Complement system Flashcards
What is the complement system?
Cascade of proteins that act to enhance phagocytosis (by opsonisation) and generate a macro molecular complex
Many of the proteins in the complement system are proteinases enzymes. Where are these produced?
Liver
Where are complement porters found?
Most bodily fluids - systemic protection
The complement system is one of the main pathways in what bodily response?
Inflammation
What are the 3 main consequences of complement activation? (COC)
Cytolysis (cell death to kill pathogen)
Cell activation (inflammatory cels)
Opsonisation of pathogens (increasing uptake by phagocytes)
What are complement components numbered from?
C1-C9
Many have sub-components a (diffuse through tissues easily) or b (don’t easily diffuse)
What features of the complement system make it a cascade?
Triggering
Amplification - substrates themselves become enzymes after binding to a proteinase
Is the triggering of the complement system fast or slow?
Fast - within microseconds
What are the 3 pathways of complement cascades?
Classical pathway
Lectin pathway
Alternative pathway
All 3 complement cascade routes (classical, lectin, alternative) lead to the cleavage of which complement component?
C3 cleavage
Key event in complement activation
What activates the classical pathway?
Antibody component of immune complexes
IgG or IgM
What activates the lectin pathway?
Lectin binding to pathogen surface via soluble protein
What activates the alternative pathway?
C3 directly binding to pathogen surface
What type of cells do all 3 pathways target in the complement system?
Bacteria
Viruses
Parasites
Fungi
Which complement pathway takes longer? Why?
Classical
Due to need for antibodies
What cells make C3? Where?
Macrophages
Liver
What does C3 naturally break down into? What do these act as/do?
C3a - chemoattract or an anaphylotoxin
C3b - bind to microbe surfaces or host cells
C3a, C4a and C5a are anaphylotoxins. What changes do they cause?
Smooth muscle contraction
Vasodilation - increases fluid in tissue and causes oedema
Activate neutrophils or mast cells
The complement system is part of which immune response?
Innate
Non-specific
What is the membrane attack complex (MAC)?
C5b,C6,C7, C8 and multiple C9
Endpoint of all complement activation pathways
What does the MAC do?
Opens bacterial cell cytosol
What happens to the bacterial cell when MAC opens the cytosol?
Loss of cellular components
Loss of homeostasis
Disrupts proton gradient
Allows penetration of host lysozyme
What is canine C3 deficiency? What does it cause?
Inherited deficiency
Lack of C3 = increased susceptibility
Trouble making antibodies against pathogens, causes increased infections e..g pyometra, pneumonia
What is porcine factor H deficiency? What does it cause?
Inherited recessive disease
Death from anaemia and renal failure
What is factor H? What happens if there is a factor H deficiency?
Stops C3b activation
Deficiency = C3 accumulation on kidneys - no serum C3