Cytokines Flashcards Preview

Inflammation > Cytokines > Flashcards

Flashcards in Cytokines Deck (22):
1

TNF

  • Source:  Macrophages, mast cells, T lymphocytes, dendritic cells
  • Stimulates expression of endothelial adhesion molecules and secretion of other cytokines
  • systemic effects in acute inflammation
  • augments neutrophil responses to stimul
  • increases microbicidal activity of macrophages (increased NO production)
  • promotes lipid and protein mobilization and suppresses appetite --> cachexia

2

IL-1

  • Source:  Macrophages, endothelial cells, some epithelial cells, dendritic cells
  • Similar to TNF
  • greater role in fever;  acute inflammation
  • Activates fibroblasts to synthesize collagen
  • stimulates proliferation of synovial and mesenchymal cells
  • stimulates TH17 responses --> induce acute inflammation

3

IL-6

  • Macrophages, other
  • Systemic effects
  • Acute phase response (acute inflammation)

4

Chemokines

  • Macrophages, endothelial cells, T lymphocytes, mast cells, other cells
  • Acute inflammation
  • Recruitment of leukocytes to sites of inflammation; migration of cells in normal tissues

5

IL-17

  • T lymphocytes
  • Recruitment of neutrophils and monocytes in both acute and chronic inflammation

6

IL-12

  • Dendritic cells, macrophages
  • Increased production of IFN-gamma
  • Chronic inflammatory response

7

IFN-gamma

  • T lymphocytes, NK cells
  • Activation of macrophages (increased microbial and tumor cell killing)
  • Chronic inflammation

8

Promote leukocyte adhesion to endothelium and migration through vessels

TNF and IL-1

9

IL-17

  • Produced mainly by a subpopulation of T lymphocytes
  • Induces chemokine secretion and neutrophil recruitment
  • Important in adaptive immunity
  • "Cold Abcesses" lack warmth and redness typical of acute inflammatory responses

10

Endothelial activation

TNF and IL-1

11

Effects of TNF and IL-1

  1. Endothelial Activation
    • increased expression of endothelial adhesion molecules
      • E- and P- selectins
      • leukocyte integrin ligands
    • increased production of inflammatory mediators
      • other cytokines and chemokines
      • growth factors
      • eicosanoids
    • increased procoagulant activity of the endothelium
  2. Leukocyte Activation
    • stimulation of function and responses of neutrophils, macrophages
    • activates fibroblasts (IL-1) to synthesize collagen
    • stimulates proliferation of synovial and mesenchymal cells
  3. Systemic Acute-phase Response
    • fever
    • sepsis
    • energy balance  (promotes lipid and protein mobilization and suppresses appetite)

12

Systemic protective effects

 

  • TNF, IL-1, IL-6
    • Brain ----> fever
    • Bone marrow   ---->  leukocyte production
  • IL-1, IL-6
    • Liver   ----->  acute phase proteins produced

13

Systemic pathologic effects

  • TNF
    • Heart  ---->  decrased cardiac output
    • Endothelium  ----> increased permeability
  • TNF, IL-1
    • Insulin resistance

14

Chemokines

  • Family of small proteins that act primarily as chemoattractants for specific leukocytes
  • categories based on arrangement of 4 conserved cysteine residues
  1. C-X-C
  2. C-C
  3. C
  4. CX3C

15

C-X-C chemokines

  • Chemokines with one amino acid residue separating the first two cysteine residues
  • Work primarily on neutrophils
  • Ex:  IL-8

16

IL-8

  • Source:  activated macrophages, endothelial cells, other cells
  • Effects:  causes activation and chemotaxis of neutrophils with limited activity on monocytes and eosinophils
  • Induced by: microbial products, IL-1, TNF

17

C-C chemokines

  • First 2 cysteine residues are adjacent
  • ex: monocyte chemoattractant protein(MCP-1), eotaxin, RANTES
  • effects:  attract monocytes, eosinophils, basophils, lymphocytes
  • NOT as potent for neutrophils

18

Eotaxin

Selectively recruits eosinophils

19

C chemokines

  • Lack the first and 3rd of the conserved cysteines
  • Ex: lymphotactin
  • Relatively specific for lymphocytes

20

CX3C chemokines

  • 3 amino acids between the 2 cysteines
  • ex:  fractalkine  (only)
  • Fractalkine
    • cell surface-bound protein induced on endothelial cells by inflammatory cytokines
      • promotes strong adhesion of monocytes and T cells to the endothelium
    • proteolysis of the membrane bound protein produces soluble form
      • potent chemoattractant for monocytes and T cells

21

Inflammatory chemokines

  • Produced in response to microbes and other stimuli
  • Increase leukocyte integrin affinity
  • Promote chemotaxis

22

Homeostatic chemokines

  • Produced constitutively in tissues
  • Affect/organize various regional cell types  (ex: B and T lymphs in spleen and l.n.)