Cytokines

Sam Shepard

STAT

signal transducer and activation of transcription

SOCS

supressor of cytokines signalling

how do SOCS act

bind to phosphotryosine residues and target proteins for degradation

Give an example of a JAK-STAT pathway involved in cell proliferation

Il-2 stimulates STAT5

How is binding of STAT to DNA controlled

availability of stats controls conformations formed as a result of cytokine signalling - different effects

What is the function of IFNy

activate macrophages

Induce B cell class switch to IgG3 ( good for opsonising bacteria/virusesand fixing complement)

What is the function of TNFa

Activates macrophages/NK cells

enhances cytotoxicity

IL-2 function

stimulates Cytotoxic Lymphocytes (CTLs)What a ad NKs to proliferate

What cytokines are involved in the formation of Th1

IFNy

TNFa

IL-2

What are the Th2 cytokines

IL-4

IL-5

IL-13

What is the function of IL-4

induce B cell proliferation and class switch to IgE

smooth muscle contraction

fluid secretion

What is the function of Il-5

augments production of IgA by B cells

IL-13 function

promote sIgE class switch

induce giblet cell proliferation

induce mucas production

Describe 3 antiviral agents produced as a result of interferon binding

IFITM1

CH25

Viperin

Describe the pathway from IFN binding to gene transcritption

1) IFN binds IFNAR1 & IFNAR2

2) STAT2 activated and binds IREF9

3) IREF9 STAT2 complex is transcriptional activator for ISRE

What is an IFNAR

interferon alpha and beta receptor subunit

What is IRF9

Interferon regulatory factor 9

ISRE

Interferon stimulated response element

What is the action of IFITM1 and CH25

Interferon induced TM protein and cholesterol hydroxyl 25 inhibit fusion between cellular and viral membranes

what is the function of Viperin

Inhibits ddhCTP - crucial for viral polymerase

Compare the roles of TNF alpha in immune and non immune cell response

Immune - binds to TRFR2, up regulates inflammatory species

Non immune - binds to TRFR1, activates cascades → protein lysis and cell death

What is LCMV

lymphatic choriomeningitus virus (classic model used to study T cells in mice)

What are the 2 strains of LCMV

Armstrong - produces acute infection

C13 - produces chronic infection

Which interleukin is involved in chronic infection?

IL-10

Whatother immune factors does IL-10 affect?

suppression of CD4+ T cells, IFN gamma, TNF alpha and IL-2 production

suppression of APC maturation and expression of MHCI and MHCII

What is the native role of IL-10?

IL-10 suppression of immune response against gut bacteria (T cell and macrophage suppression)

With knockout of IL-10:

reposing to bacteria in gut which are not causing infection

loss of structure in gut - reduced nutrient uptake and reduced life expectancy

Describe the process of sterile wound inflammation

1) DAMPs (Damadge associated molecular patterns) released from wounds and taken up by innate immune cells (macrophages, monocytes, muscle cells, neutrophils)

2) IL-6 and TNF alpha produced by innate immune cells, triggering up regulation of PDGF and VET-GEF which drive vascularisation and repair of tissue

3) When wound has healed, IL-10 and TGFB supresss immune response

PDGF

Platelet derived growth factor

Give a cell process which leads to liver cancer

Cell death promotes proliferation and regeneration with IL-6 and TNF, which can cause proliferation of unhealthy cells and cause cancer.

How are immune therapies being used to treat people with depression?

High IL-6, TNF and IL-17 in blood of patients with depression

treat with antibodies - it is possible to see some improvement!

What is an application of understanding how cytokines are involved in the generation of hematopeitic immune cells?

CAR-T cell therapy - patients own T cells engineered to bind to and destroy cancer cells by modification of the T cell receptor

what is a side effect of immune related therapies?

cytokine storm - clearing of pathogens goes wrong

What words can be used to describe cytokine interactions?

Redundant - do the same thing (IL2, 4 and 5 in proliferation)

Synergistic - both must be present for a response (e.g IL4&5 in inducing class switch to IgE)

Antagonist - work against each other (e.g IFN-gamma blocks IgE class switch)