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Module 2 > Cytokines in the Lung > Flashcards

Cytokines in the Lung Flashcards

1
Q

Define a Cytokine

A

Small secreted proteins that mediate cellular interactions in immune and inflammatory responses, cell proliferation and differentiation, and various other processes

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2
Q

Explore the similarities/differences of cytokines and chemokines

A

Cytokines can be chemotactic but are not considered chemokines unless they have the presence of variations on a conserved cysteine motif (i.e. CXC or CCL)

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3
Q

Cytokines are small proteins (around __kDa) secreted by _____ and non-immune cells. They have local (_____ and _____) and distant (_____) effects. They are active at picomolar concentrations.

A

Cytokines are small proteins (around 25kDa) secreted by immune and non-immune cells. They have local (autocrine and paracrine) and distant (endocrine) effects. They are active at picomolar​ concentrations.

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4
Q

Describe the process of IL-1B transcription

A
  • PAMP (LPS) binds to TLR4
  • Myd88 and TIRAP recruited to cytosolic domain
  • IRAK recruited
  • IRAK phosphorylated and activates TRAF6
  • TRAF6 activates NF-kB path (with IKK)
  • NF-kB upregaultes mRNA expression of pro-IL1B
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5
Q

Describe how Pro-IL-1B gets activated

A
  • Activation of Pro-IL-1B requires second signal
  • Signal recruits NLRP3, ASC and pro-caspase 1 to form the NLRP3 Inflammasome
  • Inflammasome cleaves pro-IL-1B into IL-1B
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6
Q

Name 3 cytokines which are produced as pro-cytokines. Why is this beneficial

A

IL-1β

IL-18

IL-33

Safe storage and allows rapid secretion in presence of stimulus

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7
Q

Name 5 types of receptor cytokines can signal through

A
  1. Homodimeric
  2. Heterodimeric with common chain
  3. Heterodimeric wihthout common chain
  4. TNF-receptors
  5. Chemokine receptors
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8
Q

What is the most common signalling pathway for cytokines

A

JAK/STAT pathway

JAK: Janus Kinases; STAT: Signal Transducers and Activators of Transcription​

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9
Q

Explain cytokine signalling through JAK/STAT

A

Cytokine binds to receptor

Receptor dimerises

Auto-phosphorylation of cytoplasmic domain by JAK

Recruitment of STAT and binding to phosphorylated domains

STATs are phosphorylated

Phosphorylated STATs dimerise and translocate to nucleas for gene transcription

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10
Q

JAK/STAT is one signalling pathway for cytokines. IL-1α, IL-33 and PAMPs (IL-1R and TLR respectively) can signal through what protein signal?

A

MyD88

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11
Q

Explain the cytokine sgnalling through MyD88

A

MyD88 recruited to cytoplasmic tail of receptor

Phosphorylation of signalling molecules (IRAK and TRAF6)

Activation of transcription factors

Translocation to nucleaus and upregulation of gene transcription

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12
Q

Describe how cytokine signalling can be regulated (decreased signalling) and explain the mechanism

A

Decoy receptor IL-1Rii

Mechanism: Captures IL-1 and prevents signalling receptor complex formation

Strong negative regulator of inflammation

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13
Q

Describe the two functional characteristics of cytokines

A
  1. Pleiotropic - acts on number of different cell types
  2. Multifunctional - single cytokine regulates different functions

Redundancy: different cytokines have the same function (e.g. LT and TNF-α)

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14
Q

Describe three general effects of type I IFN (IFN-α/β) (see Module 3 for more detail)

A
  1. Induce anti-viral state
  2. ↑MHC I and antigen presentation in cells
  3. ↑NK activation for viral clearance
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15
Q

Describe the local effects of IL-1β (2)

A
  1. Activates vascular endothelium
  2. Activates lymphocytes
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16
Q

Describe the systemic effects of IL-1β (2)

A
  1. Fever
  2. ↑IL-6 production
17
Q

Describe the local effects of TNF-α

A
  1. Activates vascular endothelium
  2. ↑vascular permeability
  3. ↑IgG entry
  4. ↑lymph drainage
18
Q

Describe the systemic effects of TNF-α

A
  1. Fever
  2. Metabolite mobilisation
  3. shock
19
Q

Describe the local effects of IL-6

A
  1. Lymphocyte activation
  2. Antibody production
20
Q

Describe the systemic effects of IL-6

A
  1. Fever
  2. ↑Acute-phase proteins (CRP)
21
Q

(tricky) Describe differences in controlled and uncontrolled inflammation

A
22
Q

Cytokines and T cells: CD4+ T helper cells differenctiate depending on the _____ _____ activated by _____ in close proximity or highest concentration. For instance:

  1. ___ = T-bet -> TNF and _____
  2. Th2 = ____ -> IL-4, IL-5, IL-9, IL-13
  3. Th17 = ____ -> IL-17, ____
A

Cytokines and T cells: CD4+ T helper cells differenctiate depending on the transcription factor activated by cytokines in close proximity or highest concentration. For instance:

  1. Th1 = T-bet -> TNF and IFN-γ
  2. Th2 = GATA3 -> IL-4, IL-5, IL-9, IL-13
  3. Th17 = RORγt** -> IL-17, **IL-22
23
Q

Which chromosome is the Th2 locus found in humans and mice

A

Humans: chromosome 5

Mice: chromosome 11

24
Q

Describe the effects of IL-4 in allergic asthma (3)

A
  1. Activation of naive CD4+ T cells into Th2 cells (↑IL-4, IL-5, GM-CSF
  2. ↑VCAM expression on endothelium -> cell infiltration
  3. B cell production of IgE
25
Q

Describe the effects of IL-5 in allergic asthma

A
  1. Priming and activation of eosinophils
  2. Differentiation and release from bone marrow
  3. Survival in tissue
26
Q

Describe the effects of IL-13 in allergic asthma

A
  1. Affects smooth muscles
    1. Airway hyperresponsiveness
  2. ↑chemokines and MMPs from epithelial cells
  3. Mucus production
27
Q

Define an alarmin and give examples

A

A molecule released by cells in response to damage e.g. necrosis and infection inury (usually recognised by TLRs and NLRs)

Examples: IL-33, IL-25, TSLP

therefore these are DAMPs

28
Q

IL-33 is an alarmin in asthma which stimulates mast cells and their degranulation. How are IL-33 inactivated?

A

By chymases, caspases or oxidation

Module 2 (18 decks)

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