Phagocytosis

Describe Phagocytosis

• Definition

• Performed by

• Functions

Phagocytosis

• Definition:

  • Engulfment + internalization of microbes/debris.

  • critical first- line defense against infections.

• Performed by:

  • Neutrophils

  • Macrophages

  • DCs

• Functions:

  • Eliminates pathogens

  • Clears dead cells

  • Removes immune complexes

  • Initiates adaptive immune responses

List the steps of Phagocytosis and Describe them

1. Describe the Different Receptors and their associated ligands

2. Describe the 3 different mechanisms and their receptors/ligands

3. Describe step 3 and 4

4. List and describe the different ways to kill

Steps:

1. Recognition & attachment

   • PRRs

     • C-type lectin receptors (CLRs)

       • EX: Mannose receptor; Dectin-1

       • Ligand (found on microbe): Mannans, β-glucans, LPS

     • Scavenger receptors

       • EX: SR-A; SR-B

       • Ligand: LPS, lipoteichoic acid, lipopeptide

   • Opsonin receptors

     • Collagen-domain receptor

       • EX: CD91/calreticulin

       • Opsonins (binds to microbes): MBL, C1q

     • Complement receptors

       • EX: CR1, CR3, CR4

       • Opsonin: Complement components and fragments

     • Immunoglobulin Fc receptors

       • EX: FcαRs; FcγRs

       • Opsonins: Specific IGA/G antibodies; C-reactive Protein

2. Engulfment

   1. Mech

      • Zippering:

        • Receptor engagement → clustering → actin rearrangement → extends PM out/around particle → tightly formed phagosome

          • Receptor: Fc receptor (ex: CLR); Ligand: Antibody (IgG); Mannose

      • Sinking

        • actin polymerization pulls particle down → cell → PM closes over particle

          • Receptor: Complement receptor ( CR3/4); Ligand: Cleavage products (C3b)

      • Triggered

        • Surface Molecule engagement → membrane ruffling → ruffle fold back → engulf large section of extracellular space which may contain a particle (considered non-specific engulfment)

          • Receptor: TLRs; Ligand: LPS

3. Phagosome formation

4. Phagolysosome formation

   1. Phagosome + Lysosome → Phagolysosom

      1. Decreased pH

      2. Enriched w/ degradative enzymes

5. Killing & degradation

   • Ways to Kill:

     • Via (neutrophil) Granules

       • Fuses w/ Endosome (containing pathogen)

       • Types:

         • Azurophilic (primary)

           • myeloperoxidase and defensins

         • Specific (secondary)

           • lactoferrin and lysozymes

         • Gelatinase (tertiary)

           • gelatinase

     • Via Respiratory Bursts (O2 dependent):

       • In phagolysosomes

       • Initiated by NADPH oxidase

       • Types of ROS

         • Superoxide

         • Hydrogenperoxide

         • myeloperoxidase

         • hypochlorite/ hydroxyl radical

         • NO

     • Via Lysosomal Activity (O2 Independent)

       • Fuse w/ Granules + Endosome

       • List of Hydrolytic Enzymes:

         • Proteases

         • sulfatases

         • nucleases

         • lipases,

         • phosphatases

         • glycosidases

What is Opsonization?

• Definition

• Function

Definition:

• process in which pathogens are coated w/ molecules (opsonins) that mark them for phagocytosis

Function:

• Makes Microbes/Immune Complexes easier to destroy/clear

  • especially for encapsulated bacteria,

    • its capsules prevent recognition of PRRs

  • Immune complexes can trigger inflammation

Respiratory Burst Picture