Resolution of inflammation

Question 1

What causes a t helper cell to develop into a Th1 phenotype?

Answer 1

APC releases IL-12
Naive T cell TCR binds to epitope
T bet transcription factor in naive T cell is activated

Question 2

What cytokines are typically released by Th1 cells?

Answer 2

INFy and TNFalpha

Question 3

What is the role of Th1 cells?

Answer 3

Activate M1 macrophages
Triggers inflammation

Question 4

What is the role of a M1 macrophage?

Answer 4

Inflammatory macrophage
Release IL-8 chemokine to attract neutrophils
Release Nox to aid bacteria killing
Also releases IL6 and IL12

Question 5

How is a M1 macrophage activated?

Answer 5

By PAMPs and DAMPs

Question 6

What are the different ways that a T cell can be ‘turned off’?

Answer 6

Antigen is depleted so survival signals to Th1 are lost
Th1 undergoes apoptosis
T cell anergy.
T cell activation induced apoptosis
T cell echaustion

Question 7

What is a anergic T cell?

Answer 7

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.

Question 8

How does a naive T cell develop into a Th2?

Answer 8

Exposed to epitope on PAPC
PAPC releases IL-4
GATA3 transcription factor inside the PAPC is activated

Question 9

What cytokines does a Th2 typically release?

Answer 9

IL-4
Il-13

Question 10

What is the role of a Th2 cell?

Answer 10

Phenotype is associated with turning off the adaptive immune system
Results in alternative macrophage activation (M2)

Question 11

What is the role of M2 macrophages?

Answer 11

Anti-inflammatory
INhibit T cell responses
Promote wound healing and angiogenesis
Release VEGFS and MMPs.
Have a reduced MHC2 expression

Question 12

How is long term memory present in the immune system?

Answer 12

Long life plasma cells
Naive T ceels are induced into effector or central memory cells
Quiscient T cells.

Question 13

What happens when the survival signal to a neutrophil is lost?

Answer 13

Undergoes apoptosis
Presents phosphodylerine on its surface (flipped from the inner to the outer membrane)

Question 14

How are pro-resolving macrophages made?

Answer 14

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

Question 15

Define efferocytosis

Answer 15

The process by which apoptosing cells are removed by phagocytes

Question 16

What is the role of pro-resolving macrophages?

Answer 16

Encourage wound healing and anti-inflammatory
release TGF-beta to produce inducible T reg cells

Question 17

How are inducible T reg cells generated?

Answer 17

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

Question 18

What is the role of a inducible T reg cell?

Answer 18

Reduce activation signals from dendritic cells and sequester IL-12, this prevents the activation of different phenotypes of T cell.

Question 19

What cytokines does an inducible T reg cell typically produce?

Answer 19

IL-10
TGF-beta

Question 20

What is the role of thymic derived T reg cells?

Answer 20

Conrinuous low level resolution of inflammation

Question 21

What events occur after the activation of an inducible T reg cell in order to reduce inflammation?

Answer 21

B regulatory cells are developed
Tissue resident cells return to an inactive state
Production of pro-resolving chemical mediators
Removal of pro-inflammatory mediators

Question 22

What is the process of wound healing?

Answer 22

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

Question 23

What are the different results of wound healing?

Answer 23

Functional tissue (regeneration) - when damaging stimulus removed
Non-functional scar tissue (repair) - when the damaing stimulus remains.

Question 24

What is the main difference between repaired and regenerated tissue?

Answer 24

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.

Question 25

List some growth factors involved in wound repair?

Answer 25

TGF beta
PDGF
VEGFS
EGF
FGF

Question 26

What is the role of TGF beta as a growth factor?

Answer 26

Fibroblast migration
Collagen synthesis
Monocyte migration

Question 27

What is the role of PDGFs in wound healing?

Answer 27

Angiogenesis
Collagen synthesis
Monocyte migration
Wound contraction

Question 28

What is the role of VEGFS in wound healing?

Answer 28

Angiogensis
Collagen synthesis

Question 29

What is the role of EGF in wound healing?

Answer 29

Fibroblast proliferation
Epithelial migration and proliferation
Collagenase synthesis

Question 30

What is the role of FGF in wound healing?

Answer 30

Fibroblast migration
Epithelial migration and proliferation
Collagenase synthesis

Question 31

What causes pain in a wound is a pathogen is not cleared?

Answer 31

Damaged blood vessels release bradykinise causing pain

Question 32

What are the main stages in resolution of inflammation?

Answer 32

Turning off the adaptive immune response - Th1 changes phenotype to Th2
Long term memory activation
Pro-resolving efferocytosing macrophage activation
Removal of inflammatory mediators and increase in anti-inflammatory mediators.