What it all does to us.......
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"Laurence" lharris@nwlinkDOTcom wrote in message
...
I am Laurence Harris. I live near Seattle, Washington, USA. I have
Celiac
Disorder, Hashimoto's Thyroiditis, and about five other brushes with
autoimmune disorders. I have a BS degree, have read extensively in
chemistry, biochemistry, and broad ranging medical research topics. I
have
been creating software for computers embedded in medical devices. Most
recently, software to operate a Left Ventricular Assist Device - a heart
pump, which is now successfully operating in at least two humans to good
effect.
After learning about the various medical problems that are associated with
gluten sensitive enteropathy, I saw a real puzzle staring at me. It
became
a real teaser to me, and the more I learned, the more there seemed to be
to
chase down. Since I have a lot of time available, I have jumped in with
both feet.
I have now spent months researching issues regarding how it is that many
people get AutoImmune Disorders, including Celiac Disease, Thyroiditis and
a
whole host of others.
The linking of concepts presented here is my own invention, although all
the
underlying technology is from the credible published technical works of
many
others. I have relied only on legitimate sources, mostly medical journal
articles, although some comes from informational websites put up by
various
professors at universities. Some of my information has come from years of
reading and study, although I have attempted to find current references
for
most of it since science forges on.
I am inserting a huge list of website references at the end of the text.
They are the resources I used for most of my studies. Some of the
websites
allow you to download entire journal articles as PDFs to store on your
hard
drive. I do that wherever I can, since that works better than viewing
them
in your browser. Unfortunately they are not grouped by topic, nor are
they
in any particular order. To use many of them you must open the website
and
drill down into areas having research papers, journal articles, patient
information and so on. There may be a few that require you to register to
be able to access the technical content.
The basic picture is that many people, more than have celiac disorder,
have
an immune system that reacts to some parts of the gluten protein in wheat,
barley and rye. They interpret the protein as "enemy" - an antigen -
just
as though it were a bacterium or virus. Since the immune system reacts to
foreign objects penetrating the skin, perhaps this explains why.
To follow all this you may want to go to some of the websites and read on
peptides, immune system, lymphocytes, acute and chronic inflammation.
The Immune System
The human body has wonderful ways of protecting itself. The system of
interacting parts that defends us from invading bacteria, fungi, viruses
and
other foreign matter is collectively referred to as the "immune system".
The
tale we are telling here is one not of allergies (IgE antibodies), but one
of a different, more insidious kind of immune system activity, (IgA, IgG
and
IgM antibodies).
The immune system includes cells circulating in the blood and lymph and
cells in various other places as well. It includes a variety of cell types
from those that are self-moving blob-like hunter-killer cells
(macrophages)
to several kinds of miniature chemical factories with some making
destructive toxins and others making specially shaped "antibodies" that
match up to and latch onto the fairly unique cell-surface chemicals used
by
attacking organisms as tools or protective cover.
Blood serum, T-cells, B-cells, macrophages, antibodies, bone marrow,
spleen,
lymphatic system, and various other organs all work together to detect and
destroy invasion forces. It has taken many millions of hours of research
and
study for us to come as far as we have in our understanding of what
happens
when a bacterium or virus attempts to invade our bodies. And while we have
a
lot of the picture we are still learning, still searching for missing
pieces
to this magnificent puzzle.
Cells
What we do know is that nearly every type of human cell encases fluids in
a
cell wall made of a smooth, waterproof, very flexible double-layer of
loosely coupled rod-like molecules we call a plasma membrane. The cell
wall
has various special structures embedded in it to transport materials
across
the barrier. That is how food energy gets in and how waste products get
out.
Inside each cell are a variety of different structures; some are tiny
chemical factories that convert glucose to ready-to-use chemical energy,
and
use that energy for motion, or to create other special chemicals needed
for
the cell's operation. Sometimes the chemicals are to sent out into the
rest
of the human body for use elsewhere.
Cell Identity Flags - Friend or Foe?
But dotted all around on the outside of this smooth cell wall there are
several types of special "identity flags" - specially shaped chemicals
that
are firmly anchored in the cell wall with a large specially shaped part
"waving in the breeze" telling all passing observers who they are - self.
It
is not really quite that simplistic, but it is actually a combination of
several possible types of identity markers that are recognized by cells in
the immune system, telling them "Leave me alone! I'm a friend!" And
different types of tissue have slightly differently shaped flags, all
still
self, but not quite all the same. These flags are called Human Leukocyte
Antigens (HLA) proteins.
Woe be unto cells, like bacteria, who don't know the right combination of
markers for "friend" - the immune system learns their surface markers,
creates a complimentary shaped pattern and attaches it to special
proteins,
called antibodies, that hook onto the foes' flags and tell the immune
system
"This is a bad guy! Let's take them out!" Once a particular immune system
cell recognizes an invader it can trigger cells whose job is to make
antibodies to reproduce and make lots more of these useful chemicals.
Immune Responses
Inflammation, created by the fast responders of the immune system, makes
the
area surrounding a detected invasion become porous, or permeable, so that
antibodies and various immune system cells can "get at" the offenders.
Even
blood vessel walls become rather leaky. This makes surrounding tissues
swell
and turn red.
So the various parts of the immune system work to penetrate or perforate
the
cell wall of an invading organism and make its insides all leak out. Some
immune system cells pick up the antigens and carry them around with them
like flags, telling other cells about the invader's identity. Some use the
antibody's matching pattern to latch onto the invading cells' surface
features (antigens) and get up against them to unleash little vesicles of
destructive chemicals. Others engulf an offender and digest it, or at
least
they carry away indigestible stuff.
Picture these blob-like macrophages, fairly big as blood cells go,
slipping
along in the blood stream and encountering a battle site - they send out
an
amoeba-like tentacle, a pseudopod, and pull themselves over to a marked
offender, then they ooze around it and rejoin on the other side. When it
is
fully engulfed they release chemicals, right up against the bad cell,
similar to chlorine bleach, that chemically take apart the proteins and
lipids that make up the invader's structure. Burp.
Even the lowly virus has chemical patterns that the immune system uses to
identify them. Virus surface coat chemicals are really tools to make the
virus stick to the surface of a human cell so they can get inside that
cell.
And as a virus drills through the human cell wall it leaves behind various
parts of its surface coat, sort of embedded in and floating on the human
cell wall. These too are sensed by the immune system and used to identify
cells that are being taken over by a virus. These human cells then, are
mercilessly destroyed. And the methods work. Takes about two weeks for the
immune system to detect the invasion, learn the cell-surface markers left
by
the viruses, make enough antibody factories ( B-Cells and others ), and do
the search and destroy job. When it is all done, and the antibody
production
shuts down, there are extra of these chemical factories circulating in the
blood, sort of on standby, in case the same invaders come again. They
would
be able to attack and destroy them before they ever get a foothold again.
That is learned immunity.
Immunity
Learned immunity is what we try to induce with a vaccine. A vaccine is
just
a whole lot of these cell surface markers without the offending bacterium
or
virus still attached, or at least if the cell is still there it has,
hopefully, been killed. Seems to work pretty well most of the time. So we
make a mixture of water with pieces of surface marker protein in it and
inject it into the inside of the body. The immune system sees the invading
stuff and sets up new antibody manufacturing to fight it off. Since there
are no real invaders, it is easy to clean up the debris, but the result is
that the immune system now has standby troops for that particular type of
invader. It is much better to learn immunity without having to suffer
through a full scale invasion.
The Flags are Proteins
So the cell surface markers are mostly bits of protein, which are really
just interconnected amino acids, which have shapes unique for that kind of
organism. Amino acids are some of the basic building blocks of the human
body. We get amino acids from eating and digesting meats and plant
materials, although some of them can be made by our own cells. Amino acids
also serve as a source of food energy when needed. Depending on what order
you string the amino acids together, and what other chemical bits you hook
onto the chain at various places, the whole thing folds into a three
dimensional shape. These proteins are sometimes referred to as "peptides".
(A peptide, then is just a piece of protein.) And shape is what is used by
antibodies to "recognize" a cell surface marker.
Intestinal Tract
The intestinal tract has a single cell layer, the epithelium that forms
villi - little finger-like projections that are filled with immune system
cells - lymphocytes - T cells, B cells, macrophages and so on. Below the
epithelium is something called the submucosa. and under all of it, or more
properly surrounding all of it is the muscular intestinal wall.
When gluten is present in the intestine, these immune system cells react,
and cause inflammation. Inflammation makes blood cell walls - epithelial
tissue - become leaky so that plasma containing antibodies can get at the
invasion more easily, along with lymphocytes. Unfortunately, the
epithelial
wall of the intestine becomes leakier, too. It is a positive feedback
loop
with inflammation.
And the worse the inflammation, the more of the gluten protein segments
can
get in while other stuff is getting "out" into the digestive tract.
Antibodies
Well, one part of the immune response is to turn on the manufacture of
antibodies - chemicals that physically fit like hand and glove, or plug
and
socket - that match up to the antigens. These little chemical factories
are
in the B cells. And activating a B cell with a matching antibody causes
it
to make antibodies and to replicate.
As long as antigen is being found, the B cells will be told by the T cells
and macrophages to make antibodies. Or is it the T helper cells that do
this? Any way the replicators get busy and the B cells get busy, flooding
the blood plasma with antibody chemicals that attach to the antigenic
gluten
protein. Since gluten consumes the antibodies, they have to be replaced
when more gluten comes along.
Fuzzy Logic
Well, B cell replication is designed to not be perfect. The mechanisms
that
transcribe the DNA/RNA stretches that encode antibody peptide sequences
have
a built in randomizer that will occasionally substitute a different amino
acid into the sequence than was in the original. This apparently serves
the
purpose of making the immune system more adaptable in case the original
match was not quite perfect. And if the new antibody shapes don't match
anything, they are never activated to make antibodies, and do not
replicate
further.
So under a continuous attack from an antigen, such as gluten, the
production
of antibodies is always running, perhaps even in high gear. And along
with
this high rate of activity comes continual varying of the antibody
patterns.
Unfortunately, many people have self-identification cell surface marker
peptides that bear a strong resemblance to gluten protein pieces. So when
the random variations in antibody shapes just happen to match fairly
closely
with one of these usually protective Human Leukocyte Antigens (HLA), the
particular type of tissue in the human organism that bears that particular
variation of HLA is suddenly treated as a bad guy, as INVADER, instead of
SELF. And bang! There goes the thyroid producing cells. Or the Islets of
Langerhans insulin producing cells. Or any one of a whole lot of other
tissue types.
Endomysial tissue, a connective fibrous material surrounding muscle cells
apparently is one of the targets of attack, at least as long as gluten is
revving up the B cells. I'm not sure what the difference between this
sort
of attack that only goes on as long as gluten is being consumed and the
thyroid or insulin cell attacks that seem to continue after gluten is
removed. Perhaps endomysial tissue is only in out-of-the-way places that
don't typically get visited by T cells or macrophages, and thus only
suffer
when the antibodies are being produced in large amounts to fight off
gluten.
That seems reasonable, since the gluten sets things going by showing up at
the intestinal inner wall epithelium which is just loaded with lymphocytes
to keep the fauna and flora of the inside of the intestine from getting
anywhere they shouldn't. And then there is apparently endomysial tissue
in
the submucosa of the intestine? At any rate, the intestinal villi get
destroyed after a long enough time, and since that is where a lot of
digestive enzymes are produced, food doesn't get properly digested, and
since the surface area is smaller, it doesn't get properly absorbed.
So some of these tissue types are continually exposed to lymphocytes, and
so
cause a sustained attack, while others seem to be typically sheltered, and
thus don't sustain antibody production when gluten is absent. And then
there is the increased risk of cancer that is associated with untreated
CD.
Only is a problem when the immune system is churning away. Not when all
is
quiescent.
All of this suggests that many people who never get Celiac Disease are
still
experiencing varying degrees of intestinal inflammation from the
consumption
of gluten. And there is a lot known about inflammation and its apparent
linkage to heart trouble, arthritis and a whole lot of other disorders.
And
there are all the autoimmune disorders that seem to be the result of the
churning immune system hitting the wrong combination by accident.
There is even one website by a gastroenterologist suggesting that it could
be sixty percent or more of mankind that experiences this immune response
from gluten ingestion.
Various theories have been discussed that involved trigger events to start
off the attack against self causing an autoimmune disorder. I suspect
that
that is not necessary, although it could play some role in starting some
autoimmune disorders in some people. Apparently H. Pylori bacteria, the
stuff of stomach ulcers, carried by the common housefly, can maintain a
chronic infection in the stomach that does the same sort of job as gluten
in
the intestine. At least it maintains a constant inflammatory state, and
has
an association with stomach cancers.
And supposedly there is an immune reaction in some people to bakers yeast.
So what to make of all of this? I think that because there is legitimate
research published about the increased risk of cancer in untreated Celiac
Disease (CD) patients, and that we have, in the US, only identified about
three per cent of those that actually have CD, that one could honestly
make
a statement. about the safety of consuming gluten from wheat, barley or
rye.
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STATEMENT
"Since the ingestion of gluten from wheat, barley or rye has been
demonstrated, through clinical studies with humans, to cause an elevated
risk of cancer, gluten from wheat, barley and rye should be declared a
CARCINOGENIC SUBSTANCES. To do any less is to doom our children to the
lifetime of slow poisoning that most of us have been experiencing."
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University of Chicago Hospitals Celiac disease is far more common than
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Chronic inflammatory cells
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Clonal Selection
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Dietary Soluble Fiber Resource
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Digestion and Balance
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Immune Tolerance Network
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Inflammation The Battle Within
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National Institute of Neurological Disorders and Stroke (NINDS)
http://www.ninds.nih.gov/
National Institute of Standards and Technology
http://nist.gov/
National Pork Producers Council
http://www.nppc.org/
Neuromuscular Muscle Autoantibodies
http://www.neuro.wustl.edu/neuromusc...mantibody.html
NIAID Links to Other Sites
http://www.niaid.nih.gov/information/externallinks.htm
Nikon MicroscopyU Confocal Image Gallery - Peyer's Patches
http://www.microscopyu.com/galleries...rspatches.html
NLM's Databases and Electronic Information Sources
http://www.nlm.nih.gov/databases/databases.html
No WorriesT Gluten-Free Bread Mix
http://www.noworriesbread.com/
OMIM - CELIAC DISEASE; CD
http://www.ncbi.nlm.nih.gov/entrez/d....cgi?id=212750
Pathology Teaching Menu
http://medweb.bham.ac.uk/http/depts/.../teachdir.html
Peptide bond - Wikipedia
http://en.wikipedia.org/wiki/Peptide_bond
Periodic table (WebElements)
http://www.webelements.com/
Planet Celiac--the gluten free place to be if you have celiac sprue --
recipes, books and more.
http://www.planetceliac.com/
PorkBoard
http://www.porkboard.org/Home/default.asp
PROWL - Amino Acid Properties
http://prowl.rockefeller.edu/aainfo/contents.htm
PsoriasisNet
http://www.skincarephysicians.com/ps...snet/index.htm
Science of dieting Slim pickings
http://www.nature.com/cgi-taf/DynaPa...28252a_fs.html
Seattle Celiac Support Group
http://www.seattleceliacs.com/
Seborrheic Dermatitis
http://www.aad.org/pamphlets/seborrhe.html
Skindex
http://www.skindex.com/index.html
Society for Mucosal Immunology
http://www.socmucimm.org/
Special Communication - March 8, 1995. Treatment Guidelines for
Hyperthyroidism and Hypothyroid
http://www.ama-assn.org/sci-pubs/jou..._10/sc4291.htm
Special Communication - March 8, 1995. Treatment Guidelines for
Hyperthyroidism and Hypothyroidism. (c) AMA 1996
http://www.ama-assn.org/sci-pubs/jou..._10/sc4291.htm
Specialty Laboratories - clinical reference laboratory contract research
organization
http://www.specialtylabs.com/
StopAllergy.com Ask an Allergist
http://allergist.stopallergy.com/For...lth/Allergist/
Support Groups
http://www.whatnowheat.com/Support%20Groups.htm
Swedish Medical Center Home
http://www.swedish.org/home.asp?Home
The American Gastroenterological Association - Clinical Resources (Patient
Brochures)
http://www.gastro.org/clinicalRes/brochures/ibd.html
The American Gastroenterological Association
http://www.gastro.org/
The Antibody Resource Page educational
http://www.antibodyresource.com/educational.html
The Gluten Free Kitchen
http://gfkitchen.server101.com/
The gluten free message board
http://members2.boardhost.com/gluten...html?999235741
The Great Plains Laboratory, your center of testing and analysis for
Autism,
Pervasive Developmental Disorder (PDD)
http://www.greatplainslaboratory.com/immune.html
The Merck Manual
http://www.merck.com/pubs/
The National Fibromyalgia Association
http://www.fmaware.org/
Thinner - guide to lowcarb weight loss
http://www.thinner.com/
ThirdAge - Health Newsletter - Overlooked, Under-Diagnosed Thyroid Disease
Poses a Challenge
http://www.thirdage.com/news/article...040326-01.html
Thyroid Disease Manager, your source on thyroid disease, hyperthyroidism,
hypothyroidism, thyroiditis,thyroid cancer
http://www.thyroidmanager.org/
Thyroid Disease Symptoms - Hypothyroidism Symptoms
http://www.armourthyroid.com/hypothy.../symptoms.html
TNFA promoter polymorphism and susceptibility to brucellosis - Clin Exp
Immunol, Vol 121, Issue 3, pp. 480-483 (Full Text)
http://www.blackwell-synergy.com/lin....01331.x/full/
Two distinct hemolysins in Trichomonas tenax ATCC 30207 - Oral Microbiol
Immunol, Vol 15, Issue 6, pp. 355-359 (Abstract)
http://www.blackwell-synergy.com/lin...d=bHR8zMK2xU2f
USDA NutrientDatabase
http://www.nal.usda.gov/fnic/foodcomp/search/
Van's Wheat Free Waffles.
http://www.vansintl.com/wheatfree.php
VCUendomysiumResident Cases
http://www.pathology.vcu.edu/WirSelfInst/muscle.html
virus-adeno
http://www.stanford.edu/group/virus/adeno/adeno.html
Voluntary Recall of Taco Bell Taco Shells containing StarLink Corn
http://www.cast-science.org/cast-sci...y/20000925.htm
WAFDO
http://www.wafdo.org/
WebRing hub
http://j.webring.com/hub?ring=celiac
Welcome to Medscape
http://www.medscape.com/px/urlinfo
Welcome to MedWeb
http://medweb.bham.ac.uk/
Welcome to the Gluten Intolerance Group of North America
http://www.gluten.net/
Welcome to the Incredible Edible Egg Website
http://www.aeb.org/
www.patientcenters.com -- Non-Hodgkin's Lymphoma Center -- What are the
NHLs
http://www.patientcenters.com/lymphoma/news/nhl2.html
York Nutritional Laboratories, Inc... Better health begins at home
http://www.yorkallergyusa.com/
[Report] Treatment Algorithms 2000(Table of Contents)
http://www.the-infoshop.com/study/dc...rithm_toc.html
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