The Pathogen Recognition

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A cell with three receptors. The lipopeptide receptor binds lipopeptides; the flagelin receptor binds flagelin and the peptidoglycan receptor binds peptidoglycans. A fourth receptor (the nucleic acid receptor which binds to nucleic acids) is found on the membrane of the phagosome. All four receptors have an arrow pointing to the nucleus which contains DNA. An arrow pointing out reads: production and secretion of antiviral interferons and other cytokines.
Phagocytic cells contain pattern recognition receptors (PRRs) capable of recognizing various pathogen-associated molecular patterns (PAMPs). These PRRs can be found on the plasma membrane or in internal phagosomes. When a PRR recognizes a PAMP, it sends a signal to the nucleus that activates genes involved in phagocytosis, cellular proliferation, production and secretion of antiviral interferons and proinflammatory cytokines, and enhanced intracellular killing.

Source: OpenStax Microbiology

OpenStax Microbiology

Opsonization of pathogens by antibody; complement factors C1q, C3b, and C4b; and lectins can assist phagocytic cells in recognition of pathogens and attachment to initiate phagocytosis. However, not all pathogen recognition is opsonin dependent. Phagocytes can also recognize molecular structures that are common to many groups of pathogenic microbes. Such structures are called pathogen-associated molecular patterns (PAMPs). Common PAMPs include the following:

  • peptidoglycan, found in bacterial cell walls;
  • flagellin, a protein found in bacterial flagella;
  • lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria;
  • lipopeptides, molecules expressed by most bacteria; and
  • nucleic acids such as viral DNA or RNA.

Like numerous other PAMPs, these substances are integral to the structure of broad classes of microbes.

The structures that allow phagocytic cells to detect PAMPs are called pattern recognition receptors (PRRs). One group of PRRs is the toll-like receptors (TLRs), which bind to various PAMPs and communicate with the nucleus of the phagocyte to elicit a response. Many TLRs (and other PRRs) are located on the surface of a phagocyte, but some can also be found embedded in the membranes of interior compartments and organelles. These interior PRRs can be useful for the binding and recognition of intracellular pathogens that may have gained access to the inside of the cell before phagocytosis could take place. Viral nucleic acids, for example, might encounter an interior PRR, triggering production of the antiviral cytokine interferon.

In addition to providing the first step of pathogen recognition, the interaction between PAMPs and PRRs on macrophages provides an intracellular signal that activates the phagocyte, causing it to transition from a dormant state of readiness and slow proliferation to a state of hyperactivity, proliferation, production/secretion of cytokines, and enhanced intracellular killing. PRRs on macrophages also respond to chemical distress signals from damaged or stressed cells. This allows macrophages to extend their responses beyond protection from infectious diseases to a broader role in the inflammatory response initiated from injuries or other diseases.

Source:

Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/microbiology

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