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

IgG2 27HC or inflammasome triggering phagocytosis: How does IgG2 work? Updated with exosomes and HC patterns

Hypotheses:
27HC binds cytosolic viruses and holds them outside of the cell membrane while inflammasomes create GSDM windows in the membrane for the antibodies to bind large cytosol infections.

Or HC could mark the exosomes based on what it's carrying. Cancer vs cytosol virus or mito/nuclear virus so the cd169 cells who pick up the exosomes know what they have.

IgG2 and phagocytosis by neutrophils and monocytes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1457935/
https://iai.asm.org/content/iai/63/3/1070.full.pdf

influenza and phagocytosis
http://www.jimmunol.org/content/178/4/2448

25HC and inflammatory reaction to influenza
https://www.ncbi.nlm.nih.gov/pubmed/24994901

Exosomes and HC

Exosomes and dendritic cells
https://www.nature.com/articles/s41598-017-16609-6

cd169 (of scs macrophages in the lymph) mediates capture of exosomes
http://www.bloodjournal.org/content/123/2/208?sso-checked=true

exosomes and lymph nodes
https://www.sciencedirect.com/science/article/pii/S1084952116304414

25-HC enveloped viruses and 27-HC non-enveloped viruses
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265783/

Or are these nuclear/mito viruses? Herpes, flu, HIV, and HBV are all nuclear/mito viruses that would be taken up by pDendritic

27-HC Breast cancer exosomes
https://www.researchgate.net/publication/293885899_Mass_spectrometric_detection_of_27-hydroxycholesterol_in_breast_cancer_exosomes

Cancers are started by nuclear viruses but they are are growing out of control without viral participation rather they are open book growth. (the carcionogen inhibited the virus)

scs with cd169 presents viral proteins to B cells
https://www.ncbi.nlm.nih.gov/pubmed/17934446

Does the 27HC hold the viral RNA outside of infected cells for dendritic cells?

Flu B and C infects the cytosol of cells and the 25HC secreted by macrophages would insert themselves in the membranes of cells in the region...and hold the foreign viral RNA outside of the cells?

But for type A which infects the mitochondria it would lower il-10?

How does the RNA viruses in the cytosol get seen by antibodies of the immune system if the MHC1 is for mitochondrial and nuclear infections?

the inflammasome and Actinobacillus actinomycetemcomitans
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490745/

IgG2 and Actinobacillus actinomycetemcomitans
https://iai.asm.org/content/iai/63/3/1070.full.pdf

when the inflammasomes are involved the cells get IgG2 phagocytosis by eosinophils?

The infected cells were surrounded by eosinophils
https://pdfs.semanticscholar.org/a96e/7dd46755be7d0fe30724dfe926e1859e6133.pdf

neutrophils and IgG2 killing of actinobacillus
https://iai.asm.org/content/63/3/1070

when the actinobacillus is not in the cytosol but outside of cells?

Older hypothesis post
https://angelabiggs.blogspot.com/2018/04/igg2-hypotheses-requests-role-of-25hc.html

newer hypotheses
https://angelabiggs.blogspot.com/2019/02/hypothesis-gsdm-pyroptosis-is-parasite.html

ox40l and the immune system teams involved in the 3 zones

The ox40 ligand appears on activated cells.  When the T cells finally express ox40 it must determine or verify which of the 3 zones are active.

The cytokines and cytokine receptors delineating the teams 

The ox40L appears as members of a team become activated. Ideally only one team is on at a time.  The T cells which travel between the inflammation and the lymph, talk to the rest of the immune system, and are responsible for telling the B cells which antibody to make verifies which pathway is in progress.

 So what happens in autoimmune disease when 2 of these pathways are activated at the same time on one target tissue: flu virus (cytosol) and e.coli (outside) on the pancreas triggering autoimmune diabetes.

The natural Tregs that focus the pathway reactions are not activated? unclear
https://www.ncbi.nlm.nih.gov/pubmed/30021159

Contemplating the 3 zones the immune system sees: the cytosol, the nucleus/mitochondria, and outside of the cell.