Sunday, January 22, 2017

The benzene rings of hemaggluten, the flu, and dopamine receptors

Current belief is that the flu virus binds to sialic acid through hemaggluten.  I believe they bind dopamine receptors using benzene rings.

Flu virus has a high affinity for dopamine neurons

my blog: flu and dopamine receptors based on infection patterns

flu and sialic acid binding in birds???? ahhh

Flu receptor binding in birds does not match binding in humans

It is known that the flu virus does use sialic acid to bind.  Flu drugs which are sialic acid analogs seem to slow infection rates in people

note that sialic acids are at the dopamine receptor binding region but they don't seem to alter dopamine binding

hemaggluten is responsible for flu infection

hemaggluten has benzene rings

hemaggluten based flu inhibitors

psychosis and dopamine receptor antibodies

psychosis and flu

D68 and staph: please look for this Panton-valentine marker in paralyzed patients

Wednesday, January 18, 2017

Zika, ACTH receptors, and Clatherin endocytosis: why nanochangmycin works

The recent finding by Penn state supports the prediction that Flaviviruses like Zika use melanocortin receptors. Melanocortin receptors are inhibited by clatherin inhibitors.

Zika use melanocortin receptors: specifically ACTH

Melanocortin receptors are sensitive to clatherin endocytosis inhibitors
ACTH receptor specifically

Penn state found that: nanochangmycin inhibits Zika infection through clatherin endocytosis inhibiting

The drug amantidine might work against Zika too

Guillian Barre and autoimmune cross-targeting

I have been dividing up the flaviviruses with the melanocortin receptor they could use:

mcr1   Tick borne encephalitis virus/ hepatitis C   (Thrombocytopenia due to red blood cells with mcr1)

mcr2 (ACTH receptor)   Zika (placenta, developing brain)

mcr3  West nile (kidneys)

mcr3 and mcr1  Japanese encephalitis

mcr4  Yellow fever (liver)
mcr5  Dengue (immune system T cells) (which explains the second exposure response)

I am thinking they open the door into cells using this receptor most of the time and the other melacortin receptors less well.

Thursday, January 12, 2017

The genes in Parkinson's disease, the stimulation of nerves, and the mitochondria

Parkinson's genes: pink, parkin, DJ-1, MCR, and synuclein

The genetically linked proteins involved in the development of parkinson's disease appear to have distinctively different functions.  Parkin and pink are involved in the pruning process of neurons.
 Synuclein is involved in the maturation of neurons favoring those that are used to become stronger.

The obvious overlap between these systems is the stimulation of nerves instructing these pathways. High stimulation increases cGMP which favors keeping the nerve and maturing it.

Parkinson's disease has low mitochondrial mass

mitochondrial disfunction occurs prior to disease symptoms

pink and parkin are responsible for breaking down mitochondrias

Parkin and pink are lowering the strength of the neuron by lowering the ATP levels thus favoring pruning

NO increases the concentration of cGMP which then causes the s-nitrosylation of parkin

nitrosative stress and parkinson's

normal parkin regulates the number and strength of synapses, the pruning

Over expression of synuclein in mice looks like Parkinson's

How does this happen?

the normal function of synuclein looks to be the selective maturation of neurons

(synuclein goes to the mitochondria's inner membrane)

mature neurons have changed mitochondrias

synuclein increases ATP

excitation of the brain causes increased cGMP


NO, cGMP, and synuclein...cGMP causes the redistribution of synuclein

Mycobacterias secrete cGMP as their quorum. Quorums are the communication signals between bacterias.

Mycobacterias have been linked to Parkinson's disease through nocardia, psoriasis, and tuberculosis.

Extremely high cGMP would s-nitrosylate parkin and cause too much synuclein? Does the excess cause synuclein to precipitate ? Does the excess cause feedback regulation?

excitation of the brain causes increased cGMP temporarily

But what would happen if it was continuously high?  Would you have synuclein plagues building up as a warning sign?

I say warning sign because parkinson's neuron death would occur after autoimmune cross-targeting between a virus and the mycobacteria triggers the immune system to destroy the neurons.

The DJ-1 mutation is indistinguishable from parkin

dopamine treatment decreases the amount of mitochondrial DNA: does that mean less mitochondrias?

What is interesting about this is that the Flu virus looks like it uses dopamine receptors to infect cells.  If this relationship between dopamine and the breakdown of mitochondria is real then this could help explain what we see.

Flaviviruses like west nile have also be linked to parkinson's

Flaviviruses I suggested are linked to melanocortin receptors

melanocortin receptors and Parkinson's

cells infected with the flavivirus hepatitis C have lower ATP

Since viral infections end up in different areas of the cell is it just the cytosolic viruses that lower the ATP in the right area that causes the parkinson's symptoms? because the viral infection does not last this using of ATP by the virus cannot be the cause.

Some how Flaviviruses are lowering the amount of mitochondrias, lowering the amount of ATP even  after the autoimmune disease has taken over.  Does this mean that the melanocortin receptor's pathway is responsible like the dopamine receptor?

MCR4 has been connected to weight loss

MCR3 and MCR4 have both been connected to obesity

mitochondria number and obesity?

mitochondria fusion and fat use

MCR3 and MCR4 are the meloncortin receptors of the nervous system

I had connected west nile to MCR3

MCR3 in the brain

So how does all of this fit together?
mycobacterias would put a strain on the normal system by overstimulating it and perhaps causing feedback...when a virus triggers a receptor pathway that favors decreasing the mitochondrias...the dysfunction worsens.

The autoimmune disease is actually not the main reason for the symptoms?

Antibodies found in only 11% of idopathic parkinson's

So parkinson's is cause by the loss of neurons in the substantia nigra slowly by over prunning or quickly if autoimmunity has been triggered and the immune system kills the neurons too.

The neuron cell death in parkinson's maybe driven by the autoimmune process....showing as pisa?

Pisa is the leaning to one side like the building in Italy

Wednesday, January 11, 2017

Transverse Myelitis and Autoimmune-cross-targeting

Autoimmune cross-targeting hypothesis

The layering of 2 different infections on one target triggering autoimmune disease.  A viral infection marking the inside of the target then a bacterial, or fungal, or mycobacteria infection marking the outside.

Transverse myelitis : fungal and flu N1H1 or polio cross-targeting on spinal cells ?

flu vaccine and transverse myelitis

lupus and transverse myelitis

transverse myelitis, MS,  neuromyelitis optica

flu virus and neuromyelitis optica

previous post of neuromyelitis optica

Idiopathic transverse and HLA-DR2

HLA-DR2 and the flu

polio vaccine and neuromyelitis

Fungal infection and transverse myelitis

schistosomiasis and transverse myelitis

(schistosomiasis are parasitic snail worms)

Thursday, January 5, 2017

Autoimmune cross-targeting hypothesis : simultaneous infections trigger autoimmunity

Autoimmune Cross-targeting Hypothesis. The "ins and outs" of the immune system.

  The trigger of autoimmunity has remained elusive.  Genetic susceptibility and infections contribute to the development of autoimmunity but the pathogenesis has not been clear.  This Cross-targeting hypothesis suggests that simultaneous infections on one target triggers autoimmunity.  One infection exists on the outside and one infection exists on the inside. 

Paul Ehrlich called the immune system attack on self tissue Horror autotoxicus; today it is called autoimmunity.  Under normal healthy conditions our immune system does not attack self tissue because the immune system has built up a tolerance to self proteins by educating it's B cells and T cells.  T cells are educated to recognize the inside of cells while B cells are educated to recognize the outside of our own cells.  Both of these "educations" must be compromised for the immune system to attack self.  Both the inside and the outside of a tissue must be infected. 

  In order for autoimmune disease to occur two different infections must be attacking the same target tissue.  Cross-targeting is a military term for when a target is attacked from 2 different platforms. The 2 branches of the immune system attacking at the same time on the same target but from different systems fits.  Those immune cells attacking the outside of a cell to kill large infections and  those attacking viruses on the inside.  It is this state of both B cell and T cell educations uncoupling and attacking at the same time that causes autoimmunity. There is nothing to hold the immune system back from killing the entire cell thus autoimmunity develops.

Evaluation of Hypothesis:

Everyone remembers the 1990 Awakenings movie with Robin Williams as Dr. Oliver who in 1918 dealt with a cluster of encephalitis lethargia patients.  In 1993 Dr. Andrew Church found himself with another Encephalitis cluster and he discovered that 2 infections were there not just the flu. Dr. Andrew discovered that a high number of his patients had a rare form of strep called Diplococcus along with the Spanish flu.  He has spent a life time trying to piece together this disease.   In 2011 Dr. Andrew and Dr. Russel came out with a paper proving Encephalitis lethargia was an autoimmune disease with antibodies directed at the Basal Ganglia.  This is possibly the first paper supporting cross-targeting as the trigger for autoimmune disease.

 The concept of the simultaneous activation of the immune system's inside and outside pathways triggering autoimmune disease and not the infections themselves becomes obvious with this autoimmune disease mouse model,  NOD.  The NOD, non obese diabetic, mouse model has now been shown to be caused by a mutation in the TCR,  the T cell receptor.  The TCR activates when it encounters an infected cell's HLA mailbox with foreign, typically viral, pieces in it.

Here is a simplified summary: TCR activation causes the T regulator cell to secrete il-10 and remove FoxP3.   Il-10 suppresses the T helper cells of the "outer" infection pathways.  Foxp3 suppresses the viral response of T cells so when this Foxp3 disappears the "inner" immune pathway against viruses is favored.  If there are not enough T regulator cells with TCR as the case appears to be with NOD mice there is a weak response to viral infections and an incomplete suppression of the "outer" immune pathway.  The autoimmunity occurs because both inner and outer immune systems are "on" at the same time.

  Normal, real life not model, autoimmune disease would be the result of simultaneous infections inside and outside. 

Most autoimmune diseases have dual infections triggering them and they don't have specific time tables until looked at in terms of cross-targeting infections. Typically the larger infection takes hold first and for some reason has not been eradicated before the second viral infection appears.  The autoimmune disease is not triggered unless infections are marking both the inside and the outside at the same time. Which virus does not matter. Which outer infections does not matter. It is the mere coincidence of layered infections on one target. This inside-outside pattern can be found in all autoimmune diseases.

The collection of genetic susceptibilities of autoimmune diseases, specifically the HLAs, can identify which viral infections are involved.  Each HLA mailbox is responsible for a specific zone within the cell. Viruses infect specific zones and often match up with a particular HLA mailbox. HLA-A is the mailbox for the nucleus, HLA-B is the mailbox for the mitochondria, HLA-C is the endoplasmic reticulum mailbox, and HLA-D is the cytosolic mailbox. Since susceptibility data using HLAs has been collected for each autoimmune disease we can use them to not only verify the virus we suspect but we can use them to understand the variations found within one type of autoimmune disease.  When a virus enters a host cell it uses a receptor with known pathways. These receptor pathways create the variations we see for one type of autoimmune disease.  Beyond location of the virus in the cell and what pathways are triggered,  the HLAs can be even be matched up with specific viruses revealing suspects in autoimmune diseases we have not even identified yet.  The collection of HLA genetic susceptibilities are extremely informative for the inner viral infections.

The environment and a person's medical history will help reveal the larger outer infections especially when different autoimmune diseases are found associated together.   The overlapping of autoimmune diseases can reveal which larger infections have taken hold first. There will only be one common suspect.  Further the quorum of these larger infections create distinctive problems for the hosts' health which can also be found linked to the autoimmune diseases. Once we establish which large infection we are looking at the autoimmune disease family associations make sense.

 Often these larger infectious suspects appear in each of the autoimmune diseases but the viral trigger companions are different. Viruses use specific receptors as doorknobs to enter cells.  These receptor doorknobs vary with different cell types. Viruses do not infect all cells. Only the ones with their receptor.  Thus when a larger infection has established itself on several organs and a virus appears it is only the organ where they both, virus and large infection,  are infecting that develops autoimmunity.   Hence explaining the lack of order to autoimmune disease family development.  One autoimmune disease does not lead specifically to another.  It is random chance which virus is encountered next.  Autoimmune disease development is random upon viral exposure once the larger infection has taken hold.

Analysis of the autoimmune diseases:


Narcolepsy is caused by an autoimmune attack on hypocretin cells.

Similar to Encephalitis lethargia, Narcolepsy has been associated with both a flu virus and strep but in this case inducing an autoimmune attack on the the hypocretin cells of the hypothalamus.

A group of children in England developed narcolepsy after receiving vaccinations against the flu H1N1 suggesting that it is not the virus directly rather the immune system itself causing the narcolepsy.  In other words, a section of the virus although not active still goes to and binds the target tissue bringing the immune system and triggering the autoimmune disease just like a live virus.  Foreign is foreign to the immune system wether or not the virus is active or not active.

All the children who developed narcolepsy after the vaccine had recently had a strep infection supporting the notion of an autoimmune cross-targeting event triggering the narcolepsy.

The HLA associated with Narcolepsy is HLA-DR2. The HLA-DR is a mailbox for the cytosol of the cell.   HLA-DR2 has strong correlations with flu virus H1N1.

Rheumatic fever

Rheumatic fever can trigger an autoimmune attack on the heart by cross-targeting on myocytes.

There is a high incidence of co-infection in Rheumatic fever.   Coxsackie B virus antibodies  have been found along side streptococcus antibodies in children with rheumatic fever.

The HLA for rheumatic fever is HLA-DR7.  HLA-DR is the mailbox for the cytosol.  HLA-DR7 is often found with enteroviruses.

In this case the antibodies that cross-react with strep lead the immune system to the heart marking the outside of the organ. When the coxsackie virus infects the heart cells, myocytes, an autoimmune reaction results.


Parkinson's is an autoimmune disease of the Basal ganglia's substantia nigra. 

Parkinson's disease has been associated with psoriasis' mycobacteria and nocardia.  These mycobacterias are capable of crossing the blood brain barrier.

There are 3 major types of parkinson's and 3 different virus families associated.

Idopathic, late onset parkinson's disease has been connected to flaviviruses like west nile and hepatitis C.  HLA-DR15 (odor impaired group because of melanocortin receptors used by flaviviruses)

Vascular, postencephalitic parkinson's is linked to the flu H1N1 and frontal lobe issues. HLA-DR2? (task switching impaired group because of frontal lobe)

 The parkinsonism that appears to be linked with Alzheimer's suggests a connection to herpes viruses. HLA-B (memory impaired)

All 3 virus families can trigger parkinson's disease by cross-targeting with the mycobacteria.  The type of parkinson's seems to vary depending on the virus. (maybe viruses and the receptors they use do influence the autoimmune disease somewhat)

Type 1 diabetes 

   In type one diabetes the immune system has decided to attack the pancreas. Two viruses have been associated with the development of type one diabetes the Coxsackie virus (an enterovirus) and the Flu viruses.  Both of these viruses can and do replicate inside of pancreatic cells but it only takes one virus to mark the inside. 

   Larger infections have  been found infecting pancreatic cells from the outside: mycoplasmas, e.coli, campylobactera, and candida.  So which infection is responsible for the development of autoimmune type one diabetes?  All of them and yet only one of them on the outside at a time is needed to trigger type one diabetes.

Note that the e.coli and campylobacter infections attach to intestinal cells using the blood type antigens.  Like the epithelial tissues, the pancreas has expressed the blood type antigens which means that E.coli or campylobacter will be drawn to this organ if they cross from the intestine into the body.

How do you know which infection could possibly be infecting the pancreas? E.coli is involved with bladder infections and intestinal infections.  Fungal infections tend to trigger Hashimoto's thyroid disease. (how is unknown) Mycoplasmas have been linked to rheumatoid arthritis.  You only need one of these to infect the outside of the pancreas.

As for the virus that marks the inside of the pancreatic cells either the flu or the coxsackie enterovirus can trigger the autoimmune disease but because they use different receptors to enter the pancreatic cell they may create two different variants of type one diabetes.

Dopamine receptors inhibit insulin secretion which means that a flu virus using the dopamine receptor to enter the cell would create a fast progression to diabetes compared to enteroviruses which use acetylcholine receptors.  Acetylcholine receptors increase insulin secretion so the development of diabetes would appear to be slower. This prediction of fast and slow progression fits with the HLA mailboxes associated with diabetes: HLA-DR4 and HLA-DR3.  The HLA-DR 3 has been linked to a slower progression to type one diabetes.  HLA-DR3 is linked to enteroviruses while HLA-DR4 is linked to the flu viruses.

Multiple sclerosis and the myelin of nerves

   Most autoimmune diseases appear to fit this inside and outside cross-targeting problem.  Multiple sclerosis for example has been found to appear after a shingles outbreak but not everyone with shingles develops it.  People with psoriasis have higher rates of multiple sclerosis but not everyone with psoriasis gets it. Now put into place the cross-targeting hypothesis.  Shingles is the herpes zoster virus that would mark the inside of the myelin because the oligodendrocytes and schwann cells have estrogen receptors, the receptors used by the herpes virus to infect.  While psoriasis if it is a mycobacteria infection which likes the myelin sheath marks the outside of the nerve.  The inside and the outside of the nerve's myelin would be marked to the immune system at the same time.  The immune system would be triggered to destroy all myelin.  Are people who have shingles while they have mycobacterial infections the ones at risk for multiple sclerosis?

Autism the 3 types

Autism is an autoimmune attack of the brain's cerebellum, frontal lobe, and temporal lobe.  Not damage from vaccines or infections alone but from one's own immune system; autism is an autoimmune disease.

  What about the vaccine induced autoimmunity?  This cross-targeting hypothesis can be applied to vaccine reactions. Looking at the list of what has been accused of causing autism then listing the targets they infect reveals patterns which reflect distinctively different forms of autism. Autism appears to be an autoimmune disease.

The DTP vaccine has three bacterial infections that it inoculates for : diphtheria, pertussis, and tetanus.  Only one of these bacterial infections exists in the temporal lobe of the brain and that is tetanus.  When the vaccine is given even if the disease is prevented a small amount of antibodies would end up at the temporal lobe because those virus pieces bind there.  Why pick tetanus out of this list ? Some autism patients have HHV6 with the neural autoantibodies.  This 6th disease known for it’s rash Roseola is a virus that replicates in the temporal lobe of the brain.  Applying the cross-targeting hypothesis on the temporal lobe suggest that  if a child with 6th disease gets the dtp vaccine they could develop an autoimmune attack of the temporal lobe thus developing an autism disease of this part of the brain. The CMV herpes virus could be implicated here too.  C. tetanus has been found in the guts of some children with autism.  These kids may have developed autism not because of a vaccine rather from catching a herpes virus while dealing with the C. tetanus in their system.  The key autism feature of the temporal lobe is the involvement of the senses.  Visual and hearing decoding including dyslexia has been associated with the temporal lobe.  

   What about the infamous MMR vaccine?  Autoantibodies for the measles part of that vaccine have been seen in a group of autistic kids and the measles virus pieces migrate to the cerebellum.  Clusters of autistic kids have been found to have sutterella bacteria in their system too.  Sutterella is closely related to campylobacteria which can infect the cerebellum. Does the cross-targeting of the measles vaccine and sutterella cause an autoimmune attack of the cerebellum?  Is this possible? Does campylobacteria do the same thing? Can the coxsackie virus replace the measles virus because it too infects the cerebellum?

    What about the children born with autism that were not induced by vaccines?  Pregnant women with Rheumatoid arthritis are more likely to have autistic children.  Women who catch the flu during pregnancy are more likely to have autistic kids. If we apply the cross-targeting hypothesis and look for a specific target we find the frontal lobe in this form of autism. Antibodies to the frontal lobe have been found in mother's with rheumatoid arthritis.  The flu (H1N1) when it has infected the brain of the young children has been found in the frontal lobe region.   It is possible that an unborn fetus develops an autoimmune form of autism on the frontal lobe when both of these infections occur at the same time in a pregnant woman.

Acute flaccid paralysis 

Preventing acute flaccid paralysis from d68 could be possible. What if the d68 virus is cross-targeting with staph on the nerves causing the paralysis? Staph once inside the body can infect nerves. We know that there is a strong association of eczema with staph and we know what group of children are vulnerable to d68 paralysis: those with asthma. A few with septic staph died which indicates a strong immune reaction between staph and d68 exists.  Since eczema and asthma can be linked maybe we should be treating kids with eczema and asthma for staph during outbreaks of d68.  We could prevent more cases of acute flaccid paralysis.  (note the d68 is an enterovirus like polio).

 Another viral family that can trigger acute flaccid paralysis is the flavivirus family. West nile has already been connect with cases of flaccid paralysis and it is only a matter of time before other flaviviruses are connected to it. Note that zika has been shown to cause acute myelitis, inflammation of the spinal cord, so it is quite possible that it too can cause flaccid paralysis in those with staph infections.

Herpes zoster infects these nerves too and on rare occasions has triggered acute flaccid paralysis. Have we not seen more of these in children because of the chicken pox vaccine which has become standard?

Rheumatoid arthritis

Autoimmune disease of the tendons.

Mycoplasmas and multiple viral infections? HLA-DRB1 HLA-DRB1 suggests cytosolic viruses like retroviruses and HLA-DR4 suggests the flu.

Guillain Barre

In Guillain barre the bacterial suspect is Campylobacteria Jejuni.  This infection begins in the gut but can trigger the autoimmune paralysis of the legs by triggering autoimmune cross-targeting of the peripheral nervous system after it has moved into the body from the intestine and taken residence with the nerves. Several of the flaviviruses and herpes zoster have been implicated as the viral trigger.  As the Zika virus hits Hawaii with it's sutterella issues there could be adults becoming paralyzed because Sutterella is a bacteria closely related to campylobacteria.

Bell's palsy

Two infections have been associated with Bell's palsy: herpes virus simplex and the spirochete family. Spirochetes include Borrelia, Syphilis, and Leptospira. Not everyone who has lyme disease will develop the facial numbness only those with preexisting herpes infections. Although anti-viral drugs have been found to help this condition is likely to reoccur as the herpes virus comes in and out of dormancy.  This autoimmune disease is a puzzle because HLA-DR which is not linked to herpes viruses has been implicated suggesting other viruses can trigger this autoimmune disease.

2 types of Myasthenia gravis

 There are two types of Myasthenia gravis and based on the viruses involved drastically different symptoms along with the thymus autoimmune attack. One involves the conjunctivitis and ACTH antibodies.  This type is associated with flaviviruses like west nile which use ACTH receptors.  The other type of myasthenia gravis has muscle weakness of the arms and legs.  The enteroviruses, the polio family viruses, use acetylcholine receptors. Close association with rheumatoid arthritis suggests that the outer infections are the mycoplasmas.


Alopecia is the autoimmune cross-targeting attack of hair follicles.

HLA-DQ : Reovirus : Areata Alopecia
HLA-C : Polyomavirus: Universalis Alopecia
HLA-DR : Flu : Totalis Alopecia

Is vitiligo associated with Alopecia more often because some type of skin infection is one of the triggers? Trichophyton violaceum has been associated with discord lupus and vitiligo.  If trichophyton makes tyrosol as it's quorum that could explain the pigment loss. Tyrosol inhibits tyrosinase a step in melanogenesis. Note that autoimmune antibodies to tyrosine have been found in vitiligo patients.

Rheumatoid arthritis also has a strong association with alopecia. The infection involved with Rheumatoid arthritis could be mycoplasmas which is further supported by those who have hair loss following mycoplasma pneumonia.

Nodding disease and epilepsy

Nodding disease and epilepsy are closely related.  Nodding disease, the zombie like state of those in Africa that has been connected to the black fly blindness could be due to cross-targeting of Trypanosoma brucei and polio or even the live polio vaccine because it is an enterovirus.  Epilepsy has an strong link with schizophrenia a T.gondii disease.  Epilepsy could be autoimmune cross-targeting of t.gondii, t.cruzi, or malaria with enteroviruses. The pattern here is trypanosoma and enterovirus and the medial temporal lobe.

Febrile seizures

There is also evidence of enteroviruses and the pertussis vaccine in Febrile seizures . Does the pertussis bacteria go to the same medial temporal lobe region as malaria and trypanosoma?  Could this be cross-targeting autoimmunity in a baby triggered by vaccine virus particles? Note that the specific region of the medial temporal lobe has been studied with pertussis and the hypothalamus was key.  Could the hypothalamus be what is attacked in nodding disease and epilepsy too by the immune system?


Kikuchi-Fujimoto disease is an autoimmune disease of the lymph nodes. In Japan Aspergillus oryzae is used for making miso, soy sauce, and sake. Exposure rates for aspergillus are high there. The key here is that only one virus and not a specific virus can trigger the autoimmune attack as long as the virus infects the lymph glands.  Herpes viruses and parvoviruses have been suspected but large case studies have failed to prove a direct connection.  It is suspicious that the rare acute disseminated encephalitis, an autoimmune disease of  brain and spinal cord, has been known to overlap Kikuchi-fujimoto.  Unlike multiple sclerosis this autoimmune attack on the nerves does not wax and wane, perhaps it is triggered by the parvoviruse B19.

Hashimoto's thyroid

Hashimoto's thyroid disease has antibodies to thyroid peroxidase (TPO).  All fungal infections secrete peroxidases in order to digest their surroundings.  Logically antibody cross-reactivity can occur between the fungal peroxidase and the thyroid's peroxidase. Sjoren's has strong associations with candida and Hashimoto's. Discord lupus and vitiligo has strong associations with trichophyton and Hashimoto's.  If these autoantigens to the thyroid are started by fungal infections then the inside of the thyroid still needs to be marked as foreign. Multiple viruses have been linked to triggering thyroid disease.  Any of the viruses that infect a thyroid can trigger the autoimmune attack.  Flaviviruses, enteroviruses, and even parvoviruses can infect thyroid cells.  The key to autoimmune cross-targeting is that the inside and the outside must be simultaneously marked as foreign to trigger the immune system to attack and destroy self tissue.

Graves thyroid

Graves disease is not an autoimmune cross-targeting disease; the tissue is not attacked. Antibodies generated by yersinia infections cross react, bind, and activate the TSH receptors.  The thyroid activity is stimulated. The thyroid tissue is not attacked by the immune system.  Now Graves can turn into an autoimmune variety through cross-targeting but the antibody binding the receptor is not on the cells surface very long and a virus or medication must also be marking the inside as foreign.  The window of opportunity for graves disease to become autoimmune is small because the antibody quicky cycles in with the receptor and doesn't have much of a chance to do it's job.

Celiac disease

Celiac disease is an autoimmune disease of the intestine.  Patients tend to have histories of bladder infections or Dermatitis Herpetiformis both of which are associated with e.coli infections.  Campylobacteria was also found in high concentrations in celiac patients. Either of these infections could be the larger mark on the outside of intestinal cells.

 Astroviruses have been isolated from newly diagnosed celiac disease patients.  Other intestinal lining viruses could logically trigger the cross-targeting of e.coli feathered intestinal cells.  Hepatitis B was once considered and so was rotavirus. The specific virus is not as important as the layering of inside and outside infections.

Gluten sensitivity occurs because e.coli is a membrane barrier crosser like T.gondii.  The hole created in the intestine allows gluten to pass through and heighten the immune response.  Celiac disease is an autoimmune cross-targeting on top of a membrane crossing which is why gluten seems to inflame the situation. Gluten does not cause the autoimmune cross-targeting. It has guilt by association with e.coli. 

Drug induced

The exception to this infection driven hypothesis is the drug-induced autoimmunity.  Cross-targeting is still occurring triggering when drugs are triggering the immune system but a drug replaces an infection.

Drug induced lupus can be triggered by monocycline and hydralazine.  Hydralazine is a muscle relaxer and works inside the muscles cells.  Monocycline which is an acne medication is known to penetrate muscles and cause severe muscle cramping.  Either of these drugs could replace the viral infection which marks the inside of the cell.   A patient with autoimmune liver disease makes anti-muscle antibodies which would mark the outside of muscle cells. They are the vulnerable group.  If the outside and the inside of the muscle appears marked or foreign to the immune system cross-targeting autoimmunity could result. 

Halothane hepatitis could be caused by cross-targeting too. The Halothane would replace the virus on the inside of liver cells.  A child with a pre-existing issues of e.coli might have the liver already marked on the outside.  A young girl developed hepatitis after using the anesthetic.  This particular girl also went on to develop type one diabetes. Does the girl have celiac too? Is celiac a risk factor for halothane hepatitis? 

The reverse scenario can also occur.  Hemolytic anemia is triggered when a drug like penicillin coats the outside of the red blood cells. Normally this would not be an issue but if the person had recently had the RSV virus which replicates in bone marrow or had chronic hepatitis C which might try to infect red blood cells and the virus was still visible in the red blood cells thus it might trigger autoimmunity. 

This leads us to the next autoimmune issue of recognizing and diagnosing what you are infected with. People who host parasites like t.gondii, yeasts, mycobacterias or mycoplasmas will find this hard to accept and it is still hard to diagnose.  Very little is known about the good verse the bad microbes in our digestive system but we must learn what is there in the body and what they can do.

The pathogenesis of autoimmune disease can be elucidated if autoimmune diseases are analyzed as targets and infections.   The overlapping characteristics are key to understanding what we are really looking at, which infections we are looking at.  Think of the immune system cross-targeting on one target as the trigger for autoimmune disease. What infections are shared among autoimmune disease families, what is the target tissue, and  what these infections have in common can give us not just insight into how autoimmune disease is triggered but how to prevent them and maybe even cure them.

 I need to respectfully identify Dr. Andrew Church and Dr. Russel Dale who work on Encephalitis Lethargia as the first to recognize the coexistance of two infections.

Monday, January 2, 2017

NOD mice, autoimmune-cross targeting hypothesis, and TCR receptors

The Autoimmune Cross-targeting hypothesis is that autoimmunity is triggered when two infections exist on a cell simultaneously: one on the inside like a virus and one on the outside like a bacteria. The immune system gets confused when attacking both the inside and the outside and thus the entire tissue is attacked.

How does this hypothesis fit with the known models like NOD mice?

NOD mice are deficient in TCR on T cell regulator cells

(here is a simplified summary)

TCR is the T cell receptor which looks into the MHC mailbox of infected cells.

T regulator cells wear TCR and Foxp3.  Stimulation of TCR triggers Il-10 secretion and Foxp3 to stop being worn.

Foxp3 suppresses the pathway to viral infection attack through T effector cells.

 Il-10 suppresses the pathways to large infection attack through T helper cells.  (Th1 and Th2)

Thus when there is something in a MHC mailbox the TCR is triggered and the cells progress down the viral infection pathway.

T regulator cells watch over 4 types of Tcells:  Th1 Th2 Th17 Teff

Th1 are the helper T cells involved with large infections thus stimulation of B cells.

Th2 are the helper T cells involved with hidden infections/ allergy reactions.

Th17 are the helper T cells involved with inflammation following tissue damage.

T effector cells are the T cells that go to a site of viral infections in search of antigen.

TCR ( the T cell receptor) has a key involvement with each of these T cell types.

TCR is the receptor that T cells use to look at the MHC (HLA) mailbox which reflects the internal infections.

Again, when the TCR of the T regulator cell see an antigen in this mailbox it down regulates FOXp3 which favors T effector cells to go look for viruses and secretes il-10 which inhibits the pathways to Th1 and Th2, the larger infections pathway. So what happens when TCR is removed?

Jak3 cytokine is released by damaged tissue and binds to without triggering the TCR.  Jak3 is "removing" the TCRs. When Jak3 binds to TCR it favors Th17 development.  Hence the reason that TCR deficient NOD mice have increased Th17 cells.  NOD mice simply don't have some TCRs.

NOD mice and Th17 increased

NOD mice are deficient in TCR on T cell regulators

The key here is that NOD mice develop autoimmune diabetes because of the missing TCRs. The large infection pathway is never completely off, not enough il-10 is made.

Coxsackievirus infection of NOD mice triggers diabetes (Foxp3 removed and viral pathway used)

When the Foxp3 was ablated in NOD mice diabetes occurred within 3 days. (no virus needed just the viral pathway opened)

NOD mice with just a bacterial infection have been shown not to develop diabetes (salmonella shown here but any large infection would probably show the same thing)

The reason is that the viral infection pathway is fully inhibited.  NOD mice are the missing TCRs not Foxp3.  The Foxp3 will stay on the T regulators keeping the inhibition strong. If anything NOD mice have weaker responses to viral infections because less TCRs are there to turn the viral pathway response on.

What triggers autoimmune disease is the simultaneous activation of the immune system pathways, both pathways activated at the same time: the large and the viral.

To test this: mice models with plenty of TCRs but weak binding Foxp3s then exposure to bacterias like e.coli which should trigger celiac and/or type one diabetes because the viral pathway won't be completely off.