21.5: Phagocytosis
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- Ying Liu
- City College of San Francisco
Learning Objectives
- Identify the steps in the process of phagocytosis
- Distinguish a phagosome from a lysosome
- Describe the mechanisms of how phagocytes kill pathogens
Pathogen Degradation
Once pathogen recognition and attachment occurs, the pathogen is engulfed in a vesicle and brought into the internal compartment of the phagocyte in a process called phagocytosis (Figure \(\PageIndex{3}\)). PRRs can aid in phagocytosis by first binding to the pathogen’s surface, but phagocytes are also capable of engulfing nearby items even if they are not bound to specific receptors. To engulf the pathogen, the phagocyte forms a pseudopod that wraps around the pathogen and then pinches it off into a membrane vesicle called a phagosome . Acidification of the phagosome (pH decreases to the range of 4–5) provides an important early antibacterial mechanism. The phagosome containing the pathogen fuses with one or more lysosomes, forming a phagolysosome . Formation of the phagolysosome enhances the acidification, which is essential for activation of pH-dependent digestive lysosomal enzymes and production of hydrogen peroxide and toxic reactive oxygen species. Lysosomal enzymes such as lysozyme, phospholipase, and proteases digest the pathogen. Other enzymes are involved a respiratory burst. During the respiratory burst, phagocytes will increase their uptake and consumption of oxygen, but not for energy production. The increased oxygen consumption is focused on the production of superoxide anion, hydrogen peroxide, hydroxyl radicals, and other reactive oxygen species that are antibacterial.
In addition to the reactive oxygen species produced by the respiratory burst, reactive nitrogen compounds with cytotoxic (cell-killing) potential can also form. For example, nitric oxide can react with superoxide to form peroxynitrite, a highly reactive nitrogen compound with degrading capabilities similar to those of the reactive oxygen species. Some phagocytes even contain an internal storehouse of microbicidal defensin proteins (e.g., neutrophil granules). These destructive forces can be released into the area around the cell to degrade microbes externally. Neutrophils, especially, can be quite efficient at this secondary antimicrobial mechanism.
Once degradation is complete, leftover waste products are excreted from the cell in an exocytic vesicle. However, it is important to note that not all remains of the pathogen are excreted as waste. Macrophages and dendritic cells are also antigen-presenting cells involved in the specific adaptive immune response. These cells further process the remains of the degraded pathogen and present key antigens (specific pathogen proteins) on their cellular surface. This is an important step for stimulation of some adaptive immune responses, as will be discussed in more detail in the next chapter.
Query \(\PageIndex{1}\)
Query \(\PageIndex{1}\)
When Phagocytosis Fails
Although phagocytosis successfully destroys many pathogens, some are able to survive and even exploit this defense mechanism to multiply in the body and cause widespread infection. Protozoans of the genus Leishmania are one example. These obligate intracellular parasites are flagellates transmitted to humans by the bite of a sand fly. Infections cause serious and sometimes disfiguring sores and ulcers in the skin and other tissues (Figure \(\PageIndex{4}\)). Worldwide, an estimated 1.3 million people are newly infected with leishmaniasis annually. 1
Salivary peptides from the sand fly activate host macrophages at the site of their bite. The classic or alternate pathway for complement activation ensues with C3b opsonization of the parasite. Leishmania cells are phagocytosed, lose their flagella, and multiply in a form known as an amastigote (Leishman-Donovan body) within the phagolysosome. Although many other pathogens are destroyed in the phagolysosome, survival of the Leishmania amastigotes is maintained by the presence of surface lipophosphoglycan and acid phosphatase. These substances inhibit the macrophage respiratory burst and lysosomal enzymes. The parasite then multiplies inside the cell and lyses the infected macrophage, releasing the amastigotes to infect other macrophages within the same host. Should another sand fly bite an infected person, it might ingest amastigotes and then transmit them to another individual through another bite.
There are several different forms of leishmaniasis. The most common is a localized cutaneous form of the illness caused by L. tropica , which typically resolves spontaneously over time but with some significant lymphocyte infiltration and permanent scarring. A mucocutaneous form of the disease, caused by L. viannia brasilienfsis , produces lesions in the tissue of the nose and mouth and can be life threatening. A visceral form of the illness can be caused by several of the different Leishmania species. It affects various organ systems and causes abnormal enlargement of the liver and spleen. Irregular fevers, anemia, liver dysfunction, and weight loss are all signs and symptoms of visceral leishmaniasis. If left untreated, it is typically fatal.
Key Concepts and Summary
- Phagocytes degrade pathogens through phagocytosis , which involves engulfing the pathogen, killing and digesting it within a phagolysosome , and then excreting undigested matter.
Footnotes
- 1 World Health Organization. “Leishmaniasis.” 2016. http://www.who.int/mediacentre/factsheets/fs375/en/ .