innate immunity and complement Flashcards
what are the non-cellular components of the innate immune system
- complement
- cytokines
- lactoferrin (iron binding protein)
- acute phase proteins
outline the role of the complement system in innate immunity
- 30 plasma proteins
- circulate in blood as inactive precursors
- activated in response to infection (cascade reaction => rapid amplification of activated proteins)
main roles:
- inflammation - by stimulation of histamine release from mast cells (mast cell degranulation)
- chemotactic agents - recruitments of neutrophils and macrophages to site of infection
- cell lysis - through pore formation in cell membranes including bacteria
- opsonisation - coating of surface area leading to increased phagocytosis
what is the link between innate and adaptive immunity
complement cascasde offers an alternate pathway in both innate and adaptive stepwise systems
what are the 3 different types of complement systems
- classical pathway (antibody dependent - effect of compliment strongly amplfied in the presence of an adaptive immune repsonse. link innate and adaptive immunity)
- MB-lectin pathway (antibody independent)
- alternative pathway (antibody independent)
antibody independent systems activated directly by microbial carbohydrates
what is the central role of C3
- all 3 complement pathways converge on C3
what is C3
- made by macrophages in the liver
- highest concentration of serum complement proteins in any species we can measure
- C3 breaks down naturally into C3a and C3b
- C3a acts as an anaphylotoxin or a chemoattractant
- C3b can bind microbe surfaces via carbohydrates and can bind factor H on host cells taking C3b out of circulation
what is the role of C3b in opsonisation and phagocytosis
- C3b and C4 bind to microbial surface and tage it for phagocytosis
- complement receptors expressed on multiple types of phagocytes
what is the role of C3a in triggering inflammation
- C3a, C4a and C5a are anaphylatoxins
- they change smooth muscle
- increase vasodilation
- acitvate mast cells or neutrophils
- increase fluid in the tissue and speeds up lymph flow
what happens if dog is deficient in C3
- increased susceptibility to infection
- inherited disorder
- homozygote dogs have no serum C3 (126mg/ml in normal animal)
- have trouble making antibodied against certain pathogens (e.coli etc.)
- increased risk of pyometra, pneumonia, sepsis, etc.
why is C3 important
Opsonization: Activated C3 can coat pathogens, such as bacteria or viruses, with molecules that make them more recognizable to immune cells. This process, called opsonization, promotes the phagocytosis (engulfing and destruction) of pathogens by immune cells like macrophages and neutrophils.
Inflammation: C3 activation contributes to the initiation of inflammation. It attracts immune cells to the site of infection or injury, helping to contain and eliminate pathogens, and promoting tissue repair.
Membrane Attack Complex (MAC) Formation: C3 activation also leads to the formation of the membrane attack complex, which can create pores in the membranes of pathogens. This process directly damages and destroys the pathogens by disrupting their integrity.
What is the membrane attack complex
- a central effector mechanism of the complement system and innate immune response
- an endpoint of all 3 activation pathways
- composed of C5b, C6, C7, C8 and multpile copies of C9
- forms a pore in membrane
- opens the bacterial cell/microbe cytoplasm causing: dramatic loss of cellular homeostasis, disrupts proton gradient (signalling), penetration of host lysozyme and other proteases
