Editing Lymph node (section)

== Structure ==
[[File:Lymphknoten (Schwein).jpg|thumb|240px|Cross-section of a lymph node with sections labelled.1) Capsule;   2) Subcapsular sinus;  3) [[Germinal centre]];  4) Lymphoid nodule;  5) Trabeculae|alt=]]
Lymph nodes are kidney or oval shaped and range in size from 2&nbsp;mm to 25&nbsp;mm on their long axis, with an average of 15&nbsp;mm.<ref>{{cite book |last1=Ioachim |first1=Harry L. |title=Lymph Node Pathology |date=1994 |publisher=J. B. Lippincott Company |isbn=9780397508075 |page=3 |edition=Second |url=https://archive.org/details/lymphnodepatholo02edioac/page/3/ |access-date=17 October 2022}}</ref>

Each lymph node is surrounded by a fibrous capsule (made of collagenous connective tissue<ref>{{Cite web |last=Rijnberk |first=A. |date=2009 |title=Medical History and Physical Examination in Companion Animals |url=https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/lymph-node#:~:text=Each%20lymph%20node%20is%20surrounded,surrounded%20by%20a%20lymph%20sinus.}}</ref>), which extends inside a lymph node to form [[trabecula]]e.<ref name=Wheaters2013>{{cite book |last1=Young |first1=Barbara |last2=O'Dowd |first2=Geraldine |last3=Woodford |first3=Phillip | name-list-style = vanc |title=Wheater's functional histology: a text and colour atlas.|publisher=Elsevier |location=Philadelphia |date=2013|isbn=9780702047473 |edition=6th|pages=209–210}}</ref> The substance of a lymph node is divided into the outer ''cortex'' and the inner ''medulla''.<ref name=Wheaters2013 /> These are rich with cells.<ref name="Grays2016">{{Cite book |title=Gray's anatomy : the anatomical basis of clinical practice|year=2016|isbn=9780702052309|editor=Standring, Susan|edition=41st|location=Philadelphia|pages=73–4|section=Lymphoid tissues|oclc=920806541}}</ref> The [[Hilum (anatomy)|hilum]] is an indent on the concave surface of the lymph node where lymphatic vessels leave and blood vessels enter and leave.<ref name="Grays2016" />

Lymph enters the convex side of a lymph node through multiple '''afferent lymphatic vessels''', and from there, it flows into a series of sinuses. Upon entering the lymph node, lymph first passes into a space beneath the capsule known as the '''subcapsular sinus''', then moves into the '''cortical sinuses'''. After traversing the cortex, lymph collects in the '''medullary sinuses'''. Finally, all of these sinuses drain into the '''efferent lymphatic vessels''', which carry the lymph away from the node, exiting at the hilum on the concave side.

=== Location ===
{{See also|List of lymph nodes of the human body}}
Lymph nodes are present throughout the body, are more concentrated near and within the trunk, and are divided into groups.<ref name="Grays2016" /> There are about 450 lymph nodes in the adult.<ref name="Grays2016" /> Some lymph nodes can be felt when enlarged (and occasionally when not), such as the [[axillary lymph nodes]] under the arm, the [[cervical lymph nodes]] of the head and neck and the [[inguinal lymph nodes]] near the groin crease. Most lymph nodes lie within the trunk adjacent to other major structures in the body - such as the [[paraaortic lymph nodes]] and the [[tracheobronchial lymph nodes]]. The lymphatic drainage patterns are different from person to person and even asymmetrical on each side of the same body.<ref>{{Cite web|last=Themes|first=U. F. O.|date=2018-01-06|title=Lymphatic Anatomy and Clinical Implications|url=https://entokey.com/lymphatic-anatomy-and-clinical-implications/|access-date=2020-09-21|website=Ento Key|language=en-US}}</ref><ref>{{Cite journal |last1=Pan |first1=Wei-Ren |last2=Wang |first2=De-Guang |date=2013 |title=Historical review of lymphatic studies in the head and neck |url=https://www.woundsinternational.com/uploads/resources/content_11242.pdf |journal=Journal of Lymphoedema |language=en |publisher=WoundsGroup |volume=8 |access-date=21 September 2020 |archive-date=30 July 2021 |archive-url=https://web.archive.org/web/20210730072220/https://www.woundsinternational.com/uploads/resources/content_11242.pdf |url-status=dead }}</ref>

There are no lymph nodes in the [[central nervous system]], which is separated from the body by the [[blood–brain barrier]]. Lymph from the [[meningeal lymphatic vessels]] in the CNS drains to the [[deep cervical lymph node]]s.<ref name="Dupont">{{cite journal | vauthors = Dupont G, Schmidt C, Yilmaz E, Oskouian RJ, Macchi V, de Caro R, Tubbs RS | title = Our current understanding of the lymphatics of the brain and spinal cord | journal = Clinical Anatomy | volume = 32 | issue = 1 | pages = 117–121 | date = January 2019 | pmid = 30362622 | doi = 10.1002/ca.23308 | s2cid = 53102520 | doi-access =  }}</ref> However, the CNS does innervate lymph node by [[Sympathetic nervous system|sympathetic nerves]].  These regulate [[Lymphocyte|lymphocyte proliferation and migration]], [[Antibody|antibody secretion]], [[Blood|blood perfusion]], and [[Cytokine|inflammatory cytokine production]].<ref name="z657">{{cite journal |last1=Cleypool |first1=Cindy G. J. |last2=Mackaaij |first2=Claire |last3=Lotgerink Bruinenberg |first3=Dyonne |last4=Schurink |first4=Bernadette |last5=Bleys |first5=Ronald L. A. W. |date=2021 |title=Sympathetic nerve distribution in human lymph nodes |journal=Journal of Anatomy |publisher=Wiley |volume=239 |issue=2 |pages=282–289 |doi=10.1111/joa.13422 |issn=0021-8782 |doi-access=free|pmid=33677834 |pmc=8273593 }}</ref>

===Size===
{|class="wikitable"
|+[[cutoff (value)|Upper limit]] of lymph node sizes in adults
|-
| Generally || 10&nbsp;mm<ref name="GaneshalingamKoh2009">{{cite journal|last1=Ganeshalingam|first1=Skandadas|last2=Koh|first2=Dow-Mu|title=Nodal staging|journal=Cancer Imaging|volume=9|issue=1|pages=104–111|year=2009|issn=1470-7330|doi=10.1102/1470-7330.2009.0017|pmid=20080453|pmc=2821588}}</ref><ref name="Schmidt JúniorRodrigues2007">{{cite journal|last1=Schmidt Júnior|first1=Aurelino Fernandes|last2=Rodrigues|first2=Olavo Ribeiro|last3=Matheus|first3=Roberto Storte|last4=Kim|first4=Jorge Du Ub|last5=Jatene|first5=Fábio Biscegli|title=Distribuição, tamanho e número dos linfonodos mediastinais: definições por meio de estudo anatômico|journal=Jornal Brasileiro de Pneumologia|volume=33|issue=2|year=2007|pages=134–140|issn=1806-3713|doi=10.1590/S1806-37132007000200006|pmid=17724531|doi-access=free}}</ref>
|-
| Inguinal || 10<ref name=Torabi2004>{{cite journal | vauthors = Torabi M, Aquino SL, Harisinghani MG | title = Current concepts in lymph node imaging | journal = Journal of Nuclear Medicine | volume = 45 | issue = 9 | pages = 1509–18 | date = September 2004 | pmid = 15347718 }}</ref> – 20&nbsp;mm<ref>{{cite web|url=http://bestpractice.bmj.com/best-practice/monograph/838/diagnosis/step-by-step.html|title=Assessment of lymphadenopathy|website=[[BMJ Best Practice]]|access-date=2017-03-04}} Last updated: Last updated: Feb 16, 2017</ref>
|-
| [[Pelvis]] || 10&nbsp;mm for ovoid lymph nodes, 8&nbsp;mm for rounded<ref name=Torabi2004/>
|-
!colspan=2|[[Neck]]
|-
| Generally (non-retropharyngeal) || 10&nbsp;mm<ref name=Torabi2004/><ref name=Saba2016>[https://books.google.com/books?id=q7v1CwAAQBAJ&pg=PA432 Page 432] in: {{cite book|title=Image Principles, Neck, and the Brain|author=Luca Saba|publisher=CRC Press|year=2016|isbn=9781482216202}}</ref>
|-
| [[Jugulodigastric lymph node]]s || 11mm<ref name=Torabi2004/> or 15&nbsp;mm<ref name=Saba2016/>
|-
| Retropharyngeal || 8&nbsp;mm<ref name=Saba2016/>
* Lateral retropharyngeal: 5&nbsp;mm<ref name=Torabi2004/>
|-
!colspan=2|[[Mediastinum]]
|-
| [[Mediastinum]], generally || 10&nbsp;mm<ref name=Torabi2004/>
|-
| Superior mediastinum and high paratracheal || 7mm<ref name="SharmaFidias2004"/>
|-
| Low paratracheal and subcarinal || 11&nbsp;mm<ref name="SharmaFidias2004">{{cite journal|last1=Sharma|first1=Amita|last2=Fidias|first2=Panos|last3=Hayman|first3=L. Anne|last4=Loomis|first4=Susanne L.|last5=Taber|first5=Katherine H.|last6=Aquino|first6=Suzanne L.|title=Patterns of Lymphadenopathy in Thoracic Malignancies|journal=RadioGraphics|volume=24|issue=2|year=2004|pages=419–434|issn=0271-5333|doi=10.1148/rg.242035075|pmid=15026591|s2cid=7434544}}</ref>
|-
!colspan=2| Upper abdominal
|-
| Retrocrural space || 6&nbsp;mm<ref name="DorfmanAlpern1991">{{cite journal|last1=Dorfman|first1=R E|last2=Alpern|first2=M B|last3=Gross|first3=B H|last4=Sandler|first4=M A|title=Upper abdominal lymph nodes: criteria for normal size determined with CT.|journal=Radiology|volume=180|issue=2|year=1991|pages=319–322|issn=0033-8419|doi=10.1148/radiology.180.2.2068292|pmid=2068292}}</ref>
|-
| Paracardiac || 8&nbsp;mm<ref name="DorfmanAlpern1991"/>
|-
| Gastrohepatic ligament || 8&nbsp;mm<ref name="DorfmanAlpern1991"/>
|-
| Upper paraaortic region || 9&nbsp;mm<ref name="DorfmanAlpern1991"/>
|-
| Portacaval space || 10&nbsp;mm<ref name="DorfmanAlpern1991"/>
|-
| Porta hepatis || 7&nbsp;mm<ref name="DorfmanAlpern1991"/>
|-
| Lower paraaortic region || 11&nbsp;mm<ref name="DorfmanAlpern1991"/>
|}

===Subdivisions{{Anchor|cortex|medulla}}===
[[File:Dark, light, mantle and marginal zones of a secondary follicle.png|230px|thumb|Histology of a normal [[lymphoid follicle]], showing dark, light, mantle and marginal zones]]
A lymph node is divided into compartments called ''nodules'' (or lobules), each consisting of a region of cortex with combined follicle B cells, a paracortex of T cells, and a part of the nodule in the medulla.<ref name="Willard-Mack" /> The substance of a lymph node is divided into the outer ''cortex'' and the inner ''medulla''.<ref name=Wheaters2013 /> The cortex of a lymph node is the outer portion of the node, underneath the capsule and the subcapsular sinus.<ref name=Willard-Mack/> It has an outer part and a deeper part known as the ''paracortex''.<ref name="Willard-Mack">{{cite journal | vauthors = Willard-Mack CL | title = Normal structure, function, and histology of lymph nodes | journal = Toxicologic Pathology | volume = 34 | issue = 5 | pages = 409–24 | date = 25 June 2016 | pmid = 17067937 | doi = 10.1080/01926230600867727 | doi-access = free }}</ref> The outer cortex consists of groups of mainly inactivated B cells called follicles.<ref name="Grays2016" /> When activated, these may develop into what is called a [[germinal centre]].<ref name="Grays2016" /> The deeper paracortex mainly consists of the [[T cell]]s.<ref name="Grays2016" /> Here the T-cells mainly interact with [[dendritic cell]]s, and the reticular network is dense.<ref name="katakai">{{cite journal | vauthors = Katakai T, Hara T, Lee JH, Gonda H, Sugai M, Shimizu A | title = A novel reticular stromal structure in lymph node cortex: an immuno-platform for interactions among dendritic cells, T cells and B cells | journal = International Immunology | volume = 16 | issue = 8 | pages = 1133–42 | date = August 2004 | pmid = 15237106 | doi = 10.1093/intimm/dxh113 | doi-access = free }}</ref>

The medulla contains large blood vessels, sinuses and medullary cords that contain antibody-secreting plasma cells. There are fewer cells in the medulla.<ref name="Grays2016" />

The '''medullary cords''' are cords of lymphatic tissue, and include [[plasma cell]]s, macrophages, and B cells.

=== Cells ===
In the lymphatic system a lymph node is a [[Lymphatic system#Structure|secondary lymphoid organ]].<ref name="Grays2016" /> Lymph nodes contain [[lymphocyte]]s, a type of [[white blood cell]], and are primarily made up of [[B cell]]s and [[T cells]].<ref name="Grays2016" /> B cells are mainly found in the outer cortex where they are clustered together as [[follicular B cell]]s in lymphoid follicles, and T cells and [[dendritic cells]] are mainly found in the ''paracortex''.{{sfn|Davidson's|2018|p=67}}

There are fewer cells in the medulla than the cortex.<ref name="Grays2016" /> The medulla contains plasma cells, as well as [[macrophage]]s which are present within the medullary sinuses.{{sfn|Davidson's|2018|p=67}}

As part of the reticular network, there are [[follicular dendritic cells]] in the B cell follicle and [[fibroblastic]] [[reticular cell]]s in the T cell cortex. The reticular network provides structural support and a surface for adhesion of the dendritic cells, macrophages and lymphocytes. It also allows exchange of material with blood through the [[high endothelial venules]] and provides the growth and regulatory factors necessary for activation and maturation of immune cells.<ref name=kaldjian>{{cite journal | vauthors = Kaldjian EP, Gretz JE, Anderson AO, Shi Y, Shaw S | title = Spatial and molecular organization of lymph node T cell cortex: a labyrinthine cavity bounded by an epithelium-like monolayer of fibroblastic reticular cells anchored to basement membrane-like extracellular matrix | journal = International Immunology | volume = 13 | issue = 10 | pages = 1243–53 | date = October 2001 | pmid = 11581169 | doi = 10.1093/intimm/13.10.1243 | doi-access = free }}</ref>

=== Lymph flow ===
[[File:Lymphatic immune system lymph node5-CROPPED.jpg|thumb|alt=Human lymph node|Labeled diagram of human lymph node showing the flow of [[lymph]]]]
[[File:Illu lymph node structure.png|thumb|300px|Afferent and efferent vessels]]

Lymph enters the convex side of a lymph node through multiple afferent lymphatic vessels, which form a network of lymphatic vessels ({{Langx|la|plexus}}) and flows into a space ({{Langx|la|sinus}}) underneath the capsule called the subcapsular sinus.<ref name="Grays2016" /><ref name=Wheaters2013 /> From here, lymph flows into sinuses within the cortex.<ref name=Wheaters2013 /> After passing through the cortex, lymph then collects in medullary sinuses.<ref name=Wheaters2013 /> All of these sinuses drain into the [[Lymphatic vessel#Efferent vessels|efferent lymphatic vessels]] to exit the node at the hilum on the concave side.<ref name=Wheaters2013 />

These are channels within the node lined by endothelial cells along with fibroblastic reticular cells, allowing for the smooth flow of lymph. The endothelium of the subcapsular sinus is continuous with that of the afferent lymph vessel and also with that of the similar sinuses flanking the trabeculae and within the cortex. These vessels are smaller and do not allow the passage of macrophages so that they remain contained to function within a lymph node. In the course of the lymph, lymphocytes may be activated as part of the [[adaptive immune system|adaptive immune response]].

There is usually only one efferent vessel though sometimes there may be two, in contrast to the multiple afferent channels that bring lymph into the node.<ref>{{cite book |url= https://books.google.com/books?id=2i_ToCBIt8UC&pg=PA201 |title=Histology |last1=Henrikson |first1=Ray C. |last2=Mazurkiewicz |first2=Joseph E. | name-list-style = vanc |date=1 January 1997|publisher=Lippincott Williams & Wilkins|isbn=9780683062250|language=en}}</ref> Medullary sinuses contain [[histiocyte]]s (immobile macrophages) and reticular cells, the former of which, along with T and B cells, become activated in the presence of antigens through lymphatic flow. The fewer efferent vessels allow this flow to be slowed, providing time to activate and distribute a larger number of immune cells in the event of an infection.

A lymph node contains lymphoid tissue, i.e., a meshwork or fibers called ''{{dfn|reticulum}}'' with white blood cells enmeshed in it. The regions where there are few cells within the meshwork are known as ''{{dfn|lymph sinus}}''. It is lined by reticular cells, [[fibroblast]]s and fixed macrophages.<ref name="grays">{{cite book |title=Gray's anatomy |last1=Warwick |first1=Roger| first2 =Peter L. | last2 = Williams | name-list-style = vanc |publisher=Longman|others=illustrated by Richard E. M. Moo re|year=1973|edition=Thirty-fifth |location=London |pages=588–785 |chapter=Angiology (Chapter 6) |orig-year=1858}}</ref>

===Capsule===
[[File:Gray598.png|thumb|right|Lymph node tissue showing trabeculae]]
Thin [[reticular fiber]]s (reticulin) of [[reticular connective tissue]] form a supporting meshwork inside the node.<ref name="Grays2016" />
These reticular cells also form a conduit network within the lymph node that functions as a molecular sieve, to prevent pathogens that enter the lymph node through afferent vessels re-enter the blood stream.<ref>{{cite journal |last1=Roozendaal |first1=Ramon |title=The conduit system of the lymph node |journal=International Immunology |date=September 29, 2008 |volume=20 |issue=12 |pages=1483–1487 |doi=10.1093/intimm/dxn110 |pmid=18824503 |url=https://pubmed.ncbi.nlm.nih.gov/18824503/ |access-date=22 November 2024}}</ref> The lymph node capsule is composed of [[dense irregular connective tissue]] with some plain [[collagen|collagenous fibers]], and a number of membranous processes or trabeculae extend from its internal surface. The trabeculae pass inward, radiating toward the center of the node, for about one-third or one-fourth of the space between the circumference and the center of the node. In some animals they are sufficiently well-marked to divide the peripheral or cortical portion of the node into a number of compartments (nodules), but in humans this arrangement is not obvious. The larger trabeculae springing from the capsule break up into finer bands, and these interlace to form a mesh-work in the central or medullary portion of the node. These trabecular spaces formed by the interlacing trabeculae contain the proper lymph node substance or lymphoid tissue. The node pulp does not, however, completely fill the spaces, but leaves between its outer margin and the enclosing trabeculae a channel or space of uniform width throughout. This is termed the subcapsular sinus (lymph path or lymph sinus). Running across it are a number of finer trabeculae of reticular fibers, mostly covered by ramifying cells.

===Inverted Lymph Node===
Some mammal species, such as pigs, rhinoceroses, hippopotamuses, and certain cetaceans, have so-called "inverted" lymph nodes. In these nodes, the afferent lymph carries antigens from the center (where the B-cell follicles are located) toward the periphery. Mature B and T lymphocytes exit the lymph node from its periphery directly into the general bloodstream via efferent venules. These structural differences do not appear to impact the functionality of the lymph nodes.<ref>{{cite journal | doi=10.3389/fimmu.2022.869384 | doi-access=free | title=The Internal Conduit System of the Swine Inverted Lymph Node | date=2022 | last1=Dubreil | first1=Laurence | last2=Ledevin | first2=Mireille | last3=Hervet | first3=Caroline | last4=Menard | first4=Déborah | last5=Philippe | first5=Claire | last6=Michel | first6=François J. | last7=Larcher | first7=Thibaut | last8=Meurens | first8=François | last9=Bertho | first9=Nicolas | journal=Frontiers in Immunology | volume=13 }}</ref><ref>{{cite journal | doi=10.3389/fimmu.2019.00953 | doi-access=free | title=Macrophage-B Cell Interactions in the Inverted Porcine Lymph Node and Their Response to Porcine Reproductive and Respiratory Syndrome Virus | date=2019 | last1=Bordet | first1=Elise | last2=Frétaud | first2=Maxence | last3=Crisci | first3=Elisa | last4=Bouguyon | first4=Edwige | last5=Rault | first5=Stéphane | last6=Pezant | first6=Jérémy | last7=Pleau | first7=Alexis | last8=Renson | first8=Patricia | last9=Giuffra | first9=Elisabetta | last10=Larcher | first10=Thibaut | last11=Bourge | first11=Mickael | last12=Bourry | first12=Olivier | last13=Boulesteix | first13=Olivier | last14=Langevin | first14=Christelle | last15=Schwartz-Cornil | first15=Isabelle | last16=Bertho | first16=Nicolas | journal=Frontiers in Immunology | volume=10 | page=953 | pmid=31130951 | pmc=6510060 }}</ref>