From: kja@cbnewsf.cb.att.com (krista.j.anderson)
Subject: Re: Autoimmune diseases, Allergies
Summary: immune disorders, hypersensitivities
Organization: AT&T
Date: Fri, 21 Aug 1992 19:43:41 GMT

stevem@solbourne.com (Stephen Matson) writes:
>
> I would like to find out if there have been any links between environment and
>autoimmune diseases or if allergies or  hypersensitivity can cause connective
>tissue rheumatism. 

I'm not a doctor, but have been reading about the immune system.
So, I looked up some things the other night and found "connective
tissue rheumatism" under "collagen diseases" in 1 book and most of
the same diseases under "autoimmune diseases" in another.

It seems that collagen diseases are all autoimmune diseases.  The
collagen diseases listed are:  Systemic Lupus Erythematosus (SLE),
Scleroderma, Polymyositis, Dermatomyositis, Polyarteritis Nodosa
and Polymyalgia Rheumatica.

I think the role of environment and/or foods in autoimmune
disorders is still under investigation.  There are some types of
food intolerance, for example of wheat and milk, that do involve
mechanisms of immune disorders.  In the case of Rheumatoid
Arthritis (RA), which is also an autoimmune disease, *sometimes* a
change in diet can help, and some studies show that at least in
*some* people, the RA is caused by allergies and/or intolerances.
In *some* cases of Polyarthritis when tests do not show any cause
for the symptoms, a change in diet *may* help.

In general, I think people with these diseases are suffering quite
a bit, so that even a remote chance that a change in diet may help
is worth the trouble of trying it.  So getting a food allergy book
with an elimination and reintroduction diet would be worth a try,
in my opinion.

Here are some (disorganized) notes on immune disorders.  I hope
in the future to add details and get them organized into a set of
articles.  At this time, they are still incomplete and messy.

There are 6 classes of immune disorders - 4 types of hypersensitivity,
immune deficiency disorders and autoimmune disorders.  There is
overlap of the hypersensitivities and it seems that most autoimmune
disorders can be described in terms of the hypersensitivities.  In
this article, I won't discuss deficiency disorders, but there is
also some overlap into that area.  The set of articles I'm planning
later will probably have a glossary and some immune system basics.

Type I hypersensitivity is the classic IgE mediated allergy.  It is
not known what causes atopic people's IgE antibody to bind to
"inert" substances that other people's bodies find harmless.
However, a possible deficiency of suppressor T cells is one
hypothesis.

Type II hypersensitivity, also called cytotoxic hypersensitivity, is
a problem where IgG and/or IgM antibody binds to surface proteins,
carbohydrates or haptens associated with self-cells.  Examples
include  "Goodpasture's syndrome, autoimmune hemolytic anemia,
thrombocytopenia, pernicious anemia, hyper acute renal allograft
rejection, transfusion reaction, hemolytic disease of the newborn,
some drug reactions" [1] as well as myasthenia gravis.

Apparently different types of cells are attacked, for example red
blood cells (erythrocytes) in pernicious anemia.  Another book also
includes inflammatory bowel disease as an example of Type II and
believes that Type II is can be related to food allergy. [3] 

Type III hypersensitivity is when "activation of complement by
immune complexes causes infiltration of polymophonuclear leukocytes
and release of lysosomal enzymes and permeability factors, producing
an inflammatory reaction". [1]  I had a lot of trouble trying to
understand Type III and that quote since Type III was explained
differently elsewhere.  The quote sounds less general than the term
is intended to be.  So let me try to clarify what I think Type III
means.

Ordinarily, antibody binds with 2 antigens on the same invading
cell or 2 different invading cells.  (Or it might not be a cell;
when I say "invader" I mean any foreign object bearing antigens.) 
Then complement proteins are attracted and begin the complement
cascade culminating in an explosive reaction that bursts the
invader, leaving it disabled.  Then neutrophils of the
reticuloendothelial system (i.e. the inner surfaces and/or
connective tissue of the blood vessels?) are supposed to eat the
debris and/or burst cell.

But in Type III hypersensitivity, instead of eating the debris, the
neutrophils *bond* to the immune complex of antibody, antigen-cell
and complement proteins.  This results in clumps of stuff in
healthy tissue that isn't supposed to be there.  Also, the
neutrophil then empties its load of enzymes into the general area,
damaging healthy tissue.  Eosinophils also malfunction, platelets
aggregate and mast cells disintegrate, releasing their vasodilators
and generally adding to the problem.  And during the whole thing,
the neutrophils are no longer free to fight infection at the
location or elsewhere because they're stuck to the immune
complexes.

What the quote makes unclear is that immune complexes can bond with
other cells besides polymorphonuclear leukocytes (i.e. neutrophils,
eosinophils, basophils/mast cells).  For example, in SLE,
there is a bonding in the connective tissue to collagen cells.
Also, rheumatoid arthritis is believed to be caused by a Rheumatoid
Factor (RF) antibody that forms against the body's own IgG antibody.
The result is that the harmed IgG causes inappropriate inflammation
responses in the joints.

Examples of Type III hypersensitivity are "serum sickness due to
serum, drugs, or viral hepatitis antigen; membranous
glomerlonephritis; systemic lupus erythematosus; rheumatoid
arthritis; polyareris; cryoglobulinemia." [1]

Another book says that celiac disease suggests Type III
hypersensitivity.  It says a Type I IgE response may increase
permeability of intestinal walls, facilitating Types III and IV
hypersensitivity.  People with celiac have elevated levels of IgA
antibodies against gluten as well casein, ovalbumin and beta
lactoblobulin.  But if gluten is withdrawn, all the IgA levels
drop.  The exact mechanism is still unclear to me, but somehow the
gluten (or gluten peptides) bind to intestinal cells and is then
attacked by IgA which destroys the intestinal cells in the
process.  (An certain intolerance of milk is also thought to involve
a Type III mechanism.)

There are also some substances called lectins that bind with body
cells and cause them to agglutinate, so it is hypothesized that in
some people, gluten acts as a lectin. [3]  Lectins are naturally
occuring in several foods, and it is not known exactly why they are
a problem to some people and not others.  In large concentrations
they are harmful to everyone, but why some people are more
sensitive than others may be dependent on their Major
Histocompatibility Complex (MHC) genes that determine their
specific self-identifying antigens, the Human Leukocyte Antigens
(HLA).

Type IV hypersensitivity is also known as delayed or
cell-mediated hypersensitivity and its best known example is poison
ivy.  Normally, macrophages engulf and digest invaders and then
attach the invaders' antigenic proteins on their own cell surfaces
along with HLA.  Then they present the antigen+HLA to T cells and
the T cells are supposed to become activated and activate B cells
(which make antibodies) in turn.

In Type IV, when macrophages present antigens+HLA to T cells,
instead of just becoming activated, the T cells bond with the
complexes.  This causes the T cells to release tissue-damaging
lysozyme as well as lymphokines which stimulate more macrophages.
Examples are "contact dermatitis, graft-versus-host disease,
allograft rejection, granuloma due to intracellular organisms, some
drug sensitivities, Hashimoto's thyroiditis". [1]  The quote also
lists sarcoidosis and tuberculosis, but I think the tuberculosis is
a misprint; it is the TB skin test that is a Type IV; I don't think
the TB disease is a Type IV, but I could be wrong.

References
1. Nurses Reference Library, _Diseases_, PA:Springhous, 1987.
2. _AMA Family Medial Guide_, 1982.
3. Brostoff, Jonathan and Challacombe, Stephen J., eds., _Food
   Allergy and Intolerance_, London: Bailliere Tindall, 1987.