Neutrophils

Question 1

Where do neutrophils reside?

Answer 1

In blood but attracted to site of infection

Question 2

Are neutrophils short or long lived?

Answer 2

Short lived (5 days)

Question 3

How do neutrophils sense where to do?

Answer 3

Double key mechanism to bind to blood vessel wall in inflamed tissue

Question 4

What does this double key mechanism involve?

Answer 4

Selectin Ligand (neutrophil) - Selectin (endothelium)

ICAM (endothelium) - Integrin (neutrophil)

Question 5

What are ‘endothelium Selectin’ and ‘neutrophil Integrin’ expressed in response to?

Answer 5

IL-1, TNF, LPS and C5a produced at site of inflammation

Question 6

Under normal conditions, what do neutrophils and endothelial cells express?

Answer 6

Neutrophils - Selectin Ligand
Endothelial cells - ICAM

These are incompatible so the neutrophils circulate freely

Question 7

When the tissue is infected and inflamed, what do activated macrophages release?

Answer 7

Cytokines - IL-1, TNF

Question 8

What do IL-1 and TNF stimulate expression of?

Answer 8

Selectin on the endothelial cell membrane which binds to Selectin Ligand on neutrohhils

Question 9

What is result of Selectin binding to Selectin Ligand?

Answer 9

Neutrophils slow down (but Selectin-Selectin Ligand interaction is not enough to stop neutrophils completely, but they instead ‘roll’)

Question 10

What else is secreted in inflamed and infected tissue?

Answer 10

C5a from increased complement activation

LPS from bacteria

LPS and C5a accumulate

Question 11

What does this accumulation of LPS and C5a induce?

Answer 11

Integrin expression on neutrophil surface

Integrin then binds to ICAM on endothelial cells lining blood vessel

Question 12

What does combination of Selectin-Selectin Ligand and Integrin-ICAM interaction cause?

Answer 12

Neutrophils stop ‘rolling’ and stick to vascular wall close to site of infection

Question 13

How is methionine involved in neutrophil infiltration?

Answer 13

Human proteins have Met as N-terminal amino acid

Bacterial proteins start with f-Met (formyl methionine)

Neutrophils ‘track’ f-Met peptides that infiltrate the endothelium and inflamed tissue surrounding the blood vessel

Question 14

When are f-Met peptides secreted?

Answer 14

By macrophages after phagocytosis

Question 15

How is C5a helpful?

Answer 15

Anaphylatoxins - increase vascular permeability which helps neutrophils reach inflamed tissue

Question 16

Once neutrophils are inside inflamed tissue, what happens?

Answer 16

1. Become extremely phagocytic
2. Produce cytokines to activate immune cells
3. Short-lived (pus)