Phagocytosis Flashcards
Phagocytosis
A specialised process by which particulate matter (>1um) is internalised
First observed by Eli Metchnikoff in 1883
Stages of phagocytosis
- Recognition
- Ingestion
- Digestion
Recognition - direct binding
Direct binding occurs when molecular components on the surface of microbes directly bind to phagocytes
The molecular components are called PAMPs and include things such as LPS
PAMPs are recognised by PRRs
DAMPs can also be recognised, these are altered self proteins
Recognition - indirect binding
Indirect binding occurs when proteins that have already bound to the microbes are recognised by the phagocyte
These tend to be opsonins
The most effective opsonins are produced by the complement system
C-type lectin receptors
These PRRs bind carbohydrates on extracellular pathogens
- Mannose receptor
- DC-SIGN
- Dectin-1
Scavenger receptors
These PRRs bind altered self molecules
- SR-A
- SR-B
TLRs
TLRS recognise a wide variety of PAMPs and DAMPs
They activate different signalling pathways to stimulate the production of type I interferons and inflammatory mediators
Type I interferons
Inhibit the replication of viruses
Mannose receptor
Expressed on most macrophages and dendritic cells
Binds mannose, fucose and a-mannan
Has 8 extracellular domains
Triggers internalisation of the pathogen
Dectin-1
Expressed on a variety of myeloid cells
Binds B-glucans
Triggers MAPK pathways which induce the expression of inflammatory mediators
SR-A
Expressed on all macrophages and some endothelial cells
Binds modified LDL
SR-B
Expressed on endothelial cells, dendritic cells, platelets, macrophages and monocytes
NOD-like receptors
Cytoplasmic PRRs
Trigger autophagy (self-eating)
Rig-like receptors
Cytoplasmic PRRs
Detect viral replication and induce the production of anti-viral cytokines
TLR4
TLR4 is known for binding LPS
This upregulates the transcription of TNF-a
If this occurs in the blood, it can lead to septic shock
Opsonins
Opsonins coat microbes and make them more attractive to phagocytes
They can be antibodies, complement proteins and lectins
Ingestion
Ingestion is initiated by receptor clustering
Pseudopodia surround the particle and fuse it into a phagosome
This requires a significant amount of energy and cytoskeletal rearrangement
Oxygen-independent digestion
- Acidification = protons are pumped into the phagolysosome
- Lysozyme
- Enzymes
- Defensins = form pores in cytoplasmic membranes
- Lactoferrin = bind to essential nutrients to inhibit microbial growth
- Cationic proteins = active at alkaline pH, damage microbial membranes
Oxygen-dependent digestion
- Respiratory burst
- Nitric oxide
NETosis
A mechanism exclusive to neutrophils
A net-like chemical is secreted to trap nearby pathogens
Secretion of the net causes cell death; the net traps the pathogen in the hope another phagocyte will detect and deal with it
