L6- Phagocytosis- Micro 4110

Phagocytic Receptoors

A kind of TLR on the surface of phagocytic cells, use direct binding between ligands on the surface of the microbe and receptors on the phagocytic cells. Can also use indirect binding when the microbe is opsonized

Direct binding- C-type lectin-like phagocytic receptor

Either Dectin-1 or Mannose receptor

Dectin-1

A c-type lectin-like phagocytic receptor expressed on macrophages, neutrophils, and DCs. Recognizes glucan common in the fungal wall and is responsible for phagocytosis of fungal pathogens

Mannose receptor

A c-type lectin-like phagocytic receptor that recognizes mannose sugar and is expressed on macrophages and DCs. Recognizes mannosylated ligands present on fungi, bacteria, and viruses

Direct binding- scavenger Receptors on macrophages

Phagocytic receptors, either class a which recognizes bacterial cell wall components, or class b which recognizes lipids.

Opsonization

When a microbe is covered in opsonins (mostly antibodies and complement protein C3b) that coat the protein and tag the pathogen for easier phagocytosis

Indirect binding- opsonin receptors

Complement receptors bind to complement coated or opsonized microbes, Fc receptors bind to microbes that are coated or opsonized with antibodies

After phagocytic receptors are engaged

the microbes are ingested and killed by phagocytes in the phagolysosome of macrophages and the phagolysosome plus granules of neutrophils

Antimicrobial mechanisms of macrophage phagocytes

Acidification, ROS, RNS, cathelicidin AMPs, enzymes like lysozymee and acid hydrolases

Antimicrobial mechanisms of neutrophil phagocytes

Acidification, ROS, RNS, a-Defensin, B-defensin and cathelicidin AMPs, enzymes like lysozyme and acid hydrolases, and lactoferrin (competes for iron)

Enzyme NADPH oxidase

facilitates the formation of superoxide ion within phagolysosome, extremely damaging to the captured pathogen. Converts oxygen to superoxide anion

Role of acid in phagocytes

ions are drawn in, acidification of phagolysosome activates acid hydrolases which are damaging to the pathogen

Superoxide dismutase

Enzyme that converts superoxide anion to hydrogen peroxide within the phagolysosome

Myeloperoxidase

Enzyme that converts hydrogen peroxide to hypochlorous acid in the phagolysosome

Nitric oxide synthase

Enzyme that converts L-Arginine into nitric oxide (an RNS) in the phagolysosome, occurs later on in macrophages and neutrophils than the production of ROS.

Oxygen dependent system of phagocytosis- respiratory burst

Involves production of powerful oxidizing agents, ROS and RNS

oxygen independent system of phagocytosis

includes AMPs (defensins, cathelicidins) and various other digestive enzymes (lysozymes, RNAses, DNAses, lipases, proteases, hydrolases).