Re: article: lyme disease may have physical cause

[Guest guest]

I answer to 'Your Holeyness', as this better describes the current

state of my brain. However, even a humble hole can aspire to be

filled with inspiration...

Um, yes, as I was saying...I fear I may have misled you, for I was

referring to work I think you've already read, demonstrating that

macrophage output shifts decisively toward Th1 cytokines in the

presence of Borrelia burgdorferi's OSPs. The researchers seem sure

of that result, the only part that appeared speculative was their

thought that blebs could do this as well as motile spirochetes.

These were among the gems lost in our Vatican Archives when the

forces of darkness shut down the old I & I site. I shall attempt to

recover them from my private Papal collection and repost them post

haste.

I believe the experiments are in vitro, but are well-conceived and

unlikely to be in error.

We have discussed these in the past in terms of the differentiation

of naive T cells into either the Type 1 or the Type 2 phenotype. The

borrelial OSPs force the Type 1 or " Th1 " phenotype on these

undifferentiated T-helper cells. I remain unclear on the details,

but have now read two sets of researchers saying this is bad from

the host's point of view, because we need Type 2 or " Th2 " cells to

facilitate effective antibodies.

Ordinarily, the macrophage cytokines that start all this off are

triggered by the presence of intracellular pathogens. But the

macrophages in the study were found to be clean, the shift in output

attributed to direct action of extracellular OSPs on macrophage

signalling.

This finding is what gave rise to my 'hiding in plain sight'

analogy, that by directing the immune system to act against host

cells, rather than bugs, the spirochetes are able to avoid being

targeted by antibodies even in those parts of the body where

macrophages, the white knights of the immune system, are on active

duty.

I believe this helps to explain why those who have very bad,

symptomatic Lyme often have low levels of antibodies, while those

who are fairly asymptomatic often have significantly higher levels.

If you think about it, that indicates radical immune failure.

Particularly if researchers are right in saying that disease

severity in Lyme is a function of spirochete load**. All those bugs,

where the hell are the antibodies?

This is why I don't much believe in the cross-reactivity of Bb and

host tissues. If that were true, and antibodies were doing all this

damage, surely we would detect higher antibody levels in very sick

patients.

We Lymies might prefer to think that any time there is inflammation,

that's the immune system struggling like a champ to put down the

villains. OK, sometimes maybe it zaps us by mistake, but mostly its

getting the bugs. What the 'dysfunctional Th1 response' theory says

is 'sorry, no, sometimes your pain is the bugs gain.'

Me, I want to stop the pain so bad, I'm biased in the other

direction.

Why would spirochetes have evolved OSPs that induce this behavior in

macrophages, unless it serves their survival?

I don't think there's any very dramatic therapeutic implication -

not yet, anyhow. Because we can't just shut down that Th1 response,

globally, to cope with a local phenomenon. What it mostly suggests

is what the sharper LLMDs are already saying, that successful

treatment of this infection requires some effort to moderate

inflammation, not just kill bugs.

I keep thinking we need something like a vaccine, that would assist

antibody production, but we all know what happened the last time

someone manufactured a Lyme vaccine...

One of the questions I have about all this is whether one can

distinguish in some clear way between this cytokine-fueled

inflammation and the inflammation generated by endotoxin. I fear the

answer may be 'no', because as I understand it borrelial endotoxin

is pretty much the same stuff they carry on the surface, there's

just a lot more of it sandwiched between layers of membrane, that is

released when the bugs get zapped.

So endotoxin probably has the same effect on macrophages

as 'exotoxin' [osps], and further shifts the immune system to Th1

inflammation until its cleared.

If only there was a way to kill the buggers while keeping them

intact, and sweeping the corpses out of our bodies like the

hazardous biomedical waste product they are, at least semi-

contained. Like bagging dog-doo in the park - you don't want to

disturb that crap, you just want to get it intact in a bag and hold

it away from you till you can get to a trash can.

Alright, enough blather about dog poop. I will try to find those two

studies and repost them.

Scha

>

> This repost is a fraction of a post I just deleted, having

realized it

> contains a long, technical spiel that has no point.

>

> =======================

>

> Your Holiness,

>

> Time for another Th1/Th2 showdown!

>

> Actually I'll be busy this week, but I'd be ravenous to at least

read

> what youre reading on borrelial Osps affecting macrophage

receptors in

> a super-inflammatory way. Is there a simple experiment showing

this?

>

>

> > 5) As far as Th1 vs Th2, applied to Lyme, forget all about the

> > Engineer. We have bonafide Lyme researches working on that. And

what

> > they appear to me to be saying goes like this:

> >

> > 6) If the bugs have their way, your immune system will spend all

its

> > energy waging a pointless, self-defeating battle against a

target it

> > can't see, damaging your body in the process.

> >

> > This is because the outer surface proteins of Borrelia

burgdorferi

> > act directly on macrophages, forcing them to secrete cytokines

that

> > foster inflammation rather than effective antibody formation.

[Guest guest]

, why do the bugs do that, how does it enhance their survival,

any thoughts? They're not doing it to be mean, it somehow helps them.

>

> This repost is a fraction of a post I just deleted, having realized

it

> contains a long, technical spiel that has no point.

>

> =======================

>

> Your Holiness,

>

> Time for another Th1/Th2 showdown!

>

> Actually I'll be busy this week, but I'd be ravenous to at least

read

> what youre reading on borrelial Osps affecting macrophage receptors

in

> a super-inflammatory way. Is there a simple experiment showing this?

>

>

> > 5) As far as Th1 vs Th2, applied to Lyme, forget all about the

> > Engineer. We have bonafide Lyme researches working on that. And

what

> > they appear to me to be saying goes like this:

> >

> > 6) If the bugs have their way, your immune system will spend all

its

> > energy waging a pointless, self-defeating battle against a target

it

> > can't see, damaging your body in the process.

> >

> > This is because the outer surface proteins of Borrelia burgdorferi

> > act directly on macrophages, forcing them to secrete cytokines

that

> > foster inflammation rather than effective antibody formation.

[Guest guest]

> attributed to direct action of extracellular OSPs on macrophage

> signalling.

>

> This finding is what gave rise to my 'hiding in plain sight'

> analogy, that by directing the immune system to act against host

> cells, rather than bugs, the spirochetes are able to avoid being

> targeted by antibodies even in those parts of the body where

> macrophages, the white knights of the immune system, are on active

> duty.

>

> I believe this helps to explain why those who have very bad,

> symptomatic Lyme often have low levels of antibodies, while those

> who are fairly asymptomatic often have significantly higher levels.

I wish it were this clean/obvious, but I had sky high antibodies in

the first six months or so (I kept retesting after treating), really

unbelievably high. And my own doctor had had it twice, and monitored

his treatment by his antibodies coming down. Doxy had no impact on

the antibodies and I was incredibly highly symptomatic at the time,

in a great deal of physical pain and all kinds of weird scary

symptoms.

I might test much more 'anergic' now, I think after a long time your

body stops fighting as hard.

...

>

> Why would spirochetes have evolved OSPs that induce this behavior

in

> macrophages, unless it serves their survival?

I agree unless, sadly and badly, they are bioweaponized by humans who

just want to cause other humans pain, plain and simple.

>> I keep thinking we need something like a vaccine, that would

assist

> antibody production, but we all know what happened the last time

> someone manufactured a Lyme vaccine...

YEah but they did an OspA vaccine and that's mostly expressed in the

tickgut. THe OspC vaccine was squelched. A vaccine is a good idea if

it can be made to some antigen that is unchanging and on the surface,

not hidden.

>

> One of the questions I have about all this is whether one can

> distinguish in some clear way between this cytokine-fueled

> inflammation and the inflammation generated by endotoxin. I fear

the

> answer may be 'no', because as I understand it borrelial endotoxin

> is pretty much the same stuff they carry on the surface, there's

> just a lot more of it sandwiched between layers of membrane, that

is

> released when the bugs get zapped.

I think you're probably right.

> If only there was a way to kill the buggers while keeping them

> intact, and sweeping the corpses out of our bodies like the

> hazardous biomedical waste product they are, at least semi-

> contained. Like bagging dog-doo in the park - you don't want to

> disturb that crap, you just want to get it intact in a bag and hold

> it away from you till you can get to a trash can.

>

Or find a way to stop their replication, that is a nice and quiet way

to slowly get rid of them.

[Guest guest]

I didn't mean to make it sound clean and simple, but dirty and

complicated.

The fact is, loads of patients are very sick with very low

antibodies, and some of the sickest patients take the longest to

diagnose because they show no antibodies until you start treating.

I would welcome any alternate explanation of that phenomenon you

might suggest. My point was that inflammation does not equal

antibodies, not that they can never go together but that very often

they do not.

>

>

> > attributed to direct action of extracellular OSPs on macrophage

> > signalling.

> >

> > This finding is what gave rise to my 'hiding in plain sight'

> > analogy, that by directing the immune system to act against host

> > cells, rather than bugs, the spirochetes are able to avoid being

> > targeted by antibodies even in those parts of the body where

> > macrophages, the white knights of the immune system, are on

active

> > duty.

> >

> > I believe this helps to explain why those who have very bad,

> > symptomatic Lyme often have low levels of antibodies, while

those

> > who are fairly asymptomatic often have significantly higher

levels.

>

>

> I wish it were this clean/obvious, but I had sky high antibodies

in

> the first six months or so (I kept retesting after treating),

really

> unbelievably high. And my own doctor had had it twice, and

monitored

> his treatment by his antibodies coming down. Doxy had no impact on

> the antibodies and I was incredibly highly symptomatic at the

time,

> in a great deal of physical pain and all kinds of weird scary

> symptoms.

>

> I might test much more 'anergic' now, I think after a long time

your

> body stops fighting as hard.

>

>

> ..

> >

> > Why would spirochetes have evolved OSPs that induce this

behavior

> in

> > macrophages, unless it serves their survival?

>

> I agree unless, sadly and badly, they are bioweaponized by humans

who

> just want to cause other humans pain, plain and simple.

>

>

> >> I keep thinking we need something like a vaccine, that would

> assist

> > antibody production, but we all know what happened the last time

> > someone manufactured a Lyme vaccine...

>

> YEah but they did an OspA vaccine and that's mostly expressed in

the

> tickgut. THe OspC vaccine was squelched. A vaccine is a good idea

if

> it can be made to some antigen that is unchanging and on the

surface,

> not hidden.

>

> >

> > One of the questions I have about all this is whether one can

> > distinguish in some clear way between this cytokine-fueled

> > inflammation and the inflammation generated by endotoxin. I fear

> the

> > answer may be 'no', because as I understand it borrelial

endotoxin

> > is pretty much the same stuff they carry on the surface, there's

> > just a lot more of it sandwiched between layers of membrane,

that

> is

> > released when the bugs get zapped.

>

> I think you're probably right.

>

> > If only there was a way to kill the buggers while keeping them

> > intact, and sweeping the corpses out of our bodies like the

> > hazardous biomedical waste product they are, at least semi-

> > contained. Like bagging dog-doo in the park - you don't want to

> > disturb that crap, you just want to get it intact in a bag and

hold

> > it away from you till you can get to a trash can.

> >

>

> Or find a way to stop their replication, that is a nice and quiet

way

> to slowly get rid of them.

[Guest guest]

I have no idea myself, the picture is so fricken complex and

confusing. I really don't. Some have sky high antibodies associated

with disease, some hardly any (but did they ahve sky high in the

beginning? We'll never know).

I'm glad you are seeking out the glutathione. As long as you're going

to have a PICC, let them flood you with glutathione.

Here's what I get weekly: 6 cc of Vitamin C, 1 of b5, 1 of b6 (the

other B's are too stimulating to me), 2.5 cc of magnesium sulfate,

and 1 of calcium. I made this up myself and I Know the calcium

magnesium ratio is sort of weird but I didn't want NO calcium in

there but I didn't want equal either.

Magnesium drops in lyme and replenishing it helps quench neuropathic

symtpoms like pain and buzzing.

> >

> >

> > > attributed to direct action of extracellular OSPs on macrophage

> > > signalling.

> > >

> > > This finding is what gave rise to my 'hiding in plain sight'

> > > analogy, that by directing the immune system to act against

host

> > > cells, rather than bugs, the spirochetes are able to avoid

being

> > > targeted by antibodies even in those parts of the body where

> > > macrophages, the white knights of the immune system, are on

> active

> > > duty.

> > >

> > > I believe this helps to explain why those who have very bad,

> > > symptomatic Lyme often have low levels of antibodies, while

> those

> > > who are fairly asymptomatic often have significantly higher

> levels.

> >

> >

> > I wish it were this clean/obvious, but I had sky high antibodies

> in

> > the first six months or so (I kept retesting after treating),

> really

> > unbelievably high. And my own doctor had had it twice, and

> monitored

> > his treatment by his antibodies coming down. Doxy had no impact

on

> > the antibodies and I was incredibly highly symptomatic at the

> time,

> > in a great deal of physical pain and all kinds of weird scary

> > symptoms.

> >

> > I might test much more 'anergic' now, I think after a long time

> your

> > body stops fighting as hard.

> >

> >

> > ..

> > >

> > > Why would spirochetes have evolved OSPs that induce this

> behavior

> > in

> > > macrophages, unless it serves their survival?

> >

> > I agree unless, sadly and badly, they are bioweaponized by humans

> who

> > just want to cause other humans pain, plain and simple.

> >

> >

> > >> I keep thinking we need something like a vaccine, that would

> > assist

> > > antibody production, but we all know what happened the last

time

> > > someone manufactured a Lyme vaccine...

> >

> > YEah but they did an OspA vaccine and that's mostly expressed in

> the

> > tickgut. THe OspC vaccine was squelched. A vaccine is a good idea

> if

> > it can be made to some antigen that is unchanging and on the

> surface,

> > not hidden.

> >

> > >

> > > One of the questions I have about all this is whether one can

> > > distinguish in some clear way between this cytokine-fueled

> > > inflammation and the inflammation generated by endotoxin. I

fear

> > the

> > > answer may be 'no', because as I understand it borrelial

> endotoxin

> > > is pretty much the same stuff they carry on the surface,

there's

> > > just a lot more of it sandwiched between layers of membrane,

> that

> > is

> > > released when the bugs get zapped.

> >

> > I think you're probably right.

> >

> > > If only there was a way to kill the buggers while keeping them

> > > intact, and sweeping the corpses out of our bodies like the

> > > hazardous biomedical waste product they are, at least semi-

> > > contained. Like bagging dog-doo in the park - you don't want to

> > > disturb that crap, you just want to get it intact in a bag and

> hold

> > > it away from you till you can get to a trash can.

> > >

> >

> > Or find a way to stop their replication, that is a nice and quiet

> way

> > to slowly get rid of them.

[Guest guest]

P.S. One alternate hypothesis that I do not ascribe to but would be

Occam's razor clean and simple: it's a different organism entirely

that's causing the main disease, and borrelia, babesia, bartonella are

just co-factors along for the ride. ANd that unknown organism is

unidentified/fiable.

I don't believe this because of the history of syphilis, and other

spirochetal illnesses; and other protozal illnesses like malaria.

Nonetheless it would be the simplest explanation.

[Guest guest]

> Um, yes, as I was saying...I fear I may have misled you, for I was

> referring to work I think you've already read, demonstrating that

> macrophage output shifts decisively toward Th1 cytokines in the

> presence of Borrelia burgdorferi's OSPs. The researchers seem sure

> of that result, the only part that appeared speculative was their

> thought that blebs could do this as well as motile spirochetes.

Sounds good... but this may be true to an extent of all bacteria...

after all LPS itself causes macrophages to emit inflammatory cytokines

when it binds with TLRs. So this observation in itself, without

quantitation, cant contribute to explaining the inconsistant/weak in

vivo antibody reaction to sprirochetes.

> Ordinarily, the macrophage cytokines that start all this off are

> triggered by the presence of intracellular pathogens. But the

> macrophages in the study were found to be clean, the shift in output

> attributed to direct action of extracellular OSPs on macrophage

> signalling.

I am unsure that pro-inflammatory cytokine release by mphages due to

signaling via innate immune system receptors can in fact only happen

after phagocytosis. But assuming so, how would they make sure the

mphages *stayed* clean after they were placed with borrelia? The

mphages could phagocytose the Bb - which would definitely set off

innate immune system receptors - and then rapidly degrade them.

> This is why I don't much believe in the cross-reactivity of Bb and

> host tissues. If that were true, and antibodies were doing all this

> damage, surely we would detect higher antibody levels in very sick

> patients.

I read today that Alan Steere *withdrew* his suggestion that human

leucocyte function associated antigen might become an immunotargeted

self epitope in the presence of borrelial OspA.

I agree the antibody issue is a compelling one. It might be explained

by the infection remaining mostly intracellular, but I have not

searched for an anologous example for this... also I think there might

(?) be well documented cases of sero-negative syphilis where the

organisms were clearly partying right there in the vascular lumens,

etc. I will have to check into this.

> Why would spirochetes have evolved OSPs that induce this behavior in

> macrophages, unless it serves their survival?

They cant get around it. The TLRs and other innate immune system

receptors cover bacterias favorite molecules like LPS and

peptidoglycan, the whole set of which they just cant dispense with in

any case, so far as is known. Tho I personally dont know what all the

IISR ligands are, so I dont know this personally.

But, if Bb freak out macrophages more than a usual germ, maybe that

*is* an adaptation on their part. I've heard some mycoplasmal

componants are super-antigenic in this way. I dont see why the

mycoplasma couldnt try something quieter, so the fact that they

" choose " not to may suggest that what they have is somehow adaptive.

Also, I dont understand why all bacteria dont just copy the LPS of

brucella, said to be much much less antigenic than most LPS.

> One of the questions I have about all this is whether one can

> distinguish in some clear way between this cytokine-fueled

> inflammation and the inflammation generated by endotoxin. I fear the

> answer may be 'no', because as I understand it borrelial endotoxin

> is pretty much the same stuff they carry on the surface, there's

> just a lot more of it sandwiched between layers of membrane, that is

> released when the bugs get zapped.

>

> So endotoxin probably has the same effect on macrophages

> as 'exotoxin' [osps], and further shifts the immune system to Th1

> inflammation until its cleared.

I think you are confused about these illogical terms the same way I

once was... an exotoxin is secreted, endotoxin refers to a single

substance, lipopolysaccharide (LPS). I dont think it needs to be

internal, it can be exposed on the outside of the bug - tho most

pathogenic bugs including borrelia have a polysaccharide glycocalyx on

the very outside. I do not understand how the glycocalyx doesnt

interfere with the binding of anti-Osp antibody, etc. Bb like some

other bx has complement-regulator-fixing proteins that are supposed to

keep it from being killed by complement once antibody attaches... but

why the glycocalyx doesnt make all this superfluous, I have not grasped.

All the endotoxin-created inflammation is via ligandization of

receptors and the consequent downstream immune activation. Borrelia

dont have endotoxin in the strict sense but I think the borrelial

lipoproteins ligandize some TLRs in the same way.

> If only there was a way to kill the buggers while keeping them

> intact, and sweeping the corpses out of our bodies like the

> hazardous biomedical waste product they are, at least semi-

> contained. Like bagging dog-doo in the park - you don't want to

> disturb that crap, you just want to get it intact in a bag and hold

> it away from you till you can get to a trash can.

LOL. If only there were some stronger way to kill them, period.

[Guest guest]

ERic, can you research this a bit more:

--a polysaccharide glycocalyx on

the very outside. I do not understand how the glycocalyx doesnt

interfere with the binding of anti-Osp antibody--

There was a recent study on a few strains of lactobacilli that like

mannose and latch onto the mannose coating of HIV.

Maybe the same could be done with borrelia. The way mannose is used

for ecoli bladder infections.

It would obviously take a lot longer but if they're thinking about it

with HIV why not bb. Its sort of like a natural predator idea.

What polysaccharides does borrelia use. What does it actually probably

use to adhere to the cell membrane at first. If that can be

prevented...

[Guest guest]

Delivery is a major problem for large objects like bacteria or drug

nanoparticles... how to get lactobacilli into tissues/cells, esp

privalged sites like the brain or ocular antechamber?

Good questions about glycocalyx. We must find out about this. Its very

confusing. Im going to the libe after school so maybe I can scare up

some thorough treatments of the subject.

By the way, an immense free online archive of the J Bacteriol is here:

http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive & journal=88

<jenbooks13@h...> wrote:

>

> ERic, can you research this a bit more:

>

> --a polysaccharide glycocalyx on

> the very outside. I do not understand how the glycocalyx doesnt

> interfere with the binding of anti-Osp antibody--

>

> There was a recent study on a few strains of lactobacilli that like

> mannose and latch onto the mannose coating of HIV.

>

> Maybe the same could be done with borrelia. The way mannose is used

> for ecoli bladder infections.

>

> It would obviously take a lot longer but if they're thinking about it

> with HIV why not bb. Its sort of like a natural predator idea.

>

> What polysaccharides does borrelia use. What does it actually probably

> use to adhere to the cell membrane at first. If that can be

> prevented...