Editing Tuberculosis (section)

== Pathogenesis ==
[[File:Miliary_TB_of_the_spleen.jpg|thumb|The spleen in a patient with miliary tuberculosis showing granulomas (tubercles)]]
TB infection begins when a M. tuberculosis bacterium, inhaled from the air, penetrates the lungs and reaches the [[Pulmonary alveolus|alveoli]]. Here it encounters an [[alveolar macrophage]], a cell which is part of the body's [[immune system]], which attempts to destroy it.<ref name="Ahmad-2022">{{Cite journal |last1=Ahmad |first1=Faraz |last2=Rani |first2=Anshu |last3=Alam |first3=Anwar |last4=Zarin |first4=Sheeba |last5=Pandey |first5=Saurabh |last6=Singh |first6=Hina |last7=Hasnain |first7=Seyed Ehtesham |last8=Ehtesham |first8=Nasreen Zafar |date=2022-05-06 |title=Macrophage: A Cell With Many Faces and Functions in Tuberculosis |journal=Frontiers in Immunology |volume=13 |doi=10.3389/fimmu.2022.747799 |doi-access=free |issn=1664-3224 |pmc=9122124 |pmid=35603185}}</ref> However, M. tuberculosis is able to neutralise and colonise the macrophage, leading to persistent infection.<ref name="Ahmad-2022" />

The defence mechanism of the macrophage begins when a foreign body, such as a bacterial cell, binds to [[Immune receptor|receptors]] on the surface of the macrophage. The macrophage then stretches itself around the bacterium and engulfs it. <ref>{{cite journal |vauthors=Hampton MB, Vissers MC, Winterbourn CC |date=February 1994 |title=A single assay for measuring the rates of phagocytosis and bacterial killing by neutrophils |url=http://www.jleukbio.org/cgi/pmidlookup?view=long&pmid=8301210 |journal=J. Leukoc. Biol. |volume=55 |issue=2 |pages=147–52 |doi=10.1002/jlb.55.2.147 |pmid=8301210 |s2cid=44911791 |archive-url=https://archive.today/20121228084302/http://www.jleukbio.org/cgi/pmidlookup?view=long&pmid=8301210 |archive-date=December 28, 2012 |access-date=December 19, 2014}}</ref> Once inside this macrophage, the bacterium is trapped in a compartment called a [[phagosome]]; the phagosome subsequently merges with a [[lysosome]] to form a [[phagolysosome]].<ref name="Rohde-2007">{{Cite journal |last1=Rohde |first1=Kyle |last2=Yates |first2=Robin M. |last3=Purdy |first3=Georgiana E. |last4=Russell |first4=David G. |date=2007 |title=Mycobacterium tuberculosis and the environment within the phagosome |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1600-065X.2007.00547.x |journal=Immunological Reviews |language=en |volume=219 |issue=1 |pages=37–54 |doi=10.1111/j.1600-065X.2007.00547.x |pmid=17850480 |issn=1600-065X}}</ref> The lysosome is an [[organelle]] which contains digestive enzymes; these are released into the phagolysosome and kill the invader.<ref>{{Cite book |last1=Delves |first1=P. J. |last2=Martin |first2=S. J. |last3=Burton |first3=D. R. |last4=Roit |first4=I. M.  |title=Roitt's Essential Immunology |edition=11th |year=2006 |publisher=Blackwell Publishing |location=Malden, MA |isbn=978-1-4051-3603-7 |pages=6–7}}</ref>

The M. tuberculosis bacterium is able to subvert the normal process by inhibiting the development of the phagosome and preventing it from fusing with the lysosome.<ref name="Rohde-2007" /> The bacterium is able to survive and replicate within the phagosome; it will eventually destroy its host macrophage, releasing progeny bacteria which spread the infection.<ref name="Ahmad-2022" />

In the next stage of infection, [[Macrophage|macrophages]], [[Epithelioid cell|epithelioid cells]], [[T cell|lymphocytes]] and [[Fibroblast|fibroblasts]] aggregate to form a [[granuloma]], which surrounds and isolates the infected macrophages.<ref name="Ahmad-2022" /> This does not destroy the tuberculosis bacilli, but contains them, preventing spread of the infection to other parts of the body. They are nevertheless able to survive within the granuloma.<ref name="Ahmad-2022" /><ref name="Silva-Miranda-2012">{{Cite journal |last1=Silva Miranda |first1=Mayra |last2=Breiman |first2=Adrien |last3=Allain |first3=Sophie |last4=Deknuydt |first4=Florence |last5=Altare |first5=Frederic |date=2012 |title=The Tuberculous Granuloma: An Unsuccessful Host Defence Mechanism Providing a Safety Shelter for the Bacteria? |journal=Journal of Immunology Research |language=en |volume=2012 |issue=1 |pages=139127 |doi=10.1155/2012/139127 |doi-access=free |issn=2314-7156 |pmc=3395138 |pmid=22811737}}</ref> In tuberculosis, the granuloma contains [[Necrosis|necrotic]] tissue at its centre, and appears as a small white nodule, also known as a ''[[tubercle]]'', from which the disease derives its name.<ref name="Alzayer-2025">{{Citation |last1=Alzayer |first1=Zainab |title=Primary Lung Tuberculosis |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK567737/ |access-date=2025-03-26 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=33620814 |last2=Al Nasser |first2=Yasser}}</ref>

Granulomas are most common in the lung, but they can appear anywhere in the body. As long as the infection is contained within granulomas, there are no outward symptoms and the infection is latent.<ref name="Alzayer-2025" /> However, if the immune system is unable to control the infection, the disease can progress to active TB, which can cause significant damage to the lungs and other organs.<ref name="Silva-Miranda-2012" />

If TB bacteria gain entry to the blood stream from an area of damaged tissue, they can spread throughout the body and set up many foci of infection, all appearing as tiny, white tubercles in the tissues.<ref>{{cite book| vauthors = Crowley LV |title=An introduction to human disease: pathology and pathophysiology correlations|year=2010|publisher=Jones and Bartlett|location=Sudbury, MA|isbn=978-0-7637-6591-0|page=374|url=https://books.google.com/books?id=TEiuWP4z_QIC&pg=PA374|edition=8th|url-status=live|archive-url=https://web.archive.org/web/20150906193726/https://books.google.com/books?id=TEiuWP4z_QIC&pg=PA374|archive-date=6 September 2015}}</ref> This severe form of TB disease, most common in young children and those with HIV, is called [[miliary tuberculosis]].<ref>{{cite book| vauthors = Harries AD, Maher D, Graham S |title=TB/HIV a Clinical Manual|year=2005|publisher=World Health Organization (WHO)|location=Geneva|isbn=978-92-4-154634-8|page=75|url=https://books.google.com/books?id=8dfhwKaCSxkC&pg=PA75|edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20150906195514/https://books.google.com/books?id=8dfhwKaCSxkC&pg=PA75|archive-date=6 September 2015}}</ref> People with this disseminated TB have a high fatality rate even with treatment (about 30%).<ref name="Habermann-2008">{{cite book| vauthors = Habermann TM, Ghosh A |title=Mayo Clinic internal medicine: concise textbook|year=2008|publisher=Mayo Clinic Scientific Press|location=Rochester, MN|isbn=978-1-4200-6749-1|page=789|url=https://books.google.com/books?id=YJtodBwNxokC&pg=PA789|url-status=live|archive-url=https://web.archive.org/web/20150906190055/https://books.google.com/books?id=YJtodBwNxokC&pg=PA789|archive-date=6 September 2015}}</ref><ref>{{cite journal | vauthors = Jacob JT, Mehta AK, Leonard MK | title = Acute forms of tuberculosis in adults | journal = The American Journal of Medicine | volume = 122 | issue = 1 | pages = 12–17 | date = January 2009 | pmid = 19114163 | doi = 10.1016/j.amjmed.2008.09.018 }}</ref>

In many people, the infection waxes and wanes. Tissue destruction and necrosis are often balanced by healing and [[fibrosis]].<ref name="Grosset-2003">{{cite journal |vauthors=Grosset J |date=March 2003 |title=Mycobacterium tuberculosis in the extracellular compartment: an underestimated adversary |journal=Antimicrobial Agents and Chemotherapy |volume=47 |issue=3 |pages=833–36 |doi=10.1128/AAC.47.3.833-836.2003 |pmc=149338 |pmid=12604509}}</ref> Affected tissue is replaced by scarring and cavities filled with caseous necrotic material. During active disease, some of these cavities are joined to the air passages ([[bronchi]]) and this material can be coughed up. It contains living bacteria and thus can spread the infection. Treatment with appropriate [[antibiotic]]s kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.<ref name="Grosset-2003" />