Wk16D1 IMM-10 Flashcards
(26 cards)
Key cytokines released by macrophages
IL-1b, TNF-a, IL-6, CXCL8/IL8, IL-12
IL-1b
Secreted by Macrophage
Local: Activates endothelium (e-selectin)+lymphocytes, tissue destruction for effector cell access
Systemic: Fever, IL-6 production
TNF-alpha
Secreted by Macrophage
Local: Increases TRAFFIC–Activates endothelium (e-selectin), vascular permeability, increased IgG, complement, and cells to site, increased lymph drainage.
tissue destruction for effector cell access
Systemic: Fever, Metabolites, Shock
IL-6
Secreted by Macrophage
Local: Activates lymphocytes, Ab production
Systemic: Fever, acute phase protein production
CXCL8/IL-8
Secreted by Macrophage
Local: chemotaxis of PMNs, Basos, T cells (actually binds to endothelium for rolling and forms gradient for subsequent chemotaxis)
IL-12
Secreted by Macrophage and DC
Local: Activates NK, CD4->Th1
What’s a cytokine? Interleukin? Chemokine?
small secreted/membrane proteins that bind surface receptors. Most are called IL-#. Chemokines are cytokines that induce migration, and are either CXC/CC (based on AA structure) and L/R (ligand/receptor).
TNF-a, IL-1, IL-6
Produced by macrophages, induce eachother
Endogenous pyrogens (induce fever @ hypothalamus) + mobilize fat/glycogen metabolites to support fever and immune cell production.
RHEUMATOID ARTHRITIS
Acute phase proteins
Induced by IL-6
Include Mannose-binding lectin and c-reactive protein
How are cachexia and septic shock related?
Both result from release of TNF-a. Cachexia is moderate/high release, wasting due to sustained metabolite mobilization. Shock is huge release.
Th1 development from CD4
Mac or DC secretes IL-12. Binds IL-12R and triggers tx factor T-bet. This drives TNF-a, IFN-gamma, IL-2 expression to fight intracellular pathogens.
Th2 development from CD4
Mystery cell or Ag-presented B cell secretes IL-4. Binds IL-4R, activating tx factor GATA-3. This drives IL-4/5/6 to fight extracellular pathogens.
IL-4
Th2 secreted. Induces Th2 differentiation and isotype switch to IgE.
IL-5
Eosinophil development
IL-6
Acute phase protein induction
How does one maintain Th subset bias?
IFN-gamma blocks Th2
TGF-beta blocks Th1
IL-10 blocks IL-12 synth (Th1 inducer)
Th1 vs Th2, who cares?
Depends on if you act via macrophage-activation or antibody-mediated approach. Uncontrolled Th1 is tissue damaging! Uncontrolled Th2 is IgE/mast cell/allergy/asthma.
Action of IFN-gamma
Positive feedback loop with macrophages IL-12 and NK/CD8/Th1. IFN-gamma crosslinks IFNgR1+IFNgR2 for activation.
Anti-IL-4 mAb
For asthma/allergy to decrease IgE production.
Describe the CD28/CTLA-4 battle on T-cells
They compete for B7 on activated DCs.
CD28 constitutively expressed->activates. CTLA-4 expressed following activation -> inactivates
Fas Ligand? Why make kill a lymphocyte?
Reduce antigen-specific cell # by binding Fas and inducing apoptosis. Lymphocytes become more sensitive the longer they are activated and in absence of co-stimulation.
Also, affinity maturation.
LUPUS
Tregs do what?
Produce anti-inflammatory cytokines TGF-beta, IL-10.
Tolerance to self-antigens.
CTLA-4
IL-10
Bind IL-10R to reduce B7 on APCs and limit IL-12 production (anti-inflammatory). Produced by Treg. Inactivate macrophages too
TGF-beta
Bind TGF-bR. Inhibit proliferation of activated T cells, inactivate macrophage. Anti-inflammatory, produced by Treg.
