Re: Bb architecture - antigenic variation

[Guest guest]

You're right ERic--that's why they used OspA, even tho they knew it

could cause autoimmune disease.

And that's why there will never be a good vaccine and why having

gotten lyme once you do not become immune to it.

And why Barb talks about being a voodoo doll , you keep getting

shifting antigens and your immune system responds.

> Cullen, Haake, and Adler disagree with Radolf and on the degree

> of paucity of exposed proteins in Tp and Bb. Their 30-pp 2004 paper

> in FEMS Microbiol Rev is a pretty cool treatment of spirochetal

> architecture, with applications to persistence and pathogenesis.

>

> Given that most molecular investigators seem to feel antibody to be

> the key to antispirochetal immunity, it is surprising no one of

this

> set seems to take heed of work like Hulinskas, which visualized Bb

> in seronegative patients in appreciable quantities. Since some of

> these types eg Radolf (but not Barbour) vaguely seem to be aware of

> the probable existence of abx-refractory chronic lyme borreliosis,

> you would think they would seize upon this deficiency of specific

> antibody as indicating a perhaps-fixable immune lesion possibly

> necessary to the persistence of the disease.

>

> I learned that OspC, etc, are highly polymorphic between strains.

> OspA is one of the only Osps that has been found to be fairly

> invariant. The invariance appears to be due to this Osp being

little-

> expressed in vertebrate hosts. The vertebrate adaptive immune

system

> can produce life-long immunity against a given microbial antigen,

> which ecologically selects for the great polymorphism of the Bb

> Osps. Since OspA is essentially only expressed in the tick, a much

> more primitive host, it is not subject to these pressures and

> remains the same in all strains. This is why it was used for the

> LYMERix vaccine. Vaccination of mice with most Osps and other

> exposed proteins yields immunity only to the strain from which the

> vaccine is derived.

>

> Given that most Osps cannot instill multiple-strain immunity, its

> puzzling that serology works at all in lyme disease. If Ab against

> one OspC fails to protect against an organism bearing a different

> OspC, then how can all antibodies against various OspCs bind to the

> OspC used in a western blot? Hmmm. Perhaps the WB employs not only

> Osp epitopes that are surface-exposed, but also others that are

not,

> and that therefore are not very polymorphic and not very important

> in immunity to Bb. I guess that is the most likely answer.

>

> These authors propose that antigenic variation could well be a

major

> cause of Bb persistence.

[Guest guest]

Hi ,

Do you have a link to the paper that you mention in the posting below?

Thank you ahead of time!

CELIENE

> Cullen, Haake, and Adler disagree with Radolf and on the degree

> of paucity of exposed proteins in Tp and Bb. Their 30-pp 2004 paper

> in FEMS Microbiol Rev is a pretty cool treatment of spirochetal

> architecture, with applications to persistence and pathogenesis.

>

> Given that most molecular investigators seem to feel antibody to be

> the key to antispirochetal immunity, it is surprising no one of

this

> set seems to take heed of work like Hulinskas, which visualized Bb

> in seronegative patients in appreciable quantities. Since some of

> these types eg Radolf (but not Barbour) vaguely seem to be aware of

> the probable existence of abx-refractory chronic lyme borreliosis,

> you would think they would seize upon this deficiency of specific

> antibody as indicating a perhaps-fixable immune lesion possibly

> necessary to the persistence of the disease.

>

> I learned that OspC, etc, are highly polymorphic between strains.

> OspA is one of the only Osps that has been found to be fairly

> invariant. The invariance appears to be due to this Osp being

little-

> expressed in vertebrate hosts. The vertebrate adaptive immune

system

> can produce life-long immunity against a given microbial antigen,

> which ecologically selects for the great polymorphism of the Bb

> Osps. Since OspA is essentially only expressed in the tick, a much

> more primitive host, it is not subject to these pressures and

> remains the same in all strains. This is why it was used for the

> LYMERix vaccine. Vaccination of mice with most Osps and other

> exposed proteins yields immunity only to the strain from which the

> vaccine is derived.

>

> Given that most Osps cannot instill multiple-strain immunity, its

> puzzling that serology works at all in lyme disease. If Ab against

> one OspC fails to protect against an organism bearing a different

> OspC, then how can all antibodies against various OspCs bind to the

> OspC used in a western blot? Hmmm. Perhaps the WB employs not only

> Osp epitopes that are surface-exposed, but also others that are

not,

> and that therefore are not very polymorphic and not very important

> in immunity to Bb. I guess that is the most likely answer.

>

> These authors propose that antigenic variation could well be a

major

> cause of Bb persistence.

[Guest guest]

OK now wait a sec ... the researchers didn't know the Lymerix

vaccine would cause (so-called) autoimmune disease - they thought

it would work against Lyme the way other vaccines would work. They

used OspA/B because they thought it would confer immunity.

Then all of a sudden in some of them, they became symptomatic, and

some expressed antibodies to a whole range of the Bb specific

proteins. They couldn't even interpret their own subsequent Blot

data from the vaccinated people -

I express Osp A and B on my blot, and so do others who are mainly

late stage Lyme. Osp A has been found to be in the intermediate

layer of the wall - so it may really not be up regulated at the

initial time of infection - and remember - most Doc don't even think

chronic Lyme exists - so by their way of thinking - if it's not

upregulated at the time of initial infection, and there's no such

thing as chronic Lyme - then it's not expressed..

This is how OspA got linking as the " autoimmune " protein.

Jury's still out IMO.

- Try googling OspA and B and you'll find alot of the stuff is

un published - or sorely lacking... I think the researcherthat

investigated most of the vaccinated blots name is

Fawcett - try googling his name.

But from my understanding of the researchers lack of understanding

about what's going on in the people that were vaccinated - I don't

think anyone really knows.

Barb

My new computer's up - but all my files aren't transferred back yet -

or I could cite the 2 main papers I'm referring to.

> > Cullen, Haake, and Adler disagree with Radolf and on the

degree

> > of paucity of exposed proteins in Tp and Bb. Their 30-pp 2004

paper

> > in FEMS Microbiol Rev is a pretty cool treatment of spirochetal

> > architecture, with applications to persistence and pathogenesis.

> >

> > Given that most molecular investigators seem to feel antibody to

be

> > the key to antispirochetal immunity, it is surprising no one of

> this

> > set seems to take heed of work like Hulinskas, which visualized

Bb

> > in seronegative patients in appreciable quantities. Since some

of

> > these types eg Radolf (but not Barbour) vaguely seem to be aware

of

> > the probable existence of abx-refractory chronic lyme

borreliosis,

> > you would think they would seize upon this deficiency of

specific

> > antibody as indicating a perhaps-fixable immune lesion possibly

> > necessary to the persistence of the disease.

> >

> > I learned that OspC, etc, are highly polymorphic between

strains.

> > OspA is one of the only Osps that has been found to be fairly

> > invariant. The invariance appears to be due to this Osp being

> little-

> > expressed in vertebrate hosts. The vertebrate adaptive immune

> system

> > can produce life-long immunity against a given microbial

antigen,

> > which ecologically selects for the great polymorphism of the Bb

> > Osps. Since OspA is essentially only expressed in the tick, a

much

> > more primitive host, it is not subject to these pressures and

> > remains the same in all strains. This is why it was used for the

> > LYMERix vaccine. Vaccination of mice with most Osps and other

> > exposed proteins yields immunity only to the strain from which

the

> > vaccine is derived.

> >

> > Given that most Osps cannot instill multiple-strain immunity,

its

> > puzzling that serology works at all in lyme disease. If Ab

against

> > one OspC fails to protect against an organism bearing a

different

> > OspC, then how can all antibodies against various OspCs bind to

the

> > OspC used in a western blot? Hmmm. Perhaps the WB employs not

only

> > Osp epitopes that are surface-exposed, but also others that are

> not,

> > and that therefore are not very polymorphic and not very

important

> > in immunity to Bb. I guess that is the most likely answer.

> >

> > These authors propose that antigenic variation could well be a

> major

> > cause of Bb persistence.

[Guest guest]

Jill, when you say " that's why there will never be a good vaccine "

it sounds vaguely like Nostradamus to me. Is there some well-funded

effort to find an answer to those shifty borrelia antigens you know

of, that I don't? Some concerted effort that despite a reasonable

allocation of resources and energy keeps hitting a wall?

Because the last time I checked, no such effort was under way.

I don't mean to seize unfairly on your choice of words, and should

probably explain the context in which this " never " jumped out at me,

which really has little to do with you.

We have been hearing a lot on the list lately, in the way of

confident, sweeping, declarative statements, about what we

can " never " expect to receive from the institutions of modern

medicine.

Two posters recently suggested that since it contains errors and

omissions, the whole body of peer-reviewed medical research can be

discounted, and we should never accept anything just because it's

been consistently observed under reproducible conditions - an

overreaching which comes close to inverting the ethos of the list,

as I have understood it.

In both cases, this was in lieu of actually engaging data that had

been alluded to. " Oh, published data, we all know how suspect that

is. " As opposed to what, for heavens sake?

There has also been a chorus of posts to the effect that sensible

people would never expect the medical profession to do a damn thing

for them. The rhetoric of that has at times lately approached what I

would call a survivalist mentality: grab your vetinary medicine

catalog, buy yourself an Ebay microscope, and head for the hills,

because at best the doctors are utterly indifferent, and at worst

they're malicious.

It's not that I don't understand the sentiments...anyone who knows

anything about what I've been through knows I have plenty of direct

experience of modern medicine's shortcomings.

And I have made my own points about the dangers of over-reliance on

academic research, which often overlooks (and not always innocently)

the real context in which a disease like Lyme does or does not

respond to treatment.

I just think that when you face challenges like this it becomes all

the more necessary to avoid sweeping generalizations. One does not

pick the darkest chapter of a novel to decipher the moral of the

story, and then stop reading.

My perspective is shaped by having watched friends die of AIDS at a

time when both public and private medical insitutions were largely

inert, and seeing a pariah population with a pariah illness exert

enough pressure to change that. A cure has not been forthcoming, but

I now have several friends who have been HIV+ for a great many years

and enjoy a very good state of health.

It did not require turning the world into a utopia, or purging

modern medicine of all of its faults. It left both medical and

political work of an urgent nature undone. The spectre of 85 million

Africans dying of AIDS to protect pharma company profits is enough

to remind anyone with half an IQ point of that.

But my god, you only have to look at what HAS been accomplished, to

see communities vibrant again that were on the verge of turning into

graveyards, to understand that modern medicine is far from useless,

even to those of us who bear the pariah stamp.

" Never " bothers me, unless there is some self-evident sense in which

it is true, because you can't " ACT UP " with your expectations around

your ankles. All you can do in that state is walk funny and prepare

to be mounted by people looking for easy targets.

I'm not suggesting you're in that state, Jill, or that anyone else

is here. But we have a readership that extends much further than the

active members, and for their sake as well as our own, it can't hurt

to avoid the appearance of confusing fatalism for wisdom, or

resignation for enlightenment, or a completely inadequate research

effort with one that lets us say in declarative terms what is and is

not possible.

I think you were just meaning to say 'yep, that is one troublesome

problem with those shifty surface antigens,' and saw the connection

with the selection of OSP A for the vaccine, and got carried away a

bit on the rhetoric.

I could be wrong! If you have absorbed something from your

researches that makes it seem impossible a useful vaccine will every

be developed for Lyme, please do let me know that too, I doubt I'll

reach a conclusion in which the word " never " plays a part but I

might learn something helpful.

Thanks,

> > Cullen, Haake, and Adler disagree with Radolf and on the

degree

> > of paucity of exposed proteins in Tp and Bb. Their 30-pp 2004

paper

> > in FEMS Microbiol Rev is a pretty cool treatment of spirochetal

> > architecture, with applications to persistence and pathogenesis.

> >

> > Given that most molecular investigators seem to feel antibody to

be

> > the key to antispirochetal immunity, it is surprising no one of

> this

> > set seems to take heed of work like Hulinskas, which visualized

Bb

> > in seronegative patients in appreciable quantities. Since some

of

> > these types eg Radolf (but not Barbour) vaguely seem to be aware

of

> > the probable existence of abx-refractory chronic lyme

borreliosis,

> > you would think they would seize upon this deficiency of

specific

> > antibody as indicating a perhaps-fixable immune lesion possibly

> > necessary to the persistence of the disease.

> >

> > I learned that OspC, etc, are highly polymorphic between

strains.

> > OspA is one of the only Osps that has been found to be fairly

> > invariant. The invariance appears to be due to this Osp being

> little-

> > expressed in vertebrate hosts. The vertebrate adaptive immune

> system

> > can produce life-long immunity against a given microbial

antigen,

> > which ecologically selects for the great polymorphism of the Bb

> > Osps. Since OspA is essentially only expressed in the tick, a

much

> > more primitive host, it is not subject to these pressures and

> > remains the same in all strains. This is why it was used for the

> > LYMERix vaccine. Vaccination of mice with most Osps and other

> > exposed proteins yields immunity only to the strain from which

the

> > vaccine is derived.

> >

> > Given that most Osps cannot instill multiple-strain immunity,

its

> > puzzling that serology works at all in lyme disease. If Ab

against

> > one OspC fails to protect against an organism bearing a

different

> > OspC, then how can all antibodies against various OspCs bind to

the

> > OspC used in a western blot? Hmmm. Perhaps the WB employs not

only

> > Osp epitopes that are surface-exposed, but also others that are

> not,

> > and that therefore are not very polymorphic and not very

important

> > in immunity to Bb. I guess that is the most likely answer.

> >

> > These authors propose that antigenic variation could well be a

> major

> > cause of Bb persistence.

[Guest guest]

Steere apparently said so ahead of time. I'll have to find the

reference later.

> > > Cullen, Haake, and Adler disagree with Radolf and on the

> degree

> > > of paucity of exposed proteins in Tp and Bb. Their 30-pp 2004

> paper

> > > in FEMS Microbiol Rev is a pretty cool treatment of spirochetal

> > > architecture, with applications to persistence and

pathogenesis.

> > >

> > > Given that most molecular investigators seem to feel antibody

to

> be

> > > the key to antispirochetal immunity, it is surprising no one of

> > this

> > > set seems to take heed of work like Hulinskas, which visualized

> Bb

> > > in seronegative patients in appreciable quantities. Since some

> of

> > > these types eg Radolf (but not Barbour) vaguely seem to be

aware

> of

> > > the probable existence of abx-refractory chronic lyme

> borreliosis,

> > > you would think they would seize upon this deficiency of

> specific

> > > antibody as indicating a perhaps-fixable immune lesion possibly

> > > necessary to the persistence of the disease.

> > >

> > > I learned that OspC, etc, are highly polymorphic between

> strains.

> > > OspA is one of the only Osps that has been found to be fairly

> > > invariant. The invariance appears to be due to this Osp being

> > little-

> > > expressed in vertebrate hosts. The vertebrate adaptive immune

> > system

> > > can produce life-long immunity against a given microbial

> antigen,

> > > which ecologically selects for the great polymorphism of the Bb

> > > Osps. Since OspA is essentially only expressed in the tick, a

> much

> > > more primitive host, it is not subject to these pressures and

> > > remains the same in all strains. This is why it was used for

the

> > > LYMERix vaccine. Vaccination of mice with most Osps and other

> > > exposed proteins yields immunity only to the strain from which

> the

> > > vaccine is derived.

> > >

> > > Given that most Osps cannot instill multiple-strain immunity,

> its

> > > puzzling that serology works at all in lyme disease. If Ab

> against

> > > one OspC fails to protect against an organism bearing a

> different

> > > OspC, then how can all antibodies against various OspCs bind to

> the

> > > OspC used in a western blot? Hmmm. Perhaps the WB employs not

> only

> > > Osp epitopes that are surface-exposed, but also others that are

> > not,

> > > and that therefore are not very polymorphic and not very

> important

> > > in immunity to Bb. I guess that is the most likely answer.

> > >

> > > These authors propose that antigenic variation could well be a

> > major

> > > cause of Bb persistence.

[Guest guest]

OspC is highly variable across strains in many. So OspC can't be used

relapsing remitting antigen-changing the combination of outer surface

antigens is unlimited. How can you make a vaccine? OspC comprises the

majority of the organism entering the human host, so it will get

through. I guess I'd compare it to the new flu each year, for which

they have tomake a new vaccine. It seems to me the obvious reason

once you get lyme you can still get it again and again. OspA kills

borrelia in the tick --but also causes autoimmune disease. It is

impossible to vaccinate against b. burgdorferi because it changes so

rapidly and continually it would be impossible --but it was possible

to sterilize the spirochete from the tick gut, while its surface was

largely OspA.

---

For that reason I don't think they're even making an effort--though I

did read somewhere recently about trying to make an effort with a

less immunogenic OspA. OspA is the only hope. The tick would bite you

and your blood would kill borrelia in the tick, where it was

unchangingly expressing OspA (OspA is NOT under evolutionary pressure

to mutate and change). Right now, OspA is too dangerous for us.

There has also been a chorus of posts to the effect that sensible

> people would never expect the medical profession to do a damn thing

> for them.

Well I sort of agree. I'm really disgusted by the priorities. I think

what we're getting is about equivalent to what the third world gets

with malaria prophylaxis and new malaria treatment (nada).

The rhetoric of that has at times lately approached what I

> would call a survivalist mentality: grab your vetinary medicine

> catalog, buy yourself an Ebay microscope, and head for the hills,

> because at best the doctors are utterly indifferent, and at worst

> they're malicious.

Well frankly that's how I see them. When I went to my HMO doc (and

HMO's are just places I use for diagnosis, with total cynicism) he

spent all of 2 minutes with me. My chamber was out for repair, I was

really sick, I was worried about the muscle weakness (I am now doing

my chamber daily trying to repair the damage done, and even so it's

very slow going...prior to its seam leak, I was using it every 4-5

days), which I reported to him without explaining all the details,

plus I wanted a babesia test now that I learned babesia is epidemic

in the area where I was bit five years ago. I was able to strong arm

him as I had the information about the Krause study, but he did say

to me in the luxurious 2 minutes he spent with me, " Doxycycline would

have killed babesia " and " I don't think you have it " but also, " Okay,

I'll run the test. "

Yeah, utterly indifferent would sum it up nicely. Malicious was the

previous HMO doc who, when I had cystitis pain after having cystitis

and tkaing the requisite antibiotics, told me it was a muscle strain

and I needed a phsyiotherapist, instead of ordering a more detailed

culture.

> My perspective is shaped by having watched friends die of AIDS at a

> time when both public and private medical insitutions were largely

> inert, and seeing a pariah population with a pariah illness exert

> enough pressure to change that.

They mobibilized amazingly. I think they were in power positions and

also they were a cohesive group and also even more importantly, ,

they could get HIV and still feel good and energetic for years. The

situation with TBD is so much different. We are heterogenous. We have

no unifying lifestyle to orient us into a group that can exert some

force. We don't have convincing problems--at least in AIDS you could

see certain secondary infections repeatedly, there was something

doctors could understand. How are they going to understand the

diversity of illness produced by a spirochete? They'd have to be much

more than mechanics, which most of them are. In addition, by the time

you realize what is wrecking your life, you are often too sick to

become an activist. But there *are* lyme activists, I appreciate

them, but they don't seem to get much done.

I've sat here the last few months and I think I can even see a way to

kill borrelia------I have to contact the scientists----but I don't

see how the heck I'm going to convince somebody to pony up the $ to

make what is needed. That's where I Feel discouraged. If I can figure

out something from just reading the research, it wouldn't be that

hard for brilliant scientists to do so--were they motivated.

A cure has not been forthcoming, but

> I now have several friends who have been HIV+ for a great many

years

> and enjoy a very good state of health.

The HIV patients in my doctor's office are all doing much better than

those with lyme.

> I'm not suggesting you're in that state, Jill, or that anyone else

> is here.

Well, frankly, I'm in a horrified state and you know some of the

reasons why. I see it all around me. I met a person misdiagnosed with

MS, got him to a lyme specialist (after 10 years of " ms " ). I met an

incredible person (only by phone) who has been disabled 16 years,

she's 42 now. That means she lost her childbearing years. She lost

all the good stuff of life, and she was a mover/shaker type before.

She only now discovered it's lyme. She's in a relapse now where

bedridden etc. And she found out, , is because of Nick '

Igenex, not the lousy CDC testing. Otherwise, she'd have another 16

years of not knowing. And she doesn't know what she's going to do.

And she's an incredible person.

ANd some *don't* know even now because researchers don't understand

the bug and they don't understand the coinfections. Look at this

journal I ran across, I have no idea why or what i was web surfing,

probably lyme:

http://lenorsjourney.com/myStory.htm

She's obviously a gorgeous woman with a wonderful husband and doing

well on all her immunosuppressants, relatively speaking. She's doing

well with this 'chronic illness' that appeared out of nowhere, after

she moved to Fairfield, CT on a wooded property with deer. At least

they did test for lyme, it was 'positive and negative' she says,

which probably just means late stage; they tried rocephin, it didn't

work, and that was that. She would've needed an LLMD and tests for

coinfections. I thought of explaining on her guestbook but decided

not to--relatively speaking, the woman has a wonderful life, and

she's doing okay. It's down the road I worry about, all these

immunosuppressants can lead to known side effects, ie a fatal

infection, or cancer.

Do I think TBD kicked off her illness? I do though I have no absolute

proof.

I see it all around me and this organism is too shifty, too clever,

too 'hidden', along with the coinfections (same problem--you may not

test positive for babesia, or bartonella, and they certainly don't

test you for nematodes)...

Thus we each have to make our own way and its tragic.

[Guest guest]

,

Nicely said, those are definitely things to consider.

Cullen et al, in the paper I discussed, do allude to efforts

underway to produce a 2nd-generation vaccine.

Vaccination is what virtually all modern treponemology aims at and

has aimed at for decades. But as Jill says it aint very easy. The

first successful immunization of rabbits against Tp required

something like 30 or 50 weekly injections.

No one can seem to agree on just what surface antigens there are.

For instance Tp has a recombinant gene, tprK, which it constantly

alters by inserting DNA from " bank " genes - Radolf strongly asserts

that the product of this gene is *not* exposed; others disagree.

Radolfs view begs the question of why Tp changes a protein which is

not exposed.

Cullen were also honest enough to give the real story of LYMERix

rather than saying what I have seen elsewhere - that it was

withdrawn due to unprofitability, as if that unprofitability werent

caused by fear of the adverse effects that occured: total sophistry.

However Cullen assert that the adverse effects were rare and

overperceived. If anyone has data on the prevalance of adverse

effects I'd be interested in a ref. I have one paper on this but

lord knows whether its a load of BS, I have no clue. I am still

definitely interested in what we can learn from LYMERix about how Bb

disease may be more than a simple function of Bb infection.

> > > Cullen, Haake, and Adler disagree with Radolf and on the

> degree

> > > of paucity of exposed proteins in Tp and Bb. Their 30-pp 2004

> paper

> > > in FEMS Microbiol Rev is a pretty cool treatment of

spirochetal

> > > architecture, with applications to persistence and

pathogenesis.

> > >

> > > Given that most molecular investigators seem to feel antibody

to

> be

> > > the key to antispirochetal immunity, it is surprising no one

of

> > this

> > > set seems to take heed of work like Hulinskas, which

visualized

> Bb

> > > in seronegative patients in appreciable quantities. Since some

> of

> > > these types eg Radolf (but not Barbour) vaguely seem to be

aware

> of

> > > the probable existence of abx-refractory chronic lyme

> borreliosis,

> > > you would think they would seize upon this deficiency of

> specific

> > > antibody as indicating a perhaps-fixable immune lesion

possibly

> > > necessary to the persistence of the disease.

> > >

> > > I learned that OspC, etc, are highly polymorphic between

> strains.

> > > OspA is one of the only Osps that has been found to be fairly

> > > invariant. The invariance appears to be due to this Osp being

> > little-

> > > expressed in vertebrate hosts. The vertebrate adaptive immune

> > system

> > > can produce life-long immunity against a given microbial

> antigen,

> > > which ecologically selects for the great polymorphism of the

Bb

> > > Osps. Since OspA is essentially only expressed in the tick, a

> much

> > > more primitive host, it is not subject to these pressures and

> > > remains the same in all strains. This is why it was used for

the

> > > LYMERix vaccine. Vaccination of mice with most Osps and other

> > > exposed proteins yields immunity only to the strain from which

> the

> > > vaccine is derived.

> > >

> > > Given that most Osps cannot instill multiple-strain immunity,

> its

> > > puzzling that serology works at all in lyme disease. If Ab

> against

> > > one OspC fails to protect against an organism bearing a

> different

> > > OspC, then how can all antibodies against various OspCs bind

to

> the

> > > OspC used in a western blot? Hmmm. Perhaps the WB employs not

> only

> > > Osp epitopes that are surface-exposed, but also others that

are

> > not,

> > > and that therefore are not very polymorphic and not very

> important

> > > in immunity to Bb. I guess that is the most likely answer.

> > >

> > > These authors propose that antigenic variation could well be a

> > major

> > > cause of Bb persistence.

[Guest guest]

Jill,

I dont think its clarified at all that OspA innoculation causes

autoimmune disease. Looking at the fAb results coming from Bowen, it

appears to me that another hypothesis is very viable: people could

have had asymptomatic infection with Bb to which OspA vaccination

sensitized them. Obviously this idea leaves a whole lot to be

desired, but so does the idea of OspA cross-inducing loss of self

tolerance... incidentally Steere has in the last few years abandoned

the idea of LFA-1 as an autoantigen in this connection.

Re your reply to , I totally agree that we have to take care of

ourselves, and utilize those that have the knowledge to help us in

the present. At the same time I am saddened by a sort of resigned

seperatism I see hints of, which I think is part of what is

refering to - saddened just because it is totally impractical. We

should never slacken in trying to enlighten the power elite, or

routinely express ourselves in ways where we totally arent even on

the same page as the Powers that Be. Take an article like Harvey and

Salvatos " Ancient Engine... " - IMO it would just be more practical

if the paper were phrased and deduced somewhat more conservatively,

and practicality is what matters here.

Ultimately what we still need most are highly replicable descriptive

studies of the spirochetoses... to me that means *in situ* work:

Milt Wainwright so far hasnt been able to culture Bb from ME

patients, which doesnt mean he wont eventually succeed, but DOES

mean that it will be essentially pointless even if he does, because

barring some new insight into how it is done, others groups will

fail to replicate it. I say forget culture: visualize the organism

directly, tag it with specific antibody, and tell people about it so

they can do it too.

However, the Brorsons (in MS) and Hulinska (in borrelial arthritis)

have given us in situ descriptive studies that I think have been

basically ignored, which is the worlds fault. The Brorson result has

not been re-investigated in 3.5 years and I dont think anyone has

tried to replicate the Hulinska work either. BAH.

And hey, re your idea for killing Bb, pony up dude!

[Guest guest]

, the asymptomatic/sensitized by vaccine explanation doesn't sit

well with me though I can't prove it wrong.

If someone's body is handling Bb, ie its in low #'s because their

immune system is handling it, why would a vaccine disable their immune

system so that they become so ill--?

I prefer the genetically susceptible autoimmune hypothesis as it makes

sense--and tracks with why 15-20% of those with borrelia have such a

problem with it.

My idea, no I won't pony up, LOL. Did you ever do the research for me

I asked, dude????? Nah. I have an idea and I'm fairly certain it would

work which is no big deal, the big deal is, I'm just exhausted even

thinking of trying to convince someone to do it.

[Guest guest]

Jill, good points on the strengths of the autoimmune idea.

Hows this for a batty-ass idea:

1. Mammal has borrelia strain A. Strain A wants to keep its host

indefinitely by playing nice, staying at harmlessly low numbers

since it is such a good immune evador and it probably only takes a

few of them to infect new vectors anyway.

2. More agressive borrelial strain B arrives in mouse from outside -

perfectly able to superinfect the mouse because of its different

Osps. This strain is willing to multiply more and do more damage to

the host, because the disadvantage (to it) of harming the host is

offset by the fact that it can genetically swamp any other strains

already present.

If this sort of tension between strains indeed exists, it would be

wise for strain A to upregulate its reproduction quite a bit upon

the arrival of another strain. And how might it recognize such an

arrival? By detecting the hosts adaptive immune response against the

tick-host-expressed OspA coming in from strain B. Therefore when a

human is immunized against OspA, an existing " Dr Jekyll " borrelial

infection is persuaded by the anti-OspA antibody response that a new

strain has entered the mammal and that its time to go wild or risk

being overrun by the competition.

OK, I told you it was batty! And I know this doesnt take into

account that Barb and others are naturally reactive against OspA.

Nor the fact that OspA may already be downreg'd while the organisms

are still multiplying in the feeding tick (Cullen give the

impression that that is probably so).

What did you want me to research? I could never find much on

glycocalyges besides in unreferenced textbooks like this:

http://textbookofbacteriology.net/antiimmuno.html

but if you want to get quantitative, nuts and bolts about

glycocalyges providing resistance to compliment etc, that at least

tells you some organisms and capsular molecules that have been

investigated.

Now, Tp was long thought to have an important glycocalyx, but Radolf

gives refs to people who felt they were unable to detect it using

electron microscopy. But I dont think that quite settles it. The old

school guys had in situ EM pictures suggesting its existence.

Re adhesion receptors... theres definitely alot of info out there on

them... but its hard to know what to do about it. One would hope

antibody would jam them, and would also jam the receptors that fix

complement inhibitory factor H... but apparantly not. To me the

question is *why* not. Trying to jam all the different adhesion

receptors with small-molecule drugs or short peptide drugs might be

quite a project... I havent studied the principles of small drugs

inhibiting protein-protein interactions, but I have seen a casual

reference to the fact that it is difficult... of course not all the

adhesion ligands are proteins, some are carbohydrates as you know...

but at any rate there are alot of different ones.

One reason Ab may fail to hit certain Bb targets is steric (spatial-

physical) blocking by other proteins - but only one example of this

seems to be known:

http://iai.asm.org/cgi/content/full/67/6/2874?

ijkey=2094f21bf6c721660d2a7aaeb39df486d40d2e98

> , the asymptomatic/sensitized by vaccine explanation doesn't

sit

> well with me though I can't prove it wrong.

>

> If someone's body is handling Bb, ie its in low #'s because their

> immune system is handling it, why would a vaccine disable their

immune

> system so that they become so ill--?

>

> I prefer the genetically susceptible autoimmune hypothesis as it

makes

> sense--and tracks with why 15-20% of those with borrelia have such

a

> problem with it.

>

> My idea, no I won't pony up, LOL. Did you ever do the research for

me

> I asked, dude????? Nah. I have an idea and I'm fairly certain it

would

> work which is no big deal, the big deal is, I'm just exhausted

even

> thinking of trying to convince someone to do it.

[Guest guest]

, you're right, the organism seems to have so many mechanisms of

adherence, evasion etc.

I don't think strains would compete like that. They have sex, they

don't make war. I'm not joking tho, they just exchange genes, and

the smart more virulent one gives its weapons to the weaker one.

> > , the asymptomatic/sensitized by vaccine explanation doesn't

> sit

> > well with me though I can't prove it wrong.

> >

> > If someone's body is handling Bb, ie its in low #'s because their

> > immune system is handling it, why would a vaccine disable their

> immune

> > system so that they become so ill--?

> >

> > I prefer the genetically susceptible autoimmune hypothesis as it

> makes

> > sense--and tracks with why 15-20% of those with borrelia have

such

> a

> > problem with it.

> >

> > My idea, no I won't pony up, LOL. Did you ever do the research

for

> me

> > I asked, dude????? Nah. I have an idea and I'm fairly certain it

> would

> > work which is no big deal, the big deal is, I'm just exhausted

> even

> > thinking of trying to convince someone to do it.

[Guest guest]

What are you guys hinting at here?

I'm not following.....

said

" At the same time I am saddened by a sort of resigned

seperatism I see hints of, which I think is part of what is

refering to - saddened just because it is totally impractical. We

should never slacken in trying to enlighten the power elite, or

routinely express ourselves in ways where we totally arent even on

the same page as the Powers that Be. "

Barb

> Jill,

> I dont think its clarified at all that OspA innoculation causes

> autoimmune disease. Looking at the fAb results coming from Bowen,

it

> appears to me that another hypothesis is very viable: people could

> have had asymptomatic infection with Bb to which OspA vaccination

> sensitized them. Obviously this idea leaves a whole lot to be

> desired, but so does the idea of OspA cross-inducing loss of self

> tolerance... incidentally Steere has in the last few years

abandoned

> the idea of LFA-1 as an autoantigen in this connection.

>

> Re your reply to , I totally agree that we have to take care of

> ourselves, and utilize those that have the knowledge to help us in

> the present. At the same time I am saddened by a sort of resigned

> seperatism I see hints of, which I think is part of what is

> refering to - saddened just because it is totally impractical. We

> should never slacken in trying to enlighten the power elite, or

> routinely express ourselves in ways where we totally arent even on

> the same page as the Powers that Be. Take an article like Harvey

and

> Salvatos " Ancient Engine... " - IMO it would just be more practical

> if the paper were phrased and deduced somewhat more conservatively,

> and practicality is what matters here.

>

> Ultimately what we still need most are highly replicable

descriptive

> studies of the spirochetoses... to me that means *in situ* work:

> Milt Wainwright so far hasnt been able to culture Bb from ME

> patients, which doesnt mean he wont eventually succeed, but DOES

> mean that it will be essentially pointless even if he does, because

> barring some new insight into how it is done, others groups will

> fail to replicate it. I say forget culture: visualize the organism

> directly, tag it with specific antibody, and tell people about it

so

> they can do it too.

>

> However, the Brorsons (in MS) and Hulinska (in borrelial arthritis)

> have given us in situ descriptive studies that I think have been

> basically ignored, which is the worlds fault. The Brorson result

has

> not been re-investigated in 3.5 years and I dont think anyone has

> tried to replicate the Hulinska work either. BAH.

>

> And hey, re your idea for killing Bb, pony up dude!

[Guest guest]

Wow, there haven't been many times in my life when I've gotten an a$$

chewing and it felt this goood......

I know you were not pointing any fingers and I'm not trying to

hone in on your post, but I just couldn't help myself . I read your

ever eloquent words, all the while, noting that I have exactly been

the epitome of positive thinkin' lately. I used to call it " stinkin

thinkin " I reminded me of old days when the more I tried to run

people out of my office, the more they wanted to buy. Its a gift,

friend to be able to make yourself heard and blame the language and

not the person.

I was going to write about my appointment with the endocrinologist of

last week (I waited three months for), but on second thought........

Maybe I'll meditate a little more and try to find something that was

GOD about the appointment before I write.

Nonetheless, you are right on the money. I cannot speak for others,

but I'm finding myself constantly more and more withdrawing because I

I'm not getting the appropriate care and yet I don't know how to get

better more efficient results. I don't have any medical training nor

am I a diplomat, so I have a difficult time gaining the doctor's true

attention.No matter how I go about it, I cannot make the doctors

truly understand that I MUST see three other specialist just as vital

as his field. That I want them to try to help me instead of

coriographing this song and dance just so I slip further and further

behind. That all of these diseases just make up ONE disease to me. I

wonder how they expect me to ever get well enough to stay ahead of

the game and the truth is, " they don't " nor do they mince words.

So you are so right, I pump myself up with this survivalist

attitude,but only because I need the encouragement. I need to feel

that the doctor's believe in me But once I got the central sleep

apena diagnosis their candor has shocked me. I always feel like I

have to be pumped when I go to an appointment to try and motivate

them to heal me.

I have been trying to write Ginger for three weeks, and keep tearing

it up. I TRULY don't want to sound like a bitter bitch, but have

trouble explaining the reason my care has been so disjointed is

because the doctor's keep dropping me. You can only dance around the

truth so much. If I appear that I'm not forthcoming, then will I be

believed on any issue? It is just a real dilemma, what to TELL. When

t let seping dogs lie.Obviously if I still didn't have the active

disease in all of theseareas, I could just sift out non current

things. But dangit everyhing is sill relevant.

I am just completely frozen in numbness, seeing my own roadblocks at

every paragraph. I have seen many many doctors. Even if they do not

admit it to us, they know exactly what kind of mountains we are

climbing. They know exacly how many patients will be lost in an

emerging disease. A genertion. If I try to convince a doctor to treat

me " because medicine has been so good to me " , he will see right

through it. But if I piss him off before the third paragraph, I'm up

cheap creek before I can even start.

Well, I guess even this post didn't turn out like I started out. See,

how I get sidetracked?

I'm naive but I truly believe that there is a cure for me in western

medicine. That some doctor somewhere is working on just the forumla

of meds and tests that I need. The problem that I have is how do you

link the patients with the right doctors. Even when a doctor has had

nothing to offer me, I still believe that he/she is valuable to

medicine, but that doesn't help me find the docor who has what I

need. And I don't understand why they are not more helpful in finding

someone who has that answer. Much of my disappointments is in finding

out I have to do it alone.

I'm sorry you have lost friends and acquaintences to illness. I can

see where you have come forward with much courage because your spirit

is always finding ways to shine.

Thank you for the reminders, I needed it.

Peg

> > > Cullen, Haake, and Adler disagree with Radolf and on the

> degree

> > > of paucity of exposed proteins in Tp and Bb. Their 30-pp 2004

> paper

> > > in FEMS Microbiol Rev is a pretty cool treatment of spirochetal

> > > architecture, with applications to persistence and

pathogenesis.

> > >

> > > Given that most molecular investigators seem to feel antibody

to

> be

> > > the key to antispirochetal immunity, it is surprising no one of

> > this

> > > set seems to take heed of work like Hulinskas, which visualized

> Bb

> > > in seronegative patients in appreciable quantities. Since some

> of

> > > these types eg Radolf (but not Barbour) vaguely seem to be

aware

> of

> > > the probable existence of abx-refractory chronic lyme

> borreliosis,

> > > you would think they would seize upon this deficiency of

> specific

> > > antibody as indicating a perhaps-fixable immune lesion possibly

> > > necessary to the persistence of the disease.

> > >

> > > I learned that OspC, etc, are highly polymorphic between

> strains.

> > > OspA is one of the only Osps that has been found to be fairly

> > > invariant. The invariance appears to be due to this Osp being

> > little-

> > > expressed in vertebrate hosts. The vertebrate adaptive immune

> > system

> > > can produce life-long immunity against a given microbial

> antigen,

> > > which ecologically selects for the great polymorphism of the Bb

> > > Osps. Since OspA is essentially only expressed in the tick, a

> much

> > > more primitive host, it is not subject to these pressures and

> > > remains the same in all strains. This is why it was used for

the

> > > LYMERix vaccine. Vaccination of mice with most Osps and other

> > > exposed proteins yields immunity only to the strain from which

> the

> > > vaccine is derived.

> > >

> > > Given that most Osps cannot instill multiple-strain immunity,

> its

> > > puzzling that serology works at all in lyme disease. If Ab

> against

> > > one OspC fails to protect against an organism bearing a

> different

> > > OspC, then how can all antibodies against various OspCs bind to

> the

> > > OspC used in a western blot? Hmmm. Perhaps the WB employs not

> only

> > > Osp epitopes that are surface-exposed, but also others that are

> > not,

> > > and that therefore are not very polymorphic and not very

> important

> > > in immunity to Bb. I guess that is the most likely answer.

> > >

> > > These authors propose that antigenic variation could well be a

> > major

> > > cause of Bb persistence.

[Guest guest]

Lanelle

I didn't want to touch this, I am very familiar though how

inadequate the care is. It's like your business is welcome when you

qualify for all the big pharma bandaid drugs yet when actually ill

they all go running.

Imagine the biggest and worst sign of infection in the world STIFF

NECK with or without photophobia and they all sit there and are ill

equipped to take this on because it doesn't fall under there

management plan.To actually turn up and get IV antiboiotics by the

resident ER docs is also a big hurdle that won't be met inthe

hospital system. Actually many nurses that realise the dire

predicament many patients are in recommend visiting other hospitals

in order to save lives. Many nusrses actually can see how ill we are

and how terrible our condition or state is yet the doctors do there

utmost to prove that we should be moved along.

I would also not stick my neck out for anyone doing a half ass

decent job when you have a red cell disease and no-ones looked at

your red cells????????????

If I took one third of a doctors red cells out of his body and

decreased his blood volume by another quarter I would expect not a

very functional human being.Why can't they dothe simpla math.

> > > > Cullen, Haake, and Adler disagree with Radolf and on the

> > degree

> > > > of paucity of exposed proteins in Tp and Bb. Their 30-pp

2004

> > paper

> > > > in FEMS Microbiol Rev is a pretty cool treatment of

spirochetal

> > > > architecture, with applications to persistence and

> pathogenesis.

> > > >

> > > > Given that most molecular investigators seem to feel

antibody

> to

> > be

> > > > the key to antispirochetal immunity, it is surprising no one

of

> > > this

> > > > set seems to take heed of work like Hulinskas, which

visualized

> > Bb

> > > > in seronegative patients in appreciable quantities. Since

some

> > of

> > > > these types eg Radolf (but not Barbour) vaguely seem to be

> aware

> > of

> > > > the probable existence of abx-refractory chronic lyme

> > borreliosis,

> > > > you would think they would seize upon this deficiency of

> > specific

> > > > antibody as indicating a perhaps-fixable immune lesion

possibly

> > > > necessary to the persistence of the disease.

> > > >

> > > > I learned that OspC, etc, are highly polymorphic between

> > strains.

> > > > OspA is one of the only Osps that has been found to be

fairly

> > > > invariant. The invariance appears to be due to this Osp

being

> > > little-

> > > > expressed in vertebrate hosts. The vertebrate adaptive

immune

> > > system

> > > > can produce life-long immunity against a given microbial

> > antigen,

> > > > which ecologically selects for the great polymorphism of the

Bb

> > > > Osps. Since OspA is essentially only expressed in the tick,

a

> > much

> > > > more primitive host, it is not subject to these pressures

and

> > > > remains the same in all strains. This is why it was used for

> the

> > > > LYMERix vaccine. Vaccination of mice with most Osps and

other

> > > > exposed proteins yields immunity only to the strain from

which

> > the

> > > > vaccine is derived.

> > > >

> > > > Given that most Osps cannot instill multiple-strain

immunity,

> > its

> > > > puzzling that serology works at all in lyme disease. If Ab

> > against

> > > > one OspC fails to protect against an organism bearing a

> > different

> > > > OspC, then how can all antibodies against various OspCs bind

to

> > the

> > > > OspC used in a western blot? Hmmm. Perhaps the WB employs

not

> > only

> > > > Osp epitopes that are surface-exposed, but also others that

are

> > > not,

> > > > and that therefore are not very polymorphic and not very

> > important

> > > > in immunity to Bb. I guess that is the most likely answer.

> > > >

> > > > These authors propose that antigenic variation could well be

a

> > > major

> > > > cause of Bb persistence.

[Guest guest]

was eloquently beating around the bush- I sort of suspected he

was refering to ME... or Tony...

Being Jaded with the medicial profession - doesn't mean one is

in 'survivalist' mode in the way the reference was made.

I for one would like to hear about your appointment, and your

progress.

Barb

> > > > Cullen, Haake, and Adler disagree with Radolf and on the

> > degree

> > > > of paucity of exposed proteins in Tp and Bb. Their 30-pp 2004

> > paper

> > > > in FEMS Microbiol Rev is a pretty cool treatment of

spirochetal

> > > > architecture, with applications to persistence and

> pathogenesis.

> > > >

> > > > Given that most molecular investigators seem to feel antibody

> to

> > be

> > > > the key to antispirochetal immunity, it is surprising no one

of

> > > this

> > > > set seems to take heed of work like Hulinskas, which

visualized

> > Bb

> > > > in seronegative patients in appreciable quantities. Since

some

> > of

> > > > these types eg Radolf (but not Barbour) vaguely seem to be

> aware

> > of

> > > > the probable existence of abx-refractory chronic lyme

> > borreliosis,

> > > > you would think they would seize upon this deficiency of

> > specific

> > > > antibody as indicating a perhaps-fixable immune lesion

possibly

> > > > necessary to the persistence of the disease.

> > > >

> > > > I learned that OspC, etc, are highly polymorphic between

> > strains.

> > > > OspA is one of the only Osps that has been found to be fairly

> > > > invariant. The invariance appears to be due to this Osp being

> > > little-

> > > > expressed in vertebrate hosts. The vertebrate adaptive immune

> > > system

> > > > can produce life-long immunity against a given microbial

> > antigen,

> > > > which ecologically selects for the great polymorphism of the

Bb

> > > > Osps. Since OspA is essentially only expressed in the tick, a

> > much

> > > > more primitive host, it is not subject to these pressures and

> > > > remains the same in all strains. This is why it was used for

> the

> > > > LYMERix vaccine. Vaccination of mice with most Osps and other

> > > > exposed proteins yields immunity only to the strain from

which

> > the

> > > > vaccine is derived.

> > > >

> > > > Given that most Osps cannot instill multiple-strain immunity,

> > its

> > > > puzzling that serology works at all in lyme disease. If Ab

> > against

> > > > one OspC fails to protect against an organism bearing a

> > different

> > > > OspC, then how can all antibodies against various OspCs bind

to

> > the

> > > > OspC used in a western blot? Hmmm. Perhaps the WB employs not

> > only

> > > > Osp epitopes that are surface-exposed, but also others that

are

> > > not,

> > > > and that therefore are not very polymorphic and not very

> > important

> > > > in immunity to Bb. I guess that is the most likely answer.

> > > >

> > > > These authors propose that antigenic variation could well be

a

> > > major

> > > > cause of Bb persistence.

[Guest guest]

But HIV is one virus. TBD is multiple pathogens, multiple strains of

varying virulence; and varying genetics esp. in the case of borrelia,

influencing the inflammatory response. It is so complex. And with HIV

you can have safe sex. With TBD you cannot have " safe lawn " or " safe

woods " or " safe life " unless you live in a highrise and make sure the

neighbor's dogs don't visit (They might have a country home). It is

so much more global and complex. And then, borrelia is so stealthy

and manifests in so many ways. I know I'm repeating myself

but...sorry....I see no hope from the establishment, that includes

academia and medicine. Let's hope does us good and goes into the

field, he's very very clever.

Barb, thanx for your protocol. I couldn't tolerate even those levels

of abx you did, but it's very interesting.

> > > > > Cullen, Haake, and Adler disagree with Radolf and on

the

> > > degree

> > > > > of paucity of exposed proteins in Tp and Bb. Their 30-pp

2004

> > > paper

> > > > > in FEMS Microbiol Rev is a pretty cool treatment of

> spirochetal

> > > > > architecture, with applications to persistence and

> > pathogenesis.

> > > > >

> > > > > Given that most molecular investigators seem to feel

antibody

> > to

> > > be

> > > > > the key to antispirochetal immunity, it is surprising no

one

> of

> > > > this

> > > > > set seems to take heed of work like Hulinskas, which

> visualized

> > > Bb

> > > > > in seronegative patients in appreciable quantities. Since

> some

> > > of

> > > > > these types eg Radolf (but not Barbour) vaguely seem to be

> > aware

> > > of

> > > > > the probable existence of abx-refractory chronic lyme

> > > borreliosis,

> > > > > you would think they would seize upon this deficiency of

> > > specific

> > > > > antibody as indicating a perhaps-fixable immune lesion

> possibly

> > > > > necessary to the persistence of the disease.

> > > > >

> > > > > I learned that OspC, etc, are highly polymorphic between

> > > strains.

> > > > > OspA is one of the only Osps that has been found to be

fairly

> > > > > invariant. The invariance appears to be due to this Osp

being

> > > > little-

> > > > > expressed in vertebrate hosts. The vertebrate adaptive

immune

> > > > system

> > > > > can produce life-long immunity against a given microbial

> > > antigen,

> > > > > which ecologically selects for the great polymorphism of

the

> Bb

> > > > > Osps. Since OspA is essentially only expressed in the tick,

a

> > > much

> > > > > more primitive host, it is not subject to these pressures

and

> > > > > remains the same in all strains. This is why it was used

for

> > the

> > > > > LYMERix vaccine. Vaccination of mice with most Osps and

other

> > > > > exposed proteins yields immunity only to the strain from

> which

> > > the

> > > > > vaccine is derived.

> > > > >

> > > > > Given that most Osps cannot instill multiple-strain

immunity,

> > > its

> > > > > puzzling that serology works at all in lyme disease. If Ab

> > > against

> > > > > one OspC fails to protect against an organism bearing a

> > > different

> > > > > OspC, then how can all antibodies against various OspCs

bind

> to

> > > the

> > > > > OspC used in a western blot? Hmmm. Perhaps the WB employs

not

> > > only

> > > > > Osp epitopes that are surface-exposed, but also others that

> are

> > > > not,

> > > > > and that therefore are not very polymorphic and not very

> > > important

> > > > > in immunity to Bb. I guess that is the most likely answer.

> > > > >

> > > > > These authors propose that antigenic variation could well

be

> a

> > > > major

> > > > > cause of Bb persistence.