Lecture 5: Acute-phase response Flashcards
What is the acute-phase response?
Infection or damage induces macrophages and DCs to produce cytokines which produces a systemic reaction known as the acute phase response. It is part of the innate immune system.
What organs are involved in the acute phase response and what are their roles?
The brain produces CRH and ACTH and is responsible for fever (alteration of temp set point in hypothalamus), the liver changes its pattern of plasma protein synthesis, the bone reduces EPO production and increases platelet production, increased cortisol production in the adrenal gland and decreased protein synthesis in muscles.
What cytokines are involved in stimulating the acute phase response?
IL-1beta, IL-6 and TNF-alpha
How is fever controlled by cytokines?
Pyrogenic cytokines activate COX2 which in turn activates prostaglandin E2 which act on the hypothalamus to modulate temperature.
Give examples of acute phase proteins.
C-reactive protein (CRP), mannose-binding lectin, fibrinogen, complement, serum amyloid protein (SAP)
What is the function of alpha-1-antichymotrypsin?
It is a protease inhibitor e.g. inhibits cathepsin G in neutrophils so prevents damage to tissues by proteolytic enzymes.
What is the role of alpha-1-antichymotrypsin in disease?
Deficiency is associated with liver damage and mutations have been linked to Parkinson’s
What is fibrinogen?
A coagulation protein which cross-links to form fibrin to help clot blood.
What is the function of haptoglobin?
Binds free haemoglobin that is released from erythrocytes then is transported to the spleen or liver by macrophages so the iron can be recycled.
What is mannose-binding lectin?
A soluble PRR which can activate complement.
What are pentraxins?
Pentraxins include C-reactive protein (CRP) and serum amyloid protein (SAP). CRP is a soluble PRR capable of binding to phospholipids in microbial membranes and activating complement.
What is an auto-inflammatory disease?
A reaction of the innate immune system without an obvious trigger, can result in repeated fever and inflammation
What is the common mutated gene in 3 cryopyrin-associated periodic syndromes (auto-inflammatory diseases)?
NLRP3
What does NLRP3 encode?
Part of the inflammasome which produces caspase 1 which cleaves pro-IL-1B to IL-1B
What are the 2 signals needed for the inflammasome to be activated?
Signal 1 e.g LPS to increase levels of pro-IL-1beta (to be cleaved) and signal 2 e.g. crystals, nucleic acids, ATP, LPS
