L9 - Cytokines and Chemokines COPY

Question 1

CYTOKINES BY DEFINITION

i) what are cytokines?
ii) what is a mediator?
iii) which symptom can be due to the outcome of a soluble mediator?

Answer 1

i) cytokines are immune mediators
ii) mediators are produced by a tissue ot cell and act at a distance
iii) fever can be due to soluble mediators

Question 2

HAEMATOPOIESIS

i) what causes stem cells to differentiate into a specific cell?
ii) what are bone marrow stem cells exposed to to become RBCs?
iii) give three cells fates that can arise after exposure to GM-CSF

Answer 2

i) stem cells are exposed to cytokines which causes them to differentiate
ii) bone marrow SCs exposed to EPO > RBCs
iii) GM-CSF exposure > mast cell, myeloblast, monocyte/eosinophil/basophil

Question 3

MEDIATORS OF HOST DEFENCE - INTERFERONS

i) what do they do? what do they mediate against?
ii) what cells make IFN alpha? which cells make IFN beta? which two cell types make IFN gamma?
iii) which IFN is a poor antiviral molecule?
iv) what do interferons activate? what enzyme is then activated? what does this activate which chops the viral RNA? what does this ultimately do?

Answer 3

i) they interfere with viral replication and mediate against virus

ii) lymphocytes > IFNa
fibroblasts > IFNb
lymphocytes/NK cells > IFN gamma

iii) IFN gamma is a poor antiviral molecule

iv) interferons activate transcription factors > activ enzyme OAS1 > produces poly A > poly A activates ribonuclease which chops RNA
- ultimately intereferes with viral replication

Question 4

OTHER MEDIATORS OF HOST DEFENCE

i) name three immune activators and give an example of each
ii) which two cell types can produce cytotoxins? what does they cause? give an eg of a cytotoxin
iii) which molecule is mainly a pro inflam cytokine but classed as a cytotoxin?

Answer 4

i) lymphocyte activating cytokines eg IL-1
- T cell growth factors eg IL-2, IL-7, IL-9
- macrophage activating cytokines - IFN gamma

ii) lymphocytes and macrophages can produce cytoxins that kill tumour cells eg TNF
iii) TNF is mainly a pro inflam cytokine and not a very good anti tumour molecule

Question 5

CYTOKINES IN IMMUNITY

i) which genetic condition is caused by mutation in a common signalling component of the IL-2, IL-4 and IL-7 receptors?
ii) what does this demonstrate about these molecules and receptors?
iii) studying which symptom during infection allowed the discovery of the inflammatory role of cytokines?
iv) which molecule was found to be an inflammatory mediator when released from macrophages? what does it induce?

Answer 5

i) SCID is caused by inactivation of receptor that is a common signalling component for IL-2, IL-4 and IL-7
ii) demonstrates these are essential in host defences
iii) stuyding cachexia during infection > inflam role of cytokines
iv) TNF was an inflammatory mediator released from macrophages that induces cachexia

Question 6

INFLAMMATION

i) what are the five cardinal signs of inflammation?
ii) what can most of these be explained by? (2)

Answer 6

i) heat, redness, swelling, pain, tissue damage

ii) can be explained by biol action of inflam cytokines eg IL-1 and TNF on the vascular endothelium
- or through production of prostaglandins/chemokines

Question 7

TNF MEDIATED DISEASES

i) name five TNF mediated diseases
ii) what can be given in these situations and is protective?

Answer 7

i) septic shock, multi organ filaire, RA, IBD, GvHD, diabetes
ii) can give antibods to TNF = protective

Question 8

CYTOKINES IN ALLERGY

i) which two cells can CD4 T cells differentiate into? what does this depend on? which one is important in inflam and which is important in allergy?
ii) which type of T cells are implicated in type IV hypersens reactions?
iii) label T cells 1-4

Answer 8

i) can differen to Th1 and Th2 - dep on cytokines exposed to
- Th1 = inflam
Th2 = allergy

ii) Th1 and Th2 implicated in type IV hypersens reactions
iii) 1 = Th2, 2 = Th2, 3 = Th17, 4 = Treg

Question 9

CHEMOKINES

i) what does chemotaxis mean? name a process that this mediated
ii) what role does MCP-1 play? what does IL-8 do?
iii) name a cell that releases chemokines? what can trigger this? what effect does this have on blood vessels (2) what does this allow

Answer 9

i) chemotaxis = migration towards a gradient
- mediated homing and migration of cells of the immune system and infiltration of leucocytes to site of infection

ii) MCP-1 = monocyte attractant
IL-8 = neutrophil attractant

iii) macrophages can release chemokines > vasodilation and increase permeability > inflam cells migrate into tissue

Question 10

THERAPEAUTICS

i) name a molecule that is used as a genome immune modulator in MS? what does it modulate?
ii) name two things that IFN-a can be given for?
iiii) name three factors that can aid haemopoiesis?

Answer 10

i) IFN-b used in MS - modulates the autoimm response
ii) IFNa for kaposi sarcoma and viral hepatitis
iii) haemopoiesis - G-CSF, GM-CSF, IL-11 and EPO

Question 11

USE OF CYTOKINES TO PREVENT INFLAMMATION

i) name two conditions that soluble TNF receptor or anti-TNF can be used to treat?
ii) what condition can IL-1Ra, anti IL-6 and IL-6R be used to treat?
iii) which two interleukins are important in asthma/ezcema
iv) what IL does toculizimab work against? what infection may this be useful in

Answer 11

i) anti TNF - crohns, RA, UC, psoriasis
ii) IL1Ra, anti IL-6 used in RA
iii) IL-5 and 4 important in asthma and eczema
iv) toculiz is an anti IL-6 - used in COVID 19 infection