Antibacterial Immunity

Frequently asked questions

Which innate immunity receptors are the first to recognize pathogenic bacteria?

Pathogenic bacteria are first recognized by signaling pattern-recognition receptors of the innate immune system. These include:

• Toll-like receptors (TLRs) — located on the cell surface and in endosomal membranes.
• NOD-like receptors (NOD1, NOD2) — cytosolic sensors that recognize bacterial peptidoglycans in the cytoplasm.

Interaction with these receptors triggers a cascade of reactions to produce immune defense factors.

Which bactericidal substances mediate intracellular destruction of bacteria in the phagolysosome?

Intracellular destruction of bacteria in the phagolysosome occurs through oxygen-dependent and oxygen-independent bactericidal factors. These include:

• Reactive oxygen species (O2•-, H2O2, OH•) — formed as a result of the respiratory burst.
• Reactive nitrogen species (NO, ONOO⁻).
• Cationic proteins — serprocidins, lysozyme, lactoferrin, BPI proteins.
• Acid hydrolases — myeloperoxidase, 5'-nucleotidase, β-glucuronidase.
• Bactericidal peptides — α- and β-defensins, cathelicidins.

Bactericidal activity is also supported by local medium acidification down to pH 4.5–5.0 due to V-ATPase activity.

What antiphagocytic defense mechanisms do bacteria use to escape the immune response?

To evade the immune response, bacteria utilize diverse antiphagocytic defense mechanisms leading to frustrated/incomplete phagocytosis. The main strategies include:

• Antigen masking — the capsule prevents opsonization and antibody recognition.
• Suppression of chemotaxis — synthesis of substances that reduce phagocyte migration.
• Blocking intracellular digestion — preventing the fusion of the lysosome with the phagosome and resistance to lysosomal enzymes.
• Neutralization of aggressive factors — production of enzymes that inactivate peroxide radicals.
• Phagosome destruction — lysis of the phagolysosomal membrane to enter the cytoplasm.
• Induction of apoptosis — triggering the death of the phagocytosing cell.

Which pathogenic bacteria are capable of surviving and multiplying inside phagocytes?

Bacteria capable of surviving inside phagocytes or avoiding intracellular digestion exhibit incomplete phagocytosis or intracellular survival. These include:

• Mycobacteria of tuberculosis and leprosy — capable of surviving inside phagocytes when bactericidal systems are insufficient; for mycobacteria, blockade of phagosome-lysosome fusion and inhibition of lysosomal enzymes are described.
• Francisellets (Francisella) — facultative intracellular parasites capable of avoiding digestion in phagocytes, blocking lysis in the phagolysosome, migrating into the macrophage cytoplasm, and multiplying there.
• Listeria — cause incomplete phagocytosis, exit the phagosome into the cytosol, and replicate intracellularly.
• Staphylococci — upon incomplete phagocytosis, can survive inside phagocytes, which is associated with persistent bacteremia and metastatic purulent foci.
• Causative agents of typhoid fever / acute intestinal infections — upon incomplete phagocytosis, can enter the bloodstream, developing bacteremia.

Which cytokines do Th1 lymphocytes secrete to hyperactivate macrophages during intracellular infections?

To activate macrophages during intracellular infections, Th1 lymphocytes secrete the following cytokines:

• Interferon-gamma (IFN-γ) — activates macrophages and enhances their microbicidal activity.
• Interleukin-2 (IL-2).
• Tumor necrosis factor (TNF).
• GM-CSF.

Also, during delayed-type hypersensitivity (DTH) reactions following Th1 activation, chemokine production is described, which recruits macrophages to the focus.

Through which pathway is the complement system activated upon antibody binding to the bacterial surface?

Upon antibody binding to the bacterial surface, complement activation occurs via the classical pathway. This process is initiated by immunoglobulin G (IgG) classes binding to pathogen antigens. The start of the classical pathway is the activation of the C1 component. As a result of the cascade, bacteria are opsonized by complement components (C3b, iC3b) and the membrane attack complex is formed, ultimately leading to pathogen lysis.

What specific enzymes do bacteria secrete to destroy antibodies and complement components?

To destroy antibodies and complement components, bacteria secrete specific enzymes — proteases. The production of these enzymes is one of the enzymatic defense mechanisms that allows pathogens to ignore or actively suppress immune defense factors, escaping immune surveillance and promoting chronicization of the infectious process.

Which complement system components act as chemoattractants?

Directed movement of phagocytes (chemotaxis) is stimulated by the activated complement fragments C5a and C3a.

How do secretory immunoglobulins A (sIgA) work?

They reside on mucous membranes and block the adhesion (attachment) of bacteria to epithelial cells, preventing colonization.

What happens in case of a deficiency of IgG1, IgG3, or complement component C3?

Their deficiency sharply reduces the efficiency of phagocytosis because the critical process of bacterial cell opsonization is disrupted.