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BIOL2022- Immunology, Infection & Inflammation > Innate immunity: Cytokines and Interferons > Flashcards

Innate immunity: Cytokines and Interferons Flashcards

1
Q

Interferons and Cytokines can be produced by…

A

Macrophages

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2
Q

What are the 3 main effects of Interferons and Cytokines?

A

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

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3
Q

Cell signaling through cytokine receptors is called…

A

Jaks and Stats pathway

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4
Q

What is the structure of cytokine receptors?

A

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

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5
Q

What happens in the absence of cytokine molecules?

A

2 chains remain dissociated

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6
Q

What happens upon cytokine and cytokine receptor binding?

A

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

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7
Q

What happens when JAKS are activated?

A

Phosphorylates the tyrosine residue of two cytoplasmic tails of cytokine receptors

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8
Q

What is Stat?

A

Signal transducer and activator or transcription

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9
Q

Where Stat associated in the signaling?

A

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

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10
Q

The addition of phosphate to STAT enables…

A

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

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11
Q

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

A

SH2 domain

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12
Q

What are the key steps of JAK-STAT pathway?

A
  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
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13
Q

What is JAKS?

A

Proteins

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14
Q

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

A

Tyrosine Residue

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15
Q

Why do JAKS trans-phosphorylate each other initially?

A

Increases activity of tyrosine kinase domains.
This activates JAKS

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16
Q

What happens when JAKS gets activated?

A

Phosphorylates Tyrosine Kinase on cytokine receptors

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17
Q

What is phosphorylated tyrosine called?

A

Phosphotyrosine

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18
Q

Phosphotyrosine creates docking sites for what proteins?

A

STAT proteins by SH2 domain

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19
Q

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

A

When they phosphorylated

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20
Q

Dimerization of STATs occurs straight after?

A

The phosphorylation of STAT

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21
Q

What does the dimerization of STAT protein involve?

A

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

22
Q

Where does the STAT homodimer translocate to?

A

Nucleus

23
Q

What occurs during translocation of STAT?

A

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

24
Q

What residues are found in STAT proteins?

A

Tyrosine Residues

25
Q

Inactive STAT proteins are?

A

Found in cytosol
Unphosphorylated tyrosine residues

26
Q

What effects do cytokines induce?

A

Local effects
Systemic effects

27
Q

Local effects of cytokines target which cell?

A

Endothelial Cells

28
Q

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

A

Adhesion molecules
Permeability
Chemokine expression
Activation Degranulation

29
Q

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

A

Flow rate

30
Q

Why is there an increase in adhesion molecules?

A

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

31
Q

Why is there an increase in permeability?

A

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

32
Q

Why is there a decrease in flow rate?

A

Allow white blood cells to adhere to adhesion molecules

33
Q

Why is there an increase in chemokine expression?

A

For molecules to attract other cells

34
Q

What is the collective local effects of cytokine induction?

A

Increase activation of macrophages
Degranulation of neutrophils ( release enzymes)

35
Q

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

A

Stimulate acute phase proteins (produced in the liver)

36
Q

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

A

Fever
Inhibits microbial growth

37
Q

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

A

Mobilization of cells in bone marrow
Help in innate immune response

38
Q

List the 5 cytokines

A

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

39
Q

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

A

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

40
Q

What are the local effects of cytokine TNF-alpha?

A

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

41
Q

What are the local effects of cytokine IL-6?

A

Lymphocyte activation
Increased antibody production

42
Q

Which cytokines are involved in the first innate immune response?

A

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

43
Q

What are the local effects of chemokine CXCL8?

A

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

44
Q

What are the local effects of cytokine IL-12?

A

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

45
Q

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

A

Fever
Production of IL-6

46
Q

What are the systemic effects of cytokine TNF-a?

A

Fever
Mobilization of metabolites SHOCK

47
Q

What are the systemic effects of cytokine IL-6?

A

Fever
Induces acute phase protein production

48
Q

Cell-mediated immunity mechanism to fight off the virus?

A

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

48
Q

Cell-mediated immunity mechanism to fight off the virus?

A

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

49
Q

Mechanism for allergic responses/ Anti-helminth responses?

A

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

50
Q

How are specialized immune responses generated?

A

Combination of cytokines

BIOL2022- Immunology, Infection & Inflammation (14 decks)

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