Autoimmunity to protective molecules (Re: What if......)

[Guest guest]

, they may not be undetectable at all. They may simply be ignored. A number of researchers and people like me have been trying to raise awareness and sound the alarm regarding staph for a long time. But the masses continue to believe that staph are merely contaminants to be overlooked, just as they believed until recently that our blood is always "sterile". Many docs still do believe that. penny <usenethod@...> wrote: > This

makes that title much more appropriate than intended: itsuggests that in autoimmunity, there's always a hidden germ involved,stoking the fire...Here's the main problem raised by that view. Why aren't there moreknown symptom-causing autoreactivities in the classical infectiousdiseases (especially chronic ones)? There is paroxysmal coldhemoglobinuria, which is not rare in syphilis, known to be autoimmune,and which often clears with syphilis treatment. Myasthenia gravis, pemphigus, Graves', various cytopenias, SLE (tosome extent), and more have demonstrable AI pathogeneses. If varmintsunderlie the AI, why are they all so undetectable? Is there somecommon feature that makes them highly AI-genic and also poorly virulent?I used to think there was a similar problem with explaining why somany of these diseases that respond to abx anecdotally in ourcommunity, all have the common features of being poorly responsive

(vsthe classical bacterioses), often non-progressive (or nearly so) withsome stark exceptions like MS and ALS, and culture-negative andotherwise hard to demonstrate as bacterioses. Etc. But actuallybacterial stress states are a possible explanation for the seeminglyunjustifiable coincidence of all these features. We know that stressstate bacteria are hard to kill and can be culture-negative, but theyalso tend to be small (perhaps to increase their surface area : volumeratio for better nutriment uptake). Morita states that many or moststarved cells in the environment are ultramicroscopic, ie around 200nm across. This gives them a volume 125x smaller than that of a 1-umcell and a surface area 25x smaller. If these were visible (viaimmunostain) to a light microscope or a weak EM they would probablylook like "debris" to medical microbiologists who generally reject thedoctrine of bacterial pleomorphism. The only real

sortie into thisrealm is the high-quality EM of the Wirostko/ papers, but it'shard to tell how they justify some of their identification ofbacterial bodies (others of the bodies they imaged are so bizarre andnovel as to be presumably exotrinsic, especially considering that theycould be passaged in mice). It would be great to add yersinialarthritis to this, but as I mentioned it didn't work since I can'tfind any high-quality EM out there in which the possible viability /(ultramicro)cellularity / integrity of the yersinia-staining "debris"might be discerned.

[Guest guest]

Even if there really are some triggers that can cause the immune system to self attack, at least the claim can't be made that it's "underactive". This is what drives me crazy. We should focus more on discovering exactly what's activating the immune response and how to deal with the inflammation, not assume there's no reason for the activation, or worse, that pwc's have limited immune systems to begin with. (I'm not including you in that, I know you're open minded, but I get really tired of hearing about "strengthening our immune systems"). penny <usenethod@...> wrote: > Here's the main problem raised by that view. I meant to add that a lot of the paraneoplasms (tumor-associatedimmune diseases featuring autoreactivity) and drug-induced AI statesare pretty hard to link to infection. Drug-induced lupus iswell-covered in Dubois ed 6 and drug-induced myasthenia is even moreinteresting given the well-explroed AI pathogenesis of myasthenia.

[Guest guest]

On Sun, Jul 08, 2007 at 06:57:20PM -0000, wrote:

>

>> This makes that title much more appropriate than intended: it

>>suggests that in autoimmunity, there's always a hidden germ involved,

>>stoking the fire...

>

>

>Here's the main problem raised by that view. Why aren't there more

>known symptom-causing autoreactivities in the classical infectious

>diseases (especially chronic ones)?

I was under the impression that there were already plenty of them. It's

been widely reported that the 1918 flu was so lethal mainly because it

overstimulated the immune system (thus, also, leading to its higher

lethality in the young and healthy). Many common symptoms (e.g. fever)

are consequences of immune system activation. But perhaps you are

defining autoreactivity narrowly, so that these sorts of things don't

qualify?

In any case, it's not a very profitable activity to investigate

autoreactivity in diseases long known to be caused by infections. People

do some of it; but it's not like investigating autoreactivity in diseases

considered to be autoimmune, where it's _the_ hot topic. When a disease

is known to be caused by an infection, the main subject for research is

how to kill the infection; other topics, such as autoreactivities, are

subsidiary, and gather less research effort.

> There is paroxysmal cold

>hemoglobinuria, which is not rare in syphilis, known to be autoimmune,

>and which often clears with syphilis treatment.

>

>Myasthenia gravis, pemphigus, Graves', various cytopenias, SLE (to

>some extent), and more have demonstrable AI pathogeneses. If varmints

>underlie the AI, why are they all so undetectable? Is there some

>common feature that makes them highly AI-genic and also poorly virulent?

I don't know much about those diseases.

> [...] We know that stress

>state bacteria are hard to kill and can be culture-negative, but they

>also tend to be small (perhaps to increase their surface area : volume

>ratio for better nutriment uptake).

....or perhaps for the same reason you'd get smaller if _you_ were

starved.

[Guest guest]

And, as Shoenfeld said of apoptosis, perhaps the autophagy

deficiency leads to autoantigen overload.

>

> I only now got around to reading that abstract. Very

provocative.

> I hadn't known about Shoenfeld.

>

> With regards to apoptosis defects playing a role in autoimmunity,

> there's some indication that autophagy can mediate programmed cell

> death (see e.g., PMID: 9332326, PMID: 15530778 and PMID:

15325581).

> Makes me think of the two independent autophagy genes that are

> associated with Crohn's. The recent editorial on those findings

> cited the role of autophagy in clearing intracellular pathogens,

but

> now I wonder if the role that those alleles seem to play in

Crohn's

> may have more to do with a reduced ability of clonally expanded T

> cells to experience the full measure of contraction.

>