Lecture 8 & 9- Cytokines and Naive T cell Activation

Question 1

Which cell types produce IL-1? Why do they produce it?

Answer 1

Mononuclear phagocytes (main) Leukocytes Fibroblasts Vascular endothelial cells (ECs) In response to LPS, TNF, IL-1 or CD4+ T cell stimulation

Question 2

What does IL-1 do?

Answer 2

Increases IL-2 synthesis Promotes leukocyte adhesion to EC Systemically - cachexia

Question 3

Give three functions of TNF alpha

Answer 3

Any of: - Increases expression of adhesion molecules on leukocytes and vascular ECs - increases permeability of endothelium - activates microbicidal activity of macrophages and neutrophils - induces release of IL-1, IL-6, itself - increases class I and II MHC expression - increases core body temp (systemic) - induces acute phase protein synthesis - can cause circulatory collapse and DIC if excessive levels

Question 4

What induces TNFalpha release?

Answer 4

TNFalpha signaling, or LPS binding TLR4

Question 5

What stimulates IL-6 release?

Answer 5

IL-1 and TNFalpha signalling

Question 6

What does IL-6 do?

Answer 6

Stimulates acute phase protein synthesis, promotes B cell differentiation

Question 7

What is the main function of IL-8? Give one cell type that makes it.

Answer 7

Chemotaxis and activation of neutrophils e.g antigen-activated T cells, LPS activated phagocytes, fibroblasts, ECs, platelets

Question 8

What is the main function of IL-12? Name the cell types that produce it.

Answer 8

Macrophages and dendritic cells Induces Th1 differentiation, activates NK cells

Question 9

What are the two main functions of IL-17? Which cell types makes it?

Answer 9

Th17 cells (in response to IL-23 from dendritic cells) Recruit macrophage and neutrophils to site of inflammation Release of IL-1, IL-6, TNF alpha from macrophage

Question 10

What part of the bacteria does C reactive protein bind? What function does this promote?

Answer 10

Binds phosphocholine on bacterial surface Promotes phagocytosis (opsonisation)

Question 11

Which are the type 1 interferons? Which cell types produce them?

Answer 11

IFN alpha and IFN beta Most cells

Question 12

What event induces type 1 IFN synthesis and release?

Answer 12

Binding of TLR3 by dsRNA Or, type 1 IFN signaling

Question 13

Give 4 intracellular effects of type 1 IFN signaling

Answer 13

1. Mx protein induced, traps viral proteins for degradation 2. Protein kinase R initiates antiviral signaling pathways 3. RNase cleaves viral RNA 4. MHC I expression increased to boost CD8+ T cell function

Question 14

What effect does type 1 IFN have on NK cells?

Answer 14

Activates them

Question 15

Which cells produce IL-2?

Answer 15

CD4+ and CD8+ T cells

Question 16

What major effect does IL-2 have on T cells?

Answer 16

If they express the high-affinity IL-2-R, it induces proliferation

Question 17

What are four other effects of IL-2?

Answer 17

IFN-gamma release by T cells TGFbeta release by T cells B cell stimulation NK cell stimulation

Question 18

Which cell types produce IL-4? Which inflammatory pathway absolutely requires it?

Answer 18

Produced by CD4 T cells, NK cells, mast cells Required by B cells for class switching to IgE

Question 19

Name one cell that produces TGFbeta. What are two functions?

Answer 19

Treg cells Stimulates angiogenesis, inhibits T cell proliferation, required for class switch to IgA

Question 20

Which cell types produce IFN gamma? In response to what?

Answer 20

Th1 and CD8 T cells, in response to antigen encounter and IL-2

Question 21

List four functions of IFNgamma

Answer 21

Any of: - potent activator of phagocytes and neutrophils - induces synthesis of enzymes of the respiratory burst - induces TNFalpha secretion - activates NK cells - increases MHC I and II expression - promotes B cell differentiation - promotes IgG2a synthesis (opsonising)

Question 22

Which cell types produce IL-5? Which inflammatory pathway is it important for?

Answer 22

Th2 and mast cells Stimulates eosinophil growth; important for helminth immunity

Question 23

How are chemokines classified?

Answer 23

Based on configuration of two cysteine residues at the N terminus

Question 24

What are the five types of cytokine receptors?

Answer 24

1. Immunoglobulin superfamily 2. Class 1 cytokine receptors (haematopoetin family) 3. Class 2 cytokine receptors (interferon family) 4. TNF receptors 5. Chemokine family receptors (G protein coupled)

Question 25

Give two examples where viruses make cytokine-like molecules.

Answer 25

Vaccinia and cowpox produce an IL-1beta binding protein Poxviruses produce soluble IFNgamma receptor

Question 26

What are the five attributes of cytokine function?

Answer 26

Pleitrophy Redundancy Synergy Antagonism Cascade induction

Question 27

List five cytokines secreted by activated macrophages

Answer 27

IL-1beta TNFalpha IL-6 IL-8 IL-12

Question 28

List three cytokines that cause fever

Answer 28

IL-1beta IL-6 TNFalpha

Question 29

Which cytokines induce acute phase protein synthesis?

Answer 29

IL-1, TNFalpha, IL-6

Question 30

When, other than bacterial infection, might phosphocholine be present in the body?

Answer 30

Cell damage - usually only present on the inside of the plasma membrane. If on the outside, indicates cell damage. Bound by C-reactive protein from liver, promoting complement lysis of damaged cell.

Question 31

What are three pathological, systemic effects of TNFalpha?

Answer 31

Insulin resistance Thrombosis Low cardiac output

Question 32

What cell signaling pathway is used by IFNalpha signalling?

Answer 32

JAK1/ STAT2 for IFNalpha JAK1/STAT1 for IFN gamma

Question 33

What event must occur before an activated T cell can proliferate?

Answer 33

Maturation of the IL-2 receptor (synthesis and insertion of alpha subunit) and stimulation (autocrine) by IL-2

Question 34

What is the signal that leads to stabilisation of IL-2 mRNA and increased IL-2 secretion by the T cell?

Answer 34

CD28 from T cell - B7 from macrophage interaction (signal 2 of T cell activation)

Question 35

What is the pathway by which the IL-2 receptor matures?

Answer 35

Antigen recognition by receptor >> NF AT binds IL-2 promoter region >> get IL-2 R alpha expression

Question 36

Which intracellular signaling pathway does IL-12 use to drive Th cell development? What is the transcription factor that is important, and which molecule induces it? Which Th cell results?

Answer 36

IFNgamma signaling > Tbet expression IL-12 signalling via STAT4 dependent pathway Get Th1

Question 37

Which intracellular signaling pathway does IL-4 use to direct Th cell development? Which transcription factor is also important? Which Th cell results?

Answer 37

IL-4 > STAT6 pathway GATA-3 needed Th2 results

Question 38

Name the cells.

Answer 38

Question 39

If the purple cell is a naive CD8+ T cell, what are the two circled molecules? What about the soluble molecule in the second picture?

Answer 39