Trying to understand immune-modulating

[lismom]

I am trying to understand the use of zith. I understand the tech reasons as far as intracellular, and iradicating strep. But once you've been on zith for months it's not so much about getting rid of the strep anymore. We need the higher dose of zith and my son is about 90-95% tic free now. Is time and healing the other piece to this puzzle. With saving sammy it took years of high dose and all that time was not about getting rid of the strep. Does zith help suppress the immune system some while it tries to heal. I am still confused, Help, Kathy

[Buster]

Does zith help suppress the immune system some while it tries to heal. I am still confused, Help, Kathy

 

Hi Lismom,

 

I've struggled with this too and don't have a great answer but do have another theory to add to the mix... look to the end.

 

On zith suppressing the immune system

 

Yes, azithromycin is immuno-modulating (and hence somewhat immune suppressing) and is also an anti-inflammatory The immuno-modulating effect is that azith tends to move the T helper cells from generating Th2 cells (that lead to more macrophages and antibodies) to Th1 (NK killer cells). This has several effects:

• the increased NK Killer cells can go after intracellular strep
  
• fewer antibodies are getting produced (than without)
  
• less inflammatory cytokines are generated -- reducing inflammation
  

Our immunologist believes the big benefit of azith was its anti-inflammatory property and wasn't a big believer that there was any strep left (intracellular or otherwise).

 

On whether GABHS is acting like a virus rather than like a bacteria

 

The results of high-dose augmentin seem to have helped several. This has made me wonder if perhaps there is strep lingering in the body (intracellular) but was left at such a low residual amount that it is not detectable by anything but the faulty immune system.

 

Again, all just a theory, but what if the GABHS acts a bit like a virus -- think of chicken pox for a moment. The virus can live in cells for a very long time with no ill effect until it bursts forth and starts again. So perhaps what is happening is the suceptible child's immune system isn't quite strong enough to get rid of the GABHS that's in a cell (i.e., due to low NK killer cells or an inability to flag that the cell is infected).

 

So every so often one of these cells "bursts" and the GABHS gets back out into the blood stream, runs into a T-cell and more antibodies are formed but some of the GABHS gets into another cell before the bodies found it and removed it.

 

Perhaps what is happening is that with the high-dose augmentin, when the cell bursts, the GABHS runs smack into the antibiotic (which actually is bacteriacidal at that dosage level) and the GABHS can't get back into another cell before it is destroyed. This is sort of how anti-viral's work -- I wonder if that is what is happening here.

 

No science here, just it seems to fit with what we are seeing. I think this waky strain of strep is acting like a virus rather than acting like an extra-cellular bacteria and thus has all the same problems. I really hope one of these doctors does an emm-type on this strain.

 

Anyway, my thoughts,

 

Buster

[sf_mom]

Good thoughts and my guess is M1 and M18 strains. http://www.genomenewsnetwork.org/articles/...c_bacterium.php

[peglem]

Does zith help suppress the immune system some while it tries to heal. I am still confused, Help, Kathy

 

Hi Lismom,

 

I've struggled with this too and don't have a great answer but do have another theory to add to the mix... look to the end.

 

On zith suppressing the immune system

 

Yes, azithromycin is immuno-modulating (and hence somewhat immune suppressing) and is also an anti-inflammatory The immuno-modulating effect is that azith tends to move the T helper cells from generating Th2 cells (that lead to more macrophages and antibodies) to Th1 (NK killer cells). This has several effects:

• the increased NK Killer cells can go after intracellular strep
  
• fewer antibodies are getting produced (than without)
  
• less inflammatory cytokines are generated -- reducing inflammation
  

Our immunologist believes the big benefit of azith was its anti-inflammatory property and wasn't a big believer that there was any strep left (intracellular or otherwise).

 

On whether GABHS is acting like a virus rather than like a bacteria

 

The results of high-dose augmentin seem to have helped several. This has made me wonder if perhaps there is strep lingering in the body (intracellular) but was left at such a low residual amount that it is not detectable by anything but the faulty immune system.

 

Again, all just a theory, but what if the GABHS acts a bit like a virus -- think of chicken pox for a moment. The virus can live in cells for a very long time with no ill effect until it bursts forth and starts again. So perhaps what is happening is the suceptible child's immune system isn't quite strong enough to get rid of the GABHS that's in a cell (i.e., due to low NK killer cells or an inability to flag that the cell is infected).

 

So every so often one of these cells "bursts" and the GABHS gets back out into the blood stream, runs into a T-cell and more antibodies are formed but some of the GABHS gets into another cell before the bodies found it and removed it.

 

Perhaps what is happening is that with the high-dose augmentin, when the cell bursts, the GABHS runs smack into the antibiotic (which actually is bacteriacidal at that dosage level) and the GABHS can't get back into another cell before it is destroyed. This is sort of how anti-viral's work -- I wonder if that is what is happening here.

 

No science here, just it seems to fit with what we are seeing. I think this waky strain of strep is acting like a virus rather than acting like an extra-cellular bacteria and thus has all the same problems. I really hope one of these doctors does an emm-type on this strain.

 

Anyway, my thoughts,

 

Buster

 

This does sound as though it is exactly what is happening with my daughter! So, has anybody tried a combo of zithromycin + augmentin? Or would that be a problem for some reason?

[nevergiveup]

Hey Buster, Wanted your opinion on what Shannon posted about a week ago about her immunologist Sleasman down at USF. She stated that he has seen some of the PANDAS kids from Murphy's clinic have t cell deficiencies. This apparantly is not commonly tested by immun doc. You can have normal t cell numbers but individula T1 or T2 deficiencies. Apparantly not curable. Anyway would this explain why high dose antibiotics may help. Apparantly Tanya Murphy is also starting a high dose augmentin study. Anyway just thinking there may be some correlation. If you had a t cell deficiency would that potentially let strep linger and hide out? I have an appoint down with these docs and the head of immun at USF and would like to go down with some understanding of what they are looking at? My daughter was recently diagnosed with CVID but I am wondering if there is more to all of this, we talk of super strep strains but couldn't it be faulty immune systems? However, xmrv has rocked the science world lately, hiding out in immune cells, maybe strep is hiding like viruses I agree.

[Buster]

would [ Tcell deficiency ] explain why high dose antibiotics may help.

 

I'm not sure. Certainly a T-cell deficiency would make it difficult for the body to create a sufficient response and thus the "tested effective dose" of antibiotic would probably not be very effective in people with either IgG or T-cell deficiencies. I haven't seen papers on this, but it seems to make sense.

 

Antibiotics like augmentin (in high enough dosage) can be bactericidal. So if you really aren't raising enough of an immune response then I could see that helping out the immune system by actually breaking down the cell wall of GABHS. If the strep is hiding out intracellular, then when it bursts, it'll hit a the augmentin and be taken out.

 

Similarly, antibiotics like azithromycin can go intracellular. If strep is hiding out intracellular, then azith would be effective by either preventing growth in the cell or becoming bacteriacidal for intracellular strep.

 

The antibodies are actually created by the B-cells (when activated by a T-cell). So a T-cell deficiency should actually cause less B-cell activation and hence less antibodies.

 

I suppose the actual deficiency might be the T-regulatory cells. In which case they don't detect the anti-host antibody. This seems very plausible in folks with low Igg.

 

see http://en.wikipedia.org/wiki/File:B_cell_activation.png

 

That was a long way of saying that I don't know...

 

Regards,

 

Buster

[peglem]

So, remind me, what's the diff between a T regulator cell and other Tcells?

[Buster]

would [ Tcell deficiency ] explain why high dose antibiotics may help.

 

Just ran into a very interesting 2004 paper -- http://www.pnas.org/content/101/21/8180.long from the folks in Rehovot

 

Which says:

"T cell deficiency leads to cognitive dysfunction: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions "

 

The results, by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the development of a therapeutic vaccination for fighting off cognitive dysfunction and psychiatric conditions.

 

Hmm...

 

Buster

[Buster]

So, remind me, what's the diff between a T regulator cell and other Tcells?

 

Kim posted a very nice summary here http://www.latitudes.org/forums/index.php?showtopic=5838

 

and referenced a good article http://www.physorg.com/news108987915.html

 

The short summary is that regulatory T cells (Tregs) are T cells, but the Tregs watch for things that would be anti-host. If they find something anti-host, they don't react -- meaning they stop the feedback cycle.

 

Think of it this way, a Macrophage comes along and found GABHS, the Macrophage comes along and tells a B-cell. The B-cell starts getting ready to mature and attracts T-cells. The T-regulatory cell attaches and goes "hold on, your antibody would be anti-host" and disables the B-cell. So the regulatory T-cells disable the feedback cycle and prevent more antibodies and macrophages from being produced for stuff that is antihost.

 

Buster

[peglem]

Thanks, Buster. I love the way you make things understandable!