Author: Shenzhou
Reviewed by: Shiye

  The immune system has many ways to resist invasion by a wide range of pathogens. Pathogens, however, have strategies of their own: they evade immune attack so they can survive in the body and wait for an opportunity to spread. This is known as immune evasion.

  Viruses, bacteria, and parasites do not all evade immunity in the same way.

  For viruses, immune evasion is a major cause of persistent infection and treatment failure. Their tactics include establishing latent infections, changing their antigens, and disrupting immune function.

  One of the better-known strategies is antigenic variation, which is common among many RNA viruses. When the structure of a viral antigen changes, antibodies that the body has already produced may no longer bind to it effectively. The virus can then escape antibody-mediated neutralization or opsonization. Antigenic variation may also render an existing vaccine ineffective.

  Another strategy is latent infection: a virus takes refuge in tissues or cells that the host immune system has difficulty reaching and attacking. Many viruses evade immune surveillance this way. Measles virus and herpesviruses, for example, can persist in the central nervous system, beyond the easy reach of lymphocytes. In another form of latency, the viral genome is reverse-transcribed into cDNA and remains inside host cells either integrated into the host genome or as a circular molecule. When immunity is intact, the immune system keeps the virus in check, and the host shows no abnormalities or disease. When immunity weakens, however, the virus may reactivate, resume replication, and cause recurrent infection. After HIV infects a host cell, for example, it can enter latency; latently infected cells do not express HIV antigens and can therefore escape immune detection.

  To eliminate virus-infected cells, the immune system must recognize antigenic peptides displayed on the surfaces of target cells. Many viruses interfere with or even block this antigen presentation, thereby disrupting the antiviral T-cell response. A virus may encode proteins that suppress the production of antigenic peptides or reduce the expression of MHC class I molecules, impairing antigen processing and presentation.

  Cells can curb viral replication by undergoing apoptosis. Viruses, in turn, have evolved ways to interfere with apoptosis and thereby reproduce more effectively. After entering a cell, some viruses express growth-factor-like molecules that inhibit apoptosis, bolster cell survival, and prolong its lifespan, making programmed cell death less likely.

  In addition to disrupting opsonization and changing surface antigens, bacteria have an evasive strategy unavailable to viruses. Their physical structures can help them withstand the host’s destructive and bactericidal defenses while creating a favorable environment for growth.

  Some bacteria have a capsule, microcapsule, or similar structure that protects them from phagocytosis and from bactericidal substances in body fluids, allowing them to multiply inside the host. A familiar example is the mouse experiment comparing encapsulated and unencapsulated strains of Streptococcus pneumoniae. When mice are injected with an unencapsulated strain, the bacteria are readily engulfed and cleared. With an encapsulated strain, however, the mice cannot eliminate the bacteria. The bacteria multiply rapidly, and the mice soon become gravely ill and die.

  Finally, parasites have more intricate ways of avoiding immune attack in addition to basic mechanisms such as antigenic variation. One is antigenic disguise: some parasites cloak themselves in host antigens so that they do not trigger an immune response. After schistosomes penetrate the skin, for example, they acquire host glycoproteins and glycolipids and coat their own surfaces with them, shielding themselves from immune attack.

  Parasites can also escape immune attack by expressing components that resemble host antigens, a strategy known as molecular mimicry. Plasmodium, for example, can use molecular mimicry to evade the host immune system.

  Some parasites live directly inside host immune cells and evade immunity by disrupting the normal function of the cells that would otherwise kill them. Parasites use many other tactics as well: some build barriers that isolate them from the host immune response, while others break down antibodies attached to their surfaces, preventing complement activation and thereby disabling antibody-dependent, complement-mediated lysis.

  The interplay between these evasive mechanisms and the host’s immune defenses settles into a kind of balance after a long history of coevolution.