Immunogenetics Lecture 6: The Complement System

The Complement System

• The complement system is part of the innate immune response, providing immediate defense against infection.
• It consists of over 30 proteins that work together to eliminate pathogens from the body.

Alternative Pathway

• The alternative pathway is initiated by the spontaneous activation of C3, producing C3a and C3b.
• C3b attaches to the surface of invading microbes, recruiting other complement proteins to form a cascade.
• This pathway is triggered by the presence of invading microbes and results in the activation of C3.

Activation of Complement Proteins

• The three complement activation pathways have different triggers but all result in the activation of C3, producing C3a and C3b.
• C3b binds to the surface of the target cell, leading to the formation of the membrane attack complex (MAC).
• The MAC punches through the cell membrane of the invading pathogen, causing it to burst.

Protective Outcomes

• The complement system provides the following protective outcomes:
  • Opsonization: coating of a pathogen by an opsonin, making it easier for phagocytic cells to recognize and engulf.
  • Inflammation: attracting white blood cells to the site of infection.
  • Chemotaxis: guiding white blood cells to the site of infection.
  • Cytolysis: lysis of the infected cell.

Opsonization

• Opsonins from the complement cascade include C1q, C3b, and C4b.
• Additional opsonins include mannose-binding proteins and antibodies.

Anaphylatoxins

• C3a and C5a are anaphylatoxins with potent proinflammatory functions.
• They activate mast cells, causing degranulation and the release of inflammatory chemical signals.
• C5a is a potent chemoattractant for neutrophils and other white blood cells.

Membrane Attack Complex (MAC)

• The complement proteins C6, C7, C8, and C9 assemble into a MAC.
• The MAC forms pores in the membranes of gram-negative bacteria, leading to cell lysis and death.
• The MAC is only effective against gram-negative bacteria and not gram-positive bacteria.

Cytokines

• Cytokines are soluble proteins that act as communication signals between cells.

Classical Pathway

• The classical pathway is initiated by the binding of a specific antibody to a pathogen, forming an antibody-antigen complex.
• The C1 complex is activated, leading to the recruitment and activation of the remaining classical pathway complement proteins.

Lectin Activation Pathway

• The lectin activation pathway is triggered by the binding of mannose-binding lectin to carbohydrates on the microbial surface.
• It is similar to the classical pathway but does not require the presence of antibodies.