21st July 06:01
Helminth infection can block TLR4 induction in TNBS-induced colitis (colitis allergy lymphocytes colon antibodies)
Different species of helminths may have different effects on
innate/sympathetic response at different parts of their lifecycle. The
presence of phosphorylcholine in ES-62 suggests to me the involvement of
the cholinergic nervous system, which balances out sympathetic flow.
J Gastroenterol Hepatol. 2009 Nov;24(11):1775-80.
Preventive effects of Schistosoma japoni*** ova on
trinitrobenzenesulfonic acid-induced colitis and bacterial translocation
Zhao Y, Zhang S, Jiang L, Jiang J, Liu H.
ZhongShan Hospital, Fudan University, Gastroenterology, Shanghai, China.
AIMS: To evaluate the preventive effects of Schistosoma japoni*** ova on
trinitrobenzenesulfonic acid (TNBS)-induced colitis and bacterial
translocation in mice. METHODS: BALB/c mice were randomly divided into
three groups: control group; TNBS(+)Ova(-) group; and TNBS(+)Ova(+)
group. Mice of the TNBS(+)Ova(+) group were exposed to 10 000
freeze-killed S. japoni*** ova by i.p. injection on day 1 and day 11. On
day 15, mice were challenged with TNBS to induce colitis. The following
variables were assessed: colon pathological changes; serum expression of
tumor necrosis factor-alpha (TNF-alpha), gamma-interferon (IFN-gamma)
and interleukin-10 (IL-10); expression of Toll-like receptor 4 (TLR4) in
colon; IFN-gamma, IL-10 and TLR4 mRNA expression in colon; and the
bacterial translocation rate. RESULTS: Compared to TNBS(+)Ova(-) group,
the colonic inflammation in the TNBS(+)Ova(+) group were relieved. A
highly significant elevation of IFN-gamma and TNF-alpha were observed in
the TNBS-induced colitis group. After exposure to the eggs, IFN-gamma
was significantly decreased, while TNF-alpha was similar to that of the
TNBS(+)ova(-) group. No obvious variation was seen in IL-10 expression
in TNBS-induced colitis, compared to the controls. Exposure to the eggs
led to a significant upregulation of IL-10 expression. TLR4 expression
was elevated after injected with TNBS and was downregulated in the eggs
group. Less intestinal bacterial translocation frequency was observed
when exposed to eggs. CONCLUSION: S. japoni*** ova can prevent the
TNBS-induced colitis and reduce the bacterial translocation frequency in
mice. The mechanisms were supposed to be due to the regulation of
T-helper cell 1/2 balance and TLR4 expression.
Adv Exp Med Biol. 2009;666:88-94. Related Citations, LinkOut
Immunomodulatory activity and the****utic potential of the filarial
nematode secreted product, ES-62.
Harnett W, Harnett MM.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of
Strathclyde, Glasgow, UK.
ES-62 is a protein that is actively secreted by filarial nematodes
during parasitism of the vertebrate host. The molecule is able to
directly interact with a number of cells of the immune system including
B-lymphocytes, dendritic cells, macrophages and mast cells. Interaction
appears to be dependent on complexing with TLR4 and results in
modulation of the activity of a number of signal transduction molecules
including MAP kinases, PI-3 kinase and NF-kappaB. Immunomodulatory
activity of ES-62 appears to be largely due to the presence of
phosphorylcholine (PC) moieties covalently attached to N-type glycans.
The net effect of ES-62's interaction with the immune system is the
generation of an anti-inflammatory immunological phenotype. As a
consequence of this, ES-62 demonstrates striking drug-like activity in
models of disease associated with aberrant inflammation, in particular
those associated with autoimmunity and allergy.
In schistosomiasis, a major human parasitic disease caused by helminths,
different life-stages of the parasite contribute to the developing host
immune response. To increase our understanding of the mechanisms that
play a role in shaping the host immune responses, we have investigated
the effects of schistosome glycoconjugates on the phenotype of dendritic
cells (DCs), which form a crucial link between the innate and the
adaptive immunity; Schistosoma mansoni worm glycolipids induce DC
activation as indicated by upregulation of the maturation markers CD80,
CD86 and MHC-II, as well as the production of the cytokines
interleukin-12 p40 (IL-12 p40), IL-10, IL-1beta, IL-6, IL-8 and tumor
necrosis factor-alpha (TNF-alpha). Co-culture of glycolipid-primed DCs
with naive T cells results in skewing of the T cell response towards a
Th1 profile. Remarkably, the DC activation is dependent on fucosylated
glycan moieties of the glycolipids. On the DCs, the C-type lectin
DC-SIGN and TLR4 are both critically involved in the induced activation,
as was demonstrated by using monoclonal antibodies that block
interaction of these receptors with the glycolipids. Furthermore,
whereas the worm glycolipids were not able to activate HEK 293 cells
expressing TLR4, they did show TLR4 activation after introduction of
DC-SIGN in the HEK 293-TLR4 cells. Our data provide evidence for a novel
function of DC-SIGN as an essential co-receptor for TLR4-induced
activation of human DCs. This mechanism of TLR4 activation by worm
glycolipids may contribute to eliciting Th1 immune responses in
schistosome infection [PMID 20170964]
21st July 06:01
Helminth infection can block TLR4 induction in TNBS-induced colitis (colitis autoimmune)
The parasites from raw beef tend to be pretty unhealthy but there are
some helminths in the water supply that confer substantial protection
against autoimmune disease without many negative side effects.
23rd July 17:50
Helminth infection can block TLR4 induction in TNBS-inducedcolitis
On Mon, 07 Jun 2010 19:30:00 -0600
So helminths in raw beef are unhealthy, but the helminths in
fecal-contaminated water are good for us. Is that what
I confess I do have a problem with an unstated assumption behind
your postings: People who cannot eat gluten are ill, but people
with intestinal parasites are healthy.
23rd July 17:50
Helminth infection can block TLR4 induction in TNBS-induced colitis (colitis malaria bacteria autoimmune)
It depends on the helminth species. Some of these can be quite
dangerous when they're not well adapted to life in their host - like
malaria. All or most of these helminths appear to suppress
autoimmunity. Even in M.S. patients, having a tapeworm or malaria makes
M.S. more tolerable than not having a helminth infection.
You want a species that won't cause collateral damage like the one sold
by Ovamed. There are other clinical trials taking place using other species.
It depends on the "parasite" but even thinking in terms of "parasite" is
misleading. When the helminths are relatively harmless, you should
think of them more as "probiotics" like the bacteria and fungi lining
It's not clear that helminths can be effectively used to treat Celiac
the way they've been useful in Crohn's however it does look likely that
the lack of helminth infection/colonization is what leaves one largely
vulnerable to developing an autoimmune disease in the first place. In
my personal opinion, I'd expect helminths to be effective for Celiac at
least to some extent until proven otherwise.
23rd July 17:50
Helminth infection can block TLR4 induction in TNBS-inducedcolitis (allergy allergies bacteria)
On Thu, 17 Jun 2010 01:28:10 -0600
There is no such thing as autoimmunity. The mechanism for
detecting "self" from "not self" comes from religion and
What Helminths do is lower immunity so that they will not be
rejected by their hosts. In cases of allergy (such as autoimmunity)
or transplants they might help, but lowering immunity has other dangers.
You cannot fiddle with the immune system without causing collateral damage.
I am in the process of rethinking probiotics. The whole
idea of "good" bacteria and "bad" bacteria is another inappropriate
intrusion of religion into medicine. Bacteria and fungi and helminths
do what they do. Whether the result is good or bad depends on
detailed cir***stances and not on general principles. They may
be good in one case and bad in another.
<choke> Autoimmune diseases are allergies. Allergies are hard coded
in our DNA. We need to use our brain to control our environment
and stay healthy. People want to talk about the rainbow
and how God made everything perfect just for us, but they forget
the part about being kicked out of Eden and surviving by the
sweat of our brow.
We are diverging into different species. Our DNA determines that
we cannot all live in the same environment or eat the same food.
Instead of helping people to find an environment that is good for
them, you want to alter them so that they are the same. This is
invasive medicine, bad medicine. We do not understand how the
body functions well enough to make these kinds of changes.
"Above all do no harm."
However you plan to introduce them, the answer is still *no*.
23rd July 17:50
Helminth infection can block TLR4 induction in TNBS-induced colitis (colitis chitin macrophage cancer autoimmune)
Well, have a chat with God, honey. I'm autoimmune. However much I'd
like it to go away because you don't "believe" in it, it hasn't happened.
They are not lowering immunity. They are shifting it. For instance, if
your immune system is tied up in knots because it is targeting its own
cells with autoantibodies (anti-IL-10 antibodies in M.S. spring to
mind), then helminths can improve immune function by putting a stop to
that self interference. For another example, antibodies against GM-CSF
can impair macrophage function.
Suppressing autoantibody production in either of these two examples
would "raise" immune system function, not lower it.
You don't understand the immune system. You're not "lowering" anything;
you're simply shifting around various branches.
Tregs - a class of cell stimulated by helminth infection - also fight
viral infection. Actually having helminths will lower your risk for
certain kinds of cancer by lowering your inflammation but also by
lowering your risk of viral infection. Viruses often set off both
autoimmune problems and cancer development.
Which is what we did when we started clearing helminths out of the
modern human gut and dosing ourselves with broad-spectrum antibiotics.
Some of that might have been necessary for broad human health but the
rest of us have to live with the negative side effects.
If you don't want to listen to the scientific record, then fine. But
don't accuse scientists working on the immune system of following your
own peculiar version of "religious" dogma.
No. Allegies are technically abnormal antibody responses to otherwise
innocuous foreign material - like soy, for instance.
Autoimmunity refers (typically) to the antibody-based targeting of your
own tissue and proteins in those tissues. Hence Celiac is an autoimmune
disease not simply because it's a bad reaction to wheat but because that
reaction also triggers the release of autoantibodies to targets like
transglutaminase, a molecule necessary to the functioning of your body.
Some are, like chitin, but most are acquired through the B cell antibody
23rd July 17:50
Helminth infection can block TLR4 induction in TNBS-inducedcolitis (diet allergen allergy allergies pollen)
On Mon, 21 Jun 2010 04:58:47 -0600
Don't feel special. Everyone is autoimmune. You are the one
injecting religion into this, although you may not realize it.
When we sneeze, it is caused by immunity. If instead of a virus
causing the reaction, it is pollen; then we call it an allergy.
This is purely a semantic game.
The sneeze is caused by the immune system attacking our nasal passages:
autoimmunity. This autoimmunity has survival value because the sneeze
tends to eject whatever is there. This could be a virus or a few grains of pepper.
This is not my theory, but something that a research immunologist
explained to me about thirty-five years ago. We were both computer
geeks, and he took me out to lunch to explain how allergies work.
He was doing research on using computers to recognize cancer.
He said this is the way it is, but he did not want me to use his
name. It would have jeopardized his grants.
There is no way for our immune system to recognize "self" from "not
self", because the DNA code to specify "self" would have
to be larger than our DNA code. It would have to be larger than itself.
That may be, but intestinal parasites must switch off the immune response
in the host so that they can survive. They may also do other things
We fiddled with the immune system and caused collateral damage. You
did not learn the whole lesson, and you want to fiddle some more.
It is not my version, but their own. The flaw here is in thinking
of the body as something that was designed as opposed to evolved.
In effect this anthropomorphizes God. Even the term "immune system"
is wrong, because it implies that we understand how it all functions.
We evolved. We are not partitioned into "systems". Everything
potentially affects everything else.
Soy is a recent introduction into our western diet. Many people
cannot handle it well. There is nothing abnormal about a soy allergy.
The immune system does not recognize our own tissue. It does not
recognize proteins either. It attaches to smaller patterns of charge
that occur within proteins. These patterns can occur in more than one
protein. So when your immune system attacks a microbe, it can also attack
your own body as well.
As my immunologist friend put it. "At an individual level it doesn't
work, but at a species level it works."
He searched for a simple example, but he could not think of one. I
suggested something from the old Mr. Magoo cartoons that he thought
was apt. If you recall, Mr. Magoo was a blind man who was the butt
of the jokes in a series of cartoons. They even had a Mr. Magoo ride
in Disneyland. But anyway there was a cartoon where someone rings
the doorbell, and Mr. Magoo turns the doorknob to go outside. But
the door is already open, and Mr. Magoo twists the postman's nose
Our immune systems as myopic as Mr. Magoo. That is the way the
immune system is. It is not perfect. It does not work very well.
It is what it is. It evolved instead of being designed.
We have codes for immunity in our DNA that are not normally switched on.
These are switched on through the B cell antibody system (sic) only
when we are exposed to the allergen (or something that looks like it
to Mr. Magoo). If all our immunity were switched on at once, we would
die from autoimmunity.
23rd July 17:50
Helminth infection can block TLR4 induction in TNBS-inducedcolitis (allergies lymphocytes autoimmune)
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
"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."
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.