Complement System

Question 1

Describe complement.

Answer 1

-system of plasma proteins (inert enzymes) activated by pathogen presence (cleavage)
>activated = sequential self assembly enzymatic cascade
>site of activation = surface of pathogens
*3 pathways but same effector complement components just diff molecules for initiation & the way they act against pathogens

Question 2

Describe the 3 ways of protection from pathogens.

Answer 2

1. recruitment of inflammatory & immunocompetent cells
   -chemoattractants recruit phagocytic cells to sites of complement activation
2. opsonization of pathogens
   -lg amounts of activated complement proteins that bind to pathogens opsonizing them for phagocytosis
3. killing of pathogen
   -by creating pores in membrane (MAC) -> disturbs osmotic pressure

Question 3

Describe the role of complement in adaptive immunity.

Answer 3

activates adaptive immunity via:
1. opsonization by complement that allows uptake of microbes by APC
2. B cells have complement receptors for complement proteins that enhance B cell response to complement coated microbes

Question 4

Describe the nomenclature of complement components.

Answer 4

-smaller frag = a
-larger frag = b
[exception: C2a is larger]
-alternative pathway = Factor A

Question 5

Describe the initiation of complement activation in the classical pathway.

Answer 5

-initiated by binding of C1q to pathogen
>C1q binds 3 ways:
1. binds to surface of bacterial components (proteins, lipoteichoic acid)
2. bind to CRP that initially binds to phosphocholine residue on bacterial polysaccharide
3. bind to antigen-antibody complex on pathogen

Question 6

Describe the initiation of complement activation in the lectin pathway.

Answer 6

-initiated by binding of carbohydrate-binding proteins to carbohydrates on pathogens:
>mannose binding lectin (MBL) = lectin that binds mannose containing carbohydrates on microbes
>ficolins = bind N-acetylglucosamine on microbes

Question 7

Describe the initiation of complement activation in the alternative pathway.

Answer 7

-initiated by binding of plasma C3b to pathogen

Question 8

Describe the overview of the complement cascade.

Answer 8

-each pathway makes C3 convertase (bound to pathogen)
-C3 convertase cleaves C3 =
>C3b
–>main effector molecule
–>acts as opsonin
–> binds C3 convertase -> makes C5 convertase -> converts C5 into C5a (inflammatory peptide) + C5b -> C5b initiates MAC
>C3a
–>mediator of inflammation

Question 9

Describe the activation of the complement through the lectin pathway.

Answer 9

-independent innate immune response
-lectins bind carbohydrate (sugar) residue on pathogen
-MBL & Ficolins in plasma recog microbial specific carbohydrate on microbes
-MBL (tetrameric) of C type lectin structurally similar to C1q
-MBL recog mannose, fucose, N-actylglucosamine in cell wall of bacteria/fungi & some protozoa & envelope of some viruses

Question 10

Describe the initiation of complement activation in the alternative pathway.

Answer 10

-doesnt require recognition of microbial surface by antibodies/lectins
-uses nonspecific low level hydrolysis of C3
-C3 in all pathways
-spontaneous cleavage of C3 makes C3a & C3b

Question 11

Describe the terminal membrane attack pathway.

Answer 11

GOAL = protein complex (MAC) that makes a hole in target membrane to kill microbe
>C5 convertase generated by classical & lectin pathways & C5 convertase generated by alternative pathway start MAC formation

Question 12

Describe the regulation of complement activation via control proteins.

Answer 12

-prevent complement innate defense system from acting on inappropriate targets
-classical, lectin, alternative pathways can be stopped/downreg by these control proteins
FUNCTION: inhibit protease activity or facilitate degradation of activated complement complexes