Neutrophils Flashcards
Through what process are all immune cells generated?
Haematopoiesis
What are haematopoietic cells?
The original cells. Immature and pluripotent. They can differentiate into any cell
What do you call a cell that can now longer differentiate?
Terminally differentiated
What are mast cells?
Long-lived tissue resident immune cells
Where are mast cells found?
In most tissues in the body, but are enriched at boundaries of the body (e.g. skin, blood vessels, nerves)
What are mast cell granules?
Granules that are filled with inflammatory mediaters that are rapidly released when the mast cell is activated (rapid degranulation)
What can activate mast cells?
Mast cells can be activated by various stimuli, including allergens, physical trauma, and infection
What is an example of an inflammatory mediator released in mast cell granules?
Histamine
How do mast cells sense?
They have a range of pattern recognition receptors, such as TLRs 1-7 and 9, allowing mast cells do detect pathogens/allergens
What are the consequences of degranulation (3)?
- Activate endothelial cells, which increases vascular permeability, allowing immune cells to more easily access site of infection
- Recruit neutrophils from blood
- Enhance survival of recruited cells by releasing cytokines and growth factors
What are some key functions of neutrophils?
- Degranulation (release of antimicrobial proteins)
- Phagocytosis
- NETosis
- Cell death for resolution
What is NETosis?
Neutrophils release neutrophil extracellular traps (NETs) in inflamed tissues that remain attached to the neutrophil that released it.
These NETs trap microbes, and may actively kill them
What do NETs contain?
- Antimicrobials e.g. defensins
- Proteases
- Histones
and other proteins
How do neutrophils migrate into tissues?
- Rolling: neutrophils slowly roll through blood vessels with blood flow
- Adhesion: in response to signals in a certain area (e.g. produced by mast cells), the neutrophil will fully adhere to endothelial cell
- Transmigration: neutrophils will crawl and then enter squeeze through endothelial cells, towards the site of inflammation
What is activated by neutrophils to stop them rolling and fully adhere in the blood vessel?
Integrins
What are the two methods of transmigration through endothelial cells when they are trying to get to the site of inflammation?
Paracellular- squeeze between endothelial cells lining blood vessel
Transcellular- pass directly through endothelial cells
What is the process of phagocytosis by neutrophils?
- Pathogen engulfed by neutrophil
- pH of phagosome rises and pathogen is killed
- pH of phagosome decreases, fusion with lysosomes allows acid hydrolases to degrade pathogen completely
- Neutrophil dies by apoptosis and is phagocytosed by macrophage
What is cell death for resolution?
Death of neutrophils is sensed by macrophages, which tells them to initiate anti-inflammatory response
