1) The document discusses the complement cascade and its three activation pathways: the classical, lectin, and alternative pathways. It also discusses complement deficiency diseases. 2) Case A is about a man with meningitis whose lab results show low C5 levels. Low C5 would impair the membrane attack complex and increase risk of infection. 3) Case B is about a girl with swelling and abdominal pain whose labs show low C4 and C1 inhibitor. Low C1 inhibitor causes hereditary angioedema by impairing complement regulation and the kinin system.

1. Complement cascade
DEEPA BABIN

2. The multiple activities of the
complement system.

3. The complement cascade

4. Overview of the complement activation
pathways.

5. The Classical Pathway

6. The building of a C3 activation
complex

7. C3 Activation complex

8. The function of C3a

9. Membrane Attack complex

10. Alternative pathway

11. Overview

12. Complement Deficiency
Disease
 Cl inhibitor Hereditary angioneurotic edema
 Early components of SLE and other collagen
Classical pathway C1, Vascular diseases
C2,C4
 C3 and its regulatory Severe recurrent pyogenic
Protein C3b inactivator infections
 C5 to C8 Bacteremia, mainly with
Gram negative diplococci, toxoplasmosis
 C9 No particular disease

13. Pathologic effects of a normal
complement system
 - The immune complexes produced in
autoimmune diseases may bind to vascular
endothelium and kidney glomeruli and activate
complement (MAC generation).
 - It initiates the acute inflammatory responses that
destroy the vessel walls or glomeruli and lead to
thrombosis, ischemic damage to tissues, and
scarring.
 - Some of the late complement proteins
activateprothrombinases in the circulation that
initiate thrombosis.

14. CASE STUDIES-Case A
 Case A: A 23yr man complains of fever (102oF),
headache, neck stiffness and fatigue of 2 days duration.
Lumbar puncture shows increased pressure with cloudy
cerebrospinal fluid containing large numbers of
neutrophils, increased protein, decreased glucose and
gram negative diplococci. Laboratory studies show C5
(5th component of complement) levels at 18%and normal
levels of C2, C3 and C7. The patient recovers after
institution of intravenous antibiotic therapy.

15. ?
 Case A: Why would this patient be at increased
risk for developing bacterial meningitis?
What is the relationship among the three
pathways of complement activation and bacterial
clearance?
Would a defect in C2 alone place a patient at
increased risk of developing bacterial meningitis?
Explain

16. Case B
 Case B: A 14yr girl has a long history of
excessive swelling after mild traumatic injury.
During the past 2 years she has complained of 7
episodes of intermittent abdominal pain
sometimes accompanied with watery diarrhea.
Laboratory tests show decreased levels of C4 and
normal C3 levels. C1 inhibitor levels are 20% of
normal

17. ?
 What pathologic changes would explain this
patients symptoms?
What is the effect of defective C1 esterase levels
on complement system regulation?
What other inflammatory mediator systems are
effected by C1esterase inhibitor?
Why are these patients not at significant risk for
bacterial infection?