Immunology 2 - Late Innate Immune Responses Flashcards
What are PRRs found on the cell surface for detection of?
Extracellular pathogens
What are PRRs found in the cytosol for detection of?
Intracellular pathogens
What is another name for an immune cell?
Leukocyte
Where are low levels of inactive complement system found normally?
Extracellular fluids
When the complement system is activated, what are promoted by the cascade of chemical reactions that are created?
Opsonisation of pathogens
Direct pathogen killing
Acute inflammation
Leukocyte recruitment
What are the three pathways in the complement system?
Classical pathway
Mannose-binding lectin pathway
Alternative pathway
What is C3 converted to?
C3a + C3b
What do C3a and C3b activate?
Downstream complement proteins
What is C3?
An acute phase protein
Describe the mannose-binding lectin pathway.
Mannose-binding Lectin binds to mannose residues on a pathogen’s surface
This activates the cleavage of C3 into C3a and b
Describe the alternative pathway.
C3b is involved in an amplification loop that converts more C3 to C3a and b
What is the downstream complement pathway?
Active C3b associates with other complement system proteins to produce C5 convertase which cleaves inactive C5 into active C5a and b
Active C5b associates with other complement system proteins to produce a pore-forming channel which inserts into the pathogen membrane (cell wall) called the MAC
What does MAC stand for?
Membrane Attack Complex
What enters the pathogen through the MAC and what does this cause?
Extracellular salts and water enter, causing the pathogen to swell and burst
What does opsonisation lead to?
Pathogen phagocytosis and killing
What are opsonins?
Soluble factors that bind to pathogens and enhance phagocytosis
What do C3a and C5a do?
Activate mast cells
Act directly on local blood vessels
What happens if C3b binds to a human cell?
Active C3b associates with other complement system proteins to produce C5 convertase which cleaves inactive C5 into active C5a and b
An inhibitory protein on the surface of the human cell prevents MAC
What are the local physiological signs of acute inflammation caused by?
TNF alpha
Histamine
C3a and C5a
What are the characteristics of healthy tissue?
No inflammatory mediators
Normal vasculature
Circulating neutrophils
What changes to vasculature does inflammation promote
Vascular changes like vasodilation and increased permeability
Recruitment and activation of neutrophils - transendothelial migration
What is transendothelial migration?
The movement of substances across the endothelium into or out of the cell
What are the steps of transendothelial migration?
Neutrophils move to the side of the endothelium near sites of tissue damage
Neutrophils bind to adhesion molecules on endothelial cells
Neutrophils migrate across the endothelium
Neutrophils move within the tissues via chemotaxis
Neutrophils are activated by PAMPs and TNF alpha
What are the three killing mechanisms of neutrophils?
Phagocytosis
Degranulation
NETs
What is ROS-dependent killing?
A second way of killing internalised pathogens
Which are more effective at killing, macrophages or neutrophils, and why?
Neutrophils because they have two ways of killing internal pathogens: phagocytosis and ROS-dependent mechanism
What is degranulation?
Neutrophils release anti-bacterial proteins from neutrophil granules directly into the extracellular milieu
What is the effect of degranulation?
Direct killing of extracellular pathogens bacteria and fungi
Tissue damage and potentially systemic inflammation
What does NET stand for?
Neutrophil Extracellular Trap
What are NETs?
Neutrophils induce apoptosis in order to trap and kill pathogens
What solves the problem of neutrophils causing bystander tissue damage?
Macrophages secrete wound healing anti-inflammatories
What is the acute phase response?
A systematic response that involves changes in the plasma concentrations of specific proteins in response to inflammation
What is the acute phase response driven by?
Pro-inflammatory mediators released by activated macrophages
What is the acute phase response mediated by?
Liver hepatocytes which produce a variety of acute phase proteins
What are examples of acute phase proteins?
C3
Mannose-binding Lectin (MBL)
C reactive protein (CRP)
What does C reactive protein do?
Primes certain bacteria for destruction by the complement system
Has a prognostic role - severity and duration of inflammation
What do virally-infected cells produce and release?
Small proteins called interferons
How do viruses survive?
Invading the cells of its host
What do interferons play a role in?
Immune protection against viruses
How do interferons play a role in immune protection against viruses?
Prevent replication of viruses
Signal to cells to produce anti-viral factors
Warn nearby molecules of a viral presence so T cells can identify and eliminate a viral infection
What do NK cells do?
Recognise and destroy virally-infected cells and abnormal cancer tissues
How do NK cells destroy virally infected cells?
Release cytotoxic molecules that cause abnormal cells to undergo apoptosis
Secrete pro-inflammatory mediators
