L12: Neutrophil Flashcards
Which immune system does the neutrophil belong to
Innate immune system
What type of a cell is a neutrophil
Phagocyte
Granulocytes
Therefore what does a neutrophil do when it recognises a pathogen
Phagocyte it
Kill it inside with its granules
What is the precursor of the neutrophil
Myeloblast
What happen to the number of neutrophil in infection
Increases
What is the increase in neutrophil called
Neutrophilllia
What is the half life of neutrophils
8-12 hours
Why is the half life of neutrophil short
Neutrophils under ego apoptosis
How are neutrophils activated in the blood
When inflamed or infected tissues release cytokines
What does the release of cytokine form
Chemokine concentration gradient
What does a chemokine concentration gradient do
Attract cells to the infection site
What is the other role of cytokine
Create signal that stimulates migration or stops migration
How do neutrophils get to the tissues where infection is from the blood
1) blood will vasoconstriction
2) blood flow will decrease
3) neutrophil and the endothelium will interact when selectin ligands on the neutrophils bind to the endothelium receptors called selectin
4) the endothelium will become more triggered and release chemokine which will bind to chemokine receptors on the neutrophil
5) activated integrins on the neutrophil then bind to the cell adhesion molecule on the endothelium
6) this forms an firm adhesion (neutrophil is stuck to the endothelium)
7) neutrophils squeeze through the endothelial cells to pass into the tissues
What receptors on the neutrophil binds to PAMPs that are on the pathogen
PPR
What happens to the neutrophil when PPR binds to PAMPs
1) a signal is activated via second messengers
2) cellular responses and gene expression occurs
Describe what happens when a neutrophil phagocytosis a pathogen
1) pathogen is phagocytosed into a phagasome
2) phagosome fuse with lysosomes that contain toxic granules
3) this forms a phagolysome
4) the pathogen is killed via the granules and enzymes in the phagolysome
What do granules contain to kill bacteria
Proteases
Bactericidal proteins
Superoxide anions
What happens when the granules get out out the cell
Digest components of the extracellular matrix
What are the 3 states that neutrophils exist in
Inactive
Primed
Active
What is inactive neutrophils
Rounded
No mobilisation of granules
What is primed neutrophils
Cytoskeleton mobilisation
Able to get a fast responce
What is an activated neutrophil
Response to chemotaxis
Degranulation
Reactive oxygen species release
When is the actual killing of bacteria in the neutrophil
When the phagosome fuses with the lysosome to form phagolysome
How do reactive oxygen species in the lysosome kill bacteria
Damage dna
Oxidation of polyunsaturated fatty acids in lipids
Oxidation of amino acids in proteins
Deactivate specific enzymes
What do reactive oxygen species need to kill the bacteria
Proteinases
When do neutrophil nets occur
Late function during infection when phagocytosis capacity has been reached
How does neutrophil NETs form
When the neutrophil extrudes unraveled DNA coated in bactericidal proteins
What do the neutrophil nets do to kill bacteria
Trap and kill bacteria
How to we get rid of inflammation i.e get the neutrophils to move away form the site
Via anti inflammatory signals created by cytokines of IL10
What happens to the neutrophils when they move away from the site of infection
Neutrophils become phagocytosed by macrophages
What is the process of neutrophils becoming phagocytosed by macrophages called
Efferocytosis
What happens to the neutrophils when efferocytosis does not occur
Neutrophils undergo necrosis
What does necrosis do to the cell contents
Leak out
What will neutrophil necrosis present as in clinic
Pus
What is pus
Lots of dead neutrophils
If we do not have neutrophils do we get pus formation
No
If there is too few neutrophils what are we at risk of
Encapsulated infection
What happens when there is too many neutrophils
Damage form the neutrophil granules that leak out
What does damage from the neutrophil granules lead to
Bronchiectasis
COPD
What is neutropenia
Low levels of neutrophils
What happens to the risk of infection as neutrophil count decreases
Increases
What are the main causes of neutropenia
Decreased production of bone marrow
Increased destruction
Taken out of the cell too quickly or congregating in one place
When can we get decreased production in bone marrow
Aplastic anaemia
Blood cancer
Radiation
When can we get increased destruction of neutrophils
Autoimmune neutropenia
Chemotherapy
When can we get marginalisation and sequestration
Haemodilaysis
Can it sometimes be normal to have a low neutrophil count
Yes
Why can you have a normal low number of neutrophil count
Due to ethnicity
Which ethnicity group has normal neutropenia
African
Middle East
Which disease is caused by neutrophil bystander damage
Alpha 1 anti trypsin deficiency
What happens when we get alpha 1 anti trypsin defieincey
Abnormal neutrophil elastase
What happens when you smoke and have alpha 1 anti trypsin deficiency
Lung damage and emphysema
What is chronic granulomatous disease a result of
A failure to produce reactive oxygen species
What forms in chronic granulomatous disease when there is no reactive oxygen species
Granuloma forming due to persistent activation of cells
