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Q: is most of the body's immune function handled in or by the gut ( Answered 5 out of 5 stars,   1 Comment )
Question  
Subject: is most of the body's immune function handled in or by the gut
Category: Science > Biology
Asked by: cmscott-ga
List Price: $75.00
Posted: 25 Sep 2005 02:57 PDT
Expires: 25 Oct 2005 02:57 PDT
Question ID: 572294
Is there any scientific verification for the statement that most of
our immune function is found in our gut? Specifically, can it be said
? and verified ? that a particular (large) percentage of our immune
function is handled in (or by) the large and/or small intestine?

I will be grateful for as much detail in the answer to this question
as possible. But without reference to published information (i.e.
medical or scientific journals) the answer will be useless to me.

Request for Question Clarification by pafalafa-ga on 25 Sep 2005 05:26 PDT
There's no doubt that a substantial portion of our bodies' immune
function happens in the gut.  Putting a number on it, though, is
problemmatic for a number of reasons:

--what is and isn't part of the immune system isn't very clearly
defined.   For instance, some would consider the skin to part of the
immune system, while others focus mostly on the apecialized internal
cells and structures like T-cells and such.  Without an agreed-upon
notion of what comprises the immune system, it's hard to takl about
percentages of the system -- 10% located here, 25% there, etc.

--there are many components to the immune system, and there's a
tendency to look at them as individual sub-systems.


The closest I've come to an answer to your question is an
authoritative statement about lymphocytes, a major component of the
immune system.

About half the body's lymphocytes are associated with mucus-tissues,
the other half not.  Since I believe the gut is included in the
mucus-tissue group, then clearly less than half of the lymphocytes are
associated with the gut.

It makes sense that a good chunk of the immune system would operate in
our gut, since this is a pathway for ingested food, a major source of
intake of foreign matter into the body.

On the other hand, we also need a large capability in our respiratory
system, and throughout the blood and body as well.  So saying that
'most' of the immune system is found in the gut just doesn't ring true
to me.  And the meager facts that I could uncover about the
lymphocytes seem to bear this out.

Can you tell us a bit more about your interest in this particular
topic of the gut vs rest of the body?  Where did you come across
statements attributing most of our immune function to the gut?

A bit more context might help in pinpointing an answer to your question.

Thanks,

pafalafa-ga

Clarification of Question by cmscott-ga on 25 Sep 2005 06:24 PDT
I'm working from the perspective of multiple sclerosis, an auto-immune
disease with SYMPTOMS expressed through attacks on the myelon coating
of the nerves. But the disease itself is a grave disorder of the
immune system/immune responce; my belief (and experience) is that
healing the immune system, reversing the damage done to it --
something which can, indeed, be done -- is how the disease 'MS' is
best dealt with.

You may know about 'leaky gut' -- excess permiability of the
intestinal wall which allows undigested food (and other) particles out
of the gut and into the body. In it's turn, leaky gut creates allergy
reactions which create inflamation which creates, and/or, sets up
and/or, inflames auto-immune response. This response can be any of a
number of auto-immune diseases: lupus, rheumatoid arthritus, etc. It
can also be a form of cancer, but I won't get into that.

When leaky gut is healed, when a proper diet is strictly maintained
(there are three excellent diets to stop MS progression) and when body
toxicity is cleaned up, MS is... possibly cured. It will anyway
absolutely be stopped.

The statement that most of the immune system is located in the gut can
be casually found in many books dealing with dietary healing. The
casualness is why I don't trust it... and yet, it makes sense to me in
terms of healing MS from the point of view of healing the immune
system by dealing with diet, toxicty, and leaky gut.

I hope this gives you a better idea of what I'm looking for... and I
my appologies for any spelling errors.

cmscott
Answer  
Subject: Re: is most of the body's immune function handled in or by the gut
Answered By: crabcakes-ga on 25 Sep 2005 19:31 PDT
Rated:5 out of 5 stars
 
Hello Cmscott,

     The intestinal system/gut does play a large role in the human
immune system. Whether one could say it plays the largest role is
debatable. The entire body is involved in protecting itself from
infectious organisms. From the basic action of vomiting and diarrhea,
which rids the body of bacteria and viruses, to the intricate
production of antibodies and home to lymph nodes and lymphocytes, the
intestinal tract is more active in preventing disease than we think!


Immune System:
==============

     Innate/Natural Immunity:

?One disadvantage of innate immunity is the fact that it is
nonspecific - i.e., it cannot discriminate one foreign substance from
another. Innate immune responses are uniform regardless of the nature
of the antigenic stimulus. Further, innate responses are not enhanced
by repeat exposure to the foreign substance, and they cannot adapt to
microbial counter-strategies designed to evade them. Innate immunity
is sometimes also called natural immunity.?
From the University of Florida, College of Medicine
http://medinfo.ufl.edu/pa/chuck/fall/handouts/immune1.htm

According to Cancer Research UK, the following are forms of ?built in?
protections, related to the immune system:

The skin outside the body and other lining tissues inside forming a barrier 

Mucus lining of the gut and lungs which traps invading bacteria 

Hairs which move the mucus and trapped bacteria out of the lungs 

Stomach acid which kills bacteria that have been swallowed 

Helpful bacteria growing in the bowel which prevent other bacteria
from taking over

Urine flow which flushes bacteria out of the bladder and urethra 

White blood cells called 'neutrophils' which can find and kill
bacteria and other infectious agents (Note-neutrophils are a type of
white blood cell, also known as granulocytes, segs, eosinophils, and
basophils)
http://www.cancerhelp.org.uk/netscape/help/default.asp?page=118

?This prevents entry of micro-organisms into tissues or, once they
have gained entry, eliminates them prior to the occurrence of
disease.?
1.Mechanical barriers at body surfaces, skin, mucous membranes -
disruption leads to infection.
2.Antibacterial substances in secretions, lysozyme, lactoferrin, low
pH of stomach contents.
3.Prevention of stasis. 
·Peristalsis/flow of urine/upward movement of secretions in bronchial tree. 
·Clinical relevance; urinary infection with urinary obstruction;
decreased bronchial
·Ciliary activity - bronchiectasis (Kartagener's syndrome). 
·Coughing. 
·Vomiting. 
http://www-micro.msb.le.ac.uk/mbchb/1b.html


?The normal colonization of the mammalian intestine with commensal
microbes is hypothesized to drive the development of the humoral and
cellular mucosal immune systems during neonatal life and to maintain
the physiologically normal steady state of inflammation in the gut
throughout life. Neonatal conventionally reared mice and germ-free,
deliberately colonized adult mice (gnotobiotic mice) were used to
examine the efficacy of certain intestinal microbes.?

?It has been known for decades that gut commensal microbes colonizing
neonatal mammals effect the activation and development of the systemic
immune system, especially by increasing circulating specific and
natural antimicrobial antibodies (1?6). Generally, porcine and murine
germ-free neonates and their young-adult counterparts have been
compared after deliberate colonization with defined gut enteric
bacteria.?

?Microbial colonization and infection of the gut can profoundly
influence the status of specific and nonspecific cellular and humoral
elements of the gut mucosal immune system. These interactions
contribute to the normal development of the neonatal gut mucosal
immune system. Better understanding of the microbial-host gut mucosal
interactions and their consequences may enable complementary or
alternative approaches to prophylactic and therapeutic antibiotic
therapies?
American Journal of Clinical Nutrition
http://www.ajcn.org/cgi/content/full/69/5/1046S


·?The anatomic response physically prevents threatening substances
from entering your body. Examples of the anatomic system include the
mucous membranes and the skin. If substances do get by, the
inflammatory response goes on attack.
·The inflammatory system works by excreting the invaders from your
body. Sneezing, runny noses, and fever are examples of the
inflammatory system at work. Sometimes, even though you don't feel
well while it's happening, your body is fighting illness.
·When the inflammatory response fails, the immune response goes to
work. This is the central part of the immune system and is made up of
white blood cells, which fight infection by gobbling up antigens.
About a quarter of white blood cells, called the lymphocytes, migrate
to the lymph nodes and produce antibodies, which fight disease.
http://www.factmonster.com/ipka/A0774536.html


?The gut associated immune system develops in infancy while the gut is
being colonised by the commensal bacteria. It appears that a tolerance
is established preventing an immune response to the colonic flora. The
gut mucosal barrier is also very effective in preventing infection by
the bacteria in the gut but if the mucosal barrier is breached or if
faecal bacteria enter and open wound some gut bacteria, bacteroides
spp for example are very pathogenic.
?The colonic microflora enables the colon to salvage energy and
nutrients, which escape
absorption in the small intestine.?
University of Glasgow
http://www.gla.ac.uk/departments/humannutrition/students/resources/meden/Infection.pdf


Acquired immunity:
==================

The body also has what is called acquired immunity. When we are
exposed to viruses and bacteria, the body produces antibodies to
destroy invasive organisms. The cells that produce antibodies are a
form of white blood cells, called B-lymphocytes.  The next time the
body is exposed to the same organisms, the cells remember, and produce
the antibody in response, protecting the body once again. Another form
of lymphocytes are the T-lymphocytes. These are killer cells, and
stimulate the b-lymphocytes to produce antibodies.  White cells are
produced in the bone marrow, and travel to the spleen and lymph nodes,
awaiting the call to duty. When called, they travel to the site of
infection, to destroy organisms.


From the University of Florida, College of Medicine
?Unlike innate immunity, a brief delay occurs between the introduction
of an antigen and acquired immune responses; however, these responses
are highly specific to the foreign invader. For this reason, acquired
immunity is sometimes also called specific immunity. Acquired immunity
can vary its response to an antigen making it difficult for
microorgansims to completely evade immune defenses. Finally, the
responses of acquired immunity are increased in magnitude by repeat
exposure to the specific immunogen.?
http://medinfo.ufl.edu/pa/chuck/fall/handouts/immune1.htm

From the University of Florida, College of Medicine
?Acquired immunity is mediated by cells called lymphocytes. Two
populations of lymphocytes are found in the body: B lymphocytes
(responsible for humoral immunity), and T lymphocytes (responsible for
cell-mediated immunity). Most B and T lymphocytes in the body are in a
partially differentiated "resting" stage. However, when they encounter
an antigenic stimulus they proliferate and are transformed into cells
capable of eliminating the antigen source.?
http://medinfo.ufl.edu/pa/chuck/fall/handouts/immune2.htm

?There are two distinct components of the spleen, the red pulp and the
white pulp. The red pulp consists of large numbers of sinuses and
sinusoids filled with blood and is responsible for the filtration
function of the spleen. The white pulp consists of aggregates of
lymphoid tissue and is responsible for the immunological function of
the spleen?
http://www-micro.msb.le.ac.uk/MBChB/2b.html


Mucosal System (MALT)
=====================

   ?The immune system may be viewed as an organ that is distributed
throughout the body to provide host defense against pathogens wherever
these may enter or spread. Within the immune system, a series of
anatomically distinct compartments can be distinguished, each of which
is specially adapted to generate a response to pathogens present in a
particular set of body tissues.?

?A second important point to bear in mind when considering the
immunobiology of mucosal surfaces is that the gut acts as a portal of
entry to a vast array of foreign antigens in the form of food. The
immune system has evolved mechanisms to avoid a vigorous immune
response to food antigens on the one hand and, on the other, to detect
and kill pathogenic organisms gaining entry through the gut. To
complicate matters further, most of the gut is heavily colonized by
approximately 1014 commensal microorganisms, which live in symbiosis
with their host. These bacteria are beneficial to their host in many
ways. They provide protection against pathogenic bacteria by occupying
the ecological niches for bacteria in the gut.?

?The mucosa-associated lymphoid tissues lining the gut are known as
gut-associated lymphoid tissue or GALT. The tonsils and adenoids form
a ring, known as Waldeyer's ring, at the back of the mouth at the
entrance of the gut and airways. They represent large aggregates of
mucosal lymphoid tissue, which often become extremely enlarged in
childhood because of recurrent infections, and which in the past were
victims of a vogue for surgical removal. A reduced IgA response to
oral polio vaccination has been seen in individuals who have had their
tonsils and adenoids removed, which illustrates the importance of this
subcompartment of the mucosal immune system.

The other principal sites within the gut mucosal immune system for the
induction of immune responses are the Peyer's patches of the small
intestine, the appendix (which is another frequent victim of the
surgeon's knife), and solitary lymphoid follicles of the large
intestine and rectum. Peyer's patches are an extremely important site
for the induction of immune responses in the small intestine and have
a distinctive structure, forming domelike structures extending into
the lumen of the intestine.?
This page has plenty of information, for more details, please read all
of this page!
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=imm.section.1355


?Recent studies in experimental animals and humans have shown that the
mucosal immune system, which is characterized by secretory IgA (S-IgA)
antibodies as the major humoral defence factor, contains specialized
lymphoid tissues where antigens are encountered from the environment,
are taken up and induce B- and T-cell responses. This event is
followed by an exodus of specific lymphocytes, which home to various
effector sites such as the lamina propria regions and glands. These
responses are regulated by T cells and cytokines and lead to plasma
cell differentiation and subsequent production of S-IgA antibodies in
external secretions. This knowledge has led to practical approaches
for vaccine construction and delivery into mucosal inductive sites in
an effort to elicit host protection at mucosal surfaces where the
infection actually occurs.?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1539467&dopt=Citation


From Colorado State University:
?Aside from all of its other functions, the gastrointestinal tract is
a lymphoid organ, and the lymphoid tissue within it is collectively
referred to as the gut-associated lymphoid tissue or GALT. The number
of lymphocytes in the GALT is roughly equivalent to those in the
spleen, and, based on location, these cells are distributed in three
basic populations:

(Because of copyright restrictions, only excerpts are posted here.
Please click  the link below to read all of the information)

Peyer's Patches: These are lymphoid follicles similar in many ways to
lymph nodes, located in the mucosa and extending into the submucosa of
the small intestine, especially the ileum.

Lamina propria lymphocytes: These are lymphocytes scattered in the
lamina propria of the mucosa. A majority of these cells are
IgA-secreting B cells.

Intraepithelial lymphocytes: These are lymphcytes that are positioned
in the basolateral spaces between lumenal epithelial cells, beneath
the tight junctions (they are "inside" the epithelium, but not inside
epithelial cells as the name may incorrectly suggest).

?Another important component of the GI immune system is the M or
microfold cell. M cells are a specific cell type in the intestinal
epithelium over lymphoid follicles that endocytose a variety of
protein and peptide antigens. Instead of digesting these proteins, M
cells transport them into the underlying tissue, where they are taken
up by local dendritic cells and macrophages.?

?In addition to the GALT discussed above, lymph nodes that receive
lymph draining from the gut (mesenteric nodes) and Kupffer cells
(phagocytic cells in the liver) play important roles in protecting the
body against invasion.?
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/basics/gi_immune.html



?In addition to the lymphoid tissue concentrated within the lymph
nodes and spleen, lymphoid tissue is also found at other sites, most
notably the gastrointestinal tract, respiratory tract and urogenital
tract.
Gut associated lymphoid tissue (GALT)
This comprises: 
·	tonsils, adenoids (Waldeyer's ring) 
·	Peyer's patches 
·	lymphoid aggregates in the appendix and large intestine 
·	lymphoid tissue accumulating with age in the stomach 
·	small lymphoid aggregates in the oesophagus 
·	diffusely distributed lymphoid cells and plasma cells in the lamina
propria of the gut
Large aggregates of GALT have distinct B cell follicles and T cell
areas. Antigen presenting accessory cells are also present.?

?Peyer's Patches
These are quite large aggregates of lymphoid tissue found in the small
intestine. The overlying 'dome' epithelium contains large numbers of
intraepithelial lymphocytes. Some of the epithelial cells have complex
microfolds in their surfaces. They are known as M cells and are
believed to be important in the transfer of antigen from the gut lumen
to Peyer's Patches. Peyer's Patches facilitate the generation of an
immune response within the mucosa. B cell precursors and memory cells
are stimulated by antigen in Peyer's Patches. Cells pass to the
mesenteric lymph nodes where the immune response is amplified.
Activated lymphocytes pass into the blood stream via the thoracic
duct. These cells then home in the gut and carry out their final
effector functions. HEVs are not present in Peyer's Patches and the
mechanism by which cells home in on mucosal sites is unknown. Cell
surface molecules known as addressins may have a role.?
http://www-micro.msb.le.ac.uk/MBChB/2b.html

?"Most of the time these microbes are content to live and grow in our
intestines," said John Alverdy, MD, professor of surgery at the
University of Chicago and director of the study. "They don't feel the
need or even look for the opportunity to attack. But when they detect
a threat, they have a remarkably sophisticated defense plan, based,
unfortunately, on the notion that the best defense is an overwhelming
offense."
http://www.uchospitals.edu/news/2005/20050728-pseudomonas.html

?Secretory Ig
Epithelial cells in the intestine and other secretory epitheilia (tear
duct, salivary gland, lactating mammary gland etc) possess a receptor
for polymeric Ig, which mediates secretion of antibody, predominantly
IgA also IgM into the external secretions. Secreted IgA forms a very
important defence against infection.?
http://www-immuno.path.cam.ac.uk/~immuno/part1/lec06/lec6_97.html


Autoimmunity
=============

   Even though the immune system is wonderfully protective, sometimes
this system goes awry and attacks its own components, causing
autoimmunity. While most of these reactions are self limiting, in
about 20% of the population, the reaction develops into serious and
occasionally fatal autoimmune disease. It is believed that genetic
predisposition, hormones and environmental factors may be triggers for
the autoimmune reactions.
?Approximately 50 million Americans, 20 percent of the population or
one in five people, suffer from autoimmune diseases. Women are more
likely than men to be affected; some estimates say that 75 percent of
those affected--some 30 million people--are women. Still, with these
statistics, autoimmunity is rarely discussed as a women's health
issue.?
http://www.aarda.org/questions_and_answers.html#GlossA


?When the immune system attacks an invader, it is very specific--a
particular immune system cell will only recognize and target one type
of invader. To function properly, the immune system must not only
develop this specialized knowledge of individual invaders, but it must
also learn how to recognize and not destroy cells that belong to the
body itself. Every cell carries protein markers on its surface that
identifies it in one of two ways: what kind of cell it is (e.g. nerve
cell, muscle cell, blood cell, etc.) and to whom that cell belongs.
These markers are called major histocompatability complexes (MHCs).

 When functioning properly, cells of the immune system will not attack
any other cell with markers identifying it as belonging to the body.
Conversely, if the immune system cells do not recognize the cell as
"self," they attach themselves to it and put out a signal that the
body has been invaded, which in turn stimulates the production of
substances such as antibodies that engulf and destroy the foreign
particles. In case of autoimmune disorders, the immune system cannot
distinguish between "self" cells and invader cells. As a result, the
same destructive operation is carried out on the body's own cells that
would normally be carried out on bacteria, viruses, and other such
harmful entities.?

?The reasons why the immune systems become dysfunctional in this way
is not well understood. However, most researchers agree that a
combination of genetic, environmental, and hormonal factors play into
autoimmunity. Researchers also speculate that certain mechanisms may
trigger autoimmunity. First, a substance that is normally restricted
to one part of the body, and therefore not usually exposed to the
immune system, is released into other areas where it is attacked.
Second, the immune system may mistake a component of the body for a
similar foreign component. Third, cells of the body may be altered in
some way, either by drugs, infection, or some other environmental
factor, so that they are no longer recognizable as "self" to the
immune system. Fourth, the immune system itself may be damaged, such
as by a genetic mutation, and therefore cannot function properly.?
Dr. Joseph Smith Medical Library
http://www.chclibrary.org/micromed/00039060.html


?Almost all patients presenting with autoimmune conditions have some
autoantibodies present in their serum. However they also have
autoreactive T cells present (though these are far harder to
demonstrate experimentally). It is not always known whether the
autoantibodies play an important role in the disease or are a
secondary result of the tissue damage which has been caused by the
disease process itself. This is problem is particularly difficult in
many organ-specific conditions.?

Examples of autoimmune diseases are:
SLE ? Systemic Lupus Erythematosis
Rheumatois Arthritis
Hashimoto?s Disease
Myasthenia Gravis
Addison?s Disease
Scleroderma, and others, including possibly Multiple Sclerosis.
http://www-immuno.path.cam.ac.uk/~immuno/part1/lec12/lec12_97.html


?Although the exact mechanisms of many autoimmune diseases are
unknown, several immunologic abnormalities have been identified which
seem to contribute to autoimmune reactions:
·	Molecular mimicry - Cross-reactions between antibodies to foreign
antigens and self antigens. These reactions are usually directed at a
specific organ or tissue.
·	Lymphocyte activation - As noted earlier, during development,
lymphocytes capable of reacting against self antigens in the body are
normally inactivated. However, several microorganisms have the ability
to reactivate these cells later in life leading to autoimmune
reactions. This is one explanation for the observation that many
autoimmune diseases seem to occur after certain infections.
·	Impaired immune regulation - Defects in those mechanisms designed to
turn off or suppress immune responses after they have served their
purposes can cause exaggerated "hyper-responsiveness" of T and B
Lymphocytes. For example, activated lymphocytes normally undergo
programmed cell death (apoptosis) after they have completed their
immunologic work. Defects (mutations) in those proteins that regulate
this process could promote survival of activated lymphocytes and lead
to exaggerated immune reactions.
·	Exposure of sequestered antigens - During development, some tissues
are not exposed to the immune system (CNS, spermatozoa, lens of eye,
etc.). As a result, those lymphocytes capable of reacting with this
tissues are not inactivated or deleted from the immune system. Later
in life, if these structures are exposed to the immune system because
of injury or infection, autoimmune reactions may result.
?Autoimmunity involves hypersensitivity reactions directed at self
antigens which lead to acute and/or chronic inflammation and cell
injury. Autoimmune disorders are also often called connective tissue
disorders.?
http://medinfo.ufl.edu/pa/chuck/fall/handouts/immune3.htm


MS
==

?Multiple Sclerosis occurs more often between 40 and 60 degrees
latitude. Thus, the occurrence of MS is higher in places such as
Canada, Scotland, and the South Island of New Zealand than it is in
tropical and sub-tropical areas. Even in high-risk areas, MS rarely
strikes certain racial groups (e.g. Maori and Polynesians, native
Americans, black South Africans). Perhaps children in these areas are
not exposed to some factor that would help build immunity to MS.
Symptoms usually appear between ages 20 and 40. MS seldom strikes
people under 15 or over 50.?
http://www.msakl.org.nz/who_gets.htm

?Multiple sclerosis is more common in temperate latitudes, and
migration studies indicate the involvement of an aetiological
environmental factor in pre-pubertal life; the precise nature of this
factor has never been identified and may perhaps have been overlooked.
Here we suggest a simple explanation for the latitude gradient of
multiple sclerosis, i.e. that it can be explained by the
immunosuppressant effects of sunlight mediated via suppression of the
secretion of the immunostimulatory neurohormone melatonin from the
pineal gland.

 The effects of dietary fatty acids in multiple sclerosis also
indicate the involvement of anti-inflammatory eicosanoids in its
pathogenesis. We further suggest that the exceptions to the latitude
gradient (e.g. Japan), which have previously been attributed to
genetic factors, may in fact have a dietary basis. Since sunlight also
influences the metabolism of fatty acids in the retina, it may also
influence the development of retrobulbar optic neuritis-a common
antecedent of multiple sclerosis. We suggest a re-examination of the
epidemiology of multiple sclerosis based on an understanding of the
immunological consequences of illumination of the retina by sunlight.?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8692046&dopt=Citation


National Multiple Sclerosis Society
?An abnormal autoimmune reaction in MS is believed to initiate an
attack on the myelin, resulting in bare spots and scarred areas along
the nerve. Conduction of the nerve impulse is then slowed or halted,
producing the neurologic signs and symptoms of MS. Destruction of
myelin, a process known as demyelination, can also lead to
"cross-talk" between nerves?abnormal nerve-to-nerve signaling, which
may also produce symptoms.?
?Scientists have discovered that the body heals some lesions
naturally, by stimulating oligodendrocytes in the area, or recruiting
young oligodendrocytes from further away, to begin making new myelin
at the damaged site. Research is now working to identify the molecular
signals that are used by the body to activate the oligodendrocytes so
that those signals can be mimicked to stimulate additional repair.
Scientists are also studying certain proteins known as "growth
factors" in order to identify their potential role in myelin repair.
As scientists are working to stimulate myelin repair, they are also
focusing their attention on several properties of myelin that work to
inhibit this repair. Eventually, therapies may be developed to stop
these components of myelin from inhibiting the repair process.?

?Scientists are investigating several different strategies for
stimulating the repair of myelin.
·	·Antibodies (immune proteins that attach to specific molecules) have
been successfully used to stimulate myelin repair in rodents with an
MS-like disease. Based on the outcomes from this research, the
antibodies will undergo preliminary testing for safety in people with
MS.
·	Efforts are also being made to surgically replace damaged
oligodendrocytes and nerve cells.
Scientists are working to identify potential sources of replacement
cells for those that are damaged by MS. Possible sources include:
skin-derived cells, bone marrow and umbilical-cord blood cells, fetal
cells, adult brain cells, and Schwann cells from the PNS. The
usefulness of these replacement cells will depend on finding or
creating the signals needed to stimulate their transformation and
growth into healthy new cells.?
http://www.nationalmssociety.org/Sourcebook-Myelin.asp


?Myelin is manufactured by the glial cells of the central nervous
system. Understanding how these cells function, how they form myelin,
and how they might form new myelin after disease?which is the best
hope for recovery of function?is an important and growing area of MS
research.?

?In the case of MS, the target of the immune attack is believed to be
a component of myelin in the central nervous system. Myelin is a fatty
sheath that surrounds and protects nerve fibers. Certain white blood
cells, known as "T cells," become sensitized to myelin and enter the
central nervous nervous system (CNS). Once in the CNS, these T-cells
not only injure myelin, but secrete chemicals that damage nerve fibers
(axons) and recruit more damaging immune cells to the site of
inflammation.
It is not known what causes T-cells in patients with MS to become
activated but it is postulated that both genetic and environmental
factors are important.?
http://www.nationalmssociety.org/Sourcebook-Autoimmune.asp

?MS attacks the white matter of the central nervous system (CNS). In
its classic manifestation (90% of all cases), it is characterized by
alternating relapsing/remitting phases with periods of remission
growing shorter over time. Its symptoms include any combination of
spastic paraparesis, unsteady gait, diplopia, and incontinence.?
?little attention is being given to the problems of repairing damage
already done by the disease and of restoring lost function.
Laboratories working on remyelination are relatively few in number and
their programs are under-funded. In addition, rivalry among
researchers is intense. Laboratories tend to work in isolation,
learning of each other's progress through medical journal articles
which are usually published a year or two after experiments are
completed. This fragmented approach is clearly unsuitable to
regenerating CNS myelin, a complex task which requires
multi-disciplinary skills.?
?Without myelin, nerve impulses are slowed or stopped, leading to a
constellation of neurological symptoms? There?s a nice animated
illustration on this page:
http://www.myelin.org/diseasesinbrief.htm

?Most viruses cause symptoms quickly. Certain slow-acting viruses also
reappear later, causing new symptoms. Other slow-acting viruses stay
inside the body for months or years before triggering illness.
MS might be caused by some slow-acting viruses, or might be a delayed
reaction to a common virus.?
http://www.msakl.org.nz/causes.htm 

No single organism has been found to be the cause of MS.
?It is tempting to speculate on a viral cause for MS because viruses
are known to cause demyelinating disease in animals and humans.
Demyelination, destruction of myelin?the fatty sheath the surrounds
and insulates nerve fibers in the central nervous system, causes
nerve impulses to be slowed or halted and produces the symptoms of
MS.
Data from epidemiological studies?those that analyze variations in
geographical, socioeconomic, genetic, and other factors?suggest
that exposure to an infectious agent may be involved in causing MS.
Some viruses are known to have a long latency period between time
of infection and appearance of clinical symptoms, as is thought to be
the case in multiple sclerosis.? 
http://www.nationalmssociety.org/pdf/sourcebook/viruses.pdf

?In adults, the myelin sheath can be destroyed by stroke,
inflammation, immune disorders, metabolic disorders, and nutritional
deficiencies (for example, a lack of vitamin B12). Such destruction is
called demyelination. Poisons, drugs (such as the antibiotic
ethambutol, and excessive use of alcohol can damage or destroy the
myelin sheath. If the sheath is able to repair and regenerate itself,
normal nerve function may return. However, if the sheath is severely
damaged, the underlying nerve fiber can die, causing irreversible
damage. Nerve fibers cannot regenerate themselves.?
Merck Manual
http://www.merck.com/mmhe/sec06/ch092/ch092a.html


?Highly reactive astrocytes located in newly developing multiple
sclerosis (MS) plaques, and on the rims of established plaques might
be responsible for initiating autoimmune reactions.
"Most people who work on MS focus on microglia as the main type of
cell responsible for immunological reactions, but we thought that
astrocytes might also be very important, at least in antigen
presentation," explained Esther Zeinstra, Neurologist at the
University Hospital, Groeningen, The Netherlands, spoking here
November 28 at the European Charcot Foundation Symposium.
"Like microglia, astrocytes express major histocompatibility complex
class II molecules on their surface, which are required for cells to
present [auto]antigens to T cells," Dr. Zeinstra explained. "But they
are not the only thing needed to get a full blown immunological
reaction. You also need co-stimulation, but until now it was thought
astrocytes did not express co-stimulatory molecules. However, we have
found that, in some cases, they do."
Doctor's Guide Publishing Limited
http://www.mult-sclerosis.org/news/Dec2002/AstrocytesMayPlayRoleinMSAutoimmuneReaction.html
   

 ?Autoimmune reactions often have fatal consequences. They can cause
the destruction of vital tissue, which manifests in the development of
chronic autoimmune diseases such as multiple sclerosis, rheumatoid
arthritis or diabetes. The driving forces in the progression of these
diseases are autoreactive immune cells. In most cases these
autoreactive cells are CD4+ T cells, which somehow escaped the
self-tolerance control mechanisms of the immune system. In
non-pathogenic situations CD4+ T cells act as T helper cells. They
control or mediate the activation and differentiation of other immune
cells such as cytotoxic CD8+ T cells (CTL), natural killer (NK) cells
and B cells. In the situation of chronic autoimmune diseases, however,
they are no longer just mediators but rather key players of the
(auto-)immune response. Directly or indirectly they are responsible
for the characteristic tissue destruction, triggered by the
recognition of autoantigens. These autoantigens derive from
self-proteins of the attacked tissue and are presented to the
autoreactive CD4+ T cells by antigen-presenting cells (APC) such as
macrophages or dendritic cells.?
http://www.mdc-berlin.de/englisch/research/research_areas/cancer/e_falk.htm


Diet/MS/Leaky Gut Syndrome
===========================

?Between 1949 and 1984, 150 patients with multiple sclerosis consumed
low-fat diets. Fat, oil, and protein intakes; disability; and deaths
were determined. With a daily fat consumption less than 20.1 g/day (av
17 g/day), 31% died, and average deterioration was slight. A daily
intake greater than 20 g/day (av 25 or 41 g/day) was attended by
serious disability and the deaths of 79 and 81%, respectively. Oil
intake bore an indirect relationship to fat consumption. Minimally
disabled patients who followed diet recommendations deteriorated
little if at all, and only 5% failed to survive the 34 yr of the
study, whereas 80% who failed to follow diet recommendations did not
survive the study period. The moderately disabled and severely
disabled patients who followed diet recommendations carefully did far
better than those who failed to follow the diet. In general, women
tended to do better than men. Those patients treated early did better
than those in whom treatment was delayed. High sensitivity to fats
suggests that saturated animal fats are directly involved in the
genesis of multiple sclerosis.?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1804476&dopt=Citation


?144 multiple sclerosis patients took a low-fat diet for 34 years. For
each of three categories of neurological disability (minimum,
moderate, severe) patients who adhered to the prescribed diet (less
than or equal to 20 g fat/day) showed significantly less deterioration
and much lower death rates than did those who consumed more fat than
prescribed (greater than 20 g fat/day). The greatest benefit was seen
in those with minimum disability at the start of the trial; in this
group, when those who died from non-MS diseases were excluded from the
analysis, 95% survived and remained physically active.?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1973220&dopt=Citation

?MS is characterized by perivenular infiltration of lymphocytes and
macrophages in the parenchyma of the brain, brain stem, optic nerves,
and spinal cord. Expression of adhesion molecules on the surface seems
to underlie the ability of these inflammatory cells to penetrate the
blood-brain barrier. The elevated immunoglobulin G (IgG) level in the
cerebrospinal fluid (CSF), which can be demonstrated by an oligoclonal
band pattern on electrophoresis, suggests an important humoral (ie, B
cell activation) component to MS. In fact, variable degrees of
antibody-producing plasma cell infiltration have been demonstrated in
MS lesions (see Image 1).

Molecular studies of the white matter plaque tissue have shown that
interleukin (IL)-12, a potent pro-inflammatory substance, is expressed
at high levels in early formed lesions.?
·	?Other molecules involved in activation of T and B cells have been
implicated in MS. For instance, the co-stimulatory molecule B7-1,
necessary for activation of T cells as a second signal to antigen
presentation, has been found to be elevated in early MS lesions,
suggesting a triggering role for inflammation within the CNS. Other
factors elevated in MS brain tissues include the pro-inflammatory
interferon gamma and the pro-demyelinative tumor necrosis factor alpha
molecule. In addition, interactions between molecules on the surface
of B and T cells, such as CD40 and CD40 ligand, may mediate elevated
levels of IL-12 (a pro-inflammatory cytokine) in the circulation of
patients with MS.
·	The molecular mimicry hypothesis refers to the possibility that
peripheral blood T cells may become activated to attack a foreign
antigen, then erroneously direct their attack toward brain proteins
that share similar protein epitopes.
http://www.emedicine.com/NEURO/topic228.htm


?MS prevalence increases with decreasing solar radiation, suggesting
that sunlight may be protective in MS. Since the vitamin D endocrine
system is exquisitely responsive to sunlight, and MS prevalence is
highest where environmental supplies of vitamin D are lowest, we have
proposed that the hormone, 1,25-dihydroxycholecalciferol
(1,25-(OH)2D3), may protect genetically-susceptible individuals from
developing MS. Evidence consistent with this hypothesis comes not only
from geographic studies, but also genetic and biological studies.

 Over-representation of the vitamin D receptor gene b allele was found
in Japanese MS patients, suggesting it may confer MS susceptibility.
Fish oil is an excellent vitamin D source, and diets rich in fish may
lower MS prevalence or severity. Vitamin D deficiency afflicts most MS
patients, as demonstrated by their low bone mass and high fracture
rates. However, the clearest evidence that vitamin D may be a natural
inhibitor of MS comes from experiments with experimental autoimmune
encephalomyelitis (EAE), a model of MS. Treatment of mice with
1,25-(OH)2D3 completely inhibited EAE induction and progression. The
hormone stimulated the synthesis of two anti-encephalitogenic
cytokines, interleukin 4 and transforming growth factor  -1, and
influenced inflammatory cell trafficking or apoptosis. If vitamin D is
a natural inhibitor of MS, providing supplemental vitamin D to
individuals who are at risk for MS would be advisable.?
http://www.ingentaconnect.com/content/cabi/pns/2000/00000059/00000004/art00005

?MS's extreme variability makes it a perfect disease for quacks. The
only way to know whether a treatment is effective is to follow many
patients for years to see whether those who receive the treatment do
better than those who do not. Quacks don't bother with this kind of
testing, however. They simply claim credit whenever anyone who
consults them improves. And since the majority of attacks are followed
by complete or partial recovery, persuasive quacks can acquire
patients who swear by whatever they recommend.?

Please refer to the link below to get a more in-depth description of the following:
Methods to avoid:
Adequately tested but ineffective in influencing the course of MS
Implausible and untested or inadequately tested
Implausible and known to have significant risk or side effects
Superesonant Wavenergy (SRWE) Program
"Amalgam Toxicity" Scam
Calcium EAP
Coral Calcium
Hydrogen Peroxide
Prokarin (also called Procarin)
http://www.quackwatch.org/01QuackeryRelatedTopics/ms.html

As far as diet influencing MS, as you stated, most of the sites
promoting diet are a bit shaky. Most scientific studies do not promote
a special diet, but a healthy diet, including a decrease in fats,
especially hydrogenated fats and saturated fats. Some people do
believe that diet may help ease symptoms? if a diet is healthy and
balanced and it helps you feel better, then stick with it.

Most sites that recommended diets were also promoting supplements sold
by that site, or have verly little accurate science behind them. I
would be very cautious of such sites. Since you asked for scientific
evidence, I assume you are aware of scams and unreliable sites.

I would like to say however, that when some (not necessarily reliable)
sites say you should avoid ?toxins?, that these toxins actually are
NOT good for us. So if you choose to avoid ?toxins? such as sugar,
pesticides, mercury and aspartame, it can surely do you no harm! Fad
diets, cleansing diets, etc. will not help. Drinking plenty of water,
and exercise, as permitted can help an MS patient to feel better. It
has been shown that Vitamin D seems to help as well.
http://curezone.com/diseases/toxins/

?Multiple sclerosis appears to share with many other neurological
diseases a lipid imbalance arising from faulty lipid metabolism and
involving the essential fatty acids. (1) More specifically, reductions
in levels of docosahexaenoic acid (DHA), (2) eicosapentaenoic acid
(EPA), (3) linoleic acid, (4,5) and arachidonic acid (2,5) have been
noted in nervous tissue, blood plasma and/or erythrocytes of MS
patients. Since absorption of the essential fatty acids (EFA) appears
to be normal, (6) there has been a good deal of interest in
ascertaining whether EFA supplementation may affect the clinical
course of the disorder. We will review some of the evidence suggesting
that it may have a beneficial effect.?
?Treated patients with minimal or no disability at entry had a
significantly smaller increase in disability than did controls. In
addition, treatment reduced the severity and duration of relapses at
all levels of disability and duration of illness at the time of entry
to the trials.?

Anecdotally, I had my daughter, who has MS, to ask her neurologist if
a daily fish/flax/borage oil capsule could be beneficial to her. Her
heartily recommended it, and she believes it does help her pain and
discomfort. He also indicated she may be bothered by gluten, and it
does seem to cause her a lot of itching.
http://www.findarticles.com/p/articles/mi_m0ISW/is_244/ai_111271914

?Diet: No specific dietary restrictions apply to patients with MS;
patients are encouraged to eat a balanced diet. Oral intake of calcium
and multivitamin supplements is encouraged, as are adequate vitamin D
sources. Although more studies are needed, recent observations suggest
a role for vitamin D-related pathways in MS susceptibility.?
http://www.emedicine.com/NEURO/topic228.htm

?Gluten & Multiple Sclerosis - There are numerous reports of patients
nervous disorders being allergic to gluten - a sticky protein
substance found in wheat, oats, and rye. Incidence of MS is low where
rice is the main cereal. (6)
http://www.internethealthlibrary.com/Health-problems/Multiple%20Sclerosis%20-%20researchDiet&Lifestyle.htm
?This study indicates that both dietary antioxidants and
polyunsaturated fatty acids have the potential to diminish disease
symptoms by targeting specific pathomechanisms and supporting recovery
in MS.?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16118655&query_hl=11

When searching ?leaky gut?  for this answer, the links found did not
leas to  reliable sources of information on this ?syndrome?. Here is
one of my previous answers about leaky gut:

?In researching leaky gut, very, very little was found on reputable
and reliable conventional medicine sites. The term appears to be the
name of a syndrome that alternative medicine uses to describe a
condition of having large pieces of food that ?hide? in the
intestines, and are not digested. This does not mean the food
particles enter your bloodstream though. (It just wouldn?t fit!) When
food is digested, only very tiny molecules of  protein, glucose, fats,
carbohydrates, and other  nutrients enter the bloodstream. I must say,
in 25 years of working in health care, I have never heard the term
?leaky gut?.  Now, I am not tossing alternative medicine out on its
ear here. I just want to clarify that ?leaky-gut?, as I have read so
far, does not have a great deal of credibility in conventional medical
circles.

MS patients do seem to have gastro-intestinal problems, as part of the disease.
http://www.nationalmssociety.org/Brochures-BowelProblems1.asp

?Because MS interrupts or slows the transmission of signals to and
from the brain, the electrical impulses to the muscles that are
involved in emptying your bowel can become disrupted.?
http://my.webmd.com/content/article/57/66138.htm

Other digestive syndromes that cause digestive problems are IBS
(Irritable bowel syndrome) H. pylori infection which can cause GERD, 
GERD, diverticulosis,  and several others. In IBS, the cause is
thought to be that some people?s immune system reacts with a protein
on the intestinal wall, causing inflammation, and thus digestive
problems. Over a million UA Americans suffer from IBS.

Irritable Bowel Syndrome
http://digestive.niddk.nih.gov/ddiseases/pubs/ibs_ez/


H.pylori
http://digestive.niddk.nih.gov/ddiseases/pubs/hpylori/

http://www.cdc.gov/ulcer/md.htm

GERD
http://digestive.niddk.nih.gov/ddiseases/pubs/gerd/


This is an interesting study of MS patients and leaky gut syndrome.
The study found that some MS patients do have a higher level of ?gut?
permeability.
?MS patients had increased intestinal permeability, a finding not
previously reported. High levels of CD45RO were found on circulating
CD20+ B cells from patients with MS. This has not been reported
previously in MS and is found in very few other conditions. Eight
patients with coincident MS and Crohn's disease or MS and UC were
studied. Coincident MS and UC patients expressed CD45RO on CD20+ B
cells, a finding not identified in UC patients alone. A subgroup of MS
patients has increased intestinal permeability. These patients express
CD45RO CD20+ B cells, also found in Crohn's disease.?
http://www.direct-ms.org/leaky_gut.html


This site seems to be authoritative on the topic of leaky gut. But if
you notice, it is a personal site, that links to a clinic that sells
supplements.
http://www.wehelpwhathurts.homestead.com/leakygut.html  ?

http://answers.google.com/answers/threadview?id=370070



Illustrations:
Myelin sheath
http://www.merck.com/media/mmhe2/figures/fg092_1.gif

http://www.coloradocollege.edu/idprog/Neuroscience/Cellular%20slides/23.myelin.JPG

Antibody fragments arrest damage
http://mscenter.ucsf.edu/images/technical/immune_fx.jpg



To further understand immunity, antibodies and antigens:
----------------------------------------------------------
You can purchase this entire article for $10
Antimyelin Antibodies as a Predictor of Clinically Definite Multiple
Sclerosis after a First Demyelinating Event ? ?Patients with anti-MOG
and anti-MBP antibodies had relapses more often and earlier than
patients without these antibodies. Only 9 of 39 antibody-seronegative
patients (23 percent) had a relapse, and the mean (±SD) time to
relapse was 45.1±13.7 months. In contrast, 21 of 22 patients (95
percent) with antibodies against both MOG and MBP had a relapse within
a mean of 7.5±4.4 months, and 35 of 42 patients (83 percent) with only
anti-MOG antibodies had a relapse within 14.6±9.6 months (P<0.001 for
both comparisons with antibody-seronegative patients). The adjusted
hazard ratio for the development of clinically definite multiple
sclerosis was 76.5 (95 percent confidence interval, 20.6 to 284.6)
among the patients who were seropositive for both antibodies and 31.6
(95 percent confidence interval, 9.5 to 104.5) among the patients who
were seropositive only for anti-MOG antibodies, as compared with the
seronegative patients.
Conclusions Analysis of antibodies against MOG and MBP in patients
with a clinically isolated syndrome is a rapid, inexpensive, and
precise method for the prediction of early conversion to clinically
definite multiple sclerosis. This finding may be important for the
counseling and care of patients with a first demyelinating event
suggestive of multiple sclerosis.?
New England Journal of Medicine
http://content.nejm.org/cgi/content/abstract/349/2/139

http://jimmunol.org/cgi/content/full/166/7/4751

http://www-immuno.path.cam.ac.uk/~immuno/part1/lec05/lec6_99.html

http://www-immuno.path.cam.ac.uk/~immuno/part1/lec15/lec15_97.html

MS
http://mscenter.ucsf.edu/research.htm

T-cells and B-cells
http://www.nationalmssociety.org/%5CSourcebook-T%20Cells.asp

Living with MS
http://www.msakl.org.nz/treating.htm

?Dietary intake in MS and the influence of advanced disease on
nutritional status are less well researched and documented. Both
obesity and malnutrition may occur with detrimental consequences to
functional abilities. Cognitive difficulties, dysphagia and the
side-effects of drug treatment may further contribute to deterioration
in nutritional status.
This paper aims to provide a practical overview of dietary management
in MS. It reviews the available evidence relating nutrition to MS and
discusses dietary management, with particular emphasis on the
identification and alleviation of factors affecting nutritional
status.?
http://www.blackwell-synergy.com/links/doi/10.1046/j.1365-277X.2001.00308.x/abs/

You can purchase the entire above article for $26
http://www.blackwell-synergy.com/doi/full/10.1046/j.1365-277X.2001.00308.x

Lorenzo?s Oil
http://www.myelin.org/aboutlorenzo.htm

Numerous medical journal abstracts:
http://scholar.google.com/scholar?hl=en&lr=&c2coff=1&q=autoimmune+response++%2B+Multiple+Sclerosis&btnG=Search


I hope this has answered your questions satisfactorily. If not, please
request an Answer Clarification, before rating. This will allow me to
assist you further.

Sincerely, Crabcakes


Search Terms
=============
t-cells + b-cells
immune system
Autoimmune response + multiple sclerosis
Intestinal + immunity
normal gut flora
Gut + immune response
Intestine + antibodies
demyelination + Multiple sclerosis
Myelin + antibodies
diet + multiple sclerosis
cmscott-ga rated this answer:5 out of 5 stars and gave an additional tip of: $20.00
Stunning work, really excellent. Yes: exceptional!

Comments  
Subject: Re: is most of the body's immune function handled in or by the gut
From: crabcakes-ga on 26 Sep 2005 00:17 PDT
 
Thank you for the 5 stars, compliments and the generous tip! All are appreciated!
Sincerely, Crabcakes

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