Complement System Part 1

complement system

a network of proteins that kill invaders before other defenses

function of complement system

kill pathogens, alert immune system, regulate inflammation

PAMPs

molecules that activate complement by indicating the presence of pathogens

antigen-bound antibodies

trigger complement system via classical pathway

innate immune system

complement is part of this defense system

adaptive immunity

complement system helps regulate this through antibody interaction

complement function: clearance

removes antigen-antibody complexes and damaged cells

complement function: tissue roles

aids blood vessel formation and tissue regeneration

alternative and lectin pathway

activated by microbial carbohydrates

classical pathway

activated by antigen-bound antibodies (adaptive immune response)

complement proteins

5–10% of serum proteins

C3, C6, C8 and Factor B

complement proteins made in the liver

C2, C3, C4, C5, FB, FD, FP, FI

complement proteins synthesized by macrophages

C1q

complement protein synthesized by neutrophils

C6 and C7

found in neutrophil granules

C1 to C9

complement components numbered based on discovery

C1 to C4

involved in classical pathway

C5 to C9

form membrane attack complex (MAC)

MAC

targets and lyses cell membranes

“a” in complement fragments

indicates anaphylatoxin

“b” in complement fragments

indicates binding protein

exception to a/b naming rule

C2

C3 convertase (classical/lectin)

C4b2a

C3 convertase formation

C4b binds C2a

Factor H and Factor I

regulate complement by degrading C3b

CD55 (DAF)

inhibits MAC to protect host cells

CD59

blocks MAC formation on host cells

C1q

binds to Fc portion of IgM or IgG

C1 complex components

C1q, C1r, C1s

C1 activation

C1r and C1s are activated after C1q binds antibodies

C4a and C2a

anaphylatoxins in classical pathway

C4b and C2b

bind to pathogen surface (C4b also binds host cells)

C4b2a

classical C3 convertase

C3a

anaphylatoxin that promotes inflammation

C3b

opsonin and helps form C5 convertase

C5 convertase (classical/lectin)

C4b2a3b

C5a

strong anaphylatoxin and chemoattractant

C5b

initiates formation of MAC

MAC composition

C5b + C6 + C7 + C8 + multiple C9

opsonization

process by which C3b tags pathogens for phagocytosis

classical pathway trigger

antigen–antibody complex (IgG or IgM)

lectin pathway trigger

mannose-binding lectin or ficolins binding to sugars

MASP-1 and MASP-2

serine proteases in lectin pathway

MBL

pattern recognition receptor in bloodstream

MBL-MASP complex

initiates lectin pathway by cleaving C4 and C2

C3 convertase in lectin pathway

C4b2a

C5 convertase in lectin pathway

C4b2a3b

difference of lectin and classical pathway

lectin does not require antibodies

alternative pathway trigger

spontaneous hydrolysis of C3 (tickover) or pathogen-bound C3b

Factor B

binds to C3b in alternative pathway

Factor D

cleaves Factor B into Ba and Bb

C3bBb

C3 convertase in alternative pathway

Properdin (Factor P)

stabilizes C3bBb complex

C3bBbC3b

C5 convertase in alternative pathway

amplification loop

positive feedback by C3b generating more C3b

tickover

low-level spontaneous activation of C3

alternative pathway opsonization

via C3b

alternative pathway inflammation

via C3a and C5a

all pathways MAC formation

all end in MAC (C5b-9)