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CMV more important than genes in shaping your immune response

natasa778

Senior Member
Messages
1,774
http://www.scientificamerican.com/article/your-immune-system-is-made-not-born/

In one of the most comprehensive analyses of immune function performed to date, researchers analyzed blood samples from 105 sets of healthy twins. They measured immune cell populations and their chemical messengers—204 parameters in all—before and after participants received a flu shot. Differences in three fourths of these parameters depended less on genetics than on environmental factors, such as diet and prior infections. Genetics had almost no effect on how well individuals responded to the flu vaccine, judged by antibodies produced against the injected material. And among identical twin siblings, who have the same genome, immune system features differed more strikingly within older twin pairs than in younger sets. The findings, published January 15 in Cell, argue that life habits and experiences shape our body’s defenses more than the DNA passed down from our parents.

Although prior twin studies had hinted that nonheritable factors contribute to some autoimmune disorders, such as multiple sclerosis, the recent analysis was one of the first to quantify genetic and environmental effects on the general immune system. “We were surprised by the degree of environmental influence on so many components,”

... One finding was particularly striking. A single environmental factor—a past infection with common cytomegalovirus—affected 58 percent of the tested parameters. Whereas the results don’t show whether these changes produce an overall stronger or weaker immune response, they do indicate “cytomegalovirus has a really profound effect,” Davis says. The Epstein–Barr virus, another microbe that frequently infects people, had no such effect.


... scientists are uncertain as to why the Epstein-Barr virus, which also infects most people and lingers in the body, doesn’t trigger a big ongoing immune response like cytomegalovirus does. It could be that the Epstein-Barr virus primarily infects B cells whereas cytomegalovirus can hide in a variety of cell types. Davis says his team is taking a closer look at Epstein-Barr virus’ effects on the twins’ immune parameters and plans to report the findings soon

The whole article is quite interesting, too long to copy all of it
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Interesting flag up.
As usual I shall pick holes! They say: We measured 204 different parameters, including cell population frequencies, cytokine responses, and serum proteins, and found that 77% of these are dominated (>50% of variance) and 58% almost completely determined (>80% of variance) by non-heritable influences. In addition, some of these parameters become more variable with age, suggesting the cumulative influence of environmental exposure.

Wrong. What they have found is non-heritable differences. That can be environmental but it can also be just the random behaviour of B and T cells, as I keep going on about. Moreover, that randomness will increase with age much more reliably than environmental infection influences which tend to be over and done with (plus vaccinations) in infancy. So thus far there is not a trace of evidence for an environmental factor. OK, they do find a correlation with CMV and that is very interesting - particularly since they do not find it for EBV. Environmental influences would be very plausible and there is no evidence against, but it still amuses me that all these grand immunologists still forget to read the epidemiology textbooks.
 

Hip

Senior Member
Messages
17,824
If found this excerpt from the article interesting:
Roughly one tenth of a person’s circulating T cells are specific for cytomegalovirus. “It takes a ridiculously large chunk of our immune repertoire to keep this virus in check,” Barry says. Scientists are uncertain as to why the Epstein-Barr virus, which also infects most people and lingers in the body, doesn’t trigger a big ongoing immune response like cytomegalovirus does.

I once read that in people who harbor cytomegalovirus, each time cytomegalovirus reactivates in their body, this reactivation elicits a completely new adaptive immune response. This means that the immune system keeps going, again and again, through the process of designing an antibody to disable the virus, even though the immune system still remembers and has available the cytomegalovirus antibodies it created when the virus was first caught.

I believe the result is that as a person gets older, more and more of the immune memory is used up by cytomegalovirus, because each time this virus reactivates, the immune system creates and remembers a new cytomegalovirus antibody. And I read that this leads to an accumulation of T cells that can no longer proliferate but whose presence inhibits the proliferation of other T cells.

I understand that this does not happen to the same degree with other viruses: with other viruses, if there is viral reactivation, the immune system may just rely on the same original antibodies created when the virus was first caught.

I think this cytomegalovirus reactivation phenomenon may be connected to the statement made in the above Scientific American article about one tenth of a person’s circulating T cells being specific for cytomegalovirus.



I cannot remember where I read about this cytomegalovirus reactivation phenomenon, but I found the following paper which touches on the subject:

Immune Sensing of Latent Cytomegalovirus Reactivation and its Possible Impact on Immune Senescence | SENS Research Foundation

And this paper is about experiments to rebalance the T-cell pool:

Rebalancing the aging T-cell pool to improve resistance to infection in the old age | SENS Research Foundation



Incidentally, my list of supplements and drugs that are effective against cytomegalovirus is this:
Anti-Cytomegalovirus Drugs

Valcyte (valganciclovir)

Vistide (cidofovir)

Foscavir (foscarnet)

Artesunate (anti-malaria drug). 1 2 Artesunate 10 times stronger antiviral for CMV than artemisinin

Raltegravir antiviral for cytomegalovirus 1

Methotrexate (an old arthritis drug similar to rituximab). 1

Brincidofovir (CMX001) 1

BHT (butylated hydroxytoluene). 1 Unfortunately BHT is pro-inflammatory


Anti-Cytomegalovirus Supplements

Tricin (a flavonoid found in rice bran) showed "extremely high anti-human cytomegalovirus activity" 1

Baicalein 1 2

Genistein

Terminalia chebula

Clove (eugenol on clove is antiviral for CMV; also found in basil, cinnamon, lemon balm) 1

Lactoferrin antiviral fro CMV via inhibition of cell entry 1

Chlorella vulgaris fights murine CMV in mice 1

Monolaurin (Lauricidin®) 1

Garlic extract 1

Diallyl trisulfide (allitridin) from garlic comparable to the antiviral drug ganiciclovir for treating cytomegalovirus 1

Black seed oil (Nigella sativa) for murine cytomegalovirus 1

Hypericin (from St John's wort) inactivated murine cytomegalovirus, especially on exposure to light. 1 Hypericin plus light creates singlet oxygen. Highest singlet oxygen generation with white light or 600 nm light. 1

COX-2 inhibitors blocks human CMV replication. 1 Propolis is a potent COX-2 inhibitor.

Inhibitors of prostaglandins inhibit the growth of human cytomegalovirus and reactivation of latent virus in a cell line. 1 Ginger is a potent inhibitor of prostaglandins. Alpha acids from Hops (available as Perluxan®) a potent prostaglandin inhibitor.

Alpha acids from Hops (available as Perluxan®) showed mild to moderate antiviral activity against CMV 1

Curcumin protected mice against human cytomegalovirus infection possibly by its anti-inflammatory and antioxidant effects 1


Note

DMSO reactivates CMV 1
 
Last edited:

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
Roughly one tenth of a person’s circulating T cells are specific for cytomegalovirus

Probably a stupid question but I just have to wonder.

If 10% of circulating T cells are specific for cytomegalovirus, so engaged in that task and say if someone was carrying a lot of other things which also had circulating T cells engaged for specific tasks.. maybe something else could have even a higher percent of specificity for it (something science may yet have to work out).. Could it be possible that a person could run out of available T cells for anything else which came along once say 100% were specific for certain things?

Can someone have no available free T cells left for another thing?

I carry CMV along with a toxoplasmosis (which apparently sits in ones brain, common for that to reactive in AIDS patients). I also have other things simmering away (I outbreak in some viral reactivation thing in my mouth at times when I crash).
 

missfire

Knock Down, Bounce Back
Messages
13
Interesting flag up.
As usual I shall pick holes! They say: We measured 204 different parameters, including cell population frequencies, cytokine responses, and serum proteins, and found that 77% of these are dominated (>50% of variance) and 58% almost completely determined (>80% of variance) by non-heritable influences. In addition, some of these parameters become more variable with age, suggesting the cumulative influence of environmental exposure.

Wrong. What they have found is non-heritable differences. That can be environmental but it can also be just the random behaviour of B and T cells, as I keep going on about. Moreover, that randomness will increase with age much more reliably than environmental infection influences which tend to be over and done with (plus vaccinations) in infancy. So thus far there is not a trace of evidence for an environmental factor. OK, they do find a correlation with CMV and that is very interesting - particularly since they do not find it for EBV. Environmental influences would be very plausible and there is no evidence against, but it still amuses me that all these grand immunologists still forget to read the epidemiology textbooks.

What master list of things could one test for if they were force feed saliva with CMV in it? It has remained persistent from day one indicating a secondary immune issue. I really do not know what to beg for to determine my health status. Is there a master list of things I could ask for (testing)?

persistent cmv
subclass 1
T3 uptake is low
CD 8 cells very low
CD 4 fine
HIV is fine, all obvious stuff
hearing sensitivity to sound IS WAY HIGH

What is left for looking for a reason that cmv is not resolving in a healthy young person?