Author: Shenzhou
Reviewed by: Shiye

  The immune system has an arsenal of defenses against pathogens. But pathogens have tricks of their own. By evading immune attack and surveillance, they can survive inside the body until an opportunity to spread appears. This is immune evasion.

  Viruses, bacteria, and parasites do not all pull off that escape in the same way.

  For viruses, immune evasion is a major reason infections persist and antiviral treatment fails. Their methods include latent infection, antigenic variation, and interference with immune function.

  One familiar strategy is antigenic variation, a common form of immune evasion among many RNA viruses. A change in the structure of a viral antigen can keep the body’s existing antibodies from binding to it effectively. The virus then escapes antibody-mediated neutralization or opsonization. Antigenic variation can also make an existing vaccine ineffective.

  Another strategy is latent infection. A virus hides in tissues or cells that the host immune system cannot easily reach or attack, and many viruses evade surveillance this way. Measles virus and herpesviruses, for example, can lie low in the central nervous system and avoid lymphocytes. In another form of latency, viral DNA is reverse-transcribed into cDNA inside the host cell and remains there either integrated or as a circular molecule. With normal immune function, the immune system still suppresses the virus in both cases, and the body shows no abnormality or disease. If immunity weakens, however, the virus reactivates, begins replicating again, and causes recurrent infection. HIV, for example, can enter latency after infecting a host cell. The latently infected cell expresses no HIV antigen and thus escapes the immune system’s pursuit.

  To clear a virus-infected cell, the immune system must recognize antigenic peptides presented on the target cell’s surface. Many viruses interfere with or block that presentation, disrupting the antiviral response by T cells. They may encode proteins that suppress antigenic-peptide production or reduce the expression of MHC class I molecules, hindering antigen processing and presentation.

  A cell can limit viral replication by undergoing apoptosis. Viruses counter with ways to interfere with apoptosis and improve their own reproduction. After invading a cell, some express growth-factor-like substances that inhibit apoptosis, strengthen cell survival, and extend the cell’s life, making programmed death less likely.

  Besides disrupting opsonization and varying their surface antigens, bacteria have one method viruses lack. Structural differences can help them withstand the host’s destructive and bactericidal defenses while creating favorable conditions for growth.

  A capsule, microcapsule, or similar structure can protect a bacterium from phagocytosis and from bactericidal substances in body fluids, allowing it to multiply inside the host. A familiar example is the mouse experiment comparing encapsulated and unencapsulated Streptococcus pneumoniae. Inject an unencapsulated strain, and the bacteria are readily engulfed and cleared. Inject an encapsulated strain, and the mice cannot eliminate it. The bacteria multiply rapidly; the mice soon become gravely ill and die.

  Finally, parasites supplement basic mechanisms such as antigenic variation with more intricate ways of dodging immune attack. One is antigenic disguise: a parasite covers itself in host antigens and avoids triggering an immune response. After schistosomes penetrate the skin, for example, they acquire the host’s glycoproteins and glycolipids and attach them to their own surfaces as camouflage against immune attack.

  A parasite may also express components resembling host antigens, a strategy called molecular mimicry. Plasmodium, for example, can use molecular mimicry to evade its host’s immune system.

  Some parasites live inside the host’s immune cells and survive by disrupting the normal function of the very cells that would kill them. Other tactics abound. A parasite may build a barrier that isolates it from the host immune response, or break down antibodies attached to its surface so they cannot activate complement. Either way, antibody-dependent, complement-mediated lysis fails.

  After a long history of coevolution, these evasive mechanisms and the host’s immune defenses have settled into a kind of balance.