Phagocytosis & Phagocytic Cells

Phagocytosis

  • Primary innate mechanism for removing pathogens and cellular debris

  • Sequence: recognition → engulfment → intracellular killing

  • Links innate and adaptive immunity (antigen presentation by macrophages)

Phagocytic Cell Types

  • Neutrophils

    • First leukocytes to arrive (within hours)

    • Rapid phagocytosis and release of cytotoxic granules

    • Short-lived; form pus

  • Monocytes

    • Circulate in blood; migrate after ≈ days

    • Differentiate into macrophages at infection sites

  • Macrophages

    • Tissue-resident or derived from monocytes

    • Long-lived; high phagocytic capacity

    • Secrete cytokines, present antigen, orchestrate inflammation

Pathogen Recognition

  • Two strategies

    • Opsonization: pathogen coated by opsonins (antibody, complement, C-reactive protein) → easier uptake

    • Direct PAMP detection: phagocyte Pattern Recognition Receptors (PRRs) bind Pathogen-Associated Molecular Patterns (PAMPs)

  • Key PAMP examples

    • Peptidoglycan, LPS, flagellin, lipopeptides, viral DNA/RNA

  • Toll-Like Receptors (TLRs) (subset of PRRs)

    • Cell-surface TLRs 1, 2, 4, 5, 6 detect bacterial envelope components

    • Endosomal TLRs 3, 7, 8, 9 detect viral/bacterial nucleic acids

  • PRR–PAMP binding activates phagocyte → ↑phagocytosis, cytokine/IFN production, proliferation, killing efficiency

Chemotaxis & Diapedesis (Extravasation)

  • Chemotaxis: movement along chemical gradient (cytokines, complement C5aC5a)

  • Rolling adhesion: cytokines induce endothelial adhesion molecules; leukocytes slow & roll

  • Transendothelial migration/Diapedesis: leukocytes squeeze between capillary cells into tissue

  • Arrival hierarchy: neutrophils → monocytes → macrophages (resident macrophages already present)

  • Process occurs only in capillaries (thin walls, low flow)

Key Takeaways

  • Phagocytosis requires pathogen recognition; PRRs provide opsonin-independent detection

  • PAMP–PRR interaction is both recognition and activation signal

  • Efficient immune response depends on rapid chemotaxis/diapedesis bringing vast numbers of phagocytes to the infection site