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DERMA Cytokines Copy by > cytokines copy > Flashcards

cytokines copy Flashcards

1
Q

Define pleiotropism

A

Ability of 1 cytokine to have many functions

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2
Q

Define redundancy

A

More than 1 cytokine with the same function

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3
Q

Define synergism

A

2 cytokines acting together to enhance a biological effect

Ex. IL-4 and IL-13 promote class switching in B cells to make IgE

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4
Q

Define antagonism

A

2 cytokines oppose each other’s effects

Ex: IL-4 favors Th2 response while IFN-gamma favors Th1 response

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5
Q

Describe the local and systemic effects of cytokines

A

Autocrine: acts on same cell which secreted itParacrine: acts on nearby cellsEndocrine: goes systemic and acts on distant cells

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6
Q

List the cytokines involved in innate immunity

A

IL-1
TNF-alpha
IL-6
IL-8

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7
Q

Which signaling pathway does IL-1 and TNF-alpha activate?

A

NF-KB

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8
Q

Name 2 principal cellular responses to TNF-alpha

A
  1. Gene transcription: production of IL-1/TNF-alpha, inflammatory mediators and ROS
  2. Apoptosis: Fas/FasL death via Caspase 8
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9
Q

What is the main source of TNF-alpha?

A

activated macrophages

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10
Q

What other stimuli can activate the pathway stimulated by IL-1/TNF-alpha?

A

PAMPs like LPS or peptidoglycans stimulate the NF-KB pathway resulting in IL-1/TNF-alpha production and local inflammation

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11
Q

Describe the local and systemic effects of TNF-alpha.

A

Local: -leukocyte recruitment via increased adhesion molecule expression on endo cells-self-amplifying cascade-eicosanoid synthesis via activation of phospholipase A2 and AA pathway

Moderate systemic:-pyrogen: PG synthesis by hypothalamus-stimulate hepatocytes to make acute phase proteins-cachexia-bone marrow stimulation–> increased prod of leukocytes

Massive systemic:-hypotension via decreased myocardial contraction and decreased vascular smooth muscle tone- activation of coagulation–> thrombosisAKA toxic shock!

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12
Q

Name 2 differences b/t IL-1 and TNF-alpha.

A
  1. IL-1 does NOT induce apoptosis

2. IL-1 has 3 subtypes…IL-1alpha is preformed in keratinocytes

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13
Q

What are the principle products of the pathway stimulated by IL-1/TNF-alpha?

A
  • IL-1/TNF-alpha…self-amplifying
  • ROS…antimicrobial defense
  • eicosanoids via activation of phospholipase A2
  • Bcl-2…inhibitor of Caspase 8 and apoptosis
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14
Q

How does UV light cause inflammation in the skin?

A

IL-1alpha is pre-formed and active in keratinocytes–> UV light damages keratinocytes–> release of IL-1alpha–> leukocyte recruitment via increased adhesion molecules and self-amplifying cascade

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15
Q

How does a sunburn make you not feel well?

A

Massive amounts of IL-1alpha are released from keratinocytes–> systemic circulation–> pyrogen (hypothalamus), acute phase response (liver) and cachexia

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16
Q

Give 2 specific mechanisms of action by which glucocorticoids suppress proinflammatory effects of IL-1/TNF-alpha.

A
  1. promote synthesis of IkBalpha= inhibitor of NF-KBIkBalpha dimerizes NF-KB–> sequestering it in cytolplasm–> prevents translocation to nucleus and gene transcription
  2. upregulate IL-1RA–> competes w/ IL-1alpha/beta for IL-1 rececptor
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17
Q

Describe the 3 forms of IL-1.

A

IL-1alpha
IL-1beta
IL-1RA

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18
Q

Which form of IL-1 is active when made?

A

IL-1alpha

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19
Q

Which form of IL-1 requires enzymatic activation?

A

IL-1beta

20
Q

Which form of IL-1 is counter regulatory?

A

IL-1RA

21
Q

Explain how keratinocytes upregulate the innate immune system.

A

keratinocytes express PRR (pattern recognition receptors) like TLRs, mannose receptors, C-type lectins

These receptors recognize PAMPs (pathogen associated molecular patterns) such as LPS, bacterial peptidoglycans, bacterial DNA, viral DNA.

Upon activation–> secretion of ILs, chemokines, antimicrobial peptides (beta-defensins, cathelicidins)

Keratinocytes can also be induced to express MHC II and present Ag

22
Q

Give a broad definition of the following: 1. interleukins 2. interferons 3. tumor necrosis factor 4. growth factors 5. chemokines

A
  1. IL: cytokines regulating actions b/t lymphocytes and other WBCs
  2. IFN: glycoproteins synthesized in response to viral infection
  3. TNF: cytokines from MO/T cells involved in apoptosis and inflammation
  4. growth factors: group of cytokines which stimulate cell growth and proliferation
  5. chemokines: subset of cytokines which mediate chemotaxis; aid in wound healing
23
Q

Which cells are responsible for IL-1 production?

A

IL-1alpha: keratinocytes

IL-1beta:

  • MO
  • dendritic cells
  • T/B/NK cells
  • endo cells
  • fibroblasts
24
Q

Describe the Jak-STAT pathway.

A
  1. binding of cytokine to receptor
  2. dimerization of transmembrane portions of receptor
  3. phosphorylation of JAK proteins
  4. phosphorylation of STAT proteins
  5. dissociation of STAT from JAK
  6. STAT relocates to nucleus
  7. act as transcription factors and induce gene expression
25
Q

Which cytokines use the Jak-STAT pathway?

A

IL-2, -7. -9 -10, -11, -12, -15, -21, -31, GM-CSF and IFN (alpha/beta/gamma)

26
Q

What are the main products of the Jak-STAT pathway?

A

JAK1/3= inflammation and pruritus

JAK2= hematopoiesis

27
Q

What are the main differences in function b/t Th1 and Th2 cytokines?

A 
Th1:
favor cell-mediated immunity
promote memory T cells
MO function
specific T cell responses
antiviral activity
B cells to produce IgG

Th2:
favor humoral immunity
B cells to produce IgE
promote eosinophil function

28
Q

What is the main Th1 cytokine?

A

IL-2

29
Q

What is the main Th2 cytokine?

A

IL-4;

  • promotes class switching to IgE
  • mast cell growth factor
  • promotes Th2 polarization,
  • downregulates IL-1, -6, TNF-alpha, IFN-gamma
30
Q

What was IL-2 first called after it was discovered?

A

T-cell growth factor

31
Q

List 5 effects of IL-2

A
  1. promotes T cell replication and function
  2. principle stimulator of IFN-gamma production
  3. induces Bcl-2 (anti-apoptotic factor)
  4. favors IgG production
  5. activates MO and NK cells
32
Q

Which cytokine does IL-7 mimic?

A

IL-2

33
Q

How does IL-12 regulate Th1 response?

A

suppresses IL-4/Th2 response, thereby favoring Th1 response

34
Q

Which cytokine is important for promotion of growth and differentiation of eosinophils?

A

IL-5; once called eosinophil growth factor

35
Q

What is the principal biological action of IL-31?

A

pruritus

36
Q

Describe the effects of IL-6 on the innate immune response, B cells and systemic levels.

A

innate/systemic:
Induces hepatocytes to produce acute phase proteins

Induces pyrogens which act on hypothalamus

Produces cachexia

Adaptive response:
B cells: stimulates IgM production

promotes IL-2 production

w/ IL-5, -6 stimulates IgA production

37
Q

Which cells produce IL-6?

A

MO mainly

also:
T/B cells
mast cells
endo cells
keratinocytes
fibroblasts
38
Q

Compare and contrast type I and type II interferons.

A

Compare:

  • all have anti-viral properties (Type I > Type II)
  • promote Th1 response
  • strong anti-proliferative effects of certain cells (cancer)
  • induce/increase expression of MHC I

Contrast:

  • alpha produced by MO, beta produced by fibroblasts, gamma produced by NK cells, CD8 T cells, Th1 CD4 cells
  • gamma required for MO activation
  • gamma promotes Ab mediated phagocytosis
  • gamma= inducer of chemokines and endo cell adhesion molecules
39
Q

Which interferons are type I?

A

alpha and beta

40
Q

Which interferons are type II?

A

gamma

41
Q

Which cells are the major source of IFN-gamma?

A

Th1 cells

42
Q

Describe the actions of IL-10

A

Debbie Downer

Inhibits IL-12 (activated MO and DCs) TNF-alpha, IFN-gamma, MHC II co-stimulation of T cells by APCs

43
Q

Which cells produce IL-10

A

activated MO and Th2 cells

also keratinocytes

44
Q

Name the Th1 cytokines

A

IL-2
IL-7
IL-12
IFN-gamma

45
Q

Name the Th2 cytokines

A 
IL-4
IL-5
IL-10
IL-13
IL-31

DERMA Cytokines Copy by (1 decks)

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