Lecture 5: Inflammatory Mediators II Flashcards

1
Q

What is the chief source of cytokines and chemokines in inflammation? (in charge after first 24-48 hrs)

A

Macrophages and monocytes

lymphocytes use them to communicate during immune processes

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2
Q

Cytokines and chemokines organize and maintain… (4)

A
  • cell migration and phagocytosis
  • chronic inflammatory reactions
  • healing and regeneration
  • immune responses
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3
Q

How is production of pro-inflammatory cytokines induced?

A

Nuclear signaling; NFk-B transcription pathway

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4
Q

What are interleukins?

A

Nonspecific nomenclature for cytokines

  • monokine from monocyte, lymphokine from lymphocyte
  • chemokines are a type of cytokine
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5
Q

Where do IL-1, TNF, and IL-6 come from?

A

Activated macrophages in inflammation

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6
Q

What do IL-1, TNF, and IL-6 do?

A
  • Mediate cellular phases
  • Mediate systemic responses
  • Mediate immune responses
  • Mediate healing and regeneration

Overlapping; differences not at important as similarities

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7
Q

IL-1, TNF, and IL-6 generally act ______, but can _________

A

locally; reach sufficient levels to act systemically

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8
Q

Local effects of IL-1, TNF, and IL-6:

A
  • Activation of endothelial cells (increased vascular permeability)
  • Induction of adhesion molecules on ECs, neutrophils, monocytes
  • Induction of synthesis of other cytokines and GFs
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9
Q

Systemic effects of IL-1, TNF, and IL-6:

A
  • Induction of fever (endogenous pyrogen)
  • Malaise
  • Synthesis of acute phase proteins
  • Leukocytosis (increase in white count)
  • Lymphadenitis
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10
Q

TNF-alpha has similar effect to IL-1 and IL-6, but also ________

A

activation of apoptotic death domain (TNF-R1, TRADD signaling)

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11
Q

What can monoclonal antibodies to TNF be used to treat?

A

Chronic inflammatory disorders
- rheumatoid arthritis, Crohn’s, psoriasis

  • buuut can wipe out immune response (get JC virus, TB)
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12
Q

What is a side-effect of IL-6?

A

Local production by osteoblasts will increase osteoclast activity –> bone loss

Inhibitors of IL-6 may have a role in post-menopausal osteoporosis

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13
Q

What are chemokines?

A

Chemotactic molecules (cytokines); local production to mediate chemotaxis of specific cell types

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14
Q

Describe the structure of chemokines.

A

70-80 amino acids, two conserved cysteines

  • C-C chemokines have two adjacent cysteines
  • C-X-C have an amino acid separating them
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15
Q

What is IL-8 (CXCL8)?

A

C-X-C chemokine chemotactic for neutrophils; bind CSCR-1

*also good for endothelial cell migration - angiogenesis

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16
Q

What synthesizes IL-8?

A

Macrophages, endothelial cells

17
Q

What is MCP-1?

A

Chemotactic for macrophages; from macrophages

Induces histamine release from mast cells

18
Q

What are RANTES and MIP-1?

A

Chemotactic for eosinophils (allergic response)

19
Q

List some inflammatory lymphokines that induce Th1 and Th2 responses.

A

IL-2,4,5,10,13

etc.

20
Q

What is IFN-gamma?

A

Activates macrophages; from T-cells and NK cells

Induce expression of MHC I and II
Inhibit Th2
Enhance leukocyte-endothelial adherence

21
Q

What are Type I Interferons? (alpha and beta)

A

Produced by various cells and induce resistance to viral replication in all cells

Increase MHC class I
Activate NK cells to kill virus-infected cells
22
Q

What is IL-12?

A

Synthesized by macrophages and dendritic cells

Important in all cell-mediated responses; activates T-cells

  • INDUCE Th1
  • INHIBIT Th2 pathways
23
Q

What do FGF and TNF-alpha do?

fibroblast growth factor

A
  • Stimulate fibroblasts in healing and regeneration

- Cause fibrosis

24
Q

List some angiogenic factors.

A

VEGF, FGF, PDGF (platelet-derived GF)

25
Q

What are colony-stimulating factors and what do they do?

A

GM-CSF, G-CSF, M-CSF

Differentiate granulocytes in marrow
Stimulate neutrophils, eosinophils, macrophages

26
Q

How can septic shock be caused?

A

Binding of LPS to TLRs (like TLR4) stimulates pro-inflammatory cytokine synthesis

27
Q

Where does nitric oxide come from in inflammation?

A

Endothelial cells (local vasodilation) and activated macrophages

This is iNOS

28
Q

What is nitric oxide synthesized from?

A

L-arginine (nitric oxide synthase)

- eNOS in endothelium and nNOS in neurons is constitutively expressed

29
Q

How can NO cause cancer?

A

In chronic inflammation, where it is expressed for a long period of time, its role as a ROS damages cellular DNA and can cause cancer

  • H. pylori, alcoholism, hepatitis
30
Q

Is NO long-acting?

A

No! Half-life is seconds long and only local

31
Q

What does NO do?

A

Enhance vasodilation, platelet aggregation/adhesion, bactericidal activity, inhibit leukocyte migration

Both positive and negative effects in inflammation