Important Cytokines

Question 1

Growth factors

Answer 1

• G-CSF(granulocyte colony-stim factors):
  
  • Called Factor B
  • Secreted by bone marrow, macrophages, & endothelial cells
• Fnxs:
• Stims development of neutrophils/granilocytes
• Stims proliferation & migration of endo cells
• GM-CSF
  
  • Called colony-stim factor A
  • Secreted by ^{<u><strong>T-cells,</strong></u>} macrophages, endothelial cells, fibroblasts
• Fnxs:
• Stims diff of granulocyte&monocyte progen
• Stims growth of endothelial cells

Question 2

Growth Factors

Answer 2

• _Transforming growth factors-B(TGF_B)_
• Secreted by platelets, macrophages, lymphocytes, & mast cells
• Fnxs:
• Stimulate epithelial cells & mesenchymal cell growth
• Down regs pro-inflammatory activities
• Induce class switch to IgA by plasma cells

Question 3

Interleukins

Answer 3

• IL-1
• Secreted by monocytes, macrophages, dendritic cells, endothelial cells, B-cells
• Major role in development of innate immunity-
• Enhances NK cells activity
• Increases expression of ICAMS on vascular endothelial cells
• Chemo attracts macrophages/neutrophils
• Induces synthesis of ACUTE proteins in heptocytes
• Induces fever by acting on hypothalamus
• Role in adaptive immunity:
• CO-stim activation of Th cells
• Promotes maturation & clonal expansion of B-cells
• Stims IL-6 & IL-8
• Induction of IL-2R

Question 4

Interleukins

Answer 4

• IL-2
• Secreted by T-cells
• Reffered to as T-cell growth factor
• Role in innate immunity:
• Stims growth of monocytes & macrophage
• enhances proliferation & activation of NK
• Role in adaptive immunity:
• Induces prolif-activation of Ag-primed T-cells
• Acts on B-cells to stim proliferation & Ab production
• IL-3
• Secreted by T-cells, NK, eosinophils, Mast
• Role in innate immunity:
• Supports growth & diff of hematopoietic ^{<strong>(myeloid)</strong>}
• Stims growth & histamine production of mast cells
• Adaptive immunity-Promotes growth monocytes & B-cells

Question 5

Interleukins

Answer 5

• IL-4
• Secreted by T-cells, NK, Mast
• Role in innate:
• Regs stages of hemapoiesis
• Acts w/other cytokines to stim mast cell proliferation (innate/adaptive)
• Role in adaptive:
• To reg of Th1-Th2 axis-^{<u><strong>Pushes terminal diff of Th cells to Th2 (humoral arm)</strong></u>}
• Upregs MHC-2-Ag presentation & phagocytosis by macro
• Stims proliferation, differ & activation of Ag activated B-cells
• Induces Ab class switching IgE & IgG4^{<u><strong>(fibrosis)</strong></u>}
• Increases expression of MHC-2 on resting B-cells
• Induces prolif of thymocytes & T-cells

Question 6

Interleukins

Answer 6

• IL-5
• Secreted by T-cells, Mast, & eosinophils
• Role in adaptive:
• Promotes growth & diff of eosinophils^{<u><strong>(INNATE)</strong></u>}
• Co-stims prolif & diff of activated B-cells
• Induces Ab class switching to IgA
• IL-6
• Lymphopoietin
• Secreted by marrow & thymic cells
• Role in adaptive:
• Induces diff of lymphoid stem cells into progin B & T cells
• Increases expression of IL-2 & receptor on resting T-cells
• IL-23 = Made by dendritic cells in Activation of ^{<u><strong>MEMORY T-CELLS</strong></u>}

Question 7

interleukins

Answer 7

• IL-10
• Secreted by monocytes, macrophages, keratinocytes & T-cells
• Role in Adaptive:
• Blocks production of cytokines by macrophage_^{<strong> (Downregs cell-med response)</strong>}_
• Shuts down transcription of TNF-alpha ^{<u><strong>(DOWNREGS INFLAMM RESPONSE)</strong></u>}
• Downregs MHC-2 expression on Ag presenting cell
• IL-13
• Produced by T-cells
• Anti-inflamm, inhibits macrophage inflamm cytokin production
• Enhances B-cell growth & diff

Question 8

interleukins

Answer 8

• IL-12
• Secreted by monocytes, macrophages, dendritic cells & B-cells
• Major role in adaptive immunity
• Regs Th1/Th2 axis ^{<u><strong>(promotes Th1 production)</strong></u>}
• Co-stims diff of activated CD8+ into CTLs
• Role in innate & adaptive:
• Stims prolif of NK & LAK - Ag activated Th1
• Stims production of IFN-gamma by NK & CTLS ^{<u><strong>(CD8)</strong></u>}
• IL-17
• Made by T cells, ^{<u><strong>(CD4 Tcells in BLOOD)</strong></u>}
• Role in innate:
• Induce production of IL-6 & IL-8
• Enhances surface expression of ICAM-1 on fibroblasts
• Regs expression of Comp proteins
• Chemotactic for neutrophils

Question 9

Tumor necrosis Factors (TNF-A)

Answer 9

• TNF-a
• Secreted by monocytes, macrophages, fibroblasts, B/T cells, NK
• MAJOR Role in Innate:
• Induce cytokines by inflamm cells
• Increase expression of CAMS on vascular
• Increase expression of ligands on circulating neutrophils
• Cause smooth muscle contraction
• Induce production of acute phase proteins ^{<u><strong>(C-REACTIVE &amp; MANNOSE BINDING)</strong></u>}
• Cytotoxic effect on tumor cells

Question 10

Tumor necrosis Factors (TNF-B)

Answer 10

• TNF-B
• Called Lymphotoxin
• Role in innate:
• Cytotoxic effect on tumor cells
• Enhances phagocytic activity of macrophages & neutrophils
• Inhibits prolifer of lymphoid & hemato
• Role in adaptive:
• Secreted by TH1 & CTL cells

Question 11

Interferons (TYPE 1)

Answer 11

• IFN-A: secreted by macrophages, monocytes, lymph
• IFN-B: secreted by fibroblasts & epithelial
• IFN-K: Secreted by Keratinocytes
• ALL promote production of antiviral agents by UNINFECTED cells-
• Induces production of Ds-activated inhibitor of translation ^{<u><strong>(DAI or RNA-DEPEND PROTEIN KINASE)</strong></u>}
• ALL increase expression of MHC 1 on virally infected cell

Question 12

Interferons (TYPE 2)

Answer 12

• IFN-Gamma
• Secreated by Th1, CTLs, & NK
• Fnxs:
• Enhances intracell killing by macrophages
• Increases expression of MHC 1&2
• Regs Th1-Th2 terminal diff
• Excess amounts inhibit prolif of Th2
• Excess amounts DOWN reg humoral immune response-
  
  • Induces class switch to IgG2a
  • Blocks IL-4 induced class switch to IgE & IgG1
• Mediates effects in Th1 driven DTH
• Promotes production of Anti-viral agents by UNinfected cells-BY enhancing 2/5 adeylate synthase, Ribonucleases, ^{<u><strong>(BLOCKS CASPID ASSEMBLY)</strong></u>}

Question 13

Chemokines (Rantes)

Answer 13

• Regulated upon activation Normal T-cell Expressed & Secreted
• Functions:
• Enhances extravasation by promoting chemotaxis of monocytes, basophils & eosinophils

Question 14

Chemokines (MIP-1A/1B & IL-8)

Answer 14

• MIP-1a/b:
• Monocyte/Macrophage inflammatory proteins
• Fnxs:
• Enhances extravasation by promoting chemotaxis of monocytes & macrophages
• CXCL8 or IL-8:
• Secreted by mono, macro, fibroblasts, endo, epi, keratino, B & T cells
• Role in Innate:
• Acts as a chemokine to promote extravasation-
• Recruit neutorphils to areas of injury
• Induce neutrophil adherance to endothelium
• STIMS angiogenesis ^{<u><strong>(growth of BV)</strong></u>}