From: Taka on
Okay guys, get to the point instead of discussing different
religions. Autoimmunity does exist and there are powerful mechanisms
to prevent it such as the clonal deletion, receptor editing and anergy
put to work as early as during the embryonic development. Some
educative slides:

http://www.clinimmsoc.org/teaching/slides/tolerance.ppt
http://en.wikipedia.org/wiki/Clonal_anergy

"Central tolerance occurs during lymphocyte development and operates
in the thymus and bone marrow. Here, T and B lymphocytes that
recognize self antigens are deleted before they develop into fully
immunocompetent cells, preventing autoimmunity. This process is most
active in fetal life, but continues throughout life as immature
lymphocytes are generated."
http://en.wikipedia.org/wiki/Immune_tolerance

The TREG/PGE2 way is just a less efficient "temporary solution" and I
think Kofi's evidence for the TREGs fighting viruses is a bit shaky.
Better to delete the self reacting cells than to suppress them with
dangerous compounds derived from the arachidonic acid like PGE2 - this
is useful only during pregnancies but can backfire later when employed
by the cancerous cells.

The main question for me is why the autoimmune conditions like
allergies develop. It has something to do with the overstimulation
and co-stimulation of the innate immune system by its natural ligands
via the TLRs. This could happen either due to unnatural antigen
exposure or due to higher immune system sensitivity because it is
supercharged with the arachidonic acid.

Taka
From: Kofi on
In article
<5f94c8b8-a300-4614-814c-0c4746ec8aa1(a)b35g2000yqi.googlegroups.com>,
Taka <taka0038(a)gmail.com> wrote:

> Okay guys, get to the point instead of discussing different
> religions. Autoimmunity does exist and there are powerful mechanisms
> to prevent it such as the clonal deletion, receptor editing and anergy
> put to work as early as during the embryonic development. Some
> educative slides:
>
> http://www.clinimmsoc.org/teaching/slides/tolerance.ppt
> http://en.wikipedia.org/wiki/Clonal_anergy
>
> "Central tolerance occurs during lymphocyte development and operates
> in the thymus and bone marrow. Here, T and B lymphocytes that
> recognize self antigens are deleted before they develop into fully
> immunocompetent cells, preventing autoimmunity. This process is most
> active in fetal life, but continues throughout life as immature
> lymphocytes are generated."
> http://en.wikipedia.org/wiki/Immune_tolerance
>
> The TREG/PGE2 way is just a less efficient "temporary solution" and I
> think Kofi's evidence for the TREGs fighting viruses is a bit shaky.

Look before you leap.

J Immunol. 2010 Jun 14

Skin Inflammation Arising from Cutaneous Regulatory T Cell Deficiency
Leads to Impaired Viral Immune Responses.
Freyschmidt EJ, Mathias CB, Diaz N, Macarthur DH, Laouar A, Manjunath N,
Hofer MD, Wurbel MA, Campbell JJ, Chatila TA, Oettgen HC.
Division of Immunology, Department of Medicine

Individuals with atopic dermatitis immunized with the small pox vaccine,
vaccinia virus (VV), are susceptible to eczema vaccinatum (EV), a
potentially fatal disseminated infection. Dysfunction of Forkhead box P3
(FoxP3)-positive regulatory T cells (Treg) has been implicated in the
pathogenesis of atopic dermatitis. To test whether Treg deficiency
predisposes to EV, we percutaneously VV infected FoxP3-deficient
(FoxP3(KO)) mice, which completely lack FoxP3(+) Treg. These animals
generated both fewer VV-specific CD8(+) effector T cells and
IFN-gamma-producing CD8(+) T cells than controls, had higher viral
loads, and exhibited abnormal Th2-polarized responses to the virus. To
focus on the consequences of Treg deficiency confined to the skin, we
generated mixed CCR4(KO) FoxP3(KO) bone marrow (CCR4/FoxP3) chimeras in
which skin, but not other tissues or central lymphoid organs, lack Treg.
Like FoxP3(KO) mice, the chimeras had impaired VV-specific effector T
cell responses and higher viral loads. Skin cytokine expression was
significantly altered in infected chimeras compared with controls.
Levels of the antiviral cytokines, type I and II IFNs and IL-12, were
reduced, whereas expression of the proinflammatory cytokines, IL-6,
IL-10, TGF-beta, and IL-23, was increased. Importantly, infection of
CCR4/FoxP3 chimeras by a noncutaneous route (i.p.) induced immune
responses comparable to controls. Our findings implicate allergic skin
inflammation resulting from local Treg deficiency in the pathogenesis of
EV.

PMID: 20548030

If you're impairing viral infection, you're also retarding the
development of autoimmunity since viruses cloak themselves in vairous
self-antigens to evade the immune system. This then inhibits the
development of cancer.

> Better to delete the self reacting cells than to suppress them with
> dangerous compounds derived from the arachidonic acid like PGE2 - this
> is useful only during pregnancies but can backfire later when employed
> by the cancerous cells.

What's with the hating of PGE2? If you just let it do its job properly
in the first place then it wouldn't get overactivated down the road.

>
> The main question for me is why the autoimmune conditions like
> allergies develop. It has something to do with the overstimulation
> and co-stimulation of the innate immune system by its natural ligands
> via the TLRs. This could happen either due to unnatural antigen
> exposure or due to higher immune system sensitivity because it is
> supercharged with the arachidonic acid.

I think this is part of the picture but I think you have it in reverse.
I think TLR2/4 causes excessive inflammation but of an entirely
different sort than classic "B-cell" autoimmunity. This
TLR/macrophage/mast cell response is tied in to IL-10 secretion which
ameliorates this type of autoantibody autoimmunity. This is why people
with high androgens and, say, acne are experiencing overactivated
macrophages but are less likely to have autoantigens. There's something
directly linking sympathetic flow to B-cell regulation.

But it maybe a more complicated picture. We're always talking about TLR
ligands but honestly we don't know what's an "agonist" or an
"antagonist." The original poinjt of this post is that helminths act
via the TLR/sympathetic system to inhibit intestinal inflammation.
From: Kofi on
> This is not my theory, but something that a research immunologist
> explained to me about thirty-five years ago.

Gee, nothing changes in thirty-five years in medicine. Nope. Not a
thing.
From: Josepi on
Reread the conversation thread. It appears that specific points have been
avoided and the argument rolled to create continuous input and argument.

I suspect this person is the one and same that trolls many other fields with
enough information to create a ruckuss. This is done with many different
NNTP but always has the same flavour. A few pot strring posts were made
here in the last few years towards other with this editorial grandstanding.

This is a support group and the tech info is interesting but off topic here.
alt.SUPPORT.celiac


"Kofi" <kofi(a)anon.un> wrote in message
news:kofi-219F72.21325921062010(a)news.east.earthlink.net...
Gee, nothing changes in thirty-five years in medicine. Nope. Not a
thing.

> This is not my theory, but something that a research immunologist
> explained to me about thirty-five years ago.




From: Kofi on
> My point is that we know the lymphocytes attach to small patterns
> on the surface of proteins. The potential for misrecognition
> is always there. By your choice of words you keep insisting that
> there is something that can function perfectly.

No. You keep bringing up "perfection" and "cure." I keep saying
"better" or "worse."

You're having an argument inside your head with yourself.

You've made the good the enemy of the perfect.

>
> If you understand evolution, then you know that this perfection is
> impossible. Those hardwired immunity patterns in our DNA are set up
> to mutate especially rapidly. This is how life evolves into different
> population groups that cannot share the same environment. Eventually
> the groups become species that cannot interbreed.

Well, you have problems with your view of the immune system. First,
B-cell receptor editting is its own little evolutionary dance of
recombination and variation. That is to say, B cells are constantly
evolving in their own way. Without helminths, there seems to be a
severe problem with quality control. The question here is whether a
preexisting autoimmune condition created by a lack of helminths can be
remedied by reintroducing helminths into the gut. Many people say it
can. Many people have experienced a recovery - and this has been shown
in clinical trial data.

>
> You claim to know what is supposed to be food and what is not supposed
> to be food.

I made no claim about that. You made that claim. If I were to make a
statement about diet, it would be based on evolution. On what diets did
different groups with different genes evolve?


> To come back to your example, some people can eat soy, but some
> cannot. Those who think they know what we all should eat evidence
> the clarity of madmen and religious fanatics. You would poison us
> or infect us with worms so that we can all be the same.

You invoke evolution and yet you fail to employ it properly. I'm not
suggesting we "poison" people with helminths. I'm suggesting that
throughout human history, man has been colonized with one form of
helminth or another. Some caused disease but others were well adapted
to their human hosts. When these helminths were yanked out of the body
by purifying the water supply, we were "poisoned." Our regulatory
T-cells and regulatory B-cells could no longer function the way they
were designed. These are all well-supported theories that have been
developed in the last five to ten years. If your information on
immunity is thirty years old, then you are indeed at a disadvantage in
this conversation.

> This is
> your religion: not mine. You have discovered the greatest medical
> breakthrough since physicians began using leeches to balance our four
> (or six) humors.

If you choose to cast clinical trial data as "religion" there is really
no further point to this conversation.

Gastroenterology. 2005 Apr;128(4):825-32

Trichuris suis therapy for active ulcerative colitis: a randomized
controlled trial.
Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV.
James A. Clifton Center for Digestive Diseases, Department of Internal
Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
52242, USA.

BACKGROUND & AIMS: Ulcerative colitis is most common in Western
industrialized countries. Inflammatory bowel disease is uncommon in
developing countries where helminths are frequent. People with helminths
have an altered immunological response to antigens. In animal models,
helminths prevent or improve colitis by the induction of regulatory T
cells and modulatory cytokines. This study determined the efficacy and
safety of the helminth Trichuris suis in therapy of ulcerative colitis.
METHODS: This was a randomized, double blind, placebo-controlled trial
conducted at the University of Iowa and select private practices.
Trichuris suis ova were obtained from the US Department of Agriculture.
The trial included 54 patients with active colitis, defined by an
Ulcerative Colitis Disease Activity Index of > or =4. Patients were
recruited from physician participants and were randomly assigned to
receive placebo or ova treatment. Patients received 2500 Trichuris suis
ova or placebo orally at 2-week intervals for 12 weeks. RESULTS: The
primary efficacy variable was improvement of the Disease Activity Index
to > or =4. After 12 weeks of therapy, improvement according to the
intent-to-treat principle occurred in 13 of 30 patients (43.3%) with ova
treatment compared with 4 of 24 patients (16.7%) given placebo (P =
..04). Improvement was also found with the Simple Index that was
significant by week 6. The difference in the proportion of patients who
achieved an Ulcerative Colitis Disease Activity Index of 0-1 was not
significant. Treatment induced no side effects. CONCLUSIONS: Ova therapy
seems safe and effective in patients with active colitis.

Publication Types:
* Clinical Trial
* Multicenter Study
* Randomized Controlled Trial
* Research Support, Non-U.S. Gov't

PMID: 15825065