Complement System

Complement System

1. Activation

   • Classical
     • Occurs when there are antibodies present specific to a foreign antibody
       • E.g. antibodies bound to bacteria
     • C1q binds to specific antibodies and the activates complement
   • Mannose-binding Lectin
     • The MbL binds with mannose on bacteria
       • Mannose = PAMP
       • Mannose not present on host cells
   • Alternative
     • Spontaneously activates and binds to nearby membranes
       • Host cells have control proteins on their surface
         • Inhibits further complement activation
       • Bacterial cells don't have control proteins
         • Complement activated
     • Mediated by C3
     • Used to amplify complement response further
       • Positive feedback

2. Function

   • Lysis
     • Directly kill bacteria
     • MAC = membrane attack complex forms in membrane of bacteria
       • Barrel like structure
         • Made from C6 - C9
       • Many pores form, so water enters the bacteria and ions leave
         • Bacteria swells and bursts
   • Anaphylatoxins
     • Toxins that cause anaphylaxis
     • They are released
       • Blood vessels become leaky = oedema
       • Stimulates immune cells and mast cells
     • C3a, C4a, C5a etc.
   • Opsonisation
     • Opsonins bind to pathogen membranes
     • Phagocytes have complement receptors, which bind to opsonins on bacteria
       • Encourage phagocytosis

3. Series of soluble proteins in the blood

   • Not cells
   • Called C1 - C9

4. All methods of activation converge at the stage producing the enzyme C3 convertase

   • C3 convertase splits C3 into:
     • C3a
       • An anaphylatoxin
       • Increases inflammatory response
         • Stimulates mast cell degranulation
     • C3b
       • Acts as opsonin
       • Coats immune complexes to promote their removal by spleen
       • Leads to production of C5b
         • C5b is part of MAC