Sepsis - Immunopathogenesis Flashcards
(33 cards)
What type of disease is sepsis
An inflammatory disease
What cells express pattern-recognition receptors
Macrophages
Neutrophils
Epithelial cells
What are DAMPs
Endogenous factors released during cell damage
What are PAMPs
Exogenous molecules expressed by microbes
What system most significantly contributes to the amplification of systemic inflammation in sepsis
Complement
Which 2 systems are activated by leaky vessels and blood clotting
Vascular endothelium
Coagulation
What significant phenomenon occurs to both T and B cells and characterises late immunosuppression in sepsis
Apoptosis
Immunopathogenesis of sepsis is associated with the activation of what systems
Innate immunity Complement system Vascular endothelium Coagulation system Adaptive immunity
What happens when PRRs are activated
Activation of inflammatory signalling pathways
What are PRRs
Pattern recognition receptors
What happens after inflammatory signalling pathways are activated
The pathways will converge and activate several important transcription factors which will each regulate transcription of genes encoding cytokines and chemokines
What is TNFa
A master regulatory cytokine that has a diverse array of functions on multiple different immune cell types including innate and adaptive
Describe the local effects of TNFa
TNFa stimulates expression of adhesion molecules on endothelial cells and proteins that trigger blood clotting
This recruits immune cells to the site of infection and prevents pathogens from spreading via the blood
What happens if TNFa is unsuccessful in containing microbes
Macrophages in the liver and spleen will be activated which will release TMFa systemically which ultimately leads to intravascular coagulation, preventing blood flow to organs leading to organ failure and death
What does the systemic release of TNFa lead to
Systemic vasodilation
Increased vascular permeability
Loss of blood pressure
Systemic blood clotting of microvasculature
Contributes to onset of sepsis and septic shock
When is the complement system activated
Immediately upon recognition of PAMPs and DAMPs
What occurs after the complement system is activated
The peptides C3a and C5a are generated
What is C5a
A potent chemoattractant which significantly amplifies inflammation
What is the effect on sepsis of the activation of complement
Contributes to vasodilation, tissue damage and organ failure
What is the endothelial barrier
Continuous barrier that coats the vascular system and separates the fluid phase of the blood from the tissues
Normally serves as an anticoagulant surface
Describe endothelial barrier dysfunction
Sepsis produces changes which converts the endothelium into a pro-coagulant state
This endothelium mediates loss of fluid through tight junctions and facilitates the recruitment and attachment of inflammatory cells
How can endothelial barrier dysfunction lead to septic shock
Leaky capillary membranes create a loss of plasma proteins and fluid into the extravascular space
Vasodilation alters capillary blood flow which contributes to septic shock
What should be used if a patient is in septic shock
A vasoconstrictive agent such as noradrenaline or vasopressin in order to maintain blood pressure and try to keep the patient alive
What characterises hypercoagulation caused by sepsis
Microvascular thrombi
Fibrin deposition
Neutrophil extraction trap formation
Endothelial injury
