Antimicrobial Peptides: Defensins
Human defensins are endogenous peptides that play a key role in pathogen destruction. There are two main groups of these proteins:
- $\alpha$-defensins — comprise six studied types. They can be divided by their localization:
- HNP1–HNP4 (Human neutrophil peptide 1–4): known as "neutrophil peptides". They are stored directly in neutrophil granules and used to attack engulfed microbes.
- HD5 and HD6 (Human defensin 5, 6): expressed by epithelial cells. Their primary synthesis sites are the intestines and the reproductive tract, where they maintain barrier functions.
- $\beta$-defensins — currently, six types have been discovered and described, designated by the abbreviation HBD 1–6.
Complement System: Classical Pathway
The classical pathway is closely linked to adaptive immunity mechanisms because it depends on antibody production.
- Activation trigger: The process starts when an antigen-antibody complex forms on the pathogen surface (the most typical example being the binding of immunoglobulin G, IgG).
- Starting complex: Complement component C1 attaches to the free Fc fragments of the bound antibodies.
- Mechanism of action: Activated protein C1 acts as an enzyme, cleaving components C4 and C2. The C4 molecule is split into the departing C4a fragment and the membrane-bound C4b. Similarly, the C2 molecule is split into the departing C2b fragment and the binding C2a.
- Result: The fragments fixed to the membrane unite to form the C4b2a complex, known in immunology as the classical C3 convertase.
Complement System: Lectin Pathway
The lectin pathway largely duplicates the mechanism of the classical cascade, but it does not require antibodies.
- Activation trigger: The system responds to specific carbohydrate structures on the microbe — primarily mannose.
- Starting complex: Mannose-binding lectin (MBL) attaches to carbohydrates on the pathogen cell wall. It works alongside associated serine proteases MASP1 and MASP2 (mannan-binding lectin-associated serine proteases).
- Mechanism of action: MASP enzymes assume a role analogous to component C1, similarly attacking and cleaving C4 and C2 molecules.
- Result: The final assembly produces the exact same enzyme as in the classical pathway — the C4b2a complex.
Complement System: Alternative Pathway
The alternative pathway can operate autonomously, continuously maintaining a basal level of immune readiness.
- Activation trigger: The process begins with the spontaneous hydrolysis of component C3 in plasma or the presence of a pre-formed C3b fragment that covalently binds to the microbial surface.
- Involvement of additional factors: Factor B (B) binds to the membrane-bound C3b. It is then cleaved by factor D: the Ba fragment is released, while the Bb fragment remains part of the complex. To prevent the resulting structure from degrading, it is stabilized by the protein properdin (designated by the letter P).
- Result: The C3bBb complex is formed, which is called the alternative C3 convertase.