Phagocytosis

Question 1

Phagocytosis

Answer 1

A specialised process by which particulate matter (>1um) is internalised

First observed by Eli Metchnikoff in 1883

Question 2

Stages of phagocytosis

Answer 2

1. Recognition
2. Ingestion
3. Digestion

Question 3

Recognition - direct binding

Answer 3

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

Question 4

Recognition - indirect binding

Answer 4

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

Question 5

C-type lectin receptors

Answer 5

These PRRs bind carbohydrates on extracellular pathogens

• Mannose receptor
• DC-SIGN
• Dectin-1

Question 6

Scavenger receptors

Answer 6

These PRRs bind altered self molecules

• SR-A
• SR-B

Question 7

TLRs

Answer 7

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

Question 8

Type I interferons

Answer 8

Inhibit the replication of viruses

Question 9

Mannose receptor

Answer 9

Expressed on most macrophages and dendritic cells

Binds mannose, fucose and a-mannan

Has 8 extracellular domains

Triggers internalisation of the pathogen

Question 10

Dectin-1

Answer 10

Expressed on a variety of myeloid cells

Binds B-glucans

Triggers MAPK pathways which induce the expression of inflammatory mediators

Question 11

SR-A

Answer 11

Expressed on all macrophages and some endothelial cells

Binds modified LDL

Question 12

SR-B

Answer 12

Expressed on endothelial cells, dendritic cells, platelets, macrophages and monocytes

Question 13

NOD-like receptors

Answer 13

Cytoplasmic PRRs

Trigger autophagy (self-eating)

Question 14

Rig-like receptors

Answer 14

Cytoplasmic PRRs

Detect viral replication and induce the production of anti-viral cytokines

Question 15

TLR4

Answer 15

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

Question 16

Opsonins

Answer 16

Opsonins coat microbes and make them more attractive to phagocytes

They can be antibodies, complement proteins and lectins

Question 17

Ingestion

Answer 17

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

Question 18

Oxygen-independent digestion

Answer 18

• 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

Question 19

Oxygen-dependent digestion

Answer 19

• Respiratory burst

- Nitric oxide

Question 20

NETosis

Answer 20

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