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How Pathogens Evade the Immune System

Pathogens are microorganisms that cause disease. These can be bacteria, viruses, or parasites. While the human body has many strategies to fight infection by pathogenic organisms, many of these disease-causing microbes have developed sophisticated strategies to evade the immune system. A bacterial pathogen capable of hiding in a host cell initially enters by endocytosis. Here, the pathogen induces the host cell to take it up by phagocytosis and ends up in a phagosome. These intracellular pathogens, which live inside host cells as unwanted guests, gain temporary safe harbor within the phagosome. This is because the antibodies within phagocytic cells will not penetrate the host cell. Once inside the phagosome, intracellular pathogens have 3 options to avoid being killed by the fusion of the phagosome with the lysosome which is full of digestive enzymes. A single pathogenic species can use only one of these 3 mechanisms. First, some pathogens can simply escape from the phagosome before fusion occurs. Pathogens, such as shigella and listeria, use this strategy and then undergo unrestricted growth in the cytoplasm of the host cell. These pathogen form actin tails that allow them to move within the cell and even into adjacent cells, where they continue the infection. These microbes can spread from cell to cell without ever encountering the extracellular environment where they would be vulnerable to attack. Alternatively, other pathogens, such as salmonella, escape intracellular death by modifying the phagosome membrane or other cytoplasmic components, preventing the fusion of the phagosome and lysosome. Salmonella interact serovar typhi, which cause typhoid fever, prevents phagosome-lysosome fusion after it invades intestinal cells. Salmonella exits the intestinal cell and invades awaiting macrophages. Within the phagosome, the bacteria reproduce producing a large number of salmonella bacteria. From there, macrophages spread these bacteria through the circulatory system. A 3rd way of escaping death inside a cell, performed by bacteria such as Coxiella, is simply to tolerate phago-lysosome fusion. In this “grin and bear it” strategy, Coxiella bacteria reproduce in inclusion bodies in the acidic environment of the phago-lysosome environment.