Complement

Question 1

Complement

Answer 1

Complement refers to a group of serum and cell-surface proteins with specific functions

These functions include lysis of target cells, as opsonins and regulation of inflammatory and immune responses

Question 2

Complement outcomes

Answer 2

Complement is in place to achieve:

• triggering/ amplification of inflammation
• clearance of immune complexes
• microbial killing
• development of antibody responses

Question 3

Factor C3b

Answer 3

Although there are several mechanisms by which complement can be activated, they all result in the formation of factor C3b

C3b attaches to pathogens (opsonisation) to increase phagocytosis and also helps form the membrane attack complex (MAC)

Question 4

Common pathway

Answer 4

1. C3 convertase cleaves C3 into C3a and C3b
2. C3b joins the C3 convertase complex to form C5 convertase
3. Attachment of further factors to this complex, leads to the formation of MAC

Question 5

Classical pathway activation

Answer 5

The classical pathway is activated by antibodies (IgG/ IgM) and C-reactive protein

1. The antibody/antigen complex binds C1, this activates the proteolytic activity of C1
2. C4 binds to C1 and is cleaved into C4a and C4b, C4b is covalently linked to the microbe
3. C2 binds C4b and is cleaved into C2a and C2b, C2a remainly linked to the complex
4. C4bC2a forms C3 convertase

Question 6

Alternative pathway activation

Answer 6

C3 is a relatively unstable molecule and so undergoes spontaneous cleavage into C3a and C3b

Question 7

Mannose binding lectin pathway activation

Answer 7

Mannose binding lectin binds carbohydrates on microbes

MBL is structurally similar to C1

C4 and C2 are then cleaved in the same manner as the classical pathway

Question 8

Other outcomes of complement

Answer 8

C3a, C4a and C5a are all released

However, they are all inflammatory mediators in their own right

They stimulate the respiratory burst in neutrophils, trigger mast cells and stimulate chemotaxis