Immunometabolism & Macrophage activation Flashcards

1
Q

Hvad gør M1 eller M2 makrofager?

A

M1: Cytotoxicity and Tissue Injury

M2: Immune suppression and Tissue Repair.

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2
Q

Hvordan aktiveres M1 og M2 macrofager?

A

M1: Classical activation - LPS, IFN gamma

M2: IL-4

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3
Q

Hvilken effect har metabolsimen på M1/M2 ratioen?

A

1) M1 - Glycolytisk metabolisme. M1 benytter sig a glukose og glykolysen for at skaffe energi. Dette drejer dem til en M1 fenotype. Glykolysen giver 2 NADH + 2 ATP. Ikke så meget energi, men faktisk okay hvis ikke man har et stort energibehov såsom aktiverede B-celler eks.
2) M2 - Mitochondrielt metabolisme: Benytter sig af Free Fatty Acids og er derfor afhængig af beta-oxidation, Krebs Cycle og Oxidative phosphorylation.

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4
Q

Har alle immunceller samme metabolisme?

A

Nej.

Generalt har celler med stor aktivitet (Granulocytter), cytotoxiske celler (M1/CD8+ T cells) et glykolytisk metabolisme (den er hurtig, men giver mindre energi og cellerne skal bruge det nu!), mens celler med lavt energiforbrug/aktivitet (så som Memory T-celler, M2 macrofager, naive lymphocytter osv.) har et mitokondriel metabolisme.

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5
Q

Hvilke forskellige stoffer er der i et Seahorse/OCR (Oxygen Consumption Rate) forsøg? Og hvad gør de?

A

1) Oligomycin: Blocks ATP synthase by blocking the proton channel –> Opbygger en høj proton gradient på tværs af den mitochondrielle membran.
2) FCCP: Uncoupler, inserts as a proton channel in mitochondria –> Cellen kan forbruge proton gradient og så meget oxygen som overhoved muligt.
3) Rotenone/Antimycin A: Complex 1&3 inhibitors –> cellen kan nu ikke bruge noget oxygen og afhænger af non-mitokondriel respiration.

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6
Q

Hvad er spare capacity i et OCR experiment?

A

Peak Consumption - Baseline Consumption

Altså Peak ved tilføjelsen af FCCP minus Baseline inden oligomycin tilføjes.

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7
Q

Hvad er princippet i immunometabolisme?

A

1) Aktivering af immun celle
2) Metabolisme ændre sig
3) Udarter sig i en effektor funktion

Reguleres af:
- Metabolsk stress, Metabolske regulatorer, microbiota

Resulterer i:
- Differentiering, Memory, Longevity

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8
Q

Hvad er checkpoint inhibitors? Nævn 2

A
  • Checkpoint inhibitors are inhibitors that inhibit a immune cells inhibition. Lol… That is. It stops an inhibition and activates the cell.
  • Targeting checkpoint inhibitors (CTLA4 and PD1) often via mAb reactivate T cell tumor reactivity
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9
Q

What does a high spare respiratory capacity (SRC) in an OCR experiment mean?

A

High SRC means that the cell is more reliant on mitochondrial respiration. (Oxidative Phosphorylation (OXPHOS), Beta oxidation, krebs cycle)

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10
Q

What does galactose force a cell to?

A

Galactose facilitate mitochondrial respiration as they can’t rely on glycolysis. BECAUSE, there is a rate-limiting step, so it will begin to rely more on OXPHOS be meet it needs.

And also be more dependent on FFA, glutamine and glutaminolosis

Galactose cultivation also increases MICA transcription

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11
Q

Hvilken effect har MGAT5 på metabolismen?

A

MGAT5 -/- har en større spare respiratory capacity (SRC) end WT. MGAT5 -/- celler opregulerer NKG2D (aktiverende receptor) liganden MICA fordi Propionate oxidation inducerer MICA ekspression.

Dvs. MGAT5-/- benytter mere Propionate oxidation som inducuerer MICA.

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12
Q

Hvordan kunne man ændre en M2 til en M1

A
  • Ved at blokere TCA, dette ændrer alfa ketogluterate/succinate ration.
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