February 26 Notes

I. Phagocytosis Overview:
- engulfment of microbe or large particle
a. Professional Phagocytes
-neutrophils Video of neutrophil phagocytosis
-Dendritic cells
-Macrophages- video of macrophage phagocytocsis
*Note: other cells types can engulf things but not specialized for it
b. Phagocytosis:
-receptor-mediated engulfing of a large particle ( > 1 μm) by a cell
-reaction of many cells to having a particle stuck on surface is to engulf it
-requires actin cytoskeleton rearrangement

c. Macropinocytosis  “cell drinking”
-cytoskeleton rearrangement to engulf droplet from surrounding environment
-not receptor mediated

II. Steps of Phagocytosis
a. Binding of receptors on phagocyte
1. Binding of receptors to OPSONIZED microbes
- FC receptors on phagocytes interact w/ constant region of Abs
- MBL receptors bind to MBL (or other ficolins) bound to microbial carbohydrates
2. Binding of receptors to NON-OPSONIZED microbes
- Mannose receptor of phags interacts with mannose containing molecules on microbe surface
- Dectin-1 binds to Beta-glucan carbohydrates of microbe cell walls
3. EXAMPLE of receptor that binds to BOTH an opsonin and directly to microbe surface
o Binds Ab conserved region
o Binds to Beta-glucan in bacterial cell wall
b. Actin Polymerization
- caused by action of Rho-family GTPases
c. Phagolysosome Formation
- vacuole containing microbe fuses with other vacuoles
containing antimicrobial chemicals: result = phagolysosome
1. Primary granules contain:
- Antimicrobial peptides such as defensins and
cathelicidins that poke holes in microbial
membranes b/c of amphipathic and cationic props
*concentration in phagolysosome is » 1 μM
-Lysosomes (break peptidoglycan)
-Bacterial Permeability Increasing Protein (BPIs)—poke holes in membrane
-Proteases—break down protein
2. Seconday Granules contain
-NADPH oxidase—which creates “Reactive Oxygen Intermediates”
*Have free electrons which lead to free radicals, which damage DNA and protein
* usually always found somewhere in cell vacuoles
*Microbial Resistance
-Ex: S. aureus makes catalase, which destroys
-Reactive Nitrogen Species
*also create free radicals
* work through iNOS (inducible Nitric Oxide Synthase)
*iNOS protein is not always present in cells; transcription must be turned on in response
to phagocytosis
*stimuli that turn on iNOS transcription
1. LPS (main one)
2. other bacterial products
3. cytokines such as IFN-gamma

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