lecture 5 - leucocytes & pathology Flashcards
What is the most common type of granulocyte?
Neutrophils
What is the name for the process of granulocyte production?
granulopoiesis
What is the most immature form of a granulocyte?
Myeloblast
Where does granulopoiesis occur?
Bone marrow
How long does it take for neutrophils to mature in the bone marrow?
~10 days
How long will neutrophils spend in the blood before tissue migration?
~5 days
What are the 2 key cytokines that stimulate neutrophil growth?
GM-CSF (granulocyte (monocyte) colony stimulating factor), G-CSF (Granulocyte colony stimulating factor)
What cytokine is used to stimulate neutrophil production following chemotherapy?
G-CSF (granulocyte colony stimulating factor)
What are the 5 key stages of neutrophil adhesion & migration into tissues?
Rolling, slow rolling, arrest, crawling, transmigration
What proteins aid in the adhesion and rolling of neutrophils to the endothelium?
adhesion molecules - selectin, integrin
What molecules are involved in the arrest of neutrophils during adhesion and migration?
chemokines
What are the 2 major mechanisms that neutrophils respond to bacteria with?
Apoptosis, NETosis
What are the stimuli for neutrophil response to bacteria?
inflammatory cytokines, opsonized bacteria, immune complexes, fungi/ECM components
What is opsonization?
The process where a pathogen is made susceptible to phagocytosis
What is NETosis?
The process where neutrophils die and spill out their DNA as decondensed chromatin covered in antimicrobial compunds, forming a Neutrophil Extracellular Trap (NET) that traps bacteria and yeast.
What are the pro-inflammatory effects of neutrophils?
release of self—antigen, stimulation of interferon-a/B, forming chromatin lattice (NET), presentation of antimicrobial peptidees
What are the anti-inflammatory effects of neutrophils?
uptake by macrophages, stimulation of anti-inflammatory cytokines, removal of cellular debris
What is neutrophilia?
An elevated neutrophil count in the blood.
What are the 3 main causes of neutrophilia?
Infection, steroids, chronic illness (smoking, obesity, etc)
What is a ‘left shift’ in neutrophil count?
An increase in immature neutrophils, typically due to an acute infection
What are the features of severe infection-induced neutrophilia?
‘left shift’ with high immature neutrophil count, toxic granulation (increased number of prominent granules in cells), vacuolation (autophagocytosis where cells make holes in themselves)
Why do steroids cause neutrophilia?
Steroids cause demmargination of neutrophils, meaning more remain in the blood and the count appears higher
What are the causes of neutropenia?
pancytopenia related causes (bone marrow disease, chemotherapy, etc.), drug side effect, viral infection, genetic mutation, blood group (duffy-null), fulminant bacterial infections
What are fulminant bacterial infections?
A severe, sudden bacterial infection