Question
Phagocytosis.
Answer
Phagocytosis is the process by which specialized cells (phagocytes — chiefly neutrophils and macrophages) engulf and internalize particulate material, including microorganisms, followed by intracellular killing and digestion — a central mechanism of innate immune defence.
Steps:
- Chemotaxis — phagocytes are attracted to the site of infection/inflammation by chemotactic signals (bacterial products, complement fragment C5a, chemokines, leukotriene B4).
- Recognition and attachment — the phagocyte recognizes the target microorganism, either directly via pattern-recognition receptors binding conserved microbial structures, or (much more efficiently) after the microbe has been coated with opsonins — IgG antibody (recognized by Fc receptors) or complement fragment C3b/iC3b (recognized by complement receptors) — a process called opsonization, which dramatically enhances phagocytic uptake, particularly of encapsulated organisms that otherwise resist direct recognition.
- Engulfment — the phagocyte’s plasma membrane extends pseudopods around the particle, which is progressively enclosed within a membrane-bound vacuole called a phagosome.
- Phagolysosome formation — the phagosome fuses with cytoplasmic lysosomes (containing hydrolytic enzymes) to form a phagolysosome.
- Killing and digestion — the ingested microorganism is destroyed by:
- Oxygen-dependent mechanisms — the respiratory (oxidative) burst, generating reactive oxygen species (superoxide, hydrogen peroxide, hydroxyl radicals) via NADPH oxidase, and the myeloperoxidase-hydrogen peroxide-halide system, generating highly microbicidal hypochlorite.
- Oxygen-independent mechanisms — lysozyme (digests bacterial peptidoglycan), defensins and other antimicrobial peptides, lactoferrin (iron-chelation, depriving bacteria of essential iron), and proteolytic enzymes within the lysosome.
- Digestion and exocytosis — degraded microbial debris is either exocytosed or, in antigen-presenting cells (macrophages, dendritic cells), processed peptide fragments are loaded onto MHC molecules for presentation to T lymphocytes, linking innate phagocytic clearance to the adaptive immune response.
Clinical significance: defects in phagocytic function (e.g., Chronic Granulomatous Disease, an NADPH oxidase deficiency preventing the respiratory burst) predispose to recurrent, severe bacterial and fungal infections, particularly with catalase-positive organisms; deficiency of opsonins (hypogammaglobulinaemia, complement deficiency) or of the spleen (asplenia, important for opsonin-dependent clearance) similarly predisposes to overwhelming infection, particularly with encapsulated bacteria.