Resolution of inflammation Flashcards
What causes a t helper cell to develop into a Th1 phenotype?
APC releases IL-12
Naive T cell TCR binds to epitope
T bet transcription factor in naive T cell is activated
What cytokines are typically released by Th1 cells?
INFy and TNFalpha
What is the role of Th1 cells?
Activate M1 macrophages
Triggers inflammation
What is the role of a M1 macrophage?
Inflammatory macrophage
Release IL-8 chemokine to attract neutrophils
Release Nox to aid bacteria killing
Also releases IL6 and IL12
How is a M1 macrophage activated?
By PAMPs and DAMPs
What are the different ways that a T cell can be ‘turned off’?
Antigen is depleted so survival signals to Th1 are lost
Th1 undergoes apoptosis
T cell anergy.
T cell activation induced apoptosis
T cell echaustion
What is a anergic T cell?
When a T cell is exposed to an antigen but remains hypoactive .
Often have suboptimal co-stimulation or high co-inhibition molecules.
Help turn off the adaptive immune system.
How does a naive T cell develop into a Th2?
Exposed to epitope on PAPC
PAPC releases IL-4
GATA3 transcription factor inside the PAPC is activated
What cytokines does a Th2 typically release?
IL-4
Il-13
What is the role of a Th2 cell?
Phenotype is associated with turning off the adaptive immune system
Results in alternative macrophage activation (M2)
What is the role of M2 macrophages?
Anti-inflammatory
INhibit T cell responses
Promote wound healing and angiogenesis
Release VEGFS and MMPs.
Have a reduced MHC2 expression
How is long term memory present in the immune system?
Long life plasma cells
Naive T ceels are induced into effector or central memory cells
Quiscient T cells.
What happens when the survival signal to a neutrophil is lost?
Undergoes apoptosis
Presents phosphodylerine on its surface (flipped from the inner to the outer membrane)
How are pro-resolving macrophages made?
M2 macrophages efferocytose a apoptosing neutrophil
Exposed to phosphorylcerins on the neutrophil surface and exposed to IL-10
Triggers phenotype change to a pro-resolving efferocytosing macrophage
Define efferocytosis
The process by which apoptosing cells are removed by phagocytes
What is the role of pro-resolving macrophages?
Encourage wound healing and anti-inflammatory
release TGF-beta to produce inducible T reg cells
How are inducible T reg cells generated?
Naive T cell is exposed to an antigen on an APC
APC produces IL-12 and TGF-beta
FoxP3 transcription factor is activated in the anive T cell
Develops in an inducible T reg cell
What is the role of a inducible T reg cell?
Reduce activation signals from dendritic cells and sequester IL-12, this prevents the activation of different phenotypes of T cell.
What cytokines does an inducible T reg cell typically produce?
IL-10
TGF-beta
What is the role of thymic derived T reg cells?
Conrinuous low level resolution of inflammation
What events occur after the activation of an inducible T reg cell in order to reduce inflammation?
B regulatory cells are developed
Tissue resident cells return to an inactive state
Production of pro-resolving chemical mediators
Removal of pro-inflammatory mediators
What is the process of wound healing?
1) immune response prevents infection
2) Blood clot forms a scab over the wound
3) wound contraction prevents blood loss
4) Fibroblasts secrete collagen to replace damaged ECM
VEGFs - angiogenesis for oxygen and nutrients
EGF - trigger epithelial and fibroblast proliferation
5) wound matures and closes increasing tensile strength
What are the different results of wound healing?
Functional tissue (regeneration) - when damaging stimulus removed
Non-functional scar tissue (repair) - when the damaing stimulus remains.
What is the main difference between repaired and regenerated tissue?
Regenerated tissue tends to be continuously dividing cells, and has a high cellular content
Repaired tissue tends to be quiscient cells and has a higher collagen content and lower cellular content.
