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Topic 8 Immunometablism

  • Immunemetabolism: is about interpolay between metabolism and imunology, divided into systemic immunometablism and cellular immunometabolism

  • Major metabolic pathways

    • Glycolysis: converts glucose to pyruvate for quick energy and biosynthetic
    • TCA cycle (krebs cycle): produce precursors for amino acids and lipids
    • Lipid metabolism:
      • ==FAS==: fatty acid synthesis for membrane and signals
      • ==FAO==: fatty acid oxidation for energy

  • T cell

    • Naive T cells
      • Maintain metabolic quiescence
    • T cell activation
      • undergo metabolic reprogramming
      • Key Pathway: The CD28-PI3K-AKT-mTORC1 axis is the central regulator, driving glucose uptake and glycolysis
      • transcription factors: drive glycolysis and glutaminolysis, and lipid metabolism
      • Mitochondrial Changes: rapid glycolysis; mitochondrial support nucleotide synthesis

  • Macrophage metabolism: Polarization dictates metabolic phenotype

    • M1 Macrophages (pro-informmatory)
      • Characterized by enhanced glycolysis and the pentose phosphate pathway (PPP) to support ROS (Reactive Oxygen Species, which can help to antimicrobial role) production and nucleotide synthesis.
    • M2 macrophages ( anti-inflammatory/ repair)
      • Rely on OXPHOS and fatty acid oxidation (FAO). Glycolysis is not necessary for M2 polarization.

Metabolites Act as Epigenetic Regulators

This is the central mechanistic link presented in the slides. Metabolic intermediates leave the mitochondria and directly alter the epigenome, turning genes on or off.