 |
For a complete guide on autoimmune treatments by antibiotics please
read our e-book.
Autoimmunity
Autoimmunity causes number of diseases. that are caused by
the body's own immune system getting confused and wrongly
attacking the body's good cells. Which autoimmune diseases occur
from the immune confusion depends on which body cells are
mistakenly attacked. They total over a hundred
diseases. Some of the best known diseases that are believed to be
autoimmune include thyroditis, juvenile diabetes, lupus, celiac
disease, multiple sclerosis, and C.I.D.P.
Prevalence of autoimmune diseases in the population may be 8%
or higher. However, autoimmune diseases have only been recently
classified, and are not grouped in many statistical analyses.
For example, autoimmune diseases are not recorded as a cause of
death in the CDC statistics, despite other research indicating
they are collectively one of the top ten causes of death,
particularly in women. The problem is probably that most forms
and statistical recording methods simply do not have an option
or grouping that says autoimmunity, so each autoimmune disease
is recorded separately. Another problem is that autoimmune
disorders are diverse with different problems, and do not have
an obvious common feature (whereas cancers mostly have tumors as
a common feature).
Features of
Autoimmunity
Some important features of the various autoimmune diseases as
a category include:
- Cell death: The underlying cause of the disease
is damage to cells, usually a particular type of cell.
Different cells are attacked in each autoimmune disease.
- Young people's disease: elderly people get less autoimmune diseases. It is a syndrome of young adults and
children. Surprisingly, however, the elderly have a much
higher level of autoantibodies, and get less AI
diseases.
- Non-neonatal disease: AI does not occur in
neonatal infants, at least till around 6 months, when
diseases such as Type 1 diabetes are not unknown. This delay
presumably is because neonatal immune systems are not
formed. (Or maybe mother's passive immunity from placenta
and breast feeding affects this?)
- Women targeted: although not all autoimmune
diseases show gender bias, the overall ratio for all
autoimmune cases is almost 3-1 on the side of women over
men, with around 75% of AI diseases occurring in women. AI
diseases have been reported as in the top ten causes of
women under 65. What is the role of the hormonal flux from
women's reproductive systems and its effect on AI diseases?
Interestingly, women were once more likely to get cancer,
until the environmental effects of male smoking and
occupational hazards raised male risks. Many different AI
diseases have a strong female gender bias. As the
exceptions, there is no gender bias in Type 1 diabetes or
autoimmune myocarditis.
- Trigger suspects: the possible suspects for what
triggers the start of an autoimmune disease are many, but
include: viruses, bacteria, diet, toxins, radiation, chronic
infections, and so on.
- Risk factors: genetics (significant but not
total), immune system abnormalities.
- Non genetic: although there are some inherited
sub-types, and some inheritance factors in all autoimmune
disease, autoimmunity is "polygenic" (from many genes) and
has an unclear inheritance pattern. Risks to children and
siblings of an infected person are higher but not as high as
for a true genetic disease. For example, probably only
around 4-6% chance for a Type 1 diabetic to pass the disease
to their child.
- Not contagious: autoimmunity cannot be passed by
fluids or blood under normal circumstances. Some autoimmune
diseases have been transferred between animals by the
careful transfer of immune system cells. Even this is not
dangerous for most healthy animals, and only works for
special immune-suppressed animal strains.
- Cross-placental contagion: There are cases of
mothers giving their unborn children an autoimmune disease,
including Myasthenia Gravis and Grave's disease (thyroid).
This is not common, but can occur.
- Organ-specific or systemic: Some autoimmune
diseases like Type 1 diabetes are specific to a particular
organ (pancreas cells). Other autoimmune diseases like SLE
and RA are systemic to multiple body organs. This seems to
depend on what type of cell the disease attacks. Pancreas
cells attacked by diabetes are not present in any other body
organs, whereas collagen that is attacked by RA is present
in many places in the body.
- Degenerative or fluctuating with remissions: Some
diseases degenerate to a final state, where all cells are
dead, such as Type 1 diabetes where all insulin-producing
cells die over time. Other autoimmune diseases seem to
fluctuate, such as MS, SLE and RA, and have long periods of
remission. (Why is this? These diseases have more of the
type of cells?)
- Immune involvement: There are several aspects
that show that the immune system is involved in most
autoimmune diseases. These include the presence of
antibodies in the blood and immune infection features near
or within the attacked cells themselves (i.e. lots of immune
cells).
- Antibodies present: Many autoimmune diseases are
characterized by the presence of a particular
disease-specific antibody. This is especially true of
organ-specific diseases such as Type 1 diabetes, which has
antibodies against pancreas islet cells (ICA antibodies) and
the anti-GAD protein antibodies. Systemic autoimmune
diseases such as SLE may have less specific antibodies, but
there is a strong association with anti-nuclear antibodies
(ANAs).
- Multiple antibodies: A common feature of some
autoimmune diseases is that there are multiple antibodies
against different cells in the same organ. For example, Type
1 diabetes involves some combination of insulin
autoantibodies (IAA), islet cell antibody (ICA) and GAD
antibodies. Does one antibody start the situation and cause
the others, or are all antibodies needed for disease?
Causes of
Autoimmune Disease
Autoimmunity as a theory states that the immune system itself
gets tricked into killing good normal cells. The immune system
wrongly makes antibodies to normal cells, which cause these
cells to be attacked and killed, just as if they were recognized
as unhealthy virus-infected cells. The key questions about the
cause of autoimmune diseases are:
- Triggers: what starts the immune system on the
wrong path?
- Conversion: what causes the immune system to
respond to the trigger?
- Progression: what makes the immune system keep on
with the autoimmune response?
In the prevailing theories about triggers of autoimmune
diseases, the trigger does not necessarily need to stay around.
For example, a viral infection may trigger the immune response,
but the virus need not stay as a chronic infection for the
person to develop autoimmunity.
Triggers of
Autoimmune Disease
There are several suspects in the search for triggers. In
fact, there is quite a lot of evidence for several types of
triggers, so it seems there may be multiple triggers for
autoimmune diseases. Some of the suspects include:
- Viruses: These are probably the most studied
candidate for autoimmune diseases. However, results have
been somewhat unconvincing. Finding viruses directly inside
the autoimmune infection site has been difficult, though
perhaps the viral-infected cells are already destroyed,
especially if the virus only starts the early phases of
autoimmunity. Thus a key question is whether viruses simply
initiate AI diseases, or whether they must stay around to
continue the AI reaction. It is also unclear if viruses
cause their effects because of the immune reaction against
the virus specifically, or simply because of the extra
inflammation their infection causes at a site. Evidence of
viral-AI links is quite strong and there are some AI
diseases that can actually be caused by viruses in animal
experiments. Some of the diseases with associated viral
suspects include:
-
Bacteria: There is not a strong link between
autoimmunity and bacterial infections as a trigger. However,
a few examples have been found:
-
Parasites: These are very rarely regarded as an
autoimmune disease trigger. However, there are a few rare
examples of a relationship between an AI disease and a
parasite:
- Chagas' heart disease and Trypanosoma cruzi
-
SLE/Sjogren's
syndrome and the Ochocerca volvulus nematode.
- Pemphigus foliaceous and the Simulium nigraimanum
blackfly
- Diet: There are some examples where the presence
of a particular substance in the diet might possibly be
related to an autoimmune disease:
- Cow's milk and
Type 1 diabetes: Somewhat controversial, but there
is some evidence of an association between cow's milk
and Type 1 diabetes. This idea is tied to the idea of
molecular mimicry theory as the underlying cause,
because a particular sequence of milk protein matches
the proteins of the islet cells.
-
Celiac disease and gluten: There is a clear
relationship between gluten (in wheat) and celiac
disease. But is this a trigger of celiac disease or a
secondary issue.
- Chemicals: There are examples where toxins and
chemicals have been linked to AI diseases in humans and
laboratory animals.
-
Scleroderma and metals: the risk of scleroderma to
miners is high, particular silica; other possible metals
involved are mercury, copper, iron.
- Mercury and kidney autoimmunity in rats
- Iodine and
autoimmune thyroiditis: if not causal, at least
contributes to the development of AI.
- Silicon breast implants and
SLE: this is a controversial issue.
- Medicines: There have been some examples of
medications that may trigger autoimmunity as a side effect.
- ANAs from hydralazine and procaine amide
- Erytherocyte autoantibodies and alpha methyl dopa
- Cytochrome antibodies and tienilic acid
- acetylcholine receptor antibodies and
D-penicillamine
- halothane (an anesthetic) causes AI through creating
a new antigen in the liver
- Genetics: Familial and individual clustering:
There are several key facts that show a role of genetics in
autoimmunity. The first is that getting one AI disease makes
it more likely that you are at risk for a second AI disease.
The second fact is that the families, siblings, and children
of people with an AI disease are at risk of that AI disease,
and of other AI diseases. Thirdly, certain genetically
modified animals get AI diseases (e.g. NOD mice get Type 1
diabetes), and this is in fact used to study AI diseases in
animal models of the disease. The study of genetics and AI
diseases has found numerous genes that are involved in
different AI diseases.
- Cancers: Rarely, a cancer can cause an AI
disease. There are two methods:
- Immune system tumors: Direct tumor of an immune
organ such as the thymus or bone marrow (i.e. a
thymoma or
lymphoma). However, AI disease is very rare from
these disorders, so it seems that despite their
importance to the immune system, a failure at these
sites is not the only problem required for AI disease to
result.
- Paraneoplastic autoimmune disorders: Though very
rare, there are a few types of autoimmune disease that
are caused by cancers of a different part of the body.
These are called "paraneoplastic" autoimmune disorders.
Examples include:
- Cancer Associated Retinopathy (CAR): An
autoimmune reaction against the eye retina, caused
by some types of cancers, typically lung cancer.
The mechanism of paraneoplastic AI is believed to be
that the cancer causes a hidden antigen to be shown to
the immune system. This antigen is attacked, but by
coincidence, this antigen is also at another body site
(e.g. the retina), and the immune system mistakenly
attacks the retina as an innocent bystander.
- Radiation: UV light may damage cells and release
new antigens. However, there are few examples of possible
relationships between radiation and autoimmunity.
- Immune abnormalities: Because autoimmunity is
related to the immune system, various abnormalities of the
immune system have been considered as possible triggers or
causal factors.
- Cancers of immune organs have been mentioned under
cancers.
- Thymus abnormalities: thymectomy: removal of the thymus.
Neonatal thymectomy causes oophoritis and autoimmune
gastritis in mice.
- Chronic infections or inflammation: An infection causes
heightened immune response as a natural course. It is
therefore plausible that a chronic inflammation could
possibly cause autoimmunity, or if not actually cause, at
least provide an environment in which it would flourish.
- Cells: One strange method of causing autoimmunity is to
be injected with the cells of the body. This can sometimes
upset the balance of the immune system. Some examples
include:
- Brain autoimmunity from rabies vaccinations, that
were once made from brain emulsions (modern rabies
vaccinations are not).
- Encephalitis in monkey brains after injection with
monkey brain cells.
-
Mitochondrial disorders: Not a general theory of AI,
but a possible factor in
diabetes and
MS. In diabetes, mitochondrial failure might accumulate
glutamate, leading to an excess of GAD and thus causing
anti-GAD antibodies leading to diabetes. The genetic
mitochondrial disorder Leber's Hereditary Optic Neuropathy
has been associated with MS, but no clear link between
mitochondria and MS has been found as yet.
Research on
Triggering of Autoimmune Diseases
The methods whereby a particular trigger might cause the
conversion of the immune system into an autoimmune reaction.
- Tolerance theories: thymic deletion, clonal deletion,
negative selection, apoptosis, forbidden clone, anergy,
peripheral tolerance, etc. B-cells don't go to the thymus.
- Two-signal theory: co-stimulation by an APC, dendrite,
macrophage, or B-cell, stimulates the T-cell into
activation, proliferation, or lymphokine production.
Suppressor cells. Vetoing. Anti-idiotypic (anti-id)
antibodies.
- Molecular mimicry: Difficulty getting experimental
confirmation in animal models. No known molecular mimics for
some substances (e.g. insulin/proinsulin, but there is for
islet cells and GAD).
- Epitope crossing
- Danger/damage theory: tissue destruction, activation of
macrophages, and a co-stimulatory second signal causing AI.
- Inflammation areas: Another possibility is that simply
the fact that a site of the body gets infected could perhaps
lead to an autoimmune response against that site.
- Superantigens: Most superantigens for humans are found
in bacteria, but bacterial infections are not strongly
associated with AI diseases. However, there are some
possible examples of links: Kawasaki syndrome of childhood
multi-system vasculitis, guttate psoriasis.
- Balance theory: Antigen injections can cause AI by
over-balancing. Paraneoplastic syndromes expose too much of
an already exposed antigen (in a new site). Same as the
danger theory? Rare antigens like GAD in islet cells (only
pancreas and brain)
Evidence about various theories:
- Thymus or bone marrow problems don't cause autoimmunity:
The thymus and bone marrow are the places where much of the
tolerance occurs according to negative selection theories.
The fact that thymus abnormalities only cause rare
autoimmune diseases, rather than commonly, would seem to
indicate that failure of thymic selection of T-cells has
only a minor causal effect on autoimmunity. A few rare AI
diseases do result from thymomas and lymphomas (bone marrow
disorders). This indicates that peripheral tolerance may be
more important.
Autoimmunity:
The predominant theory about autoimmune diseases is that they
are autoimmune. Though facetiously stated, it is important to
remember that autoimmunity itself is only a theory, and in fact
a relatively recent theory from the last few decades. It has
taken a long time for the many disparate diseases of different
body organs to be brought into a single disease class.
Strictly speaking, there could be other possible theories of
autoimmune diseases. If we assume that the disease involves cell
death (another assumption), then a list might look something
like:
- Theory 1: Autoimmunity: immune system kills the cells
- Theory 2: Apoptosis error: cells commit suicide for some
aberrant reason, and the immune system is only there to
clean up afterwards.
- Theory 3: External cell damage: some virus, bacteria,
toxin, or event kills the cells, and the immune system
cleans up.
Treatment of
Autoimmune Diseases
- Anti-inflammatory: steroids, NSAIDs ( Asprin).
- Immune Modulation (IVIg)
- Immune suppression
- Oral tolerizations: mucosal immunotherapy, e.g. eating
Myelin Basic Protein (MBP) might prevent MS; eating collagen
might prevent RA. Better tolerization if use cholera toxin B
as an adjuvant to the eaten antigen, actually to heighten
the immune response and somehow thereby cause tolerance.
- Monoclonal antibodies , Rituxmab , Remicade
- Competitive ligands for T-cell receptors
- Cytokines
- Cytokine antagonists
- Chemokine receptor interference
- Free radical damage avoidance: nicotinamine and islet
cells.
- Genetically altered T-cells
- Genetically altered cells to express regulatory anti-AI
cytokines
Alernative medicine:
Colostrum.
|
|
