Antimicrobial Defense: Complement System and Interferons
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VII. Antimicrobial Substances
A. The Complement System
The complement system is a vital component of the nonspecific defense system. It consists of a group of serum proteins that activate one another in a cascade to destroy invading microorganisms.
1. Evasion Mechanisms
Some bacteria evade destruction by the complement system through:
- Capsules
- Surface lipid–carbohydrate complexes
- Enzymatic destruction of C5a
2. Functional Groups
Complement proteins form a membrane attack complex that perforates the plasma membrane, causing cell lysis. They are subdivided into three functional groups:
- C1: Recognition
- C4, C2, C3: Activation
- C5–C9: Attack (complement fixation)
3. Complement System Pathways
- Classic Pathway: Antibody binding to pathogen antigens activates the cascade. While antibodies do not destroy pathogens directly, they label targets for attack and stimulate opsonization (enhancing phagocytosis).
- Lectin Pathway: Host proteins (lectins) bind to pathogen cell surface carbohydrates (mannans).
- Alternative Pathway: Complement proteins bind directly to pathogen surface molecules.
All three pathways result in the activation of C3 protein by cleaving it into C3a and C3b subunits via the enzyme C3 convertase:
- C3a: Enhances chemotaxis and acts as an inflammatory mediator.
- C3b: Activates C5 by cleaving it into C5a and C5b subunits.
4. Membrane Attack Complex (MAC)
C5b and C6–C9 insert into the bacterial cell membrane, creating a large pore. This causes an osmotic influx of H2O, leading to lysis and cell death.
B. Interferons
Interferons are polypeptides produced by virus-infected cells that provide short-acting, nonspecific resistance to viral infection in nearby cells. There are three primary types:
- IFN-alpha: Stimulates natural killer (NK) cells.
- IFN-beta: Stimulates the maturation of B and T lymphocytes and mediates inflammation.
- IFN-gamma: Inhibits cancer cells, stimulates B lymphocytes, activates macrophages, and enhances phagocytosis.