06 Phagocytosis

Page 1

Context & Source
• Lecture: “Phagocytosis” – Immunology Bl 1, Class 6 (07 / 28 / 2025)
• Instructor: Bidyut Mohanty, PhD (bmohanty@carolinas.vcom.edu)
• Text references: Abbas et al., Chapter 4 (pp 94-97) & Chapter 13 (pp 289-293, 302-303).

Key Ideas Introduced
• Core subject: mechanisms of endocytosis, exocytosis, and phagocytosis in host defense.
• Material bridges innate & adaptive immunity (ties back to previous lectures on natural barriers, PAMPs/DAMPs, PRRs, etc.).

Page 2 – Objectives

  1. Define & differentiate endocytosis vs exocytosis.
  2. Explain endocytosis’ immunological importance.
  3. Contrast three forms of micropinocytosis: caveolae-, clathrin-, and macropinocytosis.
  4. Compare phagocytosis with other endocytic routes.
  5. Name immune cells that phagocytose.
  6. Trace phagosome ➔ phagolysosome formation & cargo digestion.
  7. Outline respiratory burst steps in:
    • Neutrophils (granulocytic)
    • Mononuclear phagocytes (monocytes/macrophages)
  8. List oxygen-independent killing strategies.
  9. Distinguish dendritic cells (DCs) vs professional phagocytes in antigen processing.
  10. Link surface molecules/opsonins to phagocytosis efficiency.
  11. State phagocytosis’ roles in innate defense & adaptive up-regulation.

Page 3 – Big-Picture Map

Already-covered foundations: hematopoiesis, lymphoid organs (bone marrow, thymus, LN, spleen, MALT/GALT/BALT/NALT), PRRs (TLR, CLR, NOD, RIG), cytosolic DNA sensors.
Today’s focus slots above material into cellular uptake & killing pathways:
• Endo/exocytosis
• Micropinocytosis/macropinocytosis
• Phagocytosis and downstream antimicrobial mechanisms

Page 4 – Core Definitions

• Exocytosis – export of intracellular cargo to extracellular space.
• Endocytosis (endo = within): eukaryotic import of material via membrane invagination.
– Pinocytosis (“cell drinking”)
• Micropinocytosis – “sipping”; vesicles ≤100 nm100\,\text{nm}; can be receptor-mediated.
• Macropinocytosis – “gulping”; vesicles 0.5–5 μm0.5–5\,\mu\text{m}; actin-driven ruffles.
• Phagocytosis (“cell eating”) – uptake of particulate matter >0.5 μm0.5\,\mu\text{m} such as microbes or apoptotic bodies.

Page 5 – Functional Rationale for Endocytosis

General cells:
• Nutrient/drug uptake, receptor down-regulation.
Immune cells:
• Same as above plus
– Pathogen elimination
– Antigen presentation
– Clearance of dead/dying cells & debris.
• Mechanism: membrane invaginates ➔ endosome / endocytic vesicle.
• All nucleated cells capable, but efficiency differs.

Page 6 – Three Canonical Endocytic Routes

  1. Clathrin-mediated (Receptor-mediated micropinocytosis)
    • Vesicle diameter ≈ 100 nm100\,\text{nm}.
    • Clathrin coats pits; imports LDL, transferrin, growth factors, Ig, etc.
  2. Caveolin-mediated (Micropinocytosis via caveolae)
    • Vesicle diameter ≈ 50 nm50\,\text{nm}; flask-shaped lipid-raft pits rich in cholesterol.
    • Prominent in muscle, lung, adipocytes, endothelium, fibroblasts.
    • Functions: cholesterol/lipid trafficking, signaling, turnover of adhesive complexes.
  3. Macropinocytosis
    • Large actin-ruffles (diameter 0.5–5 μm0.5–5\,\mu\text{m}) engulf extracellular fluid.
    • Vesicle (macropinosome) fuses with lysosome for digestion.
    • Utilized heavily by APCs for high-volume antigen sampling.

Page 7 – Comparative Schematic (Key Take-aways)

• Macropinocytosis ➔ endosome maturation (early ➔ late ➔ lysosome).
• Clathrin route ➔ potential routing to Golgi.
• Caveolae ➔ caveosome ➔ ER/nuclear signaling.
• Illustrates unique trafficking fates that influence antigen processing.

Page 8 – Introduction to Phagocytosis

• Definition: receptor-facilitated, actin-myosin driven uptake of solid particles >0.5 μm0.5\,\mu\text{m} to form phagosome.
• Professional phagocytes: neutrophils, monocytes, macrophages, dendritic cells (plus occasional others).
• Utility: microbe killing, debris clearance, antigen capture.

Page 9 – Six Phases of Phagocytosis

  1. Chemotaxis & adherence – PRRs or opsonin receptors bind target.
  2. Ingestion – pseudopod extension.
  3. Phagosome formation – sealed internal vesicle.
  4. Phagolysosome formation – fusion with lysosome.
  5. Digestion – enzymatic & oxidative degradation.
  6. Exocytosis/Residual body – expulsion of indigestible remnants.

Page 10 – Opsonins (“Prepare for the table”)

• Molecules that coat targets to enhance phagocytosis.
• Major classes:
– Immunoglobulins (notably IgG – Fcγ-dependent)
– Complement fragment C3bC3b
– Various PRR ligands.
• Phagocytes express specific opsonin receptors; binding ➔ tyrosine-kinase signaling that triggers engulfment.

Page 11 – IgG-Mediated Opsonization Sequence

  1. Pathogen coated by IgG Fc portion accessible.
  2. FcγRI binds IgG Fc.
  3. Receptor clustering ➔ intracellular activating signals.
  4. Actin rearrangement ➔ phagocytosis.
  5. Killing within phagol