cytokine receptors: signalling and function

Question 1

what is a cytokine?

Answer 1

a small immunoregulatory signalling protein that is secreted by cells of the immune system
e.g. interleukins or interferons

Question 2

cytokine function

Answer 2

regulate a huge variety of physiological events

Question 3

haematopoiesis

cytokine function

Answer 3

the formation of blood cellular components
all cellular blood components are derived from hepatopoietic stem cells

Question 4

inflammation

cytokine function

Answer 4

biological response of body tissues to harmul stimuli such as pathogens
vasodilation - increased blood flow to the infected area
edema - leakage of plasma proteins
neutrophil emigration

Question 5

immunity

cytokine function

Answer 5

resistance exhibited by the host towards injury caused by microorganisms and their products
in the bone marrow, haematopoietic stem cells undergo lymphopoiesis and stead-state granulopoiesis to produce a neutrophil which travels to the blood stream of the infected tissues
systemic bacterial infection causes a decrease in lymphopoiesis and an increase in granulopoiesis to produce more neutrophils

Question 6

JAK-STAT signalling pathway

Answer 6

involves the activation of Janus Kinases (JAKs) and the subsequent phosphorylation and activation of signal transducers and activators of transcription (STATs) which then regulate gene expression

Question 7

1. cytokine receptor binding

JAK/STAT

Answer 7

cytokine binds to its receptor on the cell surface causing a conformational change

Question 8

2. activation of JAKs

JAK/STAT

Answer 8

following receptor binding, JAKs are activated and phosphorylate tyrosine residues on the receptor itself

Question 9

3. STAT recruitment

JAK/STAT

Answer 9

phosphorylated tyrosine residues act as docking sites for STAT proteins
STATs bind via their SH2 domains

Question 10

4. STAT phosphorylation

JAK/STAT

Answer 10

JAKs phosphorylates the STATs on specific tyrosine residues to activate them

Question 11

5. STAT dimerisation

JAK/STAT

Answer 11

phosphorylated STATs dimerise through their SH2 domains to form active STAT dimers

Question 12

6. nuclear translocation

JAK/STAT

Answer 12

STAT dimers translocate to the nucleus where they bind to specific DNA response elements in the promoters of target genes

Question 13

7. gene expression

JAK/STAT

Answer 13

following binding to DNA STAT dimers activate or repress the transcription of target genes

Question 14

8. termination of signalling

JAK/STAT

Answer 14

dephosphorylation of JAKs
by suppression of cytokine signalling (SOCS) proteins

Question 15

SOCS proteins

JAK/STAT

Answer 15

negative feedback regulator of cytokine receptor signalling
- competitive binding
- ubiquitylation and degradation of phosphorylated STATs or receptor subunits
- inhibition of JAK catalytic activity

Question 16

cytokine release syndrome

Answer 16

normal immune responses to viruses promote secretion of pro-inflammatory cytokines
excessive, uncontrolled production of pro-inflammatory cytokines can result in life-threatening hypoinflammatory conditions

Question 17

COVID19 cytokine storm

Answer 17

coronavirus infects lung cells
immune cells identify the virus and produce cytokines
cytokines attract more immune cells to produce more cytokines which create a cycle of inflammation that damages the lung cells
formation of fibrin causes damage
blood vessels weaken and allow fluid to fill the lung cavities which can cause respiratory failure