Tuesday, May 8, 2018

Hypothesis: Dendritic cells match up with the 3 zones of the adaptive immune system

The adaptive immune system focuses on 3 zones: outside of cells, in the cytosol of cells, and inside the mitochondria or nucleus of cells.

4 Dendritic cell types exist: FDCLymphatic dendritic, myeloid dendritic, and plasmacytoid dendritic


The germinal center is where the BCR, b cell receptor, judges the antigens outside of cells.  B cells are educated to know self of the outside.

THE OUTSIDE

The Follicular dendritic cells, FCD, are not from the bone marrow.  FDC are generated from local tissue. They have a starfish like shape and hold the antigens they collect from the lymph river up for the B cell receptor all over it's surface.   FDC never leave the lymph.

The lymphatic dendritic cell is also star shaped and hold antigens up the same way to B cells but travels from bone to the site of infection to collect antigens then goes to the lymph gland.  (these do not develop from monocytes rather CLP cells)

The BCR grabs the antigen off the dendritic cell surface, processes it and the B cell then holds it up for the FTH follicular t helper cell which then releases cytokines triggering the B cell to make antibodies. IgG1 (insulin high) or IgA (GH high) or IgE(IGF-1 high)

The B cells  hypersomatic mutation of the BCR occurs in this Germinal Center region until the BCR has strong affinity for the antigen.


The rim regions of the lymphatic gland is where the TCR, t cell receptor, judges the antigens.  The TCR  of T cells is educated for inside the cell.

THE CYTOSOL

The myeloid (conventional) dendritic wear tyro3 hands which allow them to ingest virally infected cells.
The myeloid dendritic cells then hold the cytosolic RNA viruses or proteins in MHC2 up for TH1 who then stimulate B cells to make IgG2.

Myeloid dendritic cells secrete il-12 which would favor the development of TH1.

How does the IgG2 see the cytosol RNA virus?  HYPOTHESIS: 25HC flips viral RNA that it binds in the cytosol of infected cells and holds it out.

note that the antiviral activity of 25HC is known but now it functions is unclear
https://www.nature.com/articles/srep07487


THE MITOCHONDRIA AND THE NUCLEUS

The plasmacytoid dendritic holds DNA viruses up in MHC1 to Tc which stimulates B cells to make IgG3.  Some Tc become CTL.

Both myeloid and plasmacytoid develop from circulating monocytes upon tissue entry. Plasmacytoids injected with RNA will revert to myeloids.

Note that the butterfly nets for DNA : TLR7 and TLR9 are on these plasmacytoid dendritic cells and when triggered causes the secretion of IFNalpha.


Extra:
Germinal Center B cells appear to be using insulin, growth hormone, and insulin-like-growth-factor to decide which antibody to make IgG1, IgA, or IgE.  The spleen grows into the pancreas, HG is high at the guts peyer patches, and IFG-1 is high in lymph glands near skin.

These same hormones could be determining the differentiation of monocytes where the presence of insulin determines macrophages.

Mice without IGF-1 were deficient in dendritic cells
http://www.jimmunol.org/content/176/8/4651

Insulin appears to have a relationship with macrophages
http://bio.biologists.org/content/7/1/bio026187
does it determine differentiation?

second extra:
How does the immune system see into the nucleus, mitochondria, or vacuoles ? (bacterias like to hide in vacuoles in the cytosol) HYPOTHESIS: the TH17 cells are responsible for popping these internal membranes.
http://angelabiggs.blogspot.com/2017/10/th17-called-for-second-popping-of.html








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