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In the past decade the study of autoimmunity, the failure to recognize self antigens as “self”, has grown immensely. Autoimmunity is thought by many researchers to be a result of a loss of Immunological tolerance

Molecular Mimicry Wikipedia

Introduction

What regulates our immune system ?; how does our immune system become compromised ?. Let us examine some examples of autoimmune diseases such as Fibromyalgia, Rheumatoid Arthritis and toxic overload that causes allergies, and triggers autoimmune conditions.


Immune system tolerance

Tolerance is fundamental to the immune system, involving non-self discrimination which is the ability of the immune system to discriminate between host cells ( host) and foreign invasive antigens ( non host ). B immune system cells are primed in the bone marrow to recognise foreign antigens as do T cells which are primed in the Thymus. This immune tolerance becomes compromised when a pathogen as wikipedia so eloquently put it:

‘Either the linear amino acid sequence or the conformational fit of the immunodominant epitope may be shared between the pathogen and host’.

Also referred to as cross reactivity which is, in essence, ‘molecular mimicry’ causing the immune system in its confused state to begin attacking host cells that resemble, in terms of linear amino acids that make the protein, a pathogen.

The following is what’s written in Wikipedia under Immune tolerance :

Deficits in central or peripheral tolerance cause Autoimmune disease,  resulting in syndromes such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, autoimmune polyendocrine syndrome type 1 (APS-1), immunodysregulation polyendocrinopathy enteropathy x-linked disease (IPEX) and potentially contribute to asthma,allergy and inflammatory bowel disease.’*

* Lupus is an aberrant physiological condition where the Immune system (IS)  attacks healthy tissue anywhere in the body, Rheumatoid arthritis is the IS attacking the joints, autoimmune polyendocrine syndrome type 1 (APS-1) involves the dysfunction of multiple endocrine glands, immunodysregulation polyendocrinopathy enteropathy x-linked disease (IPEX) is the dysfunction of transcription factor FOXP3 the master regulator for TReg lineage

Wikipedia confirm that deficits in immune tolerance cause autoimmune disease, so why is it written on other wikipedia sites

While the cause of rheumatoid arthritis is not clear, it is believed to involve a combination of genetic and environmental factors’   

and in terms of autoimmune disease in general it is written :

‘The cause is generally unknown’

The T Regulatory (TRegs) cells

From the previous text on Immune Tolerance it is clear that the T Regulatory cell is a major component concerning the ‘enigmatic’ ( from the perspective of conventional medicine ) Autoimmune condition in all most of its 140 variants. We have reached this conclusion since the TReg cells are responsible for regulating the immune system and maintaining immune tolerance and as already stated deficits in central or peripheral tolerance cause Autoimmune disease.  Various studies ( Weiner et al 2011 Oral Tolerance , Josefowicz et al 2012 Regulatory T cells: mechanisms of differentiation and function, and Mucida et al 2005 Oral tolerance in the absence of naturally occurring Tregs) all highlight the importance of the regulatory T cell in terms of oral tolerance.  Oral tolerance refers to the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. This means that conventional medicine’s answer up until recently, to combat autoimmune conditions, is to suppress the immune system, an extremely foolish approach since its a symptomatic suppression approach instead of attempting to find the actual cause of the autoimmune condition.  Medical studies have correctly identified TReg dysfunction citing that induction of TReg cells is a proposed mechanism of action from probiotics as described in various studies. For example the study by Di Giacinto et al 2005 Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. Felesko et al 2007 cited Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine (mice) model of asthma.

All these great scientists are picking up pieces of the Autoimmune puzzle, and some have figured it out experimenting with probiotic intervention, but most are missing the central part of the puzzle, that the gut is dysbiotic and generally particular dietary changes can fix the problem overall.


Compromised immune system caused by gut dysbiosis

When the epithelium barrier is breached, any undigested food particle or pathogenic bacteria can cross through into the body. Once this occurs and these substances get into the bloodstream the immune system as it is designed, will respond immediately, creating an inflammatory response and then attack the ‘foreign invaders’ attempting to neutralise the threat. However, since this is an abnormal occurrence, and assuming the gut balance has been disrupted already, the immune system goes into overdrive attempting to restore homeostatic conditions, but in its quest it to normalize the situation, and given certain conditions such as a barrier breach that is not fixed for a while ( a condition referred to as Leaky Gut syndrome) the immune system becomes chaotic and confused. The immune systems primary tasks is to detect infection and potential harm (Recognition), contain and eliminate infection (Effector function), control activities to avoid damage to the body ( Regulation), and react immediately to known substances ( Acquired immunity function).  

However, since the microbiome is in chaos ( unbalanced ) this crucial decision making is disrupted, causing the immune system to function inappropriately. The immune system, without the normal regulatory controls begin ‘search and destroy’ missions on any other amino acid chains ( proteins ) that resemble the original molecules that breached the mucosal firewall, the epithelial barrier.  This resultant activity is referred to as ‘Molecular Mimicry’. Depending on the protein,and its associated amino acid chains, the immune system can potentially attack any ‘like’ proteins that exist on any host organ, so in its ‘wisdom’ conventional medicine has labeled these various conditions as Autoimmune diseases including ‘Type 1 Diabetes’ ( Insulin producing cells on the pancreas ), Hashimoto’s and Graves ( In Hashimotos the  Immune system antibodies slowly destroy the thyroid hormone producing cells, while in Graves, the antibodies stimulate the thyroid gland to release excessive amount of the thyroid hormone ( Hyperthyroidism )), Inflammatory Bowel (IBD) ( intestinal lining ), Multiple sclerosis ( nerve cells, but the damage migrates to the brain neurons).    


Fibromyalgia

The National Health Service (NHS) in the UK has the following information to help people suffering with Fibromyalgia:

Causes

It’s not clear why some people develop fibromyalgia. The exact cause is unknown, but it’s likely that a number of factors are involved.  Here are some of the main factors thought to contribute to the condition:

 Abnormal pain messages

One of the main theories is that people with fibromyalgia have developed changes in the way the central nervous system processes the pain messages carried around the body. This could be due to changes to chemicals in the nervous system.  The central nervous system (brain, spinal cord and nerves) transmits information all over your body through a network of specialised cells. Changes in the way this system works may explain why fibromyalgia results in constant feelings of, and extreme sensitivity to, pain.

Chemical imbalances

Research has found that people with fibromyalgia have abnormally low levels of the hormones serotonin, noradrenaline and dopamine in their brains.  Low levels of these hormones may be a key factor in the cause of fibromyalgia, as they’re important in regulating things such as:

  • mood
  • appetite
  • sleep
  • behaviour
  • your response to stressful situations

These hormones also play a role in processing pain messages sent by the nerves. Increasing the hormone levels with medication can disrupt these signals.   Some researchers have also suggested that changes in the levels of some other hormones, such as cortisol (which is released when the body is under stress), may contribute to fibromyalgia.

Sleep problems

It’s possible that disturbed sleep patterns may be a cause of fibromyalgia, rather than just a symptom.  Fibromyalgia can prevent you from sleeping deeply and cause fatigue (extreme tiredness). People with the condition who sleep badly can also have higher levels of pain, suggesting that these sleep problems contribute to the other symptoms of fibromyalgia.

Genetics

Research has suggested that genetics may play a small part in the development of fibromyalgia, with some people perhaps more likely than others to develop the condition because of their genes.  If this is the case, genetics could explain why many people develop fibromyalgia after some sort of trigger.

Possible triggers

Fibromyalgia is often triggered by a stressful event, including physical stress or emotional (psychological) stress. Possible triggers for the condition include:

  • an injury
  • a viral infection
  • giving birth
  • having an operation
  • the breakdown of a relationship
  • being in an abusive relationship
  • the death of a loved one

However, in some cases, fibromyalgia doesn’t develop after any obvious trigger.

Chemical Imbalance..AGAIN..more stories from Hans Christian Andersen

Even the Mayo Clinic state that researchers believes  that somehow fibromyalgia acts as a pain amplifier affecting how the brain processes the pain input. Women are more likely to develop fibromyalgia than men and that there is no cure.  The NHS claim that somehow fibromyalgia sufferers have developed changes in their central nervous systems in terms of how it processes pain signals, due possibly, to chemical imbalances of serotonin, noradrenaline and dopamine in their brains.  This is why medications such as Duloxetine, Milnacipran or pregabalin which are basically Serotonin reuptake inhibitors to keep Serotonin to hang around longer.  I am sorry…I have to interject here….The whole antidepressant medication industry is built around ‘chemical imbalance’ which has been proven to be unsubstantiated, unscientific and a flawed failed theory and we have written in detail in the articles The destruction of Society’s social fabric and anti-psychotic drugs, specifically Part 8 which related to the ‘Serotonin fairytale’ :

Once upon a time.in Neurotransmitter land there was not enough serotonin to go around for the population who lived in this land so….. in 1965 a gentlemen of high standing working for the National Institute of Medical Health (NIMH) published a paper in 1965 in the American Journal of Psychiatry..that put forth a mystical hypothesis that Norepinephrine (that was in short supply) was the cause of depression, however, he did state that there existed no evidence of such but it was simply a theory.  This sparked a revolution of Serotonin seekers such as Malcolm Bowers at Yale University in 1969 , and then in 1971 researchers at Mcgill also examined the theory. All reported that serotonin ( or its metabolized form 5-Hydroxyindoleacetic Acid (5-HIAA)) were all normal in depressed people. So thats three experimental research initiatives spanning 6 years and they all concluded the same thing. You would think that would be that..the theory is wrong… so let’s move on..but no.  Scientists thought that if look hard enough, even if they have to dismember the body and disassemble the brain there must be a wastage of serotonin somewhere …maybe it falls out of the ears of depressed people or maybe it gets turned into gas and leaks out from some other orifice.

In 1974, even Bowers revisited his own research and concluded the same results.  Two researchers in the same year Joseph Mendels and Alan Frazer examined the content of monoamine ( norepinephrine, serotonin, and dopamine) depletion from the administration of Risperidone ( a herbal drug that was initially used for high blood pressure ). He found that this did not induce depression, in fact, since it is of a natural herbal extraction, it actually calmed the body, in essence, acting as an antidepressant.  Again another proof that this theory was wrong. Due to the academic arrogance of these people and with enough muster not to let this theory die…must have said ”We are going to find out what happened to this substance if its the last thing we ever do”.  A Marie Asberg in 1975 at the Karolinska Institute of Sweden had her ‘eureka’ moment announcing that 20 of her 68 depressed patients had low serotonin levels with 2 out of the 20 that actually committed suicide and declared that this may be evidence of  ‘ a biochemical subgroup of depressive disorder characterized by a disturbance of serotonin turnover. Finally Dr Joseph Coyle Professor of Neuroscience at the Harvard Medical school stated:

“ Chemical imbalance is sort of last century thinking.  It’s much more complicated than that”.      

..continuing with the information on the NHS website they say that disturbed sleep patterns could cause Fibromyalgia..I think this should be the other way round. Fibromyalgia is going to cause disturbed sleep patterns unless you find a way to sleep while you are in pain apart from alcohol intoxication, or someone hits you over the head with a hammer.  Genetics..how can you inherit pain that moves around the body..where is the logic. Triggers..they say that stress can trigger fibromyalgia…this I agree is more logical since high stress can upset normal physiological balance.

Actual cause of Fibromyalgia and Rheumatoid arthritis

First of all we need to draw our attention to one particular pathogenic strain Streptococcus, a nasty pathogen comprised of hundreds of species, that is behind such infections as meningitis, pneumonia, endocarditis ( inflammation of the myocardium, inner part of the heart), Necrotizing fasciitis ( flesh-eating disease ) and pharyngitis ( Strep throat).  Group A strain  Streptococcus pyogenes ( GAS ) can also cause Rheumatic fever and acute Glomerulonephritis Rheumatic fever that affect the kidneys.  Rheumatic fever affects the joints,kidneys and heart valves, is caused by damaging antibodies created by the immune system ( autoimmunity).  Interestingly enough it is this phyla of pathogenic bacteria namely Streptococcus zooepidemicus that is lurking in raw unpasteurized milk from a cow that has mastitis.  In a study completed in 1998, scientific researchers uncovered an association between the Streptococcus pathogen and myalgia ( fibromyalgia or muscle pain). Over 17 years ago ( 2000) Rasmussen and colleagues discovered a collagen-like surface protein  after genome sequencing was completed on various bacterial strains. This protein was designated ScIA or Streptococcal Collagen-like surface protein.

With the immune system compromised and dysregulated some hosts who have had their immune systems experience a streptococcus infection the immune system mistakes the host collagen tissue as pathogenic and launches an attack and as you may know especially if you suffer from myalgia of fibromyalgia it follows a migratory pattern where 1 week you might have pain in a shoulder muscle and then it might move to a leg muscle so the pain is moving around the body. Collagen ( greek word for glue) in the body is the most abundant structural protein used for connective tissue used in fibrous tissue found in tendons, ligaments, cartilage, bones, blood vessels, the gut, intervertebral discs and skin. The physician is baffled and has no way of diagnosing such a mysterious moving pain so he prescribes serotonin reuptake medication to make you more comfortable.  One lady I know reported to me that her physician said

“ What can I tell you, we good at diagnosing cancer but when it comes to pain we suck at it”

I salute you Doctor, at least you are honest.  Since she was experiencing pain in her upper body while sleeping her friends suggested that it might be the mattress or the pillows that were causing her pain. Given the research and association between Group A strain  Streptococcus pyogenes ( GAS ) and  Rheumatic fever and acute Glomerulonephritis Rheumatic fever, this same mechanism of action described above can also give rise to Rheumatoid arthritis another known autoimmune condition.


Allergies

This immune system chaos can also affect what the host ingests or what is put on the skin.  Anything put on the skin will end up in the bloodstream, so chemicals from lotions, shampoo, make-up, after shave etc are likely candidates to be attacked by the confused immune system. Allergies to anything can erupt at any time during the life of the host coinciding with gut dysbiosis which can occur if the host becomes toxic and nutrient deficient to the level of causing a breach in the mucosal firewall in the gut.  This breach allows large molecules to leak through the gut barrier and into the bloodstream in the line of site of the unregulated immune system since the Tregs become compromised themselves. Antihistamine medication is prescribed in an attempt to suppress histamine that is produced as a result of the allergic reaction, but as I explained in previous articles let us re-discuss where this histamine is coming from

Histamine

Mammalian and Microbiota histamine producing cells

Our microbiota consist of  Beneficial flora and Opportunistic or commensal flora where the latter can ‘bat either side of the plate’    If kept in check by our beneficial flora, the commensal colonies remain harmless, and in some cases assist the host in a beneficial way thus becoming an extension of our beneficial flora colonies. However, if the beneficial flora, our guardians become compromised or damaged then the commensal colonies overgrow and cause harm. Opportunistic flora as part of their normal metabolism create toxic by-products which are neutralized under normal healthy conditions but if an imbalance occurs these toxins begin to cause trouble. Histamine ( a metabolite from amino acid ) is a nitrogenous compound involved in the inflammatory response process and a central mediator to Pruritus ( Itching ). It is produced by Basophils ( white blood cell Leukocytes ) and Mast cells. Mast cells patrol the body looking for the enemy and spray histamines when they encounter them, inducing a greater blood flow to the infected area creating an inflammatory response.  Particular species of our commensal bacteria also produce histamine including Lactobacillus Casei, Lactobacillus delbrueckii, Proteus family,E.Coli family and Staphylococci.

Histamine degradation

On the other hand some beneficial bacteria actually degrade histamine which becomes a natural treatment or prevention against an allergic response. These bacterial histamine degraders include Bifidobacterium infantis and Bifidobacterium.longum.   Our Mammalian cells also degrade histamine by producing Diamine Oxidase an enzyme produced by epithelial cells and  another enzyme N-methyltransferase which exists in most body tissue providing your Methylation process is working efficiently. The most histamine produced is within our gut flora so it is crucial that this is kept balanced.

Methylation

This Methylation cycle occurs within each cell and 85% of methylation occurs in the liver, the rest in the kidney and testicles. The purpose for 80% of Methylation is to produce creatine for muscles, and to maintain brain and neurological health, the remainder covers some 200 other functions that include dopamine and estrogen degradation, production of Norepinephrine, Melatonin, Carnitine, Coenzyme Q10 ( for the heart ) and gene switching.  If the microbiota is unbalanced it can screw up the methylation cycle and in addition our bacteria also has a Methylation cycle and one of its purposes is to create a restriction modification cycle to defend itself against foreign DNA which occurs when a virus ( a vicious parasite ) that needs other bacterial cells for its duplication; these are called Bacteriophages.

So a small intestinal bacterial overgrowth can cause an overload of Histamine as well as an impact on the Methylation cycle by increasing folate levels, interfering with MTHFR * pathways and a decrease in B12 absorption, not to mention the negative influence on our genes. For example, the gene COMT which relates to methylation, provides instructions to make an enzyme catechol-O-methyltransferase which is used to control the production and degradation of hormones, so excess Histamine production can interfere with this process. An imbalanced gut flora allow commensals to produce too many toxins that disturb our methylation cycle causing anxiety, tension, insomnia, pain, fatigue and brain fog.

*Methylenetetrahydrofolate reductase (MTHFR) is a rate limiting enzyme used in the Methylation cycle playing a role in processing amino acids and building proteins.


Conclusions.  

We have discussed how allergies are triggered and explained that a compromised immune system can cause a myriad of autoimmune conditions, and we explained the cause of Fibromyalgia and Rheumatoid arthritis. In the next part we will discuss other common autoimmune conditions such as Celiac disease, Crohn’s disease ( Irritable Bowel syndrome), Psoriasis and Pernicious Anemia which all have a common thread… I know let’s rename these conditions ‘Auto-common Diseases.

Frank, can I borrow your doctor’s diploma? They are a little short in the latrine. –– Hawkeye

Don’t worry, I’ve never lost a patient. I never lose anything. Have you seen my stethoscope? — Hawkeye

 It’s Frank’s birthday, I wonder how old he is. Let’s saw him in half tonight and count his rings. — Hawkeye

I told you the food here should not be taken internally. — Hawkeye

 Attention all personnel. By order of Major Frank Burns, lights out in ten minutes sharp. Anyone not in their own beds at that time will have to spend the night wherever they are. — PA

 TV Series MASH quotes


Check out the previous articles in this series :

Autoimmune Disease I

Autoimmune Disease II (Gut Flora Balance, Gut Symbiosis)

Autoimmune Disease III (Thymic recruits, Immune system Battlemap,Th1/Th2 balance)

Autoimmune Disease IV (Inflammatory mediators)

Autoimmune Disease V ((Asthma, Gut Epithelium, Chronic cystitis)


References/Acknowledgments :

    1. Post-Streptococcal Glomerulonephritis  Bernardo Rodriguez Iturbe, Mark Haas 2016 NCBI
    2. Molecular Mimicry, Immunodominance, Streptococcus Wikipedia
    3. Post-Streptococcal Reactive Myalgia: A novel syndrome secondary to infection with Group A or G Streptococci  Jansen, Janssen, Macfarlane, De Jong British Journal of Rheumatology 1998
    4. Microbiome and Disease Part 1 2017 Article Eric Malouin Dr John Bergman Owners guide for humans website
    5. The destruction of Society’s social fabric and anti-psychotic drugs Part 8 2017 Article Eric Malouin Dr John Bergman Owners guide for humans website
    6. ScIA a novel collagen-like surface protein of Streptococcus pyogene Rasmussen, Eden, Bjork 2000 NCBI
    7. Fibromyalgia/Rheumatoid Arthritis causes NHS.UK Website
    8. TV Series MASH quotes swamp4077.tripod.com

 

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