Resolution of inflammation Flashcards
stages in process of reinstating homeostasis after injury/infection
terminating adaptive immune responses
inflammation resolution
wound healing and repair
what does terminating adaptive immune responses involve
regulatory cell function
removal of effector cells
long term maintenance of memory cells
why does inflammation resolution involve
return of tissue resident cells to an inactivated state
production of pro-resolving chemical mediators
removal of pro inflammatory factors
what does wound healing and repair involve
replacement of damaged cells
replacement of tissue matrix
may be healthy, function cellular tissue
why is turning off T cells crucial
T cells need repeated stimulation from signals 1 2 and 3 to function
if antigen or costimulation aren’t present and cytokine signal changes the T cells change phenotype or die
changes to T cells after responding to antigen
switch to th2 anti-inflammatory phenotype
3 things that may occur after T cell chang to th2
anergy
exhaustion
activation-induced cell death
anergy
cell can’t be activated even in optimal conditions
exhaustion
temporary state of inactivity
activation-induced cell death
excited cells die leading to transient lymphopenia
what occurs at the same time as T cells turning off
T reg cells will be generated
2 types of T reg
nTreg
iTreg
nTreg
natural/thymically derived Tree
maintain tolerance all of the time
iTreg
generated from naive T cells in tissues and reduce function of dendritic cells and other immune cells
what do both types of T reg cells express
CD4
CD25
CTLA4
FOXP3 transcription factor
what will only nTreg cells express
CD62L
why is the generation of iTreg cells from naive cells important
iTreg reduce activation signals by DC,sequester il-2 and release anti-inflammatory cytokines (Il-10 and TGF beta)
main components of inflammation resolution q
alternatively activated M2 macrophages
apoptotic neutrophils
cytokines: IL-10 and TGF beta
specific mediators of resolution
lipid mediators
proteins and peptides
gaseous mediators
purine
neuromodulators
what do lipid mediators do in inflammation resolution
‘stop’ neutrophil and eosinophil infiltration; stimulate non-phlogistic recruitment of monocytes; enhance macrophage phagocytosis of apoptotic neutrophils; increase the exit of phagocytes
what do proteins and peptides do in inflammation resolution
inhibiting, reducing, and/or modulating the expression and activity of mediators.
what do gaseous mediators do in inflammation resolution
act primarily as anti-inflammatory substances, promoting resolution of inflammatory processes.
what do neuromodulators do in inflammation resolution
block pain signals from reaching brain
examples of lipid mediators in inflammation resolution
lipoxins
resolving
protecting
maresins
examples of proteins in inflammation resolution
annexin A1
galectins
examples of gaseous mediators in inflammation resolution
hydrogen sulphide and carbon monoxide
example of purine in in inflammation resolution
adenosine
what are neuromodulators released under the control of
vagus nerve
how can apoptotic neutrophils initiate transition to resolution
apoptotic neutrophils secrete signals which attract macrophages
macrophages recognise phosphatidylserine placed on outer cell membrane in apoptosis
phagocytosis (efferocytosis) of apoptotic neutrophils change macrophage phenotype to produce resolution associated factors
TGF beta induce recruited T cells to become T reg
macrophage phenotypes
M1
M2
apoptotic cells
M1 macrophages
pro-inflammatory
activated by PAMP, DAMP and inflammatory cytokines
involved in host defences against infection
produce NO for bacterial killing
M2 macrophages
anti-inflammatory
wound healing
arise after exposure to th2 cytokines
promote angiogenesis
don’t produce NO
express reduced MHC2 and inhibit T cell responses
apoptotic macrophages
arise after efferocytosis of apoptotic neutrophils
secrete repair mediators including growth factors
activate fibroblasts and total cells to make connective tissues
recuit T reg
increase angiogenesis
what will stimulate M1 macrophages
Th1
NK
TNF alpha
IFN gamma
what will M1 macrophages secrete
TNF alpha
chemokines
IL-6
IL-1 beta
IL-12
what will stimulate M2 macrophages
IL-13 and IL-4
qhat will M2 macrophages secrete
matrix metalloproteinases
vascular endothelial growth factor, VEGF
IL-10
what will stimulate apoptotic macrophages
efferocytosis
IL-10
what will apoptotic macrophages release
IL-1 RA
VEGF
IL-10
TGF beta
what can dendritic cells be
anti-inflammatory or tolerogenic
include tociluzimab and vitamin D
what type of cytokine is TGF beta
pleiotropic
different effects under different circumstances
TGF beta predominant function
anti-inflammatory
produced in response to Th2 cytokine and is involved in promoting T reg formation along with IL-10
TGF beta with IL-6 and 23
promote production of Th17 cells, inflammatory and involved in immune-mediated chronic inflammatory diseases
TGF beta in T follicular helper cells
3 overlapping processes in wound healing
inflammation
proliferation and regeneration
maturation
inflammation in wound healing
blood vessels constrict sealing themselves off then dilate to allow immune cells and proteins in
proliferation and regeneration in wound healing
granulation tissue
new vessels grow
collagen deposited
maturation in wound healing
wound closed
remodelled to increase tensile strength and return function
