Phagocytosis

If a pathogen breaches the skin and mucous membranes, the second line of non-specific defence is phagocytosis — the ingestion and destruction of pathogens by specialised white blood cells called phagocytes. Phagocytosis was discovered by Élie Metchnikoff in 1882 (work that won him a Nobel Prize) and remains one of the most important defences. OCR specification 4.1.1 (e) requires you to describe the process of phagocytosis, including the roles of neutrophils and macrophages and the importance of antigen presentation in linking innate and adaptive immunity.

Key Definitions:

• Phagocyte — a white blood cell that engulfs pathogens.
• Phagosome — the vesicle formed when a phagocyte engulfs a pathogen.
• Lysosome — a membrane-bound vesicle containing hydrolytic enzymes (lysozymes, proteases, nucleases).
• Phagolysosome — the vesicle formed when a phagosome fuses with a lysosome.
• Antigen — a molecule (usually a protein or glycoprotein) recognised by the immune system, typically on the surface of a pathogen.

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Types of Phagocyte

There are two main phagocytes in the blood and tissues:

1. Neutrophils

• The most abundant white blood cell (40–75% of circulating leucocytes).
• Multi-lobed nucleus (polymorphonuclear).
• Short-lived (~5 days); the first to arrive at an infection site.
• Granules contain lysozymes, defensins, myeloperoxidase.
• Die after phagocytosing a few pathogens — the dead neutrophils contribute to the pus that forms at infected wounds.

2. Macrophages

• Larger, longer-lived cells derived from blood monocytes that migrate into tissues.
• Present in many tissues: Kupffer cells in the liver, microglia in the brain, alveolar macrophages in the lung.
• Much longer-lived than neutrophils (months to years).
• Essential for antigen presentation — after engulfing a pathogen, macrophages display pathogen-derived peptides on their surface to activate T cells.

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The Steps of Phagocytosis

flowchart TD
    A[Pathogen enters tissue] --> B[Chemotaxis: phagocyte moves toward cytokines/chemokines]
    B --> C[Recognition: PAMPs bind to PRRs on phagocyte surface]
    C --> D[Engulfment: plasma membrane surrounds pathogen]
    D --> E[Phagosome formed inside the cell]
    E --> F[Lysosome fuses with phagosome]
    F --> G[Phagolysosome: enzymes digest pathogen]
    G --> H[Waste products exocytosed]
    G --> I[Peptides displayed on MHC II]
    I --> J[Antigen presentation to T helper cells]

Step 1 — Chemotaxis

When pathogens invade a tissue, damaged cells and resident macrophages release cytokines (small signalling proteins). Neutrophils circulating in the blood detect these chemical signals and migrate towards the infection — this is called chemotaxis. They leave the capillaries by squeezing between endothelial cells (diapedesis) and move through the tissue toward the highest cytokine concentration.

Step 2 — Recognition

At the infection site, the phagocyte recognises the pathogen in one of two ways:

• Direct recognition of conserved pathogen molecules (PAMPs, e.g., lipopolysaccharide, flagellin, peptidoglycan) by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs).
• Opsonisation — the pathogen is first coated in proteins called opsonins (e.g., complement C3b, antibodies), which bind to receptors on the phagocyte and promote engulfment. Opsonised pathogens are engulfed far more efficiently than "naked" ones.

Step 3 — Engulfment

The phagocyte's plasma membrane forms pseudopodia (actin-driven extensions) around the pathogen. These meet on the far side and fuse, trapping the pathogen inside a membrane-bound vesicle called a phagosome.