Complement System

Question 1

Classical Pathway

Answer 1

Antibody:Antigen Complex

1- Antibody:Antigen Complex is formed and causes a conformational change on the Fc region of the antibody
2- Conformational change exposes a site that can be bound by first complement of classical pathway (C1).
3- 2 C1q globular heads bind to either pentameric IgM or two IgG molecules (requires IgG to be in high conentrations).
4- Once bound, C1r will be activated
5- Once C1r is activated it will activate C1s which will then be able to cleave complement proteins.

Question 2

Lectin Pathway

Answer 2

Lectin binding to pathogen surfaces

Same as the Classical Pathway but you have MBL (binding to mannose- FUNGI) and ficolins (Binding to oligosaccharides). They will also have MASP-1 and MASP-2

• MBL/ficolins are equivalent to C1q
• MASP-1 equivalent to C1r
• MASP-2 equivalent to C1s

Question 3

Progression of Classical and Lectin Pathway

Answer 3

1- Activated complexes cleave C4 into C4a and C4b.
2-C4b will deposit on the surface of the microorganism and bind C2.
3- C1s/MASP-2 will cleave C2 into C2a and C2b.
4-Complex C4b2a will form (C3 convertase) which will stay on the surface of the microorganism and cleave C3.
5- C3 convertase will cleave C3 into C3a and C3b. (One convertase can cleave 1000’s of C3 molecules).
6- C3b will join the C3 convertase complex and you will have C4b2a3b complex which is a C5 convertase.
7- C5 convertase will cleave C5 into C5a and C5b.
*Soluble C5a will join soluble C3a and produce local inflammatory response
*C5b will be part of final phase of complement activation MAC (Membrane attack complex) with C6,7,8,9.

Question 4

Membrane Attack Complex (MAC)

Answer 4

Important for NISSERIA! (gram - organisms). Can’t attack gram + organisms.

Question 5

C1INH

Answer 5

Inhibits C1 by dissociating C1r and C1s. Prevent’s overactivation

Question 6

C1INH deficiency

Answer 6

Failure to regulate C1. Results in systematic inflammation and edema

Question 7

CD59

Answer 7

Prevents the assembly of MAC

Question 8

CD59 Deficiency

Answer 8

Would result in inefficient Nisseria clearing. Also would prevent MAC from not forming and would lead to RBC lysis over night since that is how the system clears Ig:Ag complexes

Question 9

Immune complex clearing

Answer 9

RBC’s have CR1 receptor that bind complexes via C3b. The RBC will then carry the complex to the liver or the spleen where phagocytic cells remove the complexes from RBC surfaces.

Question 10

soluble C5a

Answer 10

Chemotaxis of neutrophils, basophils, eosinophils and monocytes

Question 11

soluble C3a, C4a and C5a

Answer 11

Anaphylatoxins- bind to mast cells and basophils. Trigger histamine release and increase vascular permeability.

Question 12

Opsonization via C3b

Answer 12

Phagocytic leukocytes have C3b receptor (C1R). When antigen is coated in C3b, it helps with ingestion of the particle. C5a also helps by stimulating the cells to ingest the C3b coated antigens.