Phagocytosis and Antimicrobial Proteins

12.5 Phagocytosis

  • Key components of Phagocytosis

    • Phagocytosis consists of several stages:

      1. Chemotaxis

        • Phagocytes detect and migrate towards chemokine gradients.

        • Chemokine receptors on phagocytic cells are responsible for this movement.

        • Movement occurs from the blood to the tissue via extravasation during inflammation.

      2. Adherence

        • Involves two kinds of adherence:

          • Direct adherence

            • Pattern Recognition Receptors (PRRs) on phagocytes recognize and bind to Pathogen-Associated Molecular Patterns (PAMPs) on microbial surfaces.

          • PAMPs are specific structures found on pathogens that are recognized by the immune system.

          • Examples of PAMPs include lipopolysaccharides, flagellin, and peptidoglycan.

          • Indirect adherence

            • Opsonization is the process where host proteins (like C3b or IgG antibodies) coat microbes to enhance their adherence to phagocytes.

            • C3b binds to the complement receptor (CR1) on phagocytes, facilitating phagocytosis.

            • IgG binds to the Fc receptor (FcR) which bridges the microbe and the phagocyte, allowing for easier recognition and ingestion.

            • Polysaccharide Capsules

              • Some bacteria (encapsulated) produce polysaccharide capsules that prevent phagocytosis. Examples:

                • Unencapsulated bacteria can be easily phagocytosed.

                • Encapsulated bacteria cannot effectively bind C3b to phagocyte receptors.

                • The capsule prevents adherence of C3b, making it harder for phagocytes to engulf the bacteria.

                • Antibodies (IgG) that bind to the capsule enhance adherence to phagocyte receptors, aiding in phagocytosis.

      3. Ingestion

        • The phagocyte extends pseudopodia to engulf the microbe, forming a phagosome.

      4. Digestion

        • The phagosome fuses with a lysosome, creating a phagolysosome.

        • This fusion activates various enzymes and processes including:

          • Lysozyme activity.

          • Other digestive enzymes.

          • Oxidative burst: a rapid release of reactive oxygen species that helps to destroy the engulfed material.

          • An acidic pH within the phagolysosome enhances the activity of enzymes.

      5. Exocytosis

        • The final stage involves the removal of waste products via exocytosis.

        • Antigens from digested microbial proteins are presented on the surface of Antigen-Presenting Cells (APCs) to activate T-cells as part of the adaptive immune response.

12.6 Antimicrobial Proteins

  • Types of Antimicrobial Proteins

    • Antimicrobial proteins play a crucial role in the innate immune response and include:

      1. Complement

        • The complement system comprises over 30 plasma proteins primarily produced by the liver.

        • Functions include enhancement of inflammation, phagocytosis, and direct microbial killing.

        • Activation occurs primarily via recognition of microbes, initiating a cascade of reactions that convert inactive complement proteins into their active forms.

        • The three pathways for complement activation include:

          • Classical pathway: Triggered by antigen-antibody immune complexes.

          • Lectin pathway: Initiated by recognition of PAMPs by lectins (e.g., Mannose-Binding Lectin).

          • Alternative pathway: Triggered by spontaneous hydrolysis on pathogenic surfaces or C3b binding to certain surfaces.

        • The complement cascade results in formation of C3 convertase, ultimately producing membrane attack complex (MAC) that can lyse microbial cells.

        • Alternative pathway steps:

          1. Initiation: Conversion of C3 to C3a and C3b.

          2. Activation: Conversion of C5 to C5a and C5b.

          3. Polymerization: Formation of MAC composed of C5b, C6, C7, C8, and C9.

          4. Result: Cell lysis occurs via the MAC.

      2. Defensins

        • Defensins are small peptides that insert into microbial membranes, causing destabilization and lysis of the pathogen.

        • Their mechanism of action involves disrupting the phospholipid bilayer of microbial cells, leading to cell death.

      3. Iron-binding proteins

        • These proteins sequester free iron, limiting its availability to microbes, which is essential for their growth.

        • Examples of iron-binding proteins include:

          • Transferrin

          • Hemoglobin

          • Lactoferrin

          • Ferritin

        • Bacteria use specific receptors and siderophores to extract iron from host proteins, which emphasizes the arms race between host defenses and microbial survival strategies.

      4. Interferons

        • Interferons are signaling molecules produced in response to viral infections.

        • They act to induce an antiviral state in neighboring cells, enhancing their resistance to viral replication.

        • Produced by virus-infected cells to communicate with surrounding cells, stimulating the immune response against viral pathogens.

  • Conclusion

    • Phagocytosis and antimicrobial proteins represent critical components of the innate immune system, protecting the host from infections and enhancing the adaptive immune response through mechanisms like antigen presentation.