11.03 Phagocytes

Phagocytes

Function

• Engulf and Destroy Pathogens: Phagocytes ingest harmful microorganisms and particles, neutralizing them.
• Remove Dead Cells: They clear cellular debris and apoptotic cells, maintaining tissue health and homeostasis.

Types of Phagocytes

1. Neutrophils

• Prevalence: Constitute approximately 60% of white blood cells.
• Lifespan: Short-lived; their numbers rapidly increase during infections.
• Migration: Travel through blood and capillaries to reach sites of infection.
• Mechanism: Utilize phagocytosis to engulf pathogens and subsequently die, contributing to pus formation.

2. Macrophages

• Size & Lifespan: Larger and more long-lived compared to neutrophils.
• Location: Predominantly found in organs such as the lungs, liver, and spleen.
• Origin: Develop from monocytes in the blood, which differentiate into macrophages within tissues.
• Immune Activation: Present pathogen antigens on their surface to activate lymphocytes, bridging innate and adaptive immunity.

Observations

• Figure A: Blood smear under light microscope; displays monocyte (precursor to macrophage), neutrophil, and lymphocyte among red blood cells.

• Figure B: Showing neutrophil cell.

Phagocytosis Process

• Phagocytosis is a multi-step process through which phagocytes eliminate pathogens and debris.

1. Initiation of Phagocytosis

• Phagocytosis can be initiated through multiple pathways, ensuring flexibility and efficiency in the immune response.

a. Chemotaxis (Primary Initiator)

• Definition: Directed movement of phagocytes toward higher concentrations of specific chemical signals at the infection site.
• Mechanism:
  • Chemical Signals Involved:
    • Complement Proteins: Part of the complement system that marks pathogens and attracts phagocytes.
    • Cytokines (e.g., Interleukins): Signaling molecules released by various cells to mediate and regulate immunity.
    • Bacterial Products: Substances released by bacteria that attract phagocytes.
    • Histamine and Other Inflammatory Mediators: Released during inflammation to increase blood flow and attract immune cells.
• Outcome: Phagocytes migrate from the bloodstream through capillary walls to the affected tissue area.

b. Resident Phagocytes (Chemotaxis-Independent Initiation)

• Definition: Phagocytes that reside permanently within tissues (e.g., macrophages in the liver, lungs [alveolar macrophages], and brain [microglia]).
• Mechanism:
  • Local Encounter: These phagocytes are already present within tissues and can immediately interact with pathogens or debris entering their local environment.
  • Minimal Migration Needed: Only slight movement within the tissue is required to encounter and engulf targets.
• Example: Alveolar macrophages in the lungs swiftly respond to inhaled pathogens without needing to migrate extensively.

c. Direct Recognition and Engagement

• Definition: Phagocytes recognize and bind to pathogens directly through pattern recognition receptors without the need for opsonins (antibodies or complement proteins).
• Role: Allows phagocytes to initiate engulfment upon encountering pathogens in their immediate vicinity, independent of chemotactic signals.

d. Contact-Mediated Phagocytosis

• Definition: Activation of phagocytes through direct cell-to-cell contact with infected or abnormal cells.
• Mechanism:
  • Recognition of “Eat Me” Signals: Infected or apoptotic cells display specific signals (e.g., phosphatidylserine) recognized by phagocytes.
  • Engulfment Trigger: These signals prompt phagocytes to engulf and remove the targeted cells without the need for chemotactic movement.
• Example: Macrophages removing apoptotic cells during tissue remodeling and repair.

2. Recognition & Attachment

• Pathogen Marking (Opsonization): Pathogens are often coated with antibodies (IgG) or complement proteins, enhancing their recognition.
• Receptor Binding: Phagocytes possess specific receptors that bind to these markers.
• Specificity: This receptor-mediated binding ensures that phagocytes selectively target pathogens while sparing host cells.

3. Engulfment (Endocytosis)

• Membrane Extension: The phagocyte’s plasma membrane extends around the pathogen.
• Phagocytic Vacuole Formation: The membrane fully engulfs the pathogen, enclosing it within a vesicle known as a phagosome.
• Internalization: The phagosome is internalized into the phagocyte’s cytoplasm.

4. Lysosome Fusion

• Phagolysosome Formation: The phagosome fuses with a lysosome, an organelle containing digestive enzymes.
• Enzyme Release: Lysosomal enzymes (e.g., proteases, lipases) are released into the phagosome.
• Pathogen Degradation: The hostile environment within the phagolysosome breaks down the pathogen’s structural components.

5. Digestion & Exocytosis

• Degradation: Enzymes digest the pathogen into smaller, harmless molecules.
• Residual Body Formation: Indigestible material remains as a residual body within the phagocyte.
• Exocytosis: Waste products are expelled from the phagocyte by merging the residual body with the plasma membrane, releasing the debris outside the cell.

Key Terms

• Chemotaxis: The movement of cells toward higher concentrations of specific chemicals, typically at sites of infection or inflammation.
• Opsonization: The process by which pathogens are marked for ingestion and destruction by phagocytes through the coating of antibodies or complement proteins.
• Endocytosis: The cellular process of engulfing external substances by enveloping them in a vesicle.
• Lysosome: An organelle containing hydrolytic enzymes used to break down ingested pathogens and debris.
• Phagolysosome: A vesicle formed by the fusion of a phagosome with a lysosome, where digestion of the engulfed material occurs.
• Reactive Oxygen Species (ROS): Highly reactive molecules used by phagocytes to destroy pathogens.
• Pattern Recognition Receptors (PRRs): Receptors on phagocytes that recognize pathogen-associated molecular patterns (PAMPs).
• Phagocytic Vacuole (Phagosome): A vesicle formed around a pathogen when it is engulfed by a phagocyte.
• Residual Body: Indigestible material remaining within a phagocyte after digestion of a pathogen.