Wk16D1 IMM-10 Flashcards Preview

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Flashcards in Wk16D1 IMM-10 Deck (26):
1

Key cytokines released by macrophages

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

2

IL-1b

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

3

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

4

IL-6

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

5

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)

6

IL-12

Secreted by Macrophage and DC
Local: Activates NK, CD4->Th1

7

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).

8

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

9

Acute phase proteins

Induced by IL-6
Include Mannose-binding lectin and c-reactive protein

10

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.

11

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.

12

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.

13

IL-4

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

14

IL-5

Eosinophil development

15

IL-6

Acute phase protein induction

16

How does one maintain Th subset bias?

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

17

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.

18

Action of IFN-gamma

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

19

Anti-IL-4 mAb

For asthma/allergy to decrease IgE production.

20

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

21

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

22

Tregs do what?

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

23

IL-10

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

24

TGF-beta

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

25

Memory cell advantages

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

26

FcgRIIb (IgG Fc receptor) role in memory
OR, How does RHOGAM work?

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).