IgG4 antibodies

Autoimmune hypothesis: Two infections on one target triggers autoimmune disease. One infection inside and one infection outside of the cell.

Does the B cell that gets pulled from outside antigen pathways to inside antigen pathways become the IgG4 producing B cell with the goal of shutting down the outside pathways?

This would mean that the IgG4 would be similar based on the large infection and the pathway stopped if the autoimmune diseases share the same large infection.    For example, all mycobacteria triggered autoimmune diseases would have the same IgG4 against aquaporins.

IgG4 antibodies represent a down-regulatory response
https://www.ncbi.nlm.nih.gov/pubmed?term=24111912

IgG4 made by Bcells that produce il-10
https://www.jacionline.org/article/S0091-6749(13)00150-4/pdf

Br1 up regulate the plasma cells to become IgG4 producing
https://www.jacionline.org/article/S0091-6749(16)30722-9/pdf


Anti-Aquaporin

Mycobacteria and other bacterial cytosol infection which involve eosinophils and macrophages in a phagocytosis method appear to develop anti-AQP ( aquaporin antibodies)

aquaporins move eosoinophils
https://www.ncbi.nlm.nih.gov/pubmed/18510218

anti-aquaporin4 and multiple sclerosis
https://www.ncbi.nlm.nih.gov/pubmed/20705110

mycobacteria and multiple sclerosis
https://www.sciencedaily.com/releases/2010/02/100226084007.htm

idiopathic demyelination and anti-AQP4
https://www.hindawi.com/journals/msi/2017/1359761/

anti-aquaporin4 in neuromyelitis
https://www.ncbi.nlm.nih.gov/pubmed/18808744

salivary glands and parkinson's disease
https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=838

salivary gland and psoriasis
https://www.ncbi.nlm.nih.gov/pubmed/7165375

salivary glands and aquaporins
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783900/

parkinson's and mycobacteria
https://www.ncbi.nlm.nih.gov/pubmed/25459140

psoriasis and mycobacteria
https://www.ncbi.nlm.nih.gov/pubmed/9657322

aquaporin and psoriasis
https://www.ncbi.nlm.nih.gov/pubmed/21400035

(Candida also has portions move to the cytosol)

SJ and salivary
https://www.ncbi.nlm.nih.gov/pubmed/1055974

Candida and SJ
https://www.ncbi.nlm.nih.gov/pubmed/12973284

SJ and MS because of salivary
https://www.jwatch.org/jn200112200000006/2001/12/20/possible-association-between-sjogrens-syndrome


Anti-insulin

Type one diabetes : coxsackie/flu  and e.coli

Neutrophils kill e.coli. How are these connected to insulin?

neutrophils suppress insulin signalling ( enzyme secreted disrupts the receptor)
https://stke.sciencemag.org/content/5/243/ec250

Insulin seems to be required for the functioning of neutrophils.
https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1189/jlb.0104050

Does anti-growth hormone match up with celiac disease and anti-IGF-1 match up with alopecia? Is the IgG4 trying to stop the outer antigen pathway?

celiac and Growth hormone deficiency
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570481/

alopecia and IGF-1 deficiency
https://www.sciencedirect.com/science/article/pii/S1087002415305372

Does it always switch to il-10 and no IFN when B switches places or is it like this?

Anti-gangliosides

Involves vacuole bacteria

Guillian-barre and anti-gangliosides
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422685/

http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2018;volume=66;issue=5;spage=1324;epage=1331;aulast=Baskar

https://www.researchgate.net/publication/325884578_Anti-ganglioside_Antibodies_in_Peripheral_Nerve_Pathology

natural killer cells

il-15 and gangliosides
https://www.ncbi.nlm.nih.gov/pubmed/16116192

gangliosides in autism
https://www.ncbi.nlm.nih.gov/pubmed/9766735

sutterella and autism spectrum disorder
https://molecularautism.biomedcentral.com/articles/10.1186/2040-2392-4-42


Anti-ANCA / anti-ANA

involves golgi/ER bacterias

salmonella and anti-ANCA
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905360/

reactive arthritis and salmonella
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195798/

anti-ANCA bind the neutrophil traps
https://www.frontiersin.org/articles/10.3389/fimmu.2017.00439/full

Anti-ANCA and Rheumatoid
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552688/

anti-nuclear in strep with tourettes
https://www.ncbi.nlm.nih.gov/pubmed/12699862

TLR8 and strep
http://www.jimmunol.org/content/195/3/1092

TLR8 is the Tcell mailbox for the Endoplasmic reticulum

polyarthritis and strep
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803937/


Anti-leiomodin

Nodding disease is triggered by the parasitic worm and what virus? The IgG4 was found against leiomodin-1.  Nodding disease is autoimmune disease of the skin where the autoantigen attacks the brain?

Autoimmune cross-targeting hypothesis: two infections on one tissue. The reaction is at the skin but then the antibody attacks the brain?

 For these worms how does this work? The Leiomodin-1 antibody bound the worms...but they were IgG4?

When exposed to cold temperatures or food the children nod their heads uncontrollably. The hippocampus of the brain is responsible for body temperature sensations and hunger urges.

The worm is not in the hippocampus but the autoantibody shows up there.
https://www.ncbi.nlm.nih.gov/pubmed/28202777

Which virus at the skin has co-infected and caused the IgG4?

Does this mean that leiomodin-1 is involved with eosinophils degranulation attack? Since eosinophils at the main cell type attacking the worms how would this work?

eosinophils and smooth muscles
https://www.ncbi.nlm.nih.gov/pubmed/23180361

The autoimmune hypothesis and BR1

B regulatory cells

There are 3 types of B regulatory cells (all with CD38 like T regs)

The ones created from naive B cells, possibly in the bloodstream could be involved in cancer.
These B regs secrete TGF-b1 and il-10 focusing the reaction on CTL pathways. Nuclear viral infections have been connected to cancer.

Bregs and cancer
https://www.hindawi.com/journals/jir/2014/215471/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891151/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549607/

I suspect il-9 involvement with these B regulatory cells but I have found no evidence yet.

The ones created from marginal zone B cells with IgM BCRs may focus the immune system like natural T regs.  These Bregs secrete il-10 and il-35 focusing the reaction on outer antigens. (do they have cd27+ because of the IgM?)

il-33 activates B1 and marginal zone B cells
http://www.jimmunol.org/content/186/4/2584
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012142/

il-33 is released by cells during necrosis (cells damaged and dying). il-33 also stimulates Th2 pathway cells like: eosinophils mast cells, and basophils.  This makes sense in that when the tissue is damaged, like a cut,  there is a risk of infection.

The ones created from  cd27+ plasma cells in the germinal center region which stops the reactions similar to inducible T regs. 

il-35 Bregs
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433835/

Hypothesis:
il-10 stops TH1 pathways (cytosol antigen)
il-35 stops CTL pathways (nuclear or mito antigen)
TGF-b1 stops TH2 pathways (outer antigen)

Corrected...some how I had this mixed up

Exosomes, internal antigens, dendritic cells, and the lymph

How do myeloid and plasmacytoid dendritic cells get viral antigens from inside infected cells? From exosomes? 

What about viruses that infect the nucleus or the mitochondria?

Cells infected with mitochondrial virus HCV secrete exosomes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479672/

When entering the lymph node the exosomes get absorbed by the SCS while larger antigens move down the conduit? how does that work?

Langerhans has the ability to pull through collagen fibers
https://www.ncbi.nlm.nih.gov/pubmed/1431200

Marginal zone B cells and pulling through collagen
https://www.cell.com/immunity/supplemental/S1074-7613(05)00339-0

The conduits in the lymph node/spleen are a network formed by collagen fibers

mDendritic and pDendritic squeeze between the scs cells using "dock8"
http://www.bloodjournal.org/content/119/19/4451?sso-checked=true
fantastic images

Are exosomes blocked from conduit travel?

Update on influenza infections

Update on influenza infections

Hypothesis:

Type A infects the cytosol and then the nucleus
Type B and C infect the cytosol

flu ssRNA and pDC/TLR7
http://europepmc.org/articles/PMC4104278/

Shows flu going into cytosol and then the nucleus
http://www.virology.ws/2009/05/06/release-of-influenza-viral-rnas-into-cells/

influenza A in the nucleus and the cytosol
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814596/

th17 and influenza A
https://www.ncbi.nlm.nih.gov/pubmed/19265125

type A goes to the mitochondria?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715299/

type A and B enter the cell differently
https://www.ncbi.nlm.nih.gov/pubmed/22855501

only the D2 receptor altered mitochondria movement ?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2467486/

Previous post:

Hypothesis: Virus families use receptor families. The flu viruses use dopamine receptors.

type A  D2

type B  D1

type C  D5

D2 receptors are expressed on the pancreas

http://www.jbc.org/content/280/44/36824.long

Type A flu viruses appear to infect pancreatic cells

http://jvi.asm.org/content/87/1/597.full

Type B influenza have produced rashes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280815/
https://www.researchgate.net/publication/259984175_Rash_associated_with_influenza_B_virus_infection

Dopamine 1 receptors are in the dermal skin layer
https://www.ncbi.nlm.nih.gov/pubmed/23241131

Previous post
http://angelabiggs.blogspot.com/2016/08/5-types-of-dopamine-receptors-and-how.html


interesting flu paper dealing with medications
https://helda.helsinki.fi/bitstream/handle/10138/44824/denisova_dissertation.pdf