At the intestine: inner antigens are processed at ILFs while outer antigens are processed in Peyer patches (hypothesis)

At the intestine: inner antigens are processed at ILFs while outer antigens are processed in Peyer patches.

ILF: inducible lymph follicle
https://www.ncbi.nlm.nih.gov/pubmed/12759424

"In contrast to the spleen, LNs and PPs, ILFs are inducible structures developed after birth due to the presence of external stimuli43"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015111/

The MRC marginal reticular cells develop here at the inducible ILF of the intestine.

pericytes in the gut
https://www.ncbi.nlm.nih.gov/pubmed/30937864

Peyer patches have the FRC fibroblast reticular cells.

Brain macrophages : pericytes
https://www.ncbi.nlm.nih.gov/pubmed/10611494

MHC2 expression by pericytes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844098/

pericytes and the BBB
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292164/

peyer patch lacking mice had no IgA only IgG from ILFs
https://www.jimmunol.org/content/jimmunol/173/2/762.full.pdf

Remember the lymph structure and the separate zones for inner and outer antigens:

Then the spleen's separate zones:

Now looking for the MRC and the FRC we find very separate zones in the intestine:

Bee allergy, t.gondii, and the cells cytosol : I am not sure what I am looking at.

cd16 is on Basophils of patients with insect venom allergy
https://www.ncbi.nlm.nih.gov/pubmed/30288810

IgG2 and insect venom allergy
https://link.springer.com/article/10.1007%2FBF00441707

malaria and IgG2
https://iai.asm.org/content/68/3/1252

t.cruzi and IgG2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1577053/

malaria also infects the cytosol
https://science.sciencemag.org/content/328/5980/862/F2

old post about Bee allergy and T.gondii
https://angelabiggs.blogspot.com/2015/04/tgondii-and-bee-venom.html

T.gondii infects the cytosol. Previous hypothesis was that IgG2 is the antibody made against cytosol infections.  I was sorting the Fc receptors with the IgGsubsets...when this occurred to me.

These are not proven just appears to be a pattern
cd16 (fcgammaRIII) binds IgG3 which is high on platelets? mito/nucl viruses
cd16 (fcgammaRIV) binds IgG2b which is high on eosinophils? cytosol infection?
cd64 (fcgammaRI) binds IgG2a cytosol virus?
cd32 (fcgammaRII) binds IgG1 and is high on Langerhans?  outer antigens

Is this why the patients with insect allergy would have cd16?

T.gondii and Bee venom

Do people with bee sting allergies have t.gondii infections?

I have connected T.gondii with a variety of things: Seizures, Epilepsy, schizophrenia....but they are all  autoimmune which means cross-targeting autoimmunity must be occurring. A virus has to trigger the attack at the target tissue from the inside.  Are these autoimmune diseases all bee sensitive because of their connection to T.gondii?


Schizophrenia: t.gondii and the cytomegavirus
http://www.sciencedaily.com/releases/2013/03/130308111315.htm

Bee sting reactions have been found in schizophrenia patients
http://www.ncbi.nlm.nih.gov/pubmed/5239954

I have connected in the past seizures/epilepsy with t.gondii and enteroviruses 
http://angelabiggs.blogspot.com/2015/01/nodding-disease-epilepsy-seizuresare.html

Seizures and bee stings 
http://epilepsyfoundation.ning.com/group/support-for-cps/forum/topics/bee-stings-and-seizures?commentId=2217546%3AComment%3A908079&xg_source=activity&groupId=2217546%3AGroup%3A819391
http://www.ncbi.nlm.nih.gov/pubmed/22100477
http://www.japi.org/february_2012/11_cr_stroke_after_multiple.pdf

epilepsy and wasp stings
http://www.ncbi.nlm.nih.gov/pubmed/8844507
http://jnnp.bmj.com/content/74/1/134.2.full

Does Apis mellifera venom (honey bee venom) effect T.gondii?

I can't see this paper to find out: 

• Effect of Bee Venom on Toxoplasma gondii Tachyzoites in vitro - Ahmad G. Hegazi, Hassan A. El-Fadaly and Ashraf M. BARAKAT (Egypt)

T.gondii is carried by mice and cats
T.cruzi is carried by kissing bugs and the dogs that eat them

T.cruzi which causes changas is killed by honey bee venom
http://www.ncbi.nlm.nih.gov/pubmed/23562368

The Kissing bug carries the T.cruzi the way mice carry T.gondii
http://blog.mysanantonio.com/animals/2013/09/san-antonio-humane-society-says-chagas-disease-possible-in-local-dogs/
note that kissing bugs are nocturnal so keep your pet in at night

Hymenoptera are the venom group of  Apoidea (bees), Vespoidea (wasps, hornets, and yellow jackets), and Formicidae (ants). 

What is it in the bee sting that Toxoplasmas dislike? perhaps the compound apamin which can cross the blood brain barrier. (our nerves don't like it either)
http://pubs.acs.org/doi/abs/10.1021/bi00682a035

Interestingly HoneyBee venom has been a remedy for malaria too.

Panafrican News Agency (PANA). 17 September 1997. Yahya el Hassan. "Curing Malaria with Bee Stings in Sudan." [Internet]. [Accessed 24 Dec. 1998].

https://books.google.com/books?id=JlSJDj5Lt98C&pg=PA153&lpg=PA153&dq=bee+stings+and+malaria&source=bl&ots=kXRWjUnlba&sig=Q7s5Av9JLOys_nMEi8I5pfzmRUg&hl=en&sa=X&ei=oeQlVZaHA8K1oQTxpoHACQ&ved=0CCkQ6AEwAg#v=onepage&q=bee%20stings%20and%20malaria&f=false

il-27, 25HC, and IgG2a against cytosol viral infections ?

il-27 induces IgG2a from Bcells
https://www.ncbi.nlm.nih.gov/pubmed/15294962

il-27 induces 25hc
https://www.researchgate.net/figure/IL-27-specifically-induces-cholesterol-25-hydroxylase-Ch25h-expression-and-25-OHC_fig1_320017159

https://www.researchgate.net/publication/320017159_IL-27-Induced_Type_1_Regulatory_T-Cells_Produce_Oxysterols_that_Constrain_IL-10_Production

25HC blocks viral entry
https://www.ncbi.nlm.nih.gov/pubmed/25501851

https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=27086126

Does 25hc help create exosomes which then binds with dendritic cells and SCS lymph cells?

cd169 binds 25HC to capture exosomes
https://www.ncbi.nlm.nih.gov/pubmed/24255917
https://www.ncbi.nlm.nih.gov/pubmed/29425504

Complement and  IgG2a
https://www.jimmunol.org/content/178/1_Supplement/S159.5
https://www.ncbi.nlm.nih.gov/pubmed/6610105

IgG2a and influenza
https://cvi.asm.org/content/13/9/981

IgG2a with viruses and parasites?
https://academic.oup.com/intimm/article/12/2/223/652665

Does 25hc hold viruses on the surface? how would complement work?

Hypothesis: il-27 cytokine is secreted by B cells when there is a viral infection or cancer damage involving the cytosol of cells.

Hypothesis: il-27 cytokine is secreted by B cells when there is a viral infection or cancer damage involving the cytosol of cells.

p53 and il-27
http://clincancerres.aacrjournals.org/content/clincanres/early/2016/05/27/1078-0432.CCR-15-2052.full.pdf

Is il-27 involved with DNA damage?

melanoma and il-27
https://www.ncbi.nlm.nih.gov/pubmed/18453571

melanoma is a cancer caused by DNA damage (from sun exposure)

DNA damage and the cytosolic sensors
http://jem.rupress.org/content/215/5/1287

B cells major source of il-27
https://www.jimmunol.org/content/200/1_Supplement/107.5

B cells produce IgG2a (class switch) after il-27
https://www.jimmunol.org/content/173/4/2479.long?utm_source=TrendMD&utm_medium=cpc&utm_campaign=J_Immunol_TrendMD_0

IgG2a against reoviruses and parasites
https://academic.oup.com/intimm/article/12/2/223/652665

il-27 attracts myeloid dendritic cells to the lymph
https://www.jimmunol.org/content/192/6/2634

previous hypothesis:
myeloid dendritic cells are involved with infections of the cytosol
plasmacytoid dendritic cells are involved with infection of the mitochondria/ nucleus

il-27 not il-35 suppresses gm-csf
https://www.nature.com/articles/s41598-017-16702-w


GM-csf is involved with vacuole bacteria and TH17 triggering

GM-csf exposed Basophil's produce il-6 and trigger th17
https://www.nature.com/articles/srep41744

GM-csf exposed mDendritic make il-23
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297527/

As a cytosol infection TH1 is involved
https://www.nature.com/articles/7310017?error=server_error

il-27 is saying it is in the cytosol..what ever it is...not a bacteria hiding in the cytosol or in a virus in the nucleus or mitochondria.

Furthermore

il-27 suppressed il-5 and il-13 from TH2 cells which is used against parasites in the cytosol. Which means il-27 could be strictly a cytokine for viruses or for DNA from cancer in the cytosol?

https://www.jimmunol.org/content/179/7/4415

When does the B cell decide to make il-27? Does the T follicular cell recognize it as DNA and signal back to the B cell?

IgG2, cytosol infections, and the lectin pathway.

Complement activation and Antibodies
https://www.ncbi.nlm.nih.gov/pubmed/20151159

Classical pathway: IgG1 and IgG3

Alternative and lectin: IgG2 and IgG4

LPS triggers the TLR4 or the lectin-mannose complement activation.  These tend to be the type of infections that can move inside of cells.  Some infections move into the vacuoles and organelles others the cytosol.

Strep has even been shown to move inside of cells allowing the bacteria to survive antibiotics. https://www.ncbi.nlm.nih.gov/books/NBK333420/

basophils as APC to TH2 inducing il-13
https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.201040588

IgG2, GSDMD, and cytosol infections

Hypothesis: GSDM pores are windows for eosinophils

Does the GSDM pore hold the infection inside of cells at the surface and allow eosinphils to phagocytosis infected cells through antibody binding at the pore?

il-13 and IgG2 production by B cells
https://www.ncbi.nlm.nih.gov/pubmed/10415009

High IgG2 and Cryptococcus neoformans 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828574/

Cryptococcus neoformans inside macrophages
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127716/

il-13 and C. neoformans
https://www.ncbi.nlm.nih.gov/pubmed/17911623

Does the GSDM pore hold the infection inside of cells at the surface and allow eosinphils to phagocytosis infected cells through antibody binding at the pore?

IgE at the skin's IGF-1  with the GSDMA pore
IgA , GH with GSDMB
IgG1,  insulin with GSDMC

IgG2 with GSDMD...all areas involving cytosol infections

High IgG2 and Plasmodium
https://iai.asm.org/content/iai/68/3/1252.full.pdf

Plasmodium are inside erythrocytes
https://academic.oup.com/femsre/article/40/5/701/2198099

eosinophils and plasmodium (malaria parasite)

mycobacteria and cytosol
https://academic.oup.com/femsre/article/43/4/341/5420823

mycobacteria and IgG2
https://gh.bmj.com/content/4/Suppl_3/A31.2

mycobacteria and GSDMD
https://www.biorxiv.org/content/biorxiv/early/2019/02/17/514125.full.pdf

Stromal cells produce cxcl13 attracting B cells and they have 3 areas of importance

Stromal cells produce cxcl13 attracting B cells and they have 3 areas of importance: two stromal cells in the lymph node ; one area is for internal antigens and  the other area is for outer antigens. The third stromal cell area is for catching infections that have escaped the gut's organs in the omentum zone.

adipose stromal cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481843/

omentum milky fat spots have adipose stromal cells (ASC) which produce the CXCL13
the B1 cells involved there are the primary source of IgM
https://www.researchgate.net/publication/265860846_Human_adipose_tissue-derived_mesenchymal_stromal_cells_promote_B-cell_motility_and_chemoattraction

Marginal Reticular cells MRC are mesenchymal stromal cells of the scs area

Fibroblastic Reticular cells  FRC are bundled into the conduit leading to the follicular dendritic cells

All 3 of these stromal subsets make cxcl13 which attract B cells and follicular T cells thus creating the germinal centers
https://www.ncbi.nlm.nih.gov/pubmed/28454789

The MRC-SCS zone creates antibodies against the inner antigens (IgG2 or IgG3)  while the FRC-FDC zone creates the antigens against the outer antigens.  (IgG1 at the spleen, IgE at the lymph, and IgA dimers in peyer patches.)  The milky spots with the ASC attract the B1 cells thus producing IgM.

MRC was thought to transport antigens from SCS to FDC which could be the differentiation of MRC into FDC of inner antigens.
http://jem.rupress.org/content/211/6/1109
https://www.ncbi.nlm.nih.gov/pubmed/?term=jem.20132409

Does SCS not present to B cells directly rather hands the antigen to MRC who presents?

Here is a paper that has the SCS handing off to a nonphagocytic cell they call ATC (antigen transporting cell ) that appears to mature into a FDC type of cell
https://www.jimmunol.org/content/131/4/1714.long

MRC as phagocyte of apoptotic B cells
https://www.ncbi.nlm.nih.gov/pubmed/29686051

Is this incase the B cells are infected?

the conduit transports soluble antigens
https://www.ncbi.nlm.nih.gov/pubmed/15664156

Langerhans bring antigen through conduit
https://www.ncbi.nlm.nih.gov/pubmed/16818784

exosomes derived from dendritic cells migrate to spleen
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320445/

cd169 mediates the capture of exosomes
https://www.ncbi.nlm.nih.gov/pubmed/24255917

25hc and viral infections
https://www.nature.com/articles/nri3755/figures/4

immature exosomes teach tolerance while mature dendritic cell exosomes induce immune reaction
https://link.springer.com/article/10.1007/s10753-012-9539-1

scs and viral infection of the central nervous system
https://www.nature.com/articles/nature09118