Innate immunity: Cytokines and Interferons

Question 1

Interferons and Cytokines can be produced by…

Answer 1

Macrophages

Question 2

What are the 3 main effects of Interferons and Cytokines?

Answer 2

a. Signal neighboring cells to put up barriers
b. Signal infected cells to die (apoptosis)
c. Recruitment of white blood cells to stimulate long-lasting immunity

Question 3

Cell signaling through cytokine receptors is called…

Answer 3

Jaks and Stats pathway

Question 4

What is the structure of cytokine receptors?

Answer 4

2 chains
1. Extracellular cytokine binding domain - binding site for cytokine molecules
2. Intracytoplasmic domain (catalytic site) binds Janus Kinases (JAKS) - tyrosine kinase activity

Question 5

What happens in the absence of cytokine molecules?

Answer 5

2 chains remain dissociated

Question 6

What happens upon cytokine and cytokine receptor binding?

Answer 6

Stabilises heterodimer
Brings together JAKS bound to cytoplasmic portions of each chain.

Question 7

What happens when JAKS are activated?

Answer 7

Phosphorylates the tyrosine residue of two cytoplasmic tails of cytokine receptors

Question 8

What is Stat?

Answer 8

Signal transducer and activator or transcription

Question 9

Where Stat associated in the signaling?

Answer 9

Bind to the PHOSPHORYLATED cytokine receptor chains
Themselves get phosphorylated by the JAKS

Question 10

The addition of phosphate to STAT enables…

Answer 10

Dimerization of STAT molecule
Migrates into the nucleus
Directly activated gene transcription

Question 11

What domain of STAT binds to the phosphorylated tails of cytokine receptors?

Answer 11

SH2 domain

Question 12

What are the key steps of JAK-STAT pathway?

Answer 12

1. Cytokine-mediated receptor dimerization
2. JAKS phosphorylates tyrosine residues
3. STATs recruitment & JAK mediated phosphorylation
4. Dimerization of STATS
5. Translocation -> transcription
   -> STAT dimer binds to STAT-binding sequences in the promoter
   ->Transcription of cytokine responsive gene

Question 13

What is JAKS?

Answer 13

Proteins

Question 14

What residue is found in the intracellular region of cytokine receptors?

Answer 14

Tyrosine Residue

Question 15

Why do JAKS trans-phosphorylate each other initially?

Answer 15

Increases activity of tyrosine kinase domains.
This activates JAKS

Question 16

What happens when JAKS gets activated?

Answer 16

Phosphorylates Tyrosine Kinase on cytokine receptors

Question 17

What is phosphorylated tyrosine called?

Answer 17

Phosphotyrosine

Question 18

Phosphotyrosine creates docking sites for what proteins?

Answer 18

STAT proteins by SH2 domain

Question 19

When do the STAT proteins dissociate from phosphate tyrosine on receptor?

Answer 19

When they phosphorylated

Question 20

Dimerization of STATs occurs straight after?

Answer 20

The phosphorylation of STAT

Question 21

What does the dimerization of STAT protein involve?

Answer 21

SH2 domain binds to phosphate tyrosine on another STAT molecule -> homodimer

Question 22

Where does the STAT homodimer translocate to?

Answer 22

Nucleus

Question 23

What occurs during translocation of STAT?

Answer 23

DNA binding domain of STAT protein attached to DNA
Transcription
Gene Expression

Question 24

What residues are found in STAT proteins?

Answer 24

Tyrosine Residues

Question 25

Inactive STAT proteins are?

Answer 25

Found in cytosol Unphosphorylated tyrosine residues

Question 26

What effects do cytokines induce?

Answer 26

Local effects Systemic effects

Question 27

Local effects of cytokines target which cell?

Answer 27

Endothelial Cells

Question 28

The local effects of cytokines that induce an increase in rate of...

Answer 28

Adhesion molecules Permeability Chemokine expression Activation Degranulation

Question 29

The local effects of cytokines that induce an decrease in rate of...

Answer 29

Flow rate

Question 30

Why is there an increase in adhesion molecules?

Answer 30

Allows white blood cells to interact Transmigrate to the site of infection

Question 31

Why is there an increase in permeability?

Answer 31

Allows fluids to reach the site of infection Swelling (characteristic of inflammatory response)

Question 32

Why is there a decrease in flow rate?

Answer 32

Allow white blood cells to adhere to adhesion molecules

Question 33

Why is there an increase in chemokine expression?

Answer 33

For molecules to attract other cells

Question 34

What is the collective local effects of cytokine induction?

Answer 34

Increase activation of macrophages Degranulation of neutrophils ( release enzymes)

Question 35

What are the systemic effects of cytokine induction on the liver?

Answer 35

Stimulate acute phase proteins (produced in the liver)

Question 36

What are the systemic effects of cytokine induction on the hypothalamus?

Answer 36

Fever Inhibits microbial growth

Question 37

What are the systemic effects of cytokine induction on the bone marrow?

Answer 37

Mobilization of cells in bone marrow Help in innate immune response

Question 38

List the 5 cytokines

Answer 38

IL-1B TNF-alpha IL-6 CXCL8 IL-12

Question 39

What are the local effects of cytokine IL-1B?

Answer 39

Activates vascular endothelium Activates lymphocytes Local tissue destruction Increases access of effector cells

Question 40

What are the local effects of cytokine TNF-alpha?

Answer 40

Activates vascular endothelium Increases vascular permeability -> leads to increased entry of Ig6, complement and cells to tissues, increased fluid drainage to lymph nodes

Question 41

What are the local effects of cytokine IL-6?

Answer 41

Lymphocyte activation Increased antibody production

Question 42

Which cytokines are involved in the first innate immune response?

Answer 42

IL-1B TNF-a IL-6 -> Local destruction

Question 43

What are the local effects of chemokine CXCL8?

Answer 43

Chemotactic factor recruits neutrophils (elimination of pathogen) basophils, and T cells to the site of infection

Question 44

What are the local effects of cytokine IL-12?

Answer 44

Activates NK cells Induces differentiation of CD4 T cell into Th1 cells Bind to macrophages Inflammatory mediators CD4 function state in the immune response against bacteria and viruses Prominently expressed

Question 45

What are the systemic effects of cytokine IL-1B?

Answer 45

Fever Production of IL-6

Question 46

What are the systemic effects of cytokine TNF-a?

Answer 46

Fever Mobilization of metabolites SHOCK

Question 47

What are the systemic effects of cytokine IL-6?

Answer 47

Fever Induces acute phase protein production

Question 48

Cell-mediated immunity mechanism to fight off the virus?

Answer 48

Viral infection- macrophage stimulated Produces IL-12 This help polarise a T cell response -> TH1 response Produces IFN-Y Further activates macrophage

Question 48

Cell-mediated immunity mechanism to fight off the virus?

Answer 48

Viral infection- macrophage stimulated Produces IL-12 This help polarise a T cell response -> TH1 response Produces IFN-Y Further activates macrophage

Question 49

Mechanism for allergic responses/ Anti-helminth responses?

Answer 49

TH2 cell Produce -> IL-4 ,IL-5, IL-6, IL-10, IL-13 B cell -> IgE antibodies Eosinophil response

Question 50

How are specialized immune responses generated?

Answer 50

Combination of cytokines