Editing Immune system (section)

=== Manipulation by pathogens ===
The success of any pathogen depends on its ability to elude host immune responses. Therefore, pathogens evolved several methods that allow them to successfully infect a host, while evading detection or destruction by the immune system.<ref name=Finlay>{{cite journal | vauthors = Finlay BB, McFadden G | s2cid = 15418509 | title = Anti-immunology: evasion of the host immune system by bacterial and viral pathogens | journal = Cell | volume = 124 | issue = 4 | pages = 767–82 | date = Feb 2006 | pmid = 16497587 | doi = 10.1016/j.cell.2006.01.034 | doi-access = free }}</ref> Bacteria often overcome physical barriers by secreting enzymes that digest the barrier, for example, by using a [[type II secretion system]].<ref>{{cite journal | vauthors = Cianciotto NP | title = Type II secretion: a protein secretion system for all seasons | journal = Trends in Microbiology | volume = 13 | issue = 12 | pages = 581–88 | date = Dec 2005 | pmid = 16216510 | doi = 10.1016/j.tim.2005.09.005 }}</ref> Alternatively, using a [[type III secretion system]], they may insert a hollow tube into the host cell, providing a direct route for proteins to move from the pathogen to the host. These proteins are often used to shut down host defenses.<ref>{{cite journal | vauthors = Winstanley C, Hart CA | title = Type III secretion systems and pathogenicity islands | journal = Journal of Medical Microbiology | volume = 50 | issue = 2 | pages = 116–26 | date = Feb 2001 | pmid = 11211218 | doi = 10.1099/0022-1317-50-2-116 }}</ref>

An evasion strategy used by several pathogens to avoid the innate immune system is to hide within the cells of their host (also called [[intracellular]] [[pathogenesis]]). Here, a pathogen spends most of its [[Biological life cycle|life-cycle]] inside host cells, where it is shielded from direct contact with immune cells, antibodies and complement. Some examples of intracellular pathogens include viruses, the [[foodborne illness|food poisoning]] bacterium ''[[Salmonella]]'' and the [[eukaryote|eukaryotic]] parasites that cause [[malaria]] (''[[Plasmodium]] spp.'') and [[leishmaniasis]] (''[[Leishmania]] spp.''). Other bacteria, such as ''[[Mycobacterium tuberculosis]]'', live inside a protective capsule that prevents [[lysis]] by complement.<ref>{{cite journal | vauthors = Finlay BB, Falkow S | title = Common themes in microbial pathogenicity revisited | journal = Microbiology and Molecular Biology Reviews | volume = 61 | issue = 2 | pages = 136–69 | date = Jun 1997 | doi = 10.1128/mmbr.61.2.136-169.1997 | pmid = 9184008 | pmc = 232605 }}</ref> Many pathogens secrete compounds that diminish or misdirect the host's immune response.<ref name=Finlay /> Some bacteria form [[biofilm]]s to protect themselves from the cells and proteins of the immune system. Such biofilms are present in many successful infections, such as the chronic ''[[Pseudomonas aeruginosa]]'' and ''[[Burkholderia cenocepacia]]'' infections characteristic of [[cystic fibrosis]].<ref>{{cite journal | vauthors = Kobayashi H | s2cid = 31788349 | title = Airway biofilms: implications for pathogenesis and therapy of respiratory tract infections | journal = Treatments in Respiratory Medicine | volume = 4 | issue = 4 | pages = 241–53 | year = 2005 | pmid = 16086598 | doi = 10.2165/00151829-200504040-00003 }}</ref> Other bacteria generate surface proteins that bind to antibodies, rendering them ineffective; examples include ''[[Streptococcus]]'' (protein G), ''[[Staphylococcus aureus]]'' (protein A), and ''[[Peptostreptococcus]] magnus'' (protein L).<ref>{{cite journal | vauthors = Housden NG, Harrison S, Roberts SE, Beckingham JA, Graille M, Stura E, Gore MG | title = Immunoglobulin-binding domains: Protein L from Peptostreptococcus magnus | journal = Biochemical Society Transactions | volume = 31 | issue = Pt 3 | pages = 716–18 | date = Jun 2003 | pmid = 12773190 | doi = 10.1042/BST0310716 | s2cid = 10322322| url = http://pdfs.semanticscholar.org/a2a4/223fb0694e0137c5c82d002e7e9e07b7143b.pdf | archive-url = https://web.archive.org/web/20190302214414/http://pdfs.semanticscholar.org/a2a4/223fb0694e0137c5c82d002e7e9e07b7143b.pdf | url-status = dead | archive-date = 2019-03-02 }}</ref>

The mechanisms used to evade the adaptive immune system are more complicated. The simplest approach is to rapidly change non-essential [[epitope]]s ([[amino acid]]s and/or sugars) on the surface of the pathogen, while keeping essential epitopes concealed. This is called [[antigenic variation]]. An example is HIV, which mutates rapidly, so the proteins on its [[viral envelope]] that are essential for entry into its host target cell are constantly changing. These frequent changes in antigens may explain the failures of [[vaccine]]s directed at this virus.<ref>{{cite journal | vauthors = Burton DR, Stanfield RL, Wilson IA | title = Antibody vs. HIV in a clash of evolutionary titans | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 42 | pages = 14943–48 | date = Oct 2005 | pmid = 16219699 | pmc = 1257708 | doi = 10.1073/pnas.0505126102 | bibcode = 2005PNAS..10214943B | doi-access = free }}</ref> The parasite ''[[Trypanosoma brucei]]'' uses a similar strategy, constantly switching one type of surface protein for another, allowing it to stay one step ahead of the antibody response.<ref>{{cite journal | vauthors = Taylor JE, Rudenko G | title = Switching trypanosome coats: what's in the wardrobe? | journal = Trends in Genetics | volume = 22 | issue = 11 | pages = 614–20 | date = Nov 2006 | pmid = 16908087 | doi = 10.1016/j.tig.2006.08.003 }}</ref> Masking antigens with host molecules is another common strategy for avoiding detection by the immune system. In HIV, the envelope that covers the [[virus|virion]] is formed from the outermost membrane of the host cell; such "self-cloaked" viruses make it difficult for the immune system to identify them as "non-self" structures.<ref>{{cite journal | vauthors = Cantin R, Méthot S, Tremblay MJ | title = Plunder and stowaways: incorporation of cellular proteins by enveloped viruses | journal = Journal of Virology | volume = 79 | issue = 11 | pages = 6577–87 | date = Jun 2005 | pmid = 15890896 | pmc = 1112128 | doi = 10.1128/JVI.79.11.6577-6587.2005 }}</ref>