Wk16D1 IMM-10

Question 1

Key cytokines released by macrophages

Answer 1

IL-1b, TNF-a, IL-6, CXCL8/IL8, IL-12

Question 2

IL-1b

Answer 2

Secreted by Macrophage
Local: Activates endothelium (e-selectin)+lymphocytes, tissue destruction for effector cell access
Systemic: Fever, IL-6 production

Question 3

TNF-alpha

Answer 3

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

Question 4

IL-6

Answer 4

Secreted by Macrophage
Local: Activates lymphocytes, Ab production
Systemic: Fever, acute phase protein production

Question 5

CXCL8/IL-8

Answer 5

Secreted by Macrophage
Local: chemotaxis of PMNs, Basos, T cells (actually binds to endothelium for rolling and forms gradient for subsequent chemotaxis)

Question 6

IL-12

Answer 6

Secreted by Macrophage and DC

Local: Activates NK, CD4->Th1

Question 7

What’s a cytokine? Interleukin? Chemokine?

Answer 7

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).

Question 8

TNF-a, IL-1, IL-6

Answer 8

Produced by macrophages, induce eachother
Endogenous pyrogens (induce fever @ hypothalamus) + mobilize fat/glycogen metabolites to support fever and immune cell production.
RHEUMATOID ARTHRITIS

Question 9

Acute phase proteins

Answer 9

Induced by IL-6

Include Mannose-binding lectin and c-reactive protein

Question 10

How are cachexia and septic shock related?

Answer 10

Both result from release of TNF-a. Cachexia is moderate/high release, wasting due to sustained metabolite mobilization. Shock is huge release.

Question 11

Th1 development from CD4

Answer 11

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.

Question 12

Th2 development from CD4

Answer 12

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.

Question 13

IL-4

Answer 13

Th2 secreted. Induces Th2 differentiation and isotype switch to IgE.

Question 14

IL-5

Answer 14

Eosinophil development

Question 15

IL-6

Answer 15

Acute phase protein induction

Question 16

How does one maintain Th subset bias?

Answer 16

IFN-gamma blocks Th2
TGF-beta blocks Th1
IL-10 blocks IL-12 synth (Th1 inducer)

Question 17

Th1 vs Th2, who cares?

Answer 17

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.

Question 18

Action of IFN-gamma

Answer 18

Positive feedback loop with macrophages IL-12 and NK/CD8/Th1. IFN-gamma crosslinks IFNgR1+IFNgR2 for activation.

Question 19

Anti-IL-4 mAb

Answer 19

For asthma/allergy to decrease IgE production.

Question 20

Describe the CD28/CTLA-4 battle on T-cells

Answer 20

They compete for B7 on activated DCs.

CD28 constitutively expressed->activates. CTLA-4 expressed following activation -> inactivates

Question 21

Fas Ligand? Why make kill a lymphocyte?

Answer 21

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

Question 22

Tregs do what?

Answer 22

Produce anti-inflammatory cytokines TGF-beta, IL-10.
Tolerance to self-antigens.
CTLA-4

Question 23

IL-10

Answer 23

Bind IL-10R to reduce B7 on APCs and limit IL-12 production (anti-inflammatory). Produced by Treg. Inactivate macrophages too

Question 24

TGF-beta

Answer 24

Bind TGF-bR. Inhibit proliferation of activated T cells, inactivate macrophage. Anti-inflammatory, produced by Treg.

Question 25

Memory cell advantages

Answer 25

Longer lifespan (need IL-15/7
Already affinity matured IgG/A (not IgM/D)
Home more specifically

Question 26

FcgRIIb (IgG Fc receptor) role in memory

OR, How does RHOGAM work?

Answer 26

Simultaneous delivery of Ag and this signal is negative for naive, positive for memory. Pathogen lightly coated with residual serum Ab will activate memory response (This is how anti-Rh IgG “RHOGAM” works).