1. 16.8 Complement
Explain the role of complement in innate immunity.
a) What are the three effects on microbes by
complement?
b) What is the common pathway/cascade of complement?
c) What are the three pathways of acAvaAng
complement?
d) What is an anAgen?
e) What is an anAbody?
f) What is a lecAn?
g) What are 2 ways bacteria might evade complement?

2. Role of Complement System in
Immunity
• Complement system is made up of over 30 proteins
synthesized by the liver, circulate in the blood
• Many complement proteins are inacAve and must be
acAvated.
• AcAvated complement acts in a cascade that causes
1. inflammaAon: dilaAon of arterioles, release of
histamine & increased permeability of capillaries
2. opsonizaAon: protein binds to microbe making it
easier to phagocyAze
3. cytolysis: a complex of several proteins can form
holes in microbe membranes causing leakiness and
cell rupture

3. The Common Pathway
• Step 1 – acAvate C3, promotes opsonizaAon
and phagocytosis
• Step 2 – acAvate C5, promotes inflammaAon
• Step 3 – form MAC, promotes cytolysis

4. Step 1: Ac*vate C3
• C3 is split into C3a and
C3b, catalyzed by C3
convertase
• C3b binds to surface to
enhance phagocytosis (opsonizaAon)
• C3b is also an enzyme that catalyzes the next step
• C3a promotes inflammaAon by sAmulaAng mast
cells to release histamine

5. Step 2: Ac*vate C5
• C3b acts as the C5 convertase,
spliWng C5 into C5a and C5b
• C5a promotes inflammaAon by
sAmulaAng mast cells to release histamine (along
with C3a)
• C5b is begins the chain reacAon of proteins
binding to the surface of a microbe

6. Step 3: Forma*on of the
Membrane A:ack
Complex
• C5b binds to the surface
of the bacterial cell
• C6, then C7 and C8 bind
in sequence
• These 4 proteins a[ract
or recruit C9 to bind
• Several C9 proteins bind
in a pa[ern to form a
huge pore puncturing
the plasma membrane
and allowing bacterial
cytoplasm to leak out ‐
cytolysis

8. 3 Ways to AcAvate Complement
• Classical pathway – anAbodies (part of
acquired immunity)
• AlternaAve pathway – a[racAon of
complement proteins to microbial cell walls
• LecAn pathway – proteins that bind to
bacterial carbohydrates

9. The Classical Pathway:
adapAve immunity
• A specific anAbody
recognizes and binds to a
bacterial cell
• C1 binds to the anAbodies
– The interacAon acAvates
enzymaAc funcAon of C1
• AcAve C1 a[racts and clips
C2 and C4 into C2a, C2b, C4a
& C4b
• C2a combines with C4b to
form an acAve C3 convertase

10. AnAbodies & AnAgens
• AnAbodies are proteins produced by B cells
• Part of our acquired immunity
• AnAbodies bind to small pieces of microbes,
called anAgens, to iniAate a variety of immune
responses
• AnAgens are substances that sAmulate the
producAon of anAbodies…anAbody generators
• The classical pathway is iniAated when an
anAbody binds to its anAgen

11. The AlternaAve Pathway:
innate immunity
• Complement proteins B, D &
F circulate throughout the
body
• Bind to microbial cell wall
components (glycolipids)
• B, D & F a[ract C3 and act as
a C3 convertase

12. The LecAn Pathway:
innate immunity
• LecAn is a protein that
recognizes and binds to
bacterial carbohydrates
• LecAn a[racts C2 & C4 and
catalyzes the spliWng of
both proteins into C2a,
C2b, C4a & C4b
• C2a combines with C4b to
form an acAve C3
convertase

13. Evading Complement
• Capsule
– The capsule is a coaAng surrounding the cell wall
– One component of the capsule is sialic acid which can
prevent opsonizaAon (too slippery for C3b)
– Another component present for some bacteria is O
polysaccharide which blocks binding of the MAC
complex (C5b, C6, C7, C8, C9)
• Secreted enzymes
– Some bacteria secrete C5a pepAdase, which destroys
C5a – impair inflammaAon and recruitment of
phagocytes