Thursday, September 21, 2017

Schizophrenia with Multiple sclerosis caused by autoimmunity triggered by a shared Herpes infection

Autoimmune cross-targeting hypothesis: autoimmunity is triggered by a large infection marking the outside of a cell and a virus marking the inside of the cell.

The overlapping of autoimmune diseases could be due to a shared this case a herpes virus.

coexistance of ms and schizophrenia

Herpes zoster and CMV with schizophrenia

In MS the nerves are the target. Mycobacteria as the large infection and there are several possible viral triggers.

These are my guesses:

HLA-B: Herpes-alpha (zoster): Relapsing remitting
HLA-C: Polyomavirus (hepatitis B) or hep C- MCR4 flavivirus : primary progressive
HLA-DR15 : Flavivirus (? ) :Secondary progressive
HLA-A: Herpes-gamma (epstein barr): progressive relapsing (or CMV?)

In schizophrenia the large infection would t.gondii or fungal and then the virus would be a herpes. The herpes infection would overlap MS.

Schizophrenia : HLA-A/B

The 3 types of schizophrenia HLA match up with the 3 types of herpes viruses

my guesses:

DISORGANIZED : HLA-A2 and HLA-A11 : beta-herpes (CMV)
CATATONIC : HLA-B16 : Alpha-herpes (zoster, simplex)
PARANOID: HLA-A9 and HLA-A3 : Gamma Herpes (EBV)


relapsing remitting MS that overlaps with the catatonic schizophrenia 
progressive relapsing MS that overlaps with the  paranoid schizophrenia (EPV) or disorganized (CMV)

Tuesday, September 19, 2017

TLR4 / TLR8, cd16, and NK cells

Just supporting the notion that TLR8 is the TLR of the ER for viral infections there

Nk cells with FcR(cd16)  will make IFNgamma and TNF

TLR8 and cd16

Hepatitis C : flavivirus and Hepatitis B : polyomavirus

Hepatitis B(a polyomavirus which infects the ER then nucleus) and Nk

Hepatitis C (a flavivirus that like yellow fever looks like it infects the ER)

Hep C infects the ER

Yellow fever and the ER

Yellow fever and Hep C I had previously suggested used the melanocortin 4 receptor which looks like it takes them to the ER

TLR 7 is the nucleus and TLR 8 is the ER

Hepatitis B with TLR7/8

Hepatits C with tlr7/8.

The KIR (cd158) is the HLA receptor on NK cells

KIR has the strongest affinity for HLA-C because when the polyomavirus infects the ER very little HLA-C makes it to the surface and these are the infected cells NK needs to destroy

TLR8 might be the weakest because many polyomaviruses inhibit the production of TLRs and HLAs from inside the endoplasmic reticulum. This absence of TLR or HLA-C could be how killer T cells evolved  to automatically kill "naked cells" and why killer T cells secrete IFN gamma.

polyomavirus tumors and NK

So how does TLR4 trigger the NK ?

TLR4 binds lipopolysaccharides on gram neg bacteria (like e.coli)

TLR4 and cd16

E.coli  binds CD16 and tries to block

NK are also triggered by aggregated antibodies

CD16 binds the aggregated IgG or complexed IgG

AXL/gas6 and the il-15 pathway for NK

il-15 is a cytokine made by macrophages and dendritic cells following viral infection

TNF alpha stimulates the secretion of il-15

TNF alpha is released by the macrophage/dendritic cell that is infected or when Nk are activated by cd16

TNF alpha and NK

Thursday, September 14, 2017

Are Nuclear or mitochondrial viral infections trapped and need to be released by Th17 's il-26 to be seen by the immune system?

il-1 beta stimulates Th17 cells.  Th17 cells produce il-26 which is a membrane pore forming.  il-26 kills bacterias but what is it doing when a viral infection is involved?

TLR9 and TLR7 have been found to increase levels of il-1 beta. il-1beta stimulates Th17.

TLR3, TLR9, TLR7, and TLR8 are located intracellularly of cells catching viral infections/foreign bacterial nucleotides via net and  when the are triggered they tell the cells to wear the correct HLA and express a specific IFN

Hypothesis of location was based on viruses snagged

TLR3 cytosol RNA virus (like the flu )
TLR9 mitochondrial DNA virus (herpes zoster)
TLR7 nuclear DNA virus (hpv, HIV)
TLR8 endoplasmic reticulum RNA virus (polyomavirus)

Review of Tlrs 3, 9, 7 and 8

the internal location of tlr 3, 9, 7 and 8

When the immune system breaks open virally infected cells if the viruses are inside the nucleus or inside the mitochondria they are still not visible. Hence the mitochondria or nucleus need to be popped.  il-26 could be the tool here.

(just like il-26 is used to create pores in mycobacterias in Crohn's disease)
(mycobacteria and crohn's)

il-26 and extracellular DNA transporter

il-26 as a pore

Nuclear viruses

HIV and tlr7

HPV16 and tlr7

note that Epstein barr and tlr7 are some how connected but it is not clear if tlr7 is a sensor for it

il-1beta and hiv

il-1beta and HPV 

il-1beta and epstein barr

il-1beta triggers the Th17

Mitochondrial viruses

Herpes zoster and tlr9
Herpes simplex 1 and tlr9

il-1beta and herpes zoster

il-1beta triggers the Th17

Note that Th17 cells make the il-26

il-26 and tlr9

tlr7 and Th17 cells

Tlr9 and Th17 cells

Previous blog post linking up TAMS, TLRs, IFNs, and HLAs

Saturday, September 9, 2017

Cells and the sugars on membrane proteins...then considering the sugars on antibodies' Fc domains

Often times the golgi has been described as the post office of the cell delivering proteins to appropriate areas of the cell. The golgi has another very important role of modifying sugars on specific parts of a protein.

When a protein is placed into the membranes these sugars identify the sections of the protein that are not to be in the cytosol.  The parts of a transmembrane protein with sugars are on the outside of the cell or on the inside of an organelle. The complete removal of mannose sugars signals that the protein is to be secreted.

The sugar Galactose on the outside of red blood cells have evolved the important duty of participating in clotting.   Called the "blood type antigen" these galactose proteins on RBC are similar to van willebrand factor protein which is involved with platelets.  The Galactose mediates the adhesion of platelets and Red blood cells to sites of vascular damage.

Type O has the weakest level of clotting
Type B has medium level clotting
Type A has the strongest level of clotting (the easiest to bind)

Bacterias, mycobacterias, and yeasts like candida grab on to the surface of cells through sugars and have evolved a strong affinity for galactose.  Obviously the ideal place to infect is where a cut is.

To combat infections our bodies have developed "lewis antigens"  The sugar Fucose of  "lewis antigens" is very similar to Galactose.  Fucose is the decoy for Galactose.  Lewis antigens are secreted into the fluids and lower the infection rate.

People who lack the genes for lewis antigens have increased rates of intestinal infections and higher rates of ulcers.

The opposite can be said for blood type antigens. Those with type A and B are at increased risk of  infections.

(if you have type A hope that you have Lewis Antigens to be decoys)

This leads to some interesting contemplations: antibodies can have lactose and that changes the binding to Fc receptors.

Read an interesting article where the Fc domain of IgG antibodies have sialic acid residues and these sugars are responsible for the inflammation properties of IgG antibodies

Does the presence  of lactose in antibodies match up with the antibodies directed against  viruses?  Does the altered Fc binding of the antibody tell the immune system that it is viral by not having lacose and having galactose instead?

Fucose, galactose, sialic and antibodies....the fucose antibodies activate NK

why is fucose on the antibody's Fc for NK ?

NK cells are involved when ER infecting polyomaviruses are involved.  No proteins make it to the surface to present antigens if the ER is infected.

does fucose helps jagged-notch binding ?

Does high amounts of galactose represent other non ER viruses?

HIV, Fc and galactose


Fucose:  lewis antigen decoy/ bacteria binds / in the antibody for polyomaviruses ...triggering nk

Galactose: clotting factor/ bacteria binds / in the antibody for other viruses  HIV etc

Sialic:  anti-inflammation when on antibody for bacteria or large infections / virus binds/  not on antibodies for viruses?

Example: sialic antibodies against T.cruzi

However....there are articles where they say the Fc closes and can not bind to the receptors with sialic acid?

So fucose deficient IgG bound FcR111A (the Fc receptor connected to NK activation) tighter!!

What exactly is happening here?

Thursday, August 24, 2017

Are Dopamine receptors used by flu viruses and strep ?

Does strep attach using dopamine receptors????

parkinson's symptoms and strep ?

sydenham's chorea and strep

strep and antibodies against dopamine receptors

strep and swollen pancreas

choline binding proteins of strep A

How does choline connect with dopamine receptors? Choline is known to increase the amount of dopamine receptors and...

choline antagonizes the dopamine receptors directly

so strep may bind to the dopamine receptors using the choline

Does the flu virus use the dopamine receptors????

the flu virus has a high affinity for dopaminergic neurons

Parkinson's symptoms and the flu

the flu and the pancreas

my previous post of dopamine receptors and A, B & C flu viruses

choline and the flu viruses' envelope

Friday, August 18, 2017

How do Herpes viruses enter into cells do they use the estrogen receptors or the Herpes-entry-mediator?

Viruses are extremely savvy.  Some viruses have evolved to bind the TAM hands of macrophages to  block the destruction of virally infected cells. (Macrophages are the immune system's vacuum)

The "herpesvirus entry mediator" is a TNF receptor. This is not the primary mode of entry of the virus rather an attempt to block the immune response.

TNF alpha is released by macrophages when they are themselves infected. (and unable to function) By blocking the receptors for TNF the viruses are trying to "block" the knowledge that macrophages are infected and stop the activation of neutrophils etc.

Neutrophils are the strongest defense of the intestine

Neutrophils do not have transcription or translation abilities and can therefore deal with viral infections better than macrophages.

Herpesvirus entry mediator

this TNF receptor has high levels in the mucosal membranes

I still contest that the main mode of Herpes viral entry on regular cells is through estrogen receptors.

Alpha-herpes viruses: Herpes simplex 1, herpes simplex 2,  herpes zoster : Estrogen-beta receptors (nerves and uterine tissue)

Beta-herpes viruses: CMV, HHV6, HHV7 :  Estrogen-related receptors (CMV binding confirmed)

Gamma-herpes viruses: EBV, HHV8 : Estrogen-alpha receptors (lymphocytes, breast involved

Estrogen-related receptors and estrogen-alpha receptors cycle to the nucleus which is why these herpes viruses can cause cancer while the Beta-estrogen receptors cycle to the mitochondria where alpha herpes viruses can hide for years.