Immunometabolism Flashcards

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1
Q

What is the function of an M2 macrophage?

A

It is important to keep homeostasis and for anti-inflammatory reactions. It is important in tissue repair and wound healing.

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2
Q

What is the function of an M1 macrophage?

A

Bacterial killing, killing tumor cells, and pro-inflammatory reactions.

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3
Q

What metabolic processes are characteristic of M2 macrophages?

A

High Ox-Phos, sustained ATP and long-lived cells

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4
Q

What metabolic processes are characteristic of M1?

A

Glycolysis and PPP
Biosynthesis / anabolism
Fast ATP
Short life

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5
Q

What metabolic processes are characteristic of M1?

A

Glycolysis and PPP
Biosynthesis/anabolism
Fast ATP
Short life

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6
Q

What is catabolism?

A

The breakdown of molecules for the creation of energy

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7
Q

What is anabolism?

A

The formation of molecules to store energy

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8
Q

What enzyme regulates the production of inflammatory cytokines in M1 macrophages?

A

GAPDH - it raises the rate of glycolysis and production of IL-1b and TNFa

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9
Q

In what ways does succinate drive inflammation?

A
  1. It induces IL-1b production through HIF-1a
  2. Succinate dehydrogenase repurposes mitochondria to drive inflammation
  3. Succinate is picked up by macrophages, leading to an inflammatory metabolic state
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10
Q

How does itaconate lead to an anti-inflammatory reaction?

A

Itaconate stops the production of succinate by inhibiting succinate dehydrogenase.

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11
Q

What are the six main pathways involved in immune metabolism?

A
  1. PPP (pentose phosphate pathway)
  2. Fatty Acid Oxidation
  3. Fatty Acid Synthesis
  4. TCA (tricarboxylic acid) cycle
  5. Glycolysis
  6. Amino Acid Metabolism
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12
Q

What gene is the central metabolic regulator of immunity?

A

mTOR.

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13
Q

What is the function of mTOR?

A

Can sense amino acids and growth factors and promote mRNA translation and lipid synthesis, in support of cell growth.

It also regulates numerous events that are crucial for T-cell and monocyte differentiation.

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14
Q

What does AMP kinase do in terms of metabolism and immunity?

A

Inhibits the function of mTOR and promotes catabolism. It is mostly active during nutrient deprivation.

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15
Q

What is the role of glycolysis in (immune) metabolism?

A

Glycolysis by itself has a low ATP generation potential, but it gives rise to many important metabolites and co-factors used for other metabolic pathways, like PPP and amino acid synthesis. This pathway is very active in rapidly proliferating cells.
Its main products are NADH and NAD+.

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16
Q

What is the role of the TCA cycle in (immune) metabolism?

A

It is the pathway most used in non-proliferative cells. Its goal is to produce ATP. These are used for long-lived cells. It is also used for amino acid and fatty acid synthesis.

17
Q

What is cataplerosis?

A

Diversion of TCA intermediates into a metabolic process (e.g. FAS)

18
Q

What is anaplerosis?

A

Diversion of TCA intermediates to the TCA cycle. Used to feed those in another pathway.