Antibacterial immunity

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

Signaling pattern recognition receptors of the innate immunity are the first to recognize pathogenic bacteria. These include:

• Toll-like receptors (TLR) — 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.

By means of which bactericidal substances does intracellular destruction of bacteria occur in the phagolysosome?

Intracellular destruction of bacteria in the phagolysosome occurs due to 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, OO*NOI).
• Cationic proteins — serprocidins, lysozyme, lactoferrin, BPI proteins.
• Acid hydrolases — myeloperoxidase, 5'-nucleotidase, β-glucuronidase.
• Bactericidal peptides — alpha and beta defensins, cathelicidins.

Bactericidal activity is also provided by local acidification of the medium to pH 4.5–5.0 due to V-ATPase activity.

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

To evade the immune response, bacteria use various antiphagocytic defense mechanisms leading to incomplete phagocytosis. The main strategies include:

• Antigen shielding — the capsule prevents opsonization and antibody recognition.
• Chemotaxis suppression — 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 aggression factors — production of enzymes that inactivate peroxide radicals.
• Phagosome destruction — lysis of the phagolysosome membrane to enter the cytoplasm.
• Apoptosis induction — triggering the death of the phagocytosing cell.

Which types of pathogenic bacteria are able to survive and multiply inside phagocytes?

Bacteria described in sources as exhibiting incomplete phagocytosis or intracellular survival have the ability to survive inside phagocytes or avoid intracellular digestion. 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.
• Francisellae — 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 inside the cell.
• Staphylococci — during incomplete phagocytosis, they can survive inside phagocytes, which is associated with persistent bacteremia and metastatic purulent foci.
• Causative agents of typhoid fever/acute intestinal infections — during incomplete phagocytosis, they can enter the blood with the development of bacteremia.

Which cytokines are secreted by Th1 lymphocytes for macrophage hyperactivation during intracellular infections?

To activate macrophages during intracellular infections, Th1 lymphocytes secrete the cytokines specified in the sources:

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

Also, during DTH following Th1 activation, the production of chemokines that recruit macrophages to the focus is described.

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 triggered by immunoglobulin G (IgG) classes that bind to pathogen antigens. The initiation of the classical pathway is marked by 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 called proteases. The production of these enzymes is a mechanism of enzymatic defense that allows pathogens to ignore or actively suppress immune defense factors, evade immune surveillance, and contribute to the chronization of the infection. The specific names of these proteases are not specified in the sources.