Complement

Question 1

Function of complement

Answer 1

Cytolysis - MAC complex

Opsonisation –> efficient uptake by APC

Initiate inflammatory response - anaphylatoxin release - C3a and C5a

Immune complex clearance

Question 2

Classical pathway activation

Answer 2

Activation of C1q by:

• IgM and IgG binding
• Binding to bacteria
• Binding to CRP

C1q + C1r +C1s --> C1q complex
C1q complex --> activation of C4 and C2 --> C4bC2b = C3 convertase
--> C3 activation
--> C4bC2bC3b
--> MAC formation - C5b6789

Question 3

Lectin Pathway activation

Answer 3

Activation of C4 and C2 by Mannin binding lectin

MBL associated wth MASP1 and 2 -analogous to C1r and C1s

C4bC2b –> C3b

• -> C4bC2bC3b
• -> C5b6789

Question 4

Alternate Pathway activation

Answer 4

C3 activated to C3b

• Surface of bacteria and viruses
• IgA immune complexes
• C3 nephritic factor

If foreign surface present C3b will bind to it

• -> binds factor B
• -> Factor B converted by factor D
• -> C3bBb
• -> Stabilsation by Properdin
• -> C3bBbProperdin = c3 convertase
• -> lots of C3b
• -> C3bBbC3b
• -> C5b6789

Question 5

Loss of C1q, C1r and C1s results in what disease?

Answer 5

SLE

Question 6

Loss of C4 results in what diseases?

Answer 6

SLE

Glomerulonephritis

Question 7

Loss of C2 results in what diseases?

Answer 7

SLE
Vasculitis
GN
Recurrent pyogenic infections

Question 8

Loss of C3 results in what diseases?

Answer 8

Recurrent pyogenic infections
GN
Immune complex diseases

Question 9

Loss of alternate pathway components results in?

Answer 9

Neisseria infections

Question 10

Loos of terminal components results in?

Answer 10

Neisseria infections

Question 11

What is the role of C1 esterase inhibitor?

Answer 11

Binds to C1r-C1s

• -> dissociation from C1q
• -> controls classical pathway activation

Also binds MASP2 –> controls MBL pathway

Also inhibits C2 kinin
Also inhibits formation of FXIIa and kallikrein –> HMW kininogen –> inhibits bradykinin

Question 12

What is the disease caused by C1 esterase inhibitor deficiency?

Answer 12

Hereditary angiooedema
Both AD and acquired types
Due to reduced or dysfunctional inhibitor

Excessive formation of FXIIa and kallikrein

• -> bradykinin release
• -> oedema of mouth, larynx and GIT

Uncontrolled activation of C1q

• -> activation and consumption of C4 and C2
• -> C2 kinin

Question 13

Treatment of HAE?

Answer 13

Preventative:

• Anabolic steroids
• Tranexamic acid
• C1-inhibitor replacement

Acute:

• C1-inhibitor protein replacement
• Bradykinin-2 receptor antagonist - Icatibant