Cytokines Flashcards

1
Q

describe cytokines

A
  • cytokines: low molecular weight proteins (MW <30 kDa) that regulate the immune response
    • over 200
    • secreted by a broad group of cells, but mainly by TH cells, dedritic cells and macrophages
    • carefully regulates (no constitutive)
    • act mostly locally
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2
Q

define interleukins, lymphokines, monokines, colony stimulating factor and chemokines

A
  • interleukins (ILs): group of cytokines secreted by leukocytes that act on leukocytes
  • lymphokines: produced mainly by lymphocytes
  • monokines: produced mainly by monocytes
  • colony stimulating factor: support growth of cells on semi-solid media
  • chemokines: cytokines that mediate chemotaxis
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3
Q

describe the mechanism of action of cytokines

A
  • bind to specific membrane receptors
  • high affinity; work at low concentrations (picomolar)
  • trigger signal transduction leading to gene expression
  • modulate immune response; stimulate/inhibit activation, proliferation, differentiation of immune cells
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4
Q

name the 5 cytokine receptor families

A

(chemokine receptor family not shown)

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5
Q

describe IL-2R (cytokine receptors: class I)

A
  • IL-2R is the most thoroughly studied cytokine receptor
    • expressed by T cells for proliferation
      • also called CD25, surface marker in mature T cells
    • complete receptor has 3 subunits–subunits together have higher affinity for IL-2
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6
Q

describe signalling via class I and class II cytokines

A
  • initiated by cytokine binding
  • activates JAK (Janus kinase)
  • phosphorylation of tyrosine
  • binding of STAT (signal transducers and activators of transcription)
  • translocation of STAT to cell’s DNA
  • transcription of specific target genes
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7
Q

describe homeostatic vs. inflammatory chemokines

A
  • homeostatic: constitutively produced in thymus and lymphoid tissue and are responsible for basal leukocyte migration
  • inflammatory: these are formed under pathological conditions
    • stimualted by IL-1, TNF-a, LPS or viruses
    • actively participate in the inflammatory response attracting immune cells to the site of inflammation
    • examples: CXCL8, CCL2 (MCP-1), CCL3 (MIP-1a), CCL5 (RANTES)
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8
Q

summarize the cytokines found in innate and adaptive immunity

A
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9
Q

describe the hematopoietic cytokines

A
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10
Q

describe the lineage of cells from a hematopoietic stem cell and the ILs involved

A
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11
Q

contrast the function of Th1 vs Th2 cytokines

A
  • Th1 cytokines activate macrophages, NK cells, and cell mediated immunity, plus the secretion of IgG isotypes
    • IgG production/complement fixation
    • macrophage activation
    • delayed type hypersensitivity (cell-mediated)
    • cytotoxic T-lymphocyte production
  • Th2 cytokines tend to favor isotype switching in the humoral immune response
    • IgE production
    • eosinophils
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12
Q

describe teh Th1/Th2 balance

A
  • in a given immune response, either a Th1 or a Th2 response may dominate
  • T helper cell cytokines of one response tend to down-regulate the other type of response
    • example: Th1 cells secrete IFN-γ, which inhibits expansion of the Th2 subset
  • balance of two subset determines response to disease
    • example: leprosy
      • tuberculoid (Th1, CMI response, good prognosis)
      • lepromatous (Th2, humoral response, bad prognosis)
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13
Q

summarize the Th1/Th2 balance

A
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14
Q

describe the role of cytokiens in disease

A
  • septic shock:
    • bacterial endotoxin (LPS) binding to TLRs
    • overproduction of IL-1 and TNF-a
  • toxic shock:
    • bacterial superantigens non-specifically activate T cells
    • overproduction of IL-1 and TNF-a
  • rheumatoid arthritis
    • TNF-a
  • lymphoid and myeloid cancers
    • high levels of IL-6
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15
Q

describe the timeline of cytokine production

A
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16
Q

describe CXCL-8 (IL-8) (chemokine)

A
  • chemoattractant for neutrophils (CXCR1, CXCR2)
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17
Q

describe CCL19/CCL21 (chemokine)

A
  • plays an important role in trafficking of T cells in thymus and in T cell and B cell migration to secondary lymphoid organs (receptor CCR7)
18
Q

describe CCL5 (RANTES) (chemokine)

A
  • chemotactic for T cells, eosinophils, and basophils
  • plays an active role in recruiting leukocytes into inflammatory sites
  • induces the proliferation and activation of certain NK cells
19
Q

describe CCL2 (MCP-1) (chemokine)

A
  • monocytic chemotactic protein-1
  • chemoattractant for monocytes, T-cells, mast cells, basophils, stem cells
20
Q

describe CCL3 (MIP-1a)

A
  • macrophage inflammatory protein-1a
  • chemoattractant for monocytes, T- and B-cells, NK cells, mast cells, basophils, dendritic cells, stem cells
21
Q

describe IL-2 (cytokines that regulate adaptive immunity)

A

IL-2

  • source: Th1 cells
  • activity: T cell growth factor
22
Q

describe IL-4 (cytokines that regulate adaptive immunity)

A

IL-4

  • source: Th2 cells
  • activity: B cell growth factor
23
Q

describe IL-5 (cytokines that regulate adaptive immunity)

A

IL-5

  • source: T cells
  • activity: B cell growth and immunoglobulin synthesis
24
Q

describe IL-7 (cytokines that regulate adaptive immunity)

A

IL-7

  • source: marrow/thymic stromal cells
  • activity: pre-B and pre-T cell growth factor
25
Q

describe IL-9 (cytokines that regulate adaptive immunity)

A

IL-9

  • source: T cells
  • activity: activates mast cells
26
Q

describe IL-10 (cytokines that regulate adaptive immunity)

A

IL-10

  • source: Th2 cells and macrophages
  • activity: inhibits Th1 and macrophage function
27
Q

describe IL-12 (cytokines that regulate adaptive immunity)

A

IL-12

  • source: B cells and macrophages
  • activity: activates NK cells, Th1 proliferation
28
Q

describe TNF-B (cytokines that regulate adaptive immunity)

A

TNF-B

  • source: T cells
  • activity: killing by cytotoxic CD8 cells
29
Q

describe IL-1 (cytokines that regulate innate immune response)

A

IL-1

  • source: monocytes, macrophages
  • activity: systemic inflammatory efefct, including fever, acute-phase protein synthesis, T-cell activation
30
Q

describe IL-6 (cytokines that regulate innate immune response)

A

IL-6

  • source: T cells, other cells
  • activity: stimulates other T cells to produce IL-2, B cells to produce immunoglobulins and stem cells
31
Q

describe IFN-a and IFN-B (cytokines that regulate innate immune response)

A

IFN-a and IFN-B

  • source: viral-infected cells
  • activity: interferes with viral replication, induces MHC class I expression
32
Q

describe IFN-γ (cytokines that regulate innate immune response)

A

IFN-γ

  • source: Th1 cells
  • activity: activates NK cells and macrophages, induces MHC class II expression
33
Q

describe TNF-a (cytokines that facilitate the innate immune response)

A

TNF-a

  • source: macrophages
  • activity: activates endothelial cells, vascular permeability
34
Q

list the proinflammatory cytokines

A

TNF, IL-1, IL-6, chemokines (mostly)

35
Q

list the anti-inflammatory cytokines

A

IL-4, IL-10, IL-13, TGF-B, IL-1

36
Q

list the antiviral cytokines

A

IFN-a, IFN-B

37
Q

list the macrophages activating cytokines

A

IFN-γ

38
Q

list the B-cell activating cytokines

A

IL-4, IL-5, IL-6, IL-21

39
Q

list the T-cell activating cytokines

A

IFN-γ, IL-2, IL-4, IL-12

40
Q

list the eosinophil and/or mast cell activating cytokines

A

IL-3, IL-4, IL-5, IL-13