Lecture 6. Neutrophils Flashcards
What are the two types of leukocytes ?
- Grnaulocytes
- Agranulocytes
What are the three types of granulocytes ?
- Neutrophils
- Eosinophils
- Basophils
What are the two types of agranulocytes ?
- Monocytes
- Lymphocytes
Where are neutrophils generated ?
In bone marrow
What sort of lifespan do neutrophils have ?
Short life span about 18 hours
What happens at the end of a neutrophils lifespan in tissues ?
They are cleared or removed
Why do the number of neutrophils in circulation remain relatively constant ?
Due to the fine balance between production and elimination
Why must neutrophils clearance mechanisms be tightly regulated ?
Because of their cytotoxic contents
What is the structure of a neutrophil ?
They are multi-nucleated
What is the structure of the nucleus in a neutrophil ?
Clearly visible and consists of three to five lobes connected by chromatin
What are the four types of granules found in the cytoplasm of the neutrophil ?
- Primary - azurophic
- Secondary - specific
- Tertiary - gelatinase
- Secretory
What are the neutrophils in terms of defence ?
The first line of defense
What is the role of the neutrophil in the innate immune system ?
Critical effector cell
What do neutrophils patrol the organisms for ?
Signs of microbial invasion and when detected, react rapidly to trap and kill invading organisms
What are the primary anti-microbial functions of the neutrophil ?
- Phagocytosis
- Degranulation
- Release of neutrophil extracellular traps (NETs)
What do neutrophils pay a detrimental role in ?
Pathogenesis of acute and chronic inflammatory disease
What can neutrophils inform or regulate ?
Immune responses for example release cytokines and chemokines
What do neutrophils comprise of ?
Multiple phenotypes (immunostimulatroy and immunosupressive) or subsets that change with time as they mature or age and also depending on the tissue microenvironment
What is the most important cell in fighting extra-cellulalar bacterial infection ?
Neutrophil
How many stages is there in formulation of granular leukocytes ?
Five
What is granulopoiesis ?
The formation of granular leukocytes
What are all stages of granulooiesis controlled by ?
Expression of specific transcription factors which direct the formation of granules
What is the retention/release of cells from the bone marrow controlled by ?
Chemokine receptors
What is the thing responsible for retention and down regulation in granulopoiesis ?
CXCR4
What is the thing responsible for release and up regulation in granulopoiesis ?
CXCR2
What is release activated by ?
Signalling through CXCR2, TLR and G-CSFR
What is a band neutrophil ?
An immature neutrophil which can sometimes leave the bone marrow
What does G-CSF stand for ?
Granulocytes conony stimulating factor
What is G-CSF ?
A growth or cytokine produced by numerous cell types
How does G-CSF mediate its effects ?
By binding to a single homodimer receptor G-CSFR
What is G-CSF in the plasma ?
Normally undetecable unless in response to infection
What does G-CSF do ?
Stimulate survival, proliferation, differentiation and functions of neutrophils
What does G-CSF induce ?
Neutrophil exit from the bone marrow
What does G-CSF interfere with ?
CXCR4-CXCL12 interaction
What does G-CSF simultaneously induce ?
CXCL1, CXCL2 and CXCL5
What are CXCL1, CXCL2, CXCL5 ?
They are ligands for CXCR2 which is highly expressed on the mature polymorphic neutrophil
What can inhibit neutrophil apoptosis ?
Locally produced G-CSF in tissue
What is G-CSF expression controlled by ?
Phagocytosis of apoptotic neutrophils