HIV/AIDS Warning: You are not logged in. Your IP address will be publicly visible if you make any edits. If you log in or create an account, your edits will be attributed to your username, along with other benefits.Anti-spam check. Do not fill this in! == Pathophysiology == {{Main|Pathophysiology of HIV/AIDS}} [[File:HIV and AIDS explained in a simple way.webm|thumb|upright=1.4|alt=video of AIDS explanation|HIV/AIDS explained in a simple way]] [[File:Hiv replication cycle.gif|thumb|upright=1.4|HIV replication cycle]] After the virus enters the body, there is a period of rapid [[viral replication]], leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles per milliliter of blood.<ref name=Piatak>{{cite journal | vauthors = Piatak M, Saag MS, Yang LC, Clark SJ, Kappes JC, Luk KC, Hahn BH, Shaw GM, Lifson JD | title = High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR | journal = Science | volume = 259 | issue = 5102 | pages = 1749β54 | date = March 1993 | pmid = 8096089 | doi = 10.1126/science.8096089 | bibcode = 1993Sci...259.1749P | s2cid = 12158927 }}</ref> This response is accompanied by a marked drop in the number of circulating [[T helper cell|CD4<sup>+</sup> T cells]]. The acute [[viremia]] is almost invariably associated with activation of [[cytotoxic T cell|CD8<sup>+</sup> T cells]], which kill HIV-infected cells, and subsequently with antibody production, or [[seroconversion]]. The CD8<sup>+</sup> T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4<sup>+</sup> T cell counts recover. A good CD8<sup>+</sup> T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.<ref name=Pantaleo1998>{{cite journal | vauthors = Pantaleo G, Demarest JF, Schacker T, Vaccarezza M, Cohen OJ, Daucher M, Graziosi C, Schnittman SS, Quinn TC, Shaw GM, Perrin L, Tambussi G, Lazzarin A, Sekaly RP, Soudeyns H, Corey L, Fauci AS | title = The qualitative nature of the primary immune response to HIV infection is a prognosticator of disease progression independent of the initial level of plasma viremia | journal = [[Proceedings of the National Academy of Sciences of the United States of America]] | volume = 94 | issue = 1 | pages = 254β58 | date = January 1997 | pmid = 8990195 | pmc = 19306 | doi = 10.1073/pnas.94.1.254 | bibcode = 1997PNAS...94..254P | doi-access = free }}</ref> Ultimately, HIV causes AIDS by depleting CD4<sup>+</sup> T cells. This weakens the immune system and allows [[opportunistic infection]]s. T cells are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4<sup>+</sup> T cell depletion differs in the acute and chronic phases.<ref name="pmid16679064">{{cite journal |vauthors=Hel Z, McGhee JR, Mestecky J |title=HIV infection: first battle decides the war |journal=Trends in Immunology |volume=27 |issue=6 |pages=274β81 |date=June 2006 |pmid=16679064 |doi=10.1016/j.it.2006.04.007}}</ref> During the acute phase, HIV-induced cell lysis and killing of infected cells by CD8<sup>+</sup> T cells accounts for CD4<sup>+</sup> T cell depletion, although [[apoptosis]] may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4<sup>+</sup> T cell numbers.<ref>{{cite book |first1=Deenan |last1=Pillay |first2=Anna Maria |last2=Genetti |first3=Robin A. |last3=Weiss |editor-first=Arie J. |editor-last=Zuckerman |display-editors=etal |title=Principles and practice of clinical virology |year=2007 |publisher=Wiley |location=Hoboken, NJ |isbn=978-0-470-51799-4 |page=905 |chapter=Human Immunodeficiency Viruses |chapter-url=https://books.google.com/books?id=4il2mF7JG1sC&pg=PA905 |edition=6th}}</ref> Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4<sup>+</sup> T cell loss occurs during the first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in the body.<ref name="pmid15365095">{{cite journal |vauthors=Mehandru S, Poles MA, Tenner-Racz K, Horowitz A, Hurley A, Hogan C, Boden D, Racz P, Markowitz M |title=Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract |journal=The Journal of Experimental Medicine |volume=200 |issue=6 |pages=761β70 |date=September 2004 |pmid=15365095 |pmc=2211967 |doi=10.1084/jem.20041196}}</ref> The reason for the preferential loss of mucosal CD4<sup>+</sup> T cells is that the majority of mucosal CD4<sup>+</sup> T cells express the [[CCR5]] protein which HIV uses as a [[co-receptor]] to gain access to the cells, whereas only a small fraction of CD4<sup>+</sup> T cells in the bloodstream do so.<ref name="pmid15365096">{{cite journal |vauthors=Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ, Nguyen PL, Khoruts A, Larson M, Haase AT, Douek DC |title=CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract |journal=The Journal of Experimental Medicine |volume=200 |issue=6 | pages=749β59 |date=September 2004 |pmid=15365096 |pmc=2211962 |doi=10.1084/jem.20040874}}</ref> A [[CCR5-Ξ32|specific genetic change]] that alters the CCR5 protein when present in both [[chromosome]]s very effectively prevents HIV-1 infection.<ref>{{cite journal |vauthors=Olson WC, Jacobson JM |title=CCR5 monoclonal antibodies for HIV-1 therapy |journal=Current Opinion in HIV and AIDS |volume=4 |issue=2 |pages=104β11 |date=March 2009 |pmid=19339948 |pmc=2760828 |doi=10.1097/COH.0b013e3283224015}}</ref> HIV seeks out and destroys CCR5 expressing CD4<sup>+</sup> T cells during acute infection.<ref name=Julio2011>{{cite book |editor-last=Aliberti |editor-first=Julio |title=Control of Innate and Adaptive Immune Responses During Infectious Diseases |publisher=Springer Verlag |location=New York |isbn=978-1-4614-0483-5 |page=145 |url=https://books.google.com/books?id=TKMpo5aINVIC&pg=PA145 |year=2011 |access-date=June 27, 2015 |archive-url=https://web.archive.org/web/20150924083412/https://books.google.com/books?id=TKMpo5aINVIC&pg=PA145 |archive-date=September 24, 2015 |url-status=live }}</ref> A vigorous immune response eventually controls the infection and initiates the clinically latent phase. CD4<sup>+</sup> T cells in mucosal tissues remain particularly affected.<ref name=Julio2011/> Continuous HIV replication causes a state of generalized immune activation persisting throughout the chronic phase.<ref name="pmid18161758">{{cite journal |vauthors=Appay V, Sauce D |title=Immune activation and inflammation in HIV-1 infection: causes and consequences |journal=The Journal of Pathology |volume=214 |issue=2 |pages=231β41 |date=January 2008 |pmid=18161758 |doi=10.1002/path.2276|s2cid=26830006 |doi-access=free }}</ref> Immune activation, which is reflected by the increased activation state of immune cells and release of pro-inflammatory [[cytokine]]s, results from the activity of several HIV [[gene product]]s and the immune response to ongoing HIV replication. It is also linked to the breakdown of the immune surveillance system of the gastrointestinal mucosal barrier caused by the depletion of mucosal CD4<sup>+</sup> T cells during the acute phase of disease.<ref name="pmid17115046">{{cite journal |vauthors=Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC |title=Microbial translocation is a cause of systemic immune activation in chronic HIV infection |journal=Nature Medicine |volume=12 |issue=12 |pages=1365β71 |date=December 2006 |pmid=17115046 |pmc=1717013 |doi=10.1038/nm1511}}</ref> Summary: Please note that all contributions to Christianpedia may be edited, altered, or removed by other contributors. If you do not want your writing to be edited mercilessly, then do not submit it here. 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