Innate immunity

What exactly do innate immunity cells recognize upon encountering a pathogen?

Innate immune cells do not recognize individual molecules, but rather common structural features — pathogen-associated and danger-associated molecular patterns.

• Pathogen-associated molecular patterns (PAMP) are conserved microbial structures foreign to the host (lipopolysaccharide, peptidoglycan, flagellin, viral RNA).
• Damage-associated molecular patterns (DAMP) are endogenous molecules released by the host's own cells during stress, injury, or cell death (heat shock proteins, uric acid).

Recognition of these patterns allows the immune system to detect danger long before clinical manifestations of infection.

What receptors do innate immune cells use to recognize pathogenicity patterns?

Innate immune cells recognize pathogenicity patterns using pattern recognition receptors (PRRs).

Based on their localization, PRRs are subdivided into:

• Membrane receptors — TLRs, C-type lectins, scavenger receptors, integrins.
• Intracellular / cytosolic receptors — NOD-like, RIG-like, DAI; the inflammasome also belongs to cytosolic sensors.
• Secreted receptors — pentraxins, collectins, complement system components, ficolins.

Functionally, PRRs provide pathogen recognition, signal transduction initiation, and synthesis of effector molecules.

What are the pathways of complement system activation?

There are three main pathways of complement system activation:

• Classical pathway.
• Lectin pathway.
• Alternative pathway.

For the complement system as a whole, the triggering mechanisms are the antigen-antibody complex and the microorganism itself. The lectin pathway can be initiated by the binding of mannose-binding lectin to microbial carbohydrates.

All three pathways converge at the stage of enzymatic complex formation — convertases. Convertases cleave the C3 component, and the ultimate goal of all pathways is the assembly of the membrane attack complex (MAC) on the target cell surface.

Which innate immune cells are professional phagocytes?

Innate immune cells involved in phagocytosis include:

• Monocytes.
• Macrophages.
• Neutrophils.
• Eosinophils.
• Basophils.

Macrophages perform phagocytosis and are potent producers of pro-inflammatory and regulatory cytokines. Neutrophils are microphages: they phagocytose bacteria and small tissue debris.

Dendritic cells belong to the antigen-presenting cells of innate immunity; they capture antigens via pinocytosis, less frequently via phagocytosis, and effectively activate naive T cells.

What stages does the phagocytosis process consist of?

Traditionally, 8 sequential stages of phagocytosis are distinguished:

• Chemotaxis — directed movement of the phagocyte toward the target.
• Adhesion — establishment of contact and attachment of the phagocyte to the object.
• Membrane activation — preparation for engulfment.
• Immersion — wrapping around the object.
• Phagosome formation — closure of the membrane and internalization.
• Phagolysosome fusion — fusion of the phagosome and lysosome.
• Killing and digestion — intracellular digestion of the object.
• Release of degradation products.

In a broader classification, these processes are combined into 4 main stages: approach, recognition and adhesion, engulfment, and destruction.

Through what mechanisms does the normal microflora provide its barrier function?

The normal microflora provides barrier function through colonization resistance—the ability to prevent pathogen colonization due to antagonistic activity. The main defense mechanisms include:

• Competition — competing with foreign flora for nutrients due to high biological potential.
• Acid production — synthesis of lactic, acetic, and other short-chain fatty acids, as well as secondary bile acids.
• Synthesis of antimicrobial substances — production of antibiotic-like substances, bacteriocins, and microbial lysozyme.

In addition, the microflora performs an immunostimulatory function: its antigens constantly stimulate the immune system.