Complement Chapter 7

Exam #1 coming up on Wednesday

(This lecture will NOT be included)

The Complement Pathway

1.

3.
(Not shown)

2.

The first
step of
Classical
complement
activation

IgM changes its conformatin when it binds to antigen

C1

C1q,r,s

Note: C2b sorry!

C4b2a bind adjacent to Ab

Classical C3
Convertase

C5 Convertase

C4b C2a C3b

Note: These are now

non-enzymatic steps !

The Classical pathway (again!)

(Wrong)
C2a

The MAC

Biological Consequences of Complement

Activation
C3b, iC3b opsonization for uptake by
phagocytic cells
C3a, C5a anaphylatoxins for chemotaxis
Inflammation!
C5b-C9 Membrane attack complex (MAC)

The Biological Consequences of Complement Activation

LECTIN PATHWAY

3. Inflammation

2. Opsonization

1. Membrane attack

Three biological activities

of complement (again)

2.
C3b, iC3b

3.

1.
C5b-9

C3a, C5a

Opsonization

Fig. 2.35 p71

Membrane Attack

The Alternative Complement Pathway (ACP)

LECTIN PATHWAY

The Alternative Pathway of Complement (APC)

Complement can be activated without antibody! Pillimer

See p173

**

The Alternative
Pathway

The Alternative C5 convertase

The Classical and the

Alternative C5 convertases

Classical -

C4b2a3b

Alternative - C3bBb3b

Fig. 2.26 p63

Thioesters and the covalent fixation of complement

(or spontaneously)

C3 forms a covalent bond with OH or NH

The breakdown of bound C3b - to iC3b and C3dg

C3b

iC3b

.and further to C3dg

Note: C3b is covalently bound to membrane

proteins or carbohydrates

Opsonization Complement receptors

The catalytic triad of Serine proteases (serine in active site!)

Nucleophilic attack of
carbonyl carbon to break
peptide bond

Basic concepts
The Complement system is a series of (inactive) serum proteins, which
can become sequentially activated, usually by proteolysis (via serine proteases!)
The activation of complement is associated with inflammation! But complement
fixation can also lead to opsonization and lysis.

Exam 1 on Wednesday. Good luck!!