15-13 Phagocytes can detect pathogens and move toward them

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• Phagocytes detect microbes by the presence of N-formylated peptides, activated complement proteins and the mediators of inflammation.
• Phagocytes attach to microbes using opsonins, such as IgG and the complement protein C3b. In the absence of opsonins, phagocytes can still attach to target microbes nonspecifically, but the process is not as efficient.

The presence of an infecting microbe sets into motion a number of host responses, one of them being inflammation. This in turn upregulates adhesion of phagocytes to blood vessel walls that allow the migration of phagocytes across vascular walls. Once inside an infected tissue, phagocytes must then detect the location of a microbe, which can be signaled in a number of ways.

1. Many microbial proteins contain N-formyl methionine at their amino terminal end, while eukaryotic proteins do not. Certain N-formylated bacterial peptides serve as chemoattractants for phagocytes.
2. The binding of antibodies to antigens triggers the classic complement pathway with subsequent release of C3a and C5a. These proteins are also chemoattractants for phagocytes.
3. The complement cascade also induces an inflammatory response, whose mediators of inflammation also draw phagocytes to the area.

From these three examples, it is obvious that the body creates a number of strong signals in response to microbial invasion, and that these signals quickly draw phagocytes to the area of infection. The rapid removal of microbes is critical in preventing a disease and having multiple attractants insures a swift reaction.

Attachment

The phagocyte must then attach to the target microorganism. Without assistance, this can be a somewhat inefficient task for the phagocytes and they are not effective killers of pathogens. Phagocytes have over 40 specific types of receptors on their cell surfaces. Some of these receptors are for chemoattractants that draw phagocytes to an area; others recognize molecules that enhance the binding of phagocytes to their targets. This enhancement of binding is termed opsonization and macromolecules that bind to a microbe and increase the efficiency of phagocytosis are opsonins. Opsonins provide molecular handles for the phagocyte to grab onto. Several different macromolecules can serve as opsonins for phagocytes. IgG antibodies have a site on their constant region that can react with an antibody binding receptor on phagocytes. This phagocyte-binding region is masked in a free antibody, but becomes accessible to phagocytes when the antibody binds to antigen. Initially, masking this site prevents free antibody from binding to phagocytes. The complement protein C3b can also serve as an opsonin. Whether triggered by the classic or alternative pathway, C3b eventually binds to the membrane surface of the complement-activating microbe. Phagocytes contain a C3b receptor, which binds to C3b and thus to the complement-triggering microbe. Opsonization of bacteria greatly increases the rate of attachment and ingestion by phagocytes. Bacteria in the blood are quickly cleared only if they are bound by opsonins.

In the absence of opsonins, phagocytes are still capable of binding to microorganisms by a mechanism that can be thought of as nonspecific attachment. This nonspecific attachment probably involves electrostatic or hydrophobic attraction between the phagocyte and microorganism. It is also possible for the phagocyte to physically trap the microbe against a tissue surface and initiate ingestion--a mechanism called surface phagocytosis. These nonspecific mechanisms of attachment are probably important early in infection to slow the microbe's progress until opsonins are available to speed up phagocytosis.

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