L13-The neutrophil response to infection Flashcards
How long do neutrophils circulate in the blood?
They circulate for 12-16 hours before being removed by tissue macrophages in the spleen, liver and bone marrow
How long can a patient survive without neutrophils?
They will die within a day from bacterial infection, this is due to the vital nature of neutrophils.
Why is it hard to transfuse neutrophils?
Due to their very short lifespan
What are the 4 stages of neutrophil migration into tissues?
- Rolling and tethering - involes the reversible binding of selectins on the endothelium to carbohydrate ligands on the neutrophils. This is not strong enough to anchor the neutrophils so they roll along the endothelium.
- Chemokines on the endothelium bind to chemokine receptors on the neutrophils which promotes neutrophil integrin activation.
- Activated integrins on neutrophils then bind to their ligands which results in firm adhesion to the endothelium.
- The neutrophil moves through the endothelium (extravasation), once within the tissue the neutrophils follow chemokine gradients.
What is LAD and what effect does this have on the patient?
Leukocyte adhesion deficiency affects integrin expression so neutrophils are inable to enter the tissues resulting in recurrent bacterial and fungal infections.
Once the neutrophils have entered the tissue how do they know where to go?
They follow a concentration gradient of chemoattractants that are released as part of the inflammatory responce.
What are the main neutrophil receptors and what are their functions?
They express complement receptors which guide them to pathogens
Fc receptors help them to bind to opsonised pathogens (covered in antibodies)
Toll like receptors allow it to bind to PAMPs on pathogens and activate complement
Which phagocytes can carry more toxic granule contents?
Neutrophils can carry more toxic than macrophages
What are the purpose of reactive oxygen species?
they are used by phagocytes to destroy pathogens and cell debris e.g. superoxide anions, hydrogen peroxide and nitric oxide.
What is the result of neutrophils killing microbes?
It is a high energy process that results in neutrophil cell death.
Why do macrophages consuming apoptotic cells not cause an inflammatory reaction?
The apoptotic cells do not have PAMPS to activate macrophage PRRs which does not elicit an inflammatory responce
What is pus?
When the number of apototic neutrophils outpace the number of macrophages able to clear them then they lyse by secondary necrosis releasing their contents into the local environment causing pus or abscess formation