Immunothrombosis Flashcards
What are the three primary mechanisms by which neutrophils combat pathogens?
Phagocytosis, degranulation, and NETosis.
What are the main components of NETs?
Extracellular DNA (cell-free DNA) decorated with bactericidal cellular proteins such as elastase, myeloperoxidase, cathepsins, and histones.
List three antimicrobial proteins found within NETs.
- Elastase
- Myeloperoxidase
- Cathepsin G
Define NETosis.
The process of NET (neutrophil extracellular trap) formation, where neutrophils release extracellular chromatin and antimicrobial proteins.
What is ‘vital NETosis’?
A process where neutrophils extrude DNA but remain viable and maintain their functional capacities.
T/F vital NETosis is the most common form of NETosis in dogs
F. It has NOT yet been demonstrated in veterinary species.
Which Toll-like receptor (TLR) is activated by lipopolysaccharide (LPS)?
Toll-like receptor 4 (TLR4).
What are the main stimulators of NETosis in dogs?
PMA (smth they use in research to activate PKC) and LPS
Describe three ways in which NETs exert their antimicrobial activities.
- Physically entrapping microorganisms
- Directly killing pathogens
- Hindering their dissemination from the point of entry.
What is immunothrombosis, and in what scenarios may it be beneficial?
A potentially beneficial physiological process that aids innate immunity and host defense against pathogen invasion.
In what scenarios can immunothrombosis be harmful?
When dysregulated or excessive, contributing to morbidity and mortality in conditions like trauma, sepsis, heat stroke, and hemolytic anemia.
What role do platelets play in NETosis?
Platelets interact with neutrophils to facilitate and amplify NETosis.
How do activated platelets interact with neutrophils to promote NETosis? Name at least two mechanisms.
- Adhesive interactions (e.g., P-selectin/PSGL-1)
- Secreting soluble mediators.
Name the content of platelets’ alpha granule and dense granules
Alpha granules have proteins= (e.g., P-selectin, vWF, PAI-I, thrombospondin, GPIIb/IIIa [integrin aIIbb3]) and coagulation factors (e.g., factors V and VIII and fibrinogen).
Dense granules have small ions and nucleotides= CASH= Ca++, ADP/ATP, serotonine, histamine
What is the role of high mobility group box–1 (HMGB-1) in NETosis, and from which cells is it released?
Facilitates NETosis by binding to its neutrophil receptor and is released from platelets.
Which of the following is NOT a function of NETs?
a) Physically trapping microorganisms.
b) Directly killing pathogens.
c) Hindering pathogen dissemination.
d) Facilitate fibrinolysis
d) Facilitate fibrinolysis
Which of the following is NOT a component found in NETs?
a) DNA
b) Histones
c) Ribosomes
d) Myeloperoxidase
c) Ribosomes.
