Humoral factors of innate immunity

Antimicrobial peptides: Defensins

Human defensins are endogenous peptides that play a key role in pathogen destruction. Two main groups of these proteins are distinguished:

1. $\alpha$-defensins — comprise six studied types. They can be divided by their localization:
2. HNP1–HNP4 (Human neutrophil peptide 1–4): known as "neutrophil peptides". They are stored directly in neutrophil granules and used to attack engulfed microbes.
3. HD5 and HD6 (Human defensine 5, 6): expressed by epithelial cells. Their primary sites of synthesis are the intestine and reproductive tract organs, where they maintain barrier functions.

1. $\beta$-defensins — currently, six types have been discovered and described, designated by the abbreviation HBD 1–6.

Complement system: Classical pathway

The classical pathway (Classical pathway) is closely linked to adaptive immunity mechanisms since 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: The complement component C1 attaches to the free Fc fragments of the bound antibodies.
• Mechanism of action: The activated C1 protein acts as an enzyme, cleaving components C4 and C2. The C4 molecule splits into the departing C4a fragment and C4b, which fixes to the membrane. Similarly, the C2 molecule splits into C2b, which leaves the reaction zone, and the binding C2a.
• Result: The membrane-fixed fragments combine to form the C4b2a complex, which is known in immunology as the classical C3 convertase.

Complement system: Lectin pathway

The lectin pathway (Lectin pathway) largely duplicates the mechanism of the classical cascade, yet it does not require the presence of antibodies.

• Activation trigger: The system responds to specific carbohydrate structures of the microbe — primarily mannose.
• Starting complex: Mannose-binding lectin (MBL) attaches to carbohydrates on the pathogen wall. Working alongside it are associated serine proteases MASP1 and MASP2 (mannan-binding lectin-associated serine protease).
• Mechanism of action: MASP enzymes take on a role analogous to the C1 component. They similarly attack and cleave C4 and C2 molecules.
• Result: Ultimately, the exact same enzyme as in the classical pathway is assembled — the C4b2a complex.

Complement system: Alternative pathway

The alternative pathway (Alternative pathway) can operate autonomously, constantly maintaining a basal level of immune readiness.

• Activation trigger: The start is marked by spontaneous hydrolysis of component C3 in plasma or the presence of a pre-formed C3b fragment, which covalently binds to the microorganism's surface.
• Involvement of additional factors: Protein factor B (B) binds to the membrane-fixed C3b. Then, under the action of factor D, it is cleaved: the Ba fragment is released, while the Bb fragment remains part of the complex. To prevent the resulting structure from disintegrating, it is stabilized by the protein properdin (designated by the letter P).
• Result: The C3bBb complex is formed, which is named the alternative C3 convertase.

Class and exam questions

What else to study on this topic

• Mechanisms of the further complement cascade following C3 convertase formation
• Formation of the membrane attack complex (MAC)
• Biochemical mechanisms of bacterial destruction by alpha- and beta-defensins
• Specific functions of HBD 1–6 in nonspecific resistance
• Regulatory proteins and complement cascade inhibitors

Other topics in "Immunology"

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