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Re: apoptosis, bacteria, phagocytes

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Is the immune system never exposed to bacteria that it has no

defences for.I know that they are trying to develop a couple of

staph areus and staph epi vaccines.Just wondering why so many people

feel that you can fix an immune response that is never there in the

first place.

...tony

> I think it may contain some logical lapses (didnt actually nail em

> down), but this paper has loads of info on pro-apoptosis by

bacteria.

> This strengthens the hypothesis that the reason NFkappaB

signalling

> has evolved to be antiapoptotic is that its impossible to keep our

> apoptosis signalling machinery completely secure from direct

> activation by proteins crafted by phagocytosis-avoiding

extracellular

> pathogens.

>

> SOmething new: its notable that epithelial cells are also of

> importance here. Causing apoptosis of nearby phagocytes allows

> pathogens to avert phagocytosis, but causing apoptosis of nearby

> epithelial cells could be equally crucial, by interrupting the

> phsyical epithelial barrier, facilitating invasion of the tissue

> beyond.

>

>

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

>

> Microbes Infect. 2003 Oct;5(12):1149-58. Related Articles, Links

>

> Fascination with bacteria-triggered cell death: the significance

of

> Fas-mediated apoptosis during bacterial infection in vivo.

>

> Menaker RJ, NL.

>

> Research Institute, Rm. 8409, Hospital for Sick Children, 555

> University Avenue, Toronto, Ont., Canada M5G 1X8.

>

> Increasing evidence indicates that bacterial pathogens have

developed

> mechanisms to modulate the apoptotic signaling cascade of host

cells

> and thereby cause disease. The Fas death receptor pathway is one

of

> the most extensively investigated apoptotic signaling pathways. In

> this review we discuss the role of Fas signaling during the

interplay

> between bacterial pathogens and the host in vivo.

>

> Publication Types:

> Review

> Review, Tutorial

>

> PMID: 14554257 [PubMed - indexed for MEDLINE]

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I dono, in some cases it just doesnt seem to come together, including

syphilis. The first time syphilis immunity was produced in a mammal I

think it required like 50 injections of attenuated organisms and the

immunity didnt last that long. So the chances that we will see an

implementable syphilis vaccine for humans is probably very small,

without some huge breakthru in immunology.

The problem may be that T. pallidum has very few binding sites for

antibody, and therefore tends to be rather unharmed by the

concentrations most mammals develop.

TB seems to be another one like lyme borreliosis, where the antibody

response is pretty spotty. I know cause I looked into the attempts to

develop serodiagnosis for TB and the people attempting it were not

very stoked. As I hazily recall(?), adoptive transfer experiments show

that antibody against TB is not very useful anyway for clearing the

infection, its Th1 cells that get things accomplished there.

THe TB vaccine people are also not very happy, but I'd guess they have

alot more to hope for than the syphilis vaccine people (who dont even

exist except at a basic science level).

I dono much about immunity and counter-immunity re staph. I know they

can survive phagocytosis, and maybe(?) lyse the macrophage. As for

antibody, for some organisms (eg Bb) the right antibody can be lethal,

but I'm not sure this is true for all. It definitely always opsonizes

the organism for phagocytosis and also allows complement to fix - but

most or all pathogens are able to prevent the formation of the lethal

complement pore complex, tho antibody-enhanced complement fixation may

overwhelm their defense abilities.

Since most of us are exposed to and/or colonized by aureus and epi,

youd think we would all have some level of response to them already.

But obviously that somehow doesnt work out too well.

>

> Is the immune system never exposed to bacteria that it has no

> defences for.I know that they are trying to develop a couple of

> staph areus and staph epi vaccines.Just wondering why so many people

> feel that you can fix an immune response that is never there in the

> first place.

>

> ..tony

>

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" Since most of us are exposed to and/or colonized by aureus and

epi,

> youd think we would all have some level of response to them

already.

> But obviously that somehow doesnt work out too well. " >>>

I alway's felt that it was tied in with the body and it's ageing

that makes one more susceptable.It's like you need high

concentrations to make infections and the older you are the more

oppurtunities are presented...There's also that point of entry like

a festering sore often not clearly evident that no-one is looking

out for. I think if you poked around your teeth especially above

caps and the like- you've got things constantly brewing.It's a shame

really that many feel there's an immune system problem for

oppurtunistic infections when it's got nothing at all to do with the

immune system, there's millions visiting doctors daily being on the

wrong side of the receiving end of bacterial infections..

>

> >

> > Is the immune system never exposed to bacteria that it has no

> > defences for.I know that they are trying to develop a couple of

> > staph areus and staph epi vaccines.Just wondering why so many

people

> > feel that you can fix an immune response that is never there in

the

> > first place.

> >

> > ..tony

> >

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> " Since most of us are exposed to and/or colonized by aureus and

> epi,

> > youd think we would all have some level of response to them

> already.

> > But obviously that somehow doesnt work out too well. " >>>

> I alway's felt that it was tied in with the body and it's ageing

> that makes one more susceptable.It's like you need high

> concentrations to make infections and the older you are the more

> oppurtunities are presented

It sure looks that way with alzheimers, which I would guess will more

likely than not get sorted out as infectious in the end. At large

ages the prevalance of alz is extreeeeeemely high. I think most

people with parkinsons are also older.

But hell, I'm 24, so my perspective is, damn. As for MS I think it

develops only rarely in the 50s. I think the rate of new cases drop

off quite alot after age 35 or so.

> ...There's also that point of entry like

> a festering sore often not clearly evident that no-one is looking

> out for. I think if you poked around your teeth especially above

> caps and the like- you've got things constantly brewing.It's a

shame

> really that many feel there's an immune system problem for

> oppurtunistic infections when it's got nothing at all to do with

the

> immune system, there's millions visiting doctors daily being on the

> wrong side of the receiving end of bacterial infections..

Maybe... but immunodeficiency is hard to disprove given that the

environment is increasingly full of wacky chemicals (which on the

other hand certainly doesnt *prove* anything). I'm not sure if we

know for certain what every last chem emitted by industry is - or if

we do know what they all are, im not sure they have all been

experimented with re safety. Also, there is the odd chem which is

grossly toxic to some mammals and not others, so I think mouse and

rat toxicity experiemnts will almost but not quite cover our ass.

Also, especially since you also tend to reject the hygeine hypothesis

(Im undecided on that one myself), your model has a hard time showing

why so many of these diseases appear to be on the rise. There are

data re Crohns disease going back to the 1940s, which you can read

online (free text), from your favorite guys the mayo clinic. It looks

pretty clear that the disease has come up from scanty to common

before plateauing in the 70s. If you dont like mayo, check out

similar data from Japan, where the same curve happened, but 2 or 3

decades delayed as compared to Mayo country, Minnesota, USA. I dont

think theres any degree of consensus on MS clearly growing more

common... autism on the other hand? awfully rapid growth in our own

time sure looks likely, tho some still insist it could be

artifactual, and special things like thimerosol have to be looked at

re that one; who knows if its typically an infectious condition. CFS?

Some act like its pretty much new, especiallt the non-epidemic kind,

but if you go thru 1910s, 1920s volumes of J Psychol & Neurol youll

find quite a few people youd recognize as one of us, all of whom (as

far as I've seen) were of course treated as neurotics, probably

exhausted and deranged by continually repressing their appalling

desire to try having sex upside down, or some unbelieveable freudian

crap like that. But it does seem rather likely CFS has gone up in

incidence last century. How do you explain all that? My views dont

generate any particularly clear ideas about why such increases in

prevalance would come about, but I dont think yours do either.

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