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A diagram with 3 steps. The first step states: leukocytes in the blood respond to chemical attractants released by pathogens and chemical signals from nearby injured cells. An injury to the surface of the skin is labeled: injured/infected cells secrete chemical signals into the blood. Pathogens are present in the wound. Neutrophils and monocytes are in the blood stream; and the outside of the vessel is labeled capillary epithelial cells. A resident macrophage engulfs the pathogens and releases proinflammatory chemotactic cytokines. The second step states: the leukocytes squeeze between the cells of the capillary wall as they follow the chemical signals to where they are most concentrated (positive chemotaxis). The leukocytes emigrate to the site of injury and infection. The chemical signals present include C5a and cytokines. The third panel states: Within the damaged tissue, neutrophils release chemicals that break apart pathogens. Monocytes differentiate into macrophages. Neutrophils and macrophages phagocytize pathogens and cellular debris. Neutrophils release cytotoxic chemicals from granules into tissue.
Damaged cells and macrophages that have ingested pathogens release cytokines that are proinflammatory and chemotactic for leukocytes. In addition, activation of complement at the site of infection results in production of the chemotactic and proinflammatory C5a. Leukocytes exit the blood vessel and follow the chemoattractant signal of cytokines and C5a to the site of infection. Granulocytes such as neutrophils release chemicals that destroy pathogens. They are also capable of phagocytosis and intracellular killing of bacterial pathogens.
  • Explain the role of adhesion molecules in the process of extravasation.

Pathogen recognition

As described in the previous section, 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 ( [link] ). 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.

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.
Practice MCQ 3

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Source:  OpenStax, Microbiology. OpenStax CNX. Nov 01, 2016 Download for free at http://cnx.org/content/col12087/1.4
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