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Flashcards in Complement Deck (13):
1

Function of complement

Cytolysis - MAC complex

Opsonisation --> efficient uptake by APC

Initiate inflammatory response - anaphylatoxin release - C3a and C5a

Immune complex clearance

2

Classical pathway activation

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

3

Lectin Pathway activation

Activation of C4 and C2 by Mannin binding lectin

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

C4bC2b --> C3b
--> C4bC2bC3b
--> C5b6789

4

Alternate Pathway activation

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

5

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

SLE

6

Loss of C4 results in what diseases?

SLE
Glomerulonephritis

7

Loss of C2 results in what diseases?

SLE
Vasculitis
GN
Recurrent pyogenic infections

8

Loss of C3 results in what diseases?

Recurrent pyogenic infections
GN
Immune complex diseases

9

Loss of alternate pathway components results in?

Neisseria infections

10

Loos of terminal components results in?

Neisseria infections

11

What is the role of C1 esterase inhibitor?

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

12

What is the disease caused by C1 esterase inhibitor deficiency?

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

13

Treatment of HAE?

Preventative:
- Anabolic steroids
- Tranexamic acid
- C1-inhibitor replacement

Acute:
- C1-inhibitor protein replacement
- Bradykinin-2 receptor antagonist - Icatibant