L13 Neutrophils Flashcards
What are its relative numbers in the blood?
Neutrophils is the most numerous white cell in the blood.
What is its key effect?
Controlling infections as part of innate immune system by phagocytosis and killing invading bacterial and fungal pathogens.
How long do neutrophils live for?
In the blood live for 12-16 hours
Where are neutrophils
In the blood in the absence of infection and when there is one rapidly recruited from the blood to tissues.
What happens in the absence of neutrophils?
Overwhelming bacterial and fungal infection
How does neutrophil migration work?
Rolling/tethering - neutrophils’ carb ligands bind to selectins on activated endothelium
Triggering - chemokines
Firm adhesion - chemokine receptors on neutrophils bind to chemokines on endothelium which activates neutrophils and their integrins. Activated integrins on neutrophils bind to their ligands - ICAMs, resulting in firm adhesion and shape change allowing extravasation
Extravasation - enter between cells into tissues
Leukocyte adhesion deficiency and neutrophils? Que passo?
Genetic mutation affecting phagocyte integrin expression, so they get recurrent bacterial and fungal infection due tot he fact that their neutrophils are inhibited in exiting blood vessels into tissues.
What happens once neutrophils enter tissues?
Neutrophils move via a conc gradient of chemoattractants for which they express receptors C5aR, C3aR, released as part of inflammatory response. hey get activated by these chemokines the closer they move.
What type of receptors do neutrophils have?
PRRs
Complement receptors - C5aR, C3aR
Immunoglobulin receptors - Fc receptors –> recognise opsonised bacteria
How does phagocytosis occur?
phagocyte cell membrane surrounds
What granules do neutrophils contain?
Proteases, bacteriocidal, superoxide anions capable of killing bacteria. If outside the cell they degrade anything around and activate other immune cells.
What 3 states do neutrophils exist in?
Quiescent: rounded, no mobilisation of granules
Primed: cytoskeletal mobilisation- polarised, bullet shaped, able to amount a fast response tenfold larger than in non=primed activated cells
Activated: chemotaxis, degranulation, ROS release
Is IL-10 anti or pro-inflammatory?
Anti-inflammatory, can attract neutrophils away from site of infections.
How is inflammation resolved with respect to neutrophils
IL-10 anti-inflammatory molecule - attracts neutrophils away from inflammation to facilitate inflammation resolution, some neutrophils phagocytosed by macrophages - efferocytosis.
When retrogade chemotaxis or efferocytosis doesnt occur or gets overwhelmed, celsl undergo necrosis which allows damaging contents to leak damaging tissue.
What does pus contain?
too many neutrophils for macrophages to clear
What happens when you have too many neutrophils?
Damage from neutrophil granules
What happens when you have too few neutrophils?
congenital defects that result in severe infection
What can happen when neutrophil infection is impaired?
Failure of neutrophil migration - LAD
Failure of superoxie - chronic granulomatous disease
Failure of granules
-MPO deficiency, chediak higashi
What are some causes of neutropenia?
Decreased production in bone marrow due to aplastic anaemia, cancer, hereditory disorders of neutropenia and radiation.
Increased destruction due to autoimmune neutropenia or chemo
Marginalisation and sequestration - haemodialysis and hypersplenism
Benign ethnic neutropenia - 25-50% of African and some ethnic groups of middle east peoples have <1.5x10^9.
What are the classes of neutropenia?
MILD - minimal risk 1.5-1.0x10^9
MODERATE - moderate risk 0.5-1.0x10^9
SEVERE - severe risk of infection at <0.5x10^9
What links are there between neutrophils and chronic disease?
COPD, interstitial lung disease, diabetes, IHD, inflammatory liver & bowel disease, most diseases associated with age so immunosenescence a role?
What is chronic granulomatous disease?
A failure to produce oxygen species or an oxidative burst, reccurent and severe infections, get granulomas in tissues, before antibiotics died before age 5
What is alpha anti-trypsin deficiency?
disease of unopposed neutrophil action, its an inhibitory protein that controls neutrophil elastase, lung damage in smokers due to unopposed actions of neutrophil elastase result in emphysema
