Cytokines

Question 1

What are cytokines?

Answer 1

Soluble peptides secreted mainly by immune cells

Question 2

What do cytokines do? (3)

Answer 2

• Chemical messengers that cause biological response
• Communicate with and outside immune system
• Involved in acute and chronic responses

Question 3

What are 8 actions and attributes of cytokines?

Answer 3

• Autocrine
• Paracrine
• Endocrine
• Pleiotropy
• Redundancy
• Synergism
• Antagonism
• Cascade introduction

Question 4

What does it mean to have autocrine function?

Answer 4

Acts on the cell that secreted it (auto = self)

Question 5

What does it mean to have paracrine function?

Answer 5

Acts on local cells

Question 6

What does it mean to have endocrine function?

Answer 6

Acts systemically

Question 7

What is pleiotropy?

Answer 7

When one gene/cytokine influences 2 or more cells
- Important to consider when therapy targets cytokine receptors

Question 8

What is redundancy in context of cytokines?

Answer 8

When more than 1 cytokine has the same or similar effects

Question 9

What is synergism?

Answer 9

Different cytokines working together to amplify an effect

Question 10

What is antagonism?

Answer 10

When the effect of one cytokine inhibits the effects of another cytokine

Question 11

What is cascade induction?

Answer 11

The action of one cytokine on its target cell causes the cell to make 1 or more cytokines that trigger other cells
- May result in cytokine storm

Question 12

What are interleukins?

Answer 12

Cytokines that are mainly produced by leukocytes

Question 13

What are the most common interleukins? (Hint: there are 5)

Answer 13

IL:
- 2
- 4
- 5
- 6
- 10

Question 14

What are the haematopoietin superfamily?

Answer 14

Cytokines that cause haematopoietic cells to differentiate
- Includes some interleukins and granulocyte monocyte colony stimulating factor (GM-CSF)

Question 15

What are interferons?

Answer 15

Interfere with viral replication

Question 16

What are the 2 main types of interferons?

Answer 16

• Type 1 (IFNα and IFNβ)
• Type 2 (IFNγ)

Question 17

What makes Type 1 IFN?

Answer 17

Made during viral infection and mainly secreted by leukocytes and fibroblasts

Question 18

What makes Type 2 IFN?

Answer 18

Effector T cells and activated NK cells
- activate macrophages in response to danger/inflammation

Question 19

What does tumor necrosis factor do?

Answer 19

• Pro-inflammatory with some anti-inflammatory effect (depends on cell it’s acting on)
• Highly pleomorphic

Question 20

What secretes tumor necrosis factor?

Answer 20

• Macrophages
• Activated T-cells (esp CD4)

Question 21

This is a common target for immunotherapy in many autoimmune diseases but can render the patient susceptible to infections

Answer 21

Tumor necrosis factor

Question 22

What are chemokines?

Answer 22

Small proteins that signal leukocytes to come to inflamed tissue

Question 23

What do chemokines bind to?

Answer 23

Chemokines receptors on immune cells
- Mainly G protein-coupled receptors

Question 24

What do TNF receptors bind?

Answer 24

TNF and non-cytokine ligands (CD40 and FasL)

Question 25

What is CD40?

Answer 25

Non-cytokine ligand that can bind to TNF receptor - Co-stimulators molecule on APCs

Question 26

What is FasL?

Answer 26

Non-cytokine death ligand that initiates apoptosis

Question 27

What type of receptor are most chemokine receptors?

Answer 27

G protein-coupled receptors (GPCRs)

Question 28

Tell me what happens in cytokine signalling starting from the outside of the cell

Answer 28

- Extracellular domain bind cytokine - cytoplasmic tail undergoes phosphorylation - msg transmitted to activate intracellular signalling and influence gene expression

Question 29

What do many Type 1 cytokine receptors have in common?

Answer 29

Common γ chain with IL-2 receptor —> redundancy

Question 30

What do Type 2 receptors mainly bind?

Answer 30

Interferons

Question 31

What type of cell secretes pro-inflammatory cytokines?

Answer 31

Macrophages

Question 32

What type of effect do cytokines secreted by macrophages have?

Answer 32

Local and systemic **Local** IL-1β causes local tissue destruction and increases lymphocyte access **Systemic** TNF and IL-6 are pyrogenic

Question 33

What cytokines are called the “pyrogenic” cytokines?

Answer 33

TNF and IL-6 - Cause synthesis of PGE2 —> heat production and vasoconstriction by acting on the hypothalamus

Question 34

What is sepsis?

Answer 34

Systemic inflammation caused by an overactive immune response to an infection

Question 35

What role do cytokines play in cancer?

Answer 35

Can inhibit or promote cancer

Question 36

What is a soluble receptor?

Answer 36

Receptor that is floating around in the plasma

Question 37

What is the purpose of a soluble receptor?

Answer 37

Acts as a mop for excess cytokines in plasma

Question 38

Why are older people more prone to sepsis?

Answer 38

Immune system is less able to regulate itself and prevent overactive response to infection

Question 39

Why can some immunotherapies cause cytokine release syndrome?

Answer 39

R/t pleiotropy 1 cytokine is influencing many different cells and can cause unintended effects if this isn’t taken into consideration

Question 40

What do Type 1 receptors do?

Answer 40

- Pro-inflammatory response

Question 41

What do Type 2 receptors do?

Answer 41

- Anti-inflammatory