Complement Flashcards
What roles does the complement system play?
Recognises pathogen/ danger signals + triggers responses that can directly lyse pathogens, opsonise pathogens, act as a chemoattractant, trigger degranulation of mast cells
How can complement proteins be measured?
In serum of all animals
Describe the different modes of action of complement proteins
- direct inhibitors/ blockade
- decay accelerator factors- e.g. CD55
- Found on many WBCs surfaces speeds up the decay of convertases
- CD59 inhibits the formation of MAC on host surfaces
Name the 3 complement pathways
- Classical pathway
- Alternative pathway
- MB-lectin pathway
How do the complement pathways differ?
Classical = reliant on Ab being produced, longer Alternative = quickest, binds directly to pathogen surface MB-lectin = reliant on another protein for activation (mannose), binds surface via soluble protein
What is the activating signal of classical complement pathway?
Ag:Ab complex
What is the activating signal of the alternative complement pathway?
C3 binding to pathogen carbohydrates/ proteins
What is the activating signal of the MB-lectin complement pathway?
Host mannose- binding lectins: pathogen mannose
What are the effectors of the complement pathways?
cell phagocytosis, cell lysis, WBC recruitment + activation
What are targets of the complement pathways?
bacteria, viruses, parasites, fungi
How is C3 made?
Made by macrophages in the liver
What is the highest concentration of serum complement proteins?
C3
Describe the breakdown of C3?
C3 breaks down naturally into C3a + C3b
- C3a acts as an anaphylatoxin/ chemoattractant
- C3b can bind microbe surfaces via CHO, C3b can bind Factor H on host cells taking C3b out of circulation
Which complement proteins are anaphylatoxins?
C3a, C4a, C5a
What effect do anaphylatoxins have?
smooth muscle contraction, increases vasodilation, activates mast cells/ neutrophils, increases fluid in the tissue + speeds up lymph flow
What is the Membrane Attack Complex
Central effector mechanism of complement system + immune response
Explain the Membrane Attack Complex
= endpoint of all 3 activation pathways
- composed of C5b, C6, C7, C8 + multiple copies of C9
What does the MAC do?
opens bacterial cell cytosol = loss of cellular homeostasis, disrupts protein gradient (signalling), penetration of host lysozyme + other proteases
