Th1-Th2-Th17 Responses

 

The yin-yang of cytokines. The balance between pro-inflammatory cytokines and anti-inflammatory cytokines is critical in determining outcome. Chemokines have preferred partners that link cell trafficking to function, as indicated. Angiogenesis, tissue replacement (fibrosis) and regeneration predominantly fall within the influence of the more anti-inflammatory axis. 

https://www.researchgate.net/figure/The-yin-yang-of-cytokines-The-balance-between-pro-inflammatory-cytokines-and_fig1_232736146

 

 

https://www.researchgate.net/figure/235730606_fig2_Balance-between-pro-and-anti-inflammatory-cytokines

 

https://www.researchgate.net/figure/Pro-and-Anti-inflammatory-cytokines-balance-IgA_fig1_305405169

https://www.selfhacked.com/blog/il-10/

Higher IL-10 was associated with more white matter volume in visual areas and tracts [12].

https://www.selfhacked.com/blog/il-10/

 

 

https://www.sinobiological.com/Proinflammatory-cytokines-list.html

 

 

File:Th1-Th2-Th17-Treg origin.png - Wikipedia
https://en.wikipedia.org/wiki/File:Th1-Th2-Th17-Treg_origin.png

 

Inflammation and Cancer

https://oncohemakey.com/inflammation-and-cancer/

 

Cell-Mediated Immunity

Cell-mediated immunity is the result of cooperation between innate and adaptive immunity to
destroy virus infected cells before they can produce more virus
damage pathogenic bacteria, fungi, and parasites
eliminiate cancerous cells that lack normal cell surface proteins
Cells involved in immunity can be divided into
primary effector cells such as
granulocytes
macrophages
CD8+ T-cells
natural killer (NK) cells
secondary support cells such as
CD4+ helper T-cells
dendritic cells
Cell-mediated immunity can result from
innate immune response
activation of T-cells
coordination of cells via cytokines
Important Cytokines in Cellular Immunity
Cytokines are key coordinators of the cellular immune response by promoting
vascular changes near the site of inflammation
recruiting of other target cells
differentiation of target cells
signaling to distant organs
Cytokines can be secreted by a variety of cells including
activated macrophages
helper T-cells
killer T-cells

Effector Mechanisms
Macrophage and neutrophil killing depends upon
oxygen-dependent mechanisms such as respiratory burst
oxygen-independent mechanisms including
hydrolytic enzymes that destroy peptides
defensins that form holes in bacterial membranes
lactoferrin that binds iron and denies it to bacteria
lysozyme that cleaves bacterial peptidoglycan walls


NK and cytotoxic CD8+ T-cell killing depends upon three mechanisms including
exocytosis of cytotoxic granules containing
granzymes that are apoptosis activating serine proteases
perforin that makes a hole in membranes
Fas ligand that directly signals target cells to undergo apoptosis
cytokine signaling mainly through TNF pathways that also induce apoptosis
Notably NK cells are inhibited by MHC complexes on the surface of cells

Cell-Mediated Immunity - Immunology - Medbullets Step 1
https://step1.medbullets.com/immunology/105050/cell-mediated-immunity

 

Potential mechanism behind the hygiene hypothesis

Potential mechanism behind the hygiene hypothesis - Thryve - Medium
https://medium.com/@thryve/potential-mechanism-behind-the-hygiene-hypothesis-b26ab5d212c5

 

Radiation Research 178(6) , October 2012 

Cytokinnes in Radiobiological Response: An Review

University of California, Los Angeles

Dörthe Schauem Evelyn L Kachikwu, William H Mcbride

Cytokines function in many roles that are highly relevant to radiation research.

This review focuses on how cytokines are structurally organized, how they are induced by radiation, and how they orchestrate mesenchymal, epithelial and immune cell interactions in irradiated tissues.

Pro-inflammatory cytokines are the major components of immediate early gene programs and as such can be rapidly activated after tissue irradiation. They converge with the effects of ionizing radiation in that both generate free radicals including reactive oxygen and nitrogen species (ROS/RNS). "Self" molecules secreted or released from cells after irradiation feed the same paradigm by signaling for ROS and cytokine production.

As a result, multilayered feedback control circuits can be generated that perpetuate the radiation tissue damage response. The pro-inflammatory phase persists until such times as perceived challenges to host integrity are eliminated.

Antioxidant, anti-inflammatory cytokines then act to restore homeostasis. The balance between pro-inflammatory and anti-inflammatory forces may shift to and fro for a long time after radiation exposure, creating waves as the host tries to deal with persisting pathogenesis.

Individual cytokines function within socially interconnected groups to direct these integrated cellular responses. They hunt in packs and form complex cytokine networks that are nested within each other so as to form mutually reinforcing or antagonistic forces. This yin-yang balance appears to have redox as a fulcrum.

Because of their social organization, cytokines appear to have a considerable degree of redundancy and it follows that an elevated level of a specific cytokine in a disease situation or after irradiation does not necessarily implicate it causally in pathogenesis.

In spite of this, "driver" cytokines are emerging in pathogenic situations that can clearly be targeted for therapeutic benefit, including in radiation settings. Cytokines can greatly affect intrinsic cellular radiosensitivity, the incidence and type of radiation tissue complications, bystander effects, genomic instability and cancer. Minor and not so minor, polymorphisms in cytokine genes give considerable diversity within populations and are relevant to causation of disease. Therapeutic intervention is made difficult by such complexity; but the potential prize is great.

 

The yin-yang of cytokines. The balance between pro-inflammatory cytokines and anti-inflammatory cytokines is critical in determining outcome. Chemokines have preferred partners that link cell trafficking to function, as indicated. Angiogenesis, tissue replacement (fibrosis) and regeneration predominantly fall within the influence of the more anti-inflammatory axis. 

 

Cytokines drive the formation of inflammatory lesions working together with DAMPS to generate a pro-inflammatory, pro-oxidant microenvironment. The vasculature becomes leaky, allowing infiltration by neutrophils, and then macrophages and lymphocytes that migrate along chemokine gradients. Acute phase proteins, including cytokines, are generated along with a fair measure of cell death. In the periphery, cells may become more resistant to death and infection. Hypoxia may occur and in time the lesion resolves under the influence of anti-inflammatory cytokines and cells. Macrophages develop an M2 rather than an M1 phenotype. Angiogenesis and/or vasculogenesis assists either tissue regeneration or replacement with extracellular materials (fibrosis).

 

 

ROS can be generated from many sources following irradiation. Released nucleotides including ATP can activate P2X purinergic receptors to open the cation pore and trigger calcium-dependent intracellular processes. This is required for activation of NADPH oxidases that can also be activated by TLR signaling to generate superoxide. Radiation damage to mitochondria is another potential source of ROS. Further DAMP and pro-inflammatory cytokines signaling, the DNA damage response through Bax, and the formation of inflammasomes can all perpetuate ROS generation by forming positive feedback circuits. Adenosine can be generated from nucleotides by ectonucleotidases such as CD39 to signal through the adenosine receptors (AR) to negatively regulate inflammation, as does the production of anti-inflammatory cytokines. 

 

(PDF) Cytokines in Radiobiological Responses: A Review
https://www.researchgate.net/publication/232736146_Cytokines_in_Radiobiological_Responses_A_Review

 

https://www.researchgate.net/figure/Effects-of-Th1-Th2-on-tumor-progression-Naive-T-cells-become-Th1-cells-or-Th2-cells_fig2_319208977

 

https://www.researchgate.net/figure/Categorization-of-cytokines-into-pro-atherogenic-and-anti-atherogenic-cytokines-based-on_fig2_5363737

 

How to Increase IL-10 Anti-Inflammatory Cytokine
Written by Joe Cohen, BS | Last updated: March 3, 2020

The Good
We usually think of cytokines as ^bad ̄ and inflammatory. IL-10 is an important exception.

IL-10 is anti-inflammatory cytokine because it decreases various immune cells such as Th1 AND Th2 cells [2, 1], neutrophils [5], macrophages and natural killer cells [6]. The last three are the guns of the immune system.

It also decreases a host of cytokines (IFNy, IL-2, TNF, and GM-CSF) and other alarm bells of the immune system (MHCII) [7].

It inhibits Nf-kB [6], the master control of inflammation (in two ways: by suppressing IKK activity and NF-κB DNA binding [8]).

It inhibits COX-2 [9], which is involved in migraines, pain, and inflammation. COX-2 is classically blocked by NSAIDs such as aspirin and ibuprofen.

By inhibiting mast cells, it counteracts the inflammatory effect that these cells have at the site of an allergic reaction [10].

IL-10 decreases obesity by reducing overeating and decreasing insulin and leptin resistance in the hypothalamus, the gland that controls appetite (by inhibiting cytokines, Nf-kB, and ER stress) [11].

How to Increase IL-10 Anti-Inflammatory Cytokine - SelfHack
https://selfhack.com/blog/il-10/