Friday, November 24, 2017

Cytokine families

The functionality of cytokines becomes obvious when they are organized into groups.

Type one cytokines work primarily at the Hematopoiesis and these can be divided into 3 groups:

Cytokines using beta chains, cytokines using gamma chains, and the GP130 cytokines.

The development from myeloid progenitor cells involves the beta chain cytokines;

the development from lymphoid progenitor cells involves the gamma chain cytokines;

 and the GP130 cytokines are powerful regulators.  GP130 cytokines control neutrophils,

macrophages, natural killer cells, the "on switches or launch codes" for B cell development il-4 and

il-12, and the  "on switch " for either Treg or TH17 cells.

cytokine receptor family review
http://www.sinobiological.com/Cytokine-Families-Cytokine-Family-a-5797.html

The GP130 Family: il-6, il-11, and TGF-beta

il-6 monocytes to macrophages
https://www.ncbi.nlm.nih.gov/pubmed/10848814

il-6 controls il-4
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196041/

il-11 stops the macrophages from producing il-12
https://www.ncbi.nlm.nih.gov/pubmed/11940481

il-11 and Nk development
https://www.ncbi.nlm.nih.gov/pubmed/15499555

TGF beta and TH17
https://link.springer.com/chapter/10.1007/978-1-4419-9371-7_3

(TH17 can be started by il-6 or TGF-beta1 but it is my hypothesis that different cytokines result )

GP130
https://en.wikipedia.org/wiki/Glycoprotein_130

il-10 is the stop cytokine

il-10 stops pg130 cytokines (neutrophils macrophages and NKs)

il-10 stops T FH cells from secreting il-4 and il-21 which stops the GC from producing B cells

 il-10 and gp130
https://www.ncbi.nlm.nih.gov/pubmed/22140267


Cytokines using Beta chains: il-3, il-5, GM-CSF are all on the myeloid side

Cytokines using Gamma chains: il-2, il-7, il-15, il-21, il-4, il-9  are all on the lymphoid side


The il-1 family cytokines and Chemokines

When an infection occurs the first cytokine made by macrophages and monocytes is the  il-1 family cytokines.

il-1 family cytokines trigger cells to cytokine rain. This produces massive amounts of chemokines.

il-1 induces fibroblasts to produce chemokines which are attractant proteins.

il-1 also induces the expression of adhesion proteins so the arriving immune system knows where to stick.


The IFN family cytokines 
These cytokines identify where inside the host cell the virus is hiding and coordinates the immune response attack. Which HLA to express and which TAM hands to wear.

cytosol            TLR4     IFNbeta      HLA-D               Tyro3
Nucleus/ Mito    TLR7/9   IFNalpha    HLA-A HLA-B   Mer
Endoplasmic R   TLR 8     IFNgamma HLA-C                 Axl
Golgi               TLR3 IFN lambda


The il-20 Family Cytokines: the H+ pore cytokines il-20, il-19, il-24, and il-26 ? this hypothesis is still being tested

il-26 and pore structure...and TLR9
https://www.ncbi.nlm.nih.gov/pubmed/?term=il-26+pore

The TH17 cells are involved with the second popping.

il-23 and il-6 trigger Th17 secreting cytokines against hiding bacteria: il-24 the golgi and il-22 the vacuoles.

(dendritic cells secrete il-23 after TLR4 stimulation and B cells secrete il-6 after TLR4 stimulation which is two sources of verification. )

When the virus is hiding in the nucleus or the mitochondria these organelles must be opened in order for the virus to be seen.

il-21 is made by Tcd8+ cells exposed to il-6  and TGF-B1 ( secreted when the mitochondria and nuclear TLR 9/7  of cells are triggered) cause Th17 to secrete il-19 the mitochondria and il-26 the nuclear pore.

Summary:
 il-24 golgi
il-22 vacuoles
il-19 mitochondria ?
il-26 nuclear membrane  (or extra cellular bacteria)

is il-20  the plasma membrane?

il-24 salmonella in the golgi
https://www.ncbi.nlm.nih.gov/pubmed/19830736    il-24 salmonella
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC204495/  Salmonella and golgi

il-22 inhibited autophagy
http://www.ijbs.com/v08p0249.htm

autophagy is required for hyper mucus production
https://www.ncbi.nlm.nih.gov/pubmed/26671423
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044763/

Is il-19 the mitochondria and il-26  the nucleus?
http://angelabiggs.blogspot.com/2018/02/il-19-is-mitochondrial-pore-il-26-is.html



 il-18 is the ER which means the cells have lost their self proteins and can be attacked like an infection but still need the TH17 because the infection is hiding in the ER.



il-35 is the complete stop cytokine, one level up from il-10, this cytokine stops inflammation as well as the immune reaction.  The key cytokine of Treg and Breg suppressing reactions. 

il-35 is secreted by T regulatory and is required for their function
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008395/

il-35 and B regulatory cells
https://f1000.com/prime/718289707
http://www.sciencedirect.com/science/article/pii/S0091674917314343

il-35 stops th17
https://www.ncbi.nlm.nih.gov/pubmed/17874423 

This Th17 section with the hiding infections is a hypothesis and needs to be proven.

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