innate immunity and complement

Question 1

what are the non-cellular components of the innate immune system

Answer 1

• complement
• cytokines
• lactoferrin (iron binding protein)
• acute phase proteins

Question 2

outline the role of the complement system in innate immunity

Answer 2

• 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

Question 3

what is the link between innate and adaptive immunity

Answer 3

complement cascasde offers an alternate pathway in both innate and adaptive stepwise systems

Question 4

what are the 3 different types of complement systems

Answer 4

• 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

Question 5

what is the central role of C3

Answer 5

• all 3 complement pathways converge on C3

Question 6

what is C3

Answer 6

• 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

Question 7

what is the role of C3b in opsonisation and phagocytosis

Answer 7

• C3b and C4 bind to microbial surface and tage it for phagocytosis
• complement receptors expressed on multiple types of phagocytes

Question 8

what is the role of C3a in triggering inflammation

Answer 8

• 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

Question 9

what happens if dog is deficient in C3

Answer 9

• 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.

Question 10

why is C3 important

Answer 10

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.

Question 11

What is the membrane attack complex

Answer 11

• 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