Complement System

• What is the role of the complement system in immunology?

  It amplifies the inflammatory response to destroy and clear foreign antigens.
• How does the complement system tag invaders for clearance?

  By opsonizing and directing the adaptive immune system to the site of inflammation.
• In what form do complement proteins circulate in the blood?

  In biologically inactive form.
• What are zymogens in the context of complement proteins?

  Inactive precursors that are converted into active enzymes in a precise order.
• What is the role of serine proteases in the complement system?

  They have enzymatic activities that are crucial for complement activation.
• What housekeeping roles does the complement system perform?

  It assists antibodies in the destruction of antigens.
• What types of cellular debris does the complement system recognize?

  Apoptotic cells and immune complexes.
• What is the end product of the complement system's action?

  Lysis of the cell.
• What are the main functions of the complement system in host defense?

  • Opsonization (enhancement of phagocytosis)
  • Chemotaxis (movement of cells towards inflammation)
  • Lysis of bacterial and mammalian cells
  • Stimulation of inflammatory response
• How does the complement system interface between innate and adaptive immunity?

  • Augmentation of antibody response
  • Enhancement of immunologic memory
• What is the role of the complement system in waste disposal?

  • Clearance or removal of immune complexes from tissues
• Where are most plasma complement proteins synthesized?

  In the liver.
• Which complement components are produced by interstitial epithelial cells?

  C1 components.
• Where is Factor D produced?

  In adipose tissue.
• What additional sources contribute to early complement components?

  Monocytes and macrophages.
• What is the classical pathway in the complement system?

  The main antibody-directed mechanism for triggering complement activation.
• Which immunoglobulin classes can activate the classical pathway?

  IgM, IgG1, IgG2, and IgG3.
• Why is IgM considered the most efficient in activating the classical pathway?

  Because it has multiple binding sites.
• Which immunoglobulin class is not included in the classical pathway activation?

  IgG4.
• What substances can initiate the classical cascade?

  CRP, viruses, mycoplasmas, protozoa, and gram-negative bacteria.
• What are the three stages of the classical pathway in the complement system?

  1. Initiation or recognition: C1 binds to antigen-antibody complex.
  2. Activation unit: Production of C5 convertase.
  3. Membrane attack complex (MAC): End product is cell lysis.
• What is the function of C1q in the complement system?

  It binds to the Fc region of IgM and IgG.
• What happens after C1q binds to the Fc region of antibodies?

  C1r activates C1s.
• What does C1s do when activated?

  It cleaves C2 and C4.
• What are the products of cleaving C4 and C2?

  C4 forms C4a and C4b; C2 forms C2a and C2b.
• How is C3 convertase formed in the classical pathway?

  C4b and C2a combine to form C3 convertase (C4b2a).
• What happens when C3 binds to C3 convertase?

  It is cleaved into C3a and C3b.
• What is the role of C3b in the complement system?

  It binds to C3 convertase to form C5 convertase (C4b2a3b).
• What happens when C5 binds to C5 convertase?

  It is cleaved into C5a and C5b.
• What does C5b do in the complement system?

  It combines with C6, C7, C8, and C9 to form the membrane attack complex (C5b6789).
• What is the function of C9 in the membrane attack complex?


  It polymerizes to cause cell lysis.
• What is the lectin pathway in the complement system?

  • Activated by recognition of surface moieties on pathogens.
  • Mannose Binding Lectin (MBL) binds to mannose on microbial surfaces.
  • MBL initiates cleavage of C4 and C2, similar to the classical pathway.
• What happens when mannose binding lectin binds to a microbe?

  MASP1 and MASP2 are activated.
• What does MASP2 do in the lectin pathway?

  It initiates the cleavage of C4 and C2.
• What are the steps in the lectin pathway after MBL binds to a microbe?

  1. MASP1 and MASP2 are activated.
  2. MASP2 cleaves C4 and C2.
  3. C4b and C2a combine to form C3 convertase (C4b2a).
  4. C3 binds to C3 convertase and is cleaved into C3a and C3b.
  5. C3b binds to C3 convertase to form C5 convertase (C4b2a3b).
  6. C5 binds to C5 convertase and is cleaved into C5a and C5b.
  7. C5b combines with C6, C7, C8, and C9 to form the membrane attack complex.
• What is the alternative pathway in the complement system?


  • Also known as the bypass pathway.
  • Does not require antibodies for activation.
  • Involves factors like C3, Factor B, Factor D, and Properdin.
• What triggers the alternative pathway?

  Bacterial cell walls containing lipopolysaccharide, fungal cell walls, and virally infected cells.
• What is the role of Factor H in the alternative pathway?

  It is the principal soluble regulator of the alternative pathway.
• What are the steps in the alternative pathway after C3(H2O) recognizes activating surfaces?

  1. C3(H2O) binds to Factor B.
  2. Factor B is cleaved by Factor D into Ba and Bb.
  3. Bb binds to C3b to form C3 convertase (C3bBb).
  4. C3 binds to C3 convertase and is cleaved into C3a and C3b.
  5. C3b binds to C3 convertase to form C5 convertase (C3bBb3b).
  6. C5 binds to C5 convertase and is cleaved into C5a and C5b.
  7. C5b combines with C6, C7, C8, and C9 to form the membrane attack complex.
• What are the differences between the classical and alternative pathways?

  • Classical pathway requires antibodies and has a recognition unit (C1).
  • Alternative pathway does not require antibodies and lacks a recognition unit.
  • Classical pathway requires calcium; alternative pathway bypasses this requirement.