) The only researcher I have discussed this with thinks that the low NK cell function is the reason for herpes viruses going crazy, and that there is another underlying cause for the NK cell dysfunction. I think figuring out the cause of the NK cell dysfunction will be they key to this illness.

Genetic pre-disposition to low perforin?
 

allyb

Senior Member
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127
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yorkshire/lancashire border, England
Thanks heapsreal,
I read somewhere but cant remember where that the herpes virus affects the memory of the NK cell, so to speak?

Hi allyb- That's a good question. I am not a scientist but have a biology background, so hopefully someone will correct me if I make a mistake. A single gene mutation is something you are born with and is passed down from your parents. So the deficient states talked about in heapsreal's link are not caused by herpes viruses. But our situations could be different, since as far as we know CFS patients weren't born with deficient NK cells (although I suspect we don't know that for sure.) The only researcher I have discussed this with thinks that the low NK cell function is the reason for herpes viruses going crazy, and that there is another underlying cause for the NK cell dysfunction. I think figuring out the cause of the NK cell dysfunction will be they key to this illness.

Thank you searcher, I am trying to understand this and make it relevant to me to do so.

But our situations could be different, since as far as we know CFS patients weren't born with deficient NK cells.

This would make sense because I never caught anything until I had an open mouth wound in hospital last year in my late 40is until then I was as fit as could be. Surly if I had a deficiency I would had caught other things before this and suffered poor health, wouldnt I??

We are trying to understand how chronic infections sneak past the usually highly effective immune armoury and covertly establish disease.

It would seem like I had a highly effective immune for 48years

Their results, which have been published in the Journal of Immunology show that a viral gene called K3 rapidly disables the antigen-processing machinery normally used by dendritic cells to alert the immune system to infections.
This would seem to make sense to me (a simple soul)
This gene quickly helps the virus to hide from the immune system by subverting normal antigen presentation to T cells, which have the critical task of destroying virally-infected cells, Dr Belz said. The virus carries out a top-secret operation. It shuts down the normal mechanisms that allow the immune system to recognise an infection and then boards the antigen-presenting cells which ferry the virus through the blood and tissues, allowing it to spread throughout the body and establish system infection.

But it cant be detected so our tests are clear...... right?

Are our T cells compromised in ME/CFS?

Floydguy

Genetic pre-disposition to low perforin?
What is perforin and please could you explain it.
 

globalpilot

Senior Member
Messages
626
Location
Ontario
Rodney Dietert is a toxicologist and has taken an interest in immune system dysfunction and CFS and particularly what agents disrupt immune dysfunction. There is a table here listing the different dysfunctions and agents known to cause the dysfunction.

http://www.cfids-cab.org/rc/Dietert.pdf



Hi allyb- That's a good question. I am not a scientist but have a biology background, so hopefully someone will correct me if I make a mistake. A single gene mutation is something you are born with and is passed down from your parents. So the deficient states talked about in heapsreal's link are not caused by herpes viruses. But our situations could be different, since as far as we know CFS patients weren't born with deficient NK cells (although I suspect we don't know that for sure.) The only researcher I have discussed this with thinks that the low NK cell function is the reason for herpes viruses going crazy, and that there is another underlying cause for the NK cell dysfunction. I think figuring out the cause of the NK cell dysfunction will be they key to this illness.