Lymph Node Development

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Introduction

Basic structure of an adult lymph node.
Schematic of lymph node.

Lymphatic vasculature drains lymph fluid from the organ tissue space and returns it to the blood vasculature for recirculation. The lymph node lies on the path of lymph vessels and these structures monitor and carry out immune surveillance of this fluid for antigens and pathogens, trapping them within the lymph nodes and generating immune responses.

In early node development, vein endothelial cells form a spherical body (lymph sac) that is surrounded and then invaded by mesenchymal cells that contribute the lymph node stroma. The current mouse model shows lymphoid tissue inducer cells initially regulating the activation of mesenchymal lymphoid tissue organizer cells.[1]

The reticular cells that form the stroma of the node were also initially seen as purely structural and supportive, more recent studies have shown that the reticular network that they form is also part of the immune process.


Immune Links: immune | blood | spleen | thymus | Lymphatic | lymph node | Antibody | Med Lecture - Lymphatic Structure | Med Practical | Immune Movies | vaccination | bacterial infection | Abnormalities | Category:Immune
Historic Embryology  
1909 Lymph glands | 1912 Development of the Lymphatic System | 1918 Gray's Lymphatic Images | 1916 Pig Lymphatics | 1919 Chicken Lymphatic | 1921 Spleen | 1922 Pig Stomach Lymphatics | 1932 Cat Pharyngeal Tonsil | Historic Disclaimer

Some Recent Findings

  • Subcapsular Sinus Macrophages: The Seat of Innate and Adaptive Memory in Murine Lymph Nodes[2] "Subcapsular sinus (SCS) macrophages are strategically positioned at the lymph-tissue interface in the lymph node to trap and present antigen to B cells. Recent murine data has shown that SCS macrophages also prevent the systemic spread of lymph-borne pathogens and are capable of activating a diverse range of innate effector and adaptive memory cells, including follicular memory T cells and memory B cells (Bmems), that are either pre-positioned or rapidly recruited to the subcapsular niche following infection and inflammation. Furthermore, Bmems are rapidly reactivated to differentiate into plasma cells in subcapsular proliferative foci (SPF)."
  • Morphometric development of sheep (Ovis aries) lymph nodes in fetal period[3] "To this end, 60 pieces of sheep fetuses collected from Ahvaz slaughterhouse were fixated in 10% formalin and then divided into four categories based on crown-rump length (CRL) following gender and weight determinations. Mandibular, caudal superficial cervical (prescapular), caudal mediastinum, jejunal mesenteric and popliteal lymph nodes were evaluated in five lymphocenters of head, neck, thoracic cavity, abdominal viscera and pelvic limbs, respectively. ...Gender had no effect on study parameters in 32 male and 28 female fetuses. Study of sheep fetuses' lymph nodes revealed no macroscopic lymph node development by day 45, while all nodes were observable after the day 59. The shortest lymph node was mandibular node and the longest one was caudal mediastinum. Based on the results, it seemed that although the size of lymph nodes grows by age, this increase is not the same for all nodes and groups."
  • Development of the LYVE-1 gene with an acidic-amino-acid-rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity[4] "CRSBP-1 (mammalian LYVE-1) is a membrane glycoprotein highly expressed in lymphatic endothelial cells (LECs). It has multiple ligands, including hyaluronic acid (HA) and growth factors/cytokines (e.g., PDGF-BB and VEGF-A) containing CRS motifs (clusters of basic amino-acid residues). ... Lymph nodes represent the only major recent innovation of the adaptive immune systems in evolution particularly to mammals and bird. Here we demonstrate that the development of the LYVE-1 gene with the AAAR domain in evolution is associated with acquisition of lymph nodes and adaptive immunity. LYVE-1 from other species, which have no lymph nodes, lack the AAAR domain and efficient adaptive immunity. Synthetic CRSBP-1 ligands PDGF and VEGF peptides, which contain the CRS motifs of PDGF-BB and VEGF-A, respectively, specifically bind to CRSBP-1 but do not interact with either PDGFβR or VEGFR2. These peptides function as adjuvants by enhancing adaptive immunity of pseudorabies virus (PRV) vaccine in pigs. These results support the notion that LYVE-1 is involved in adaptive immunity in mammals."
  • Lymph Node Stroma Dynamics and Approaches for Their Visualization[5] "Lymphoid stromal cells are best known as the architectural cells of lymphoid organs. For decades, they have been considered as inert elements of the immune system but this view has changed dramatically in recent years, when it was discovered that they are endowed with critical immunoregulatory functions. It is now accepted that without them, the adaptive immune response would be compromised, if not abrogated entirely. Here, we review the function of the major lymphoid stromal cell types; the way they remodel upon inflammation; discuss the available tools to track their behavior; and introduce several methodological approaches that we believe will help improving our knowledge of these pivotal cell types."
More recent papers  
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Search term: Lymph Nodes Embryology | Lymph Nodes Development | Lymph Nodes | tissue inducer cell | mesenchymal lymphoid tissue organizer cell

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Development of secondary lymphoid organs in relation to lymphatic vasculature[6] "Although the initial event in lymphatic endothelial specification occurs slightly before the initiation of lymph node formation in mice, the development of lymphatic vessels and lymph nodes occurs within the same embryonic time frame. Specification of lymphatic endothelial cells starts around embryonic day 10 (E10), followed by endothelial cell budding and formation of the first lymphatic structures. Through lymphatic endothelial cell sprouting these lymph sacs give rise to the lymphatic vasculature which is complete by E15.5 in mice. It is within this time frame that lymph node formation is initiated and the first structure is secured in place. As lymphatic vessels are crucially involved in the functionality of the lymph nodes, the recent insight that both structures depend on common developmental signals for their initiation provides a molecular mechanism for their coordinated formation. Here, we will describe the common developmental signals needed to properly start the formation of lymphatic vessels and lymph nodes and their interdependence in adult life."
  • Lymph sacs are not required for the initiation of lymph node formation[7] "As proposed by Florence Sabin more than a century ago and recently validated, the mammalian lymphatic vasculature has a venous origin and is derived from primitive lymph sacs scattered along the embryonic body axis. Also as proposed by Sabin, it has been generally accepted that lymph nodes originate from those embryonic primitive lymph sacs. However, we now demonstrate that the initiation of lymph node development does not require lymph sacs."

Early Development

  1. lymph sacs (primitive lymph sacs) form from endothelial cells.
  2. bud from the veins during early development
  3. then form buds that branch and form the lymphatic network.
  4. lymphoid tissue inducer cells - (LTi) first hematopoietic cells to enter and induce lymphoid tissue development.

Molecular

Prox1

  • expressed by lymphatic endothelial cells.

Reticular Cells

Mesoderm derived fibroblastic reticular cells (FRCs, RCs) form the stromal supporting network of cells and extracellular matrix in secondary lymphoid organs (lymph nodes, spleen and thymus). These specialized myofibroblasts form the structural "sponge" within lymphoid tissue, through with T cells, B cells, dendritic cells (DCs), plasma cells and macrophages interact and move.[8]

  • synthesise reticular fibres (type III collagen) that form the main extracellular matrix component
  • differentiate as distinct subpopulations distributed in the cortical and medullar regions
    • T cell zone fibroblastic reticular cells (TRCs)
  • bind dendritic cells that initiate immunity by presenting antigens to T lymphocytes also initiate remodelling of lymph node RCs
  • may regulate cellular traffic and activation of specific lymphocyte populations


Model of Reticular Network Formation[9]

Reticular network formation model.jpg

Accumulation of lymphocytes induces alteration of mesenchymal progenitors. Lymphocytes and differentiated FRCs gradually degrade preexisting matrix, and FRCs weave RF meshwork from the newly produced components. Mature RN forms and antigen presentation occur on the stromal reticulum.


Lymph node cells 01.jpg

Lymph Node and Reticular Cell Classification[10]

Molecular

  • express myofibroblast markers - desmin, vimentin, CD90, CD73, CD103, α-smooth muscle actin (αSMA) and ERTR7 antigen.
  • express - podoplanin (PDPN), platelet-derived growth factor receptor-α (PDGFRA) and genes from antigen presentation and cytokine response pathways.
  • lack of expression of CD45 and CD31.


Links: Connective Tissue Development

Dendritic Cells

Dendritic cells (DCs, antigen-presenting cells, APCs) present antigens and induce a primary immune response in resting naïve T lymphocytes. These cells originate from the same common progenitor as monocytes.[11] Recently it has been shown that recirculation of antigen-bearing dendritic cells in remote lymphoid organs can prime T cells in other locations.[12]

In 2011 Ralph M. Steinman received half the Nobel Prize half of the award to to Ralph M. Steinman for his discovery of the dendritic cell and its role in adaptive immunity.

Adult Lymph Node

  • Encapsulated organ (1 mm - 2 cm)
  • In lymph vessel pathways “filter”
  • Afferent- towards node
  • Efferent- away from node
  • Location throughout the entire body - Concentrated in axilla, groin, mesenteries
  • Antigen transformed lymphocytes from the blood
Lymph node cartoon 02.jpg

Legend

  • B - B-cell zones
  • DC - dendritic cells
  • FRC - fibroblastic reticular cells
  • HEV - high endothelial venues

Lymph Node Cartoon Gallery

Links: Immunobiology - Figure 1.8. Organization of a lymph node | MBoC Figure 24-16. A simplified drawing of a human lymph node
Lymph node structure 02.jpg Schematic representation of the organization of a lymph node.[13]
  • Afferent lymphatics enter lymph nodes and deliver lymph to the subcapsular sinus (SCS), which forms a channel around the periphery of the lymph node.
  • Lymphatic sinuses run from the SCS through the cortex to the medulla, and exit the lymph node via efferent lymphatic vessels on the opposite, hilar, side of the organ.
  • B cell follicles containing follicular dendritic cell (FDC) networks are arranged in the lymph node cortex and are separated from the SCS by a layer of marginal reticular cells (MRC).
  • T cells zones in the paracortex, which contain many fibroblastic reticular cells (FRC), are separated by the cortical ridge, an area rich in T cells, dendritic cells (DCs), blood vessels, and FRC.
  • Blood vessels enter and exit the lymph node on the hilar side, and snake through the lymph node like the branches of a tree.
  • Specialized high endothelial venules (HEVs) in the paracortex and cortical ridge allow entry of leukocytes from the blood.

Lymph node structure 01.jpg

Mesenteric Lymph Node

Gastrointestinal tract intestine immune cartoon 01.jpg

Gastrointestinal tract intestine immune overview showing mesenteric lymph nodes.[14]

Histology

Lymph Node Histology: Subcapsular Sinus | Follicle | Germinal Centre | Medullary Cords and Sinuses | High Endothelial Venules | Macrophages | Node cartoons

Adult Lymph Node Structure

  • Capsule - dense connective tissue
  • Trabeculae - dense connective tissue
  • Reticular Tissue - Reticular cells and fibers, supporting meshwork
  • Macrophages - process antigen, difficult to distinguish from the reticular cells.

Lymph node histology 02.jpg Lymph node histology 03.jpg

Lymph

  • enters the node through afferent vessels
  • filters through the sinuses
  • leaves through efferent vessels

Subcapsular sinus = marginal sinus

Lymph node histology 01.jpg

Continuation of trabecular sinus

Lymph node histology 04.jpg

Adult Lymphocytes

Lymphocyte Electron Micrographs

Cell Trafficking into and out of Lymph Nodes

Lymph node cartoon 02.jpg

Lymphocyte Traffic in and out of the Lymph Node[15]

The following data is from an in vivo mouse study[16] of live adult mouse lymphocytes (T and B cells) imaged within a lymph node.

Both lymphocyte types:

  • Spend 8 to 24 h in the lymph node interstitium.
  • Transit across a lymphatic endothelium to exit.
  • Enter a network of medullary sinuses.
  • Drain from sinuses into efferent lymphatic vessels.

Lymphocyte Migration Speeds

T cells - 10–12 μm/min in the follicle diffuse cortex, peak velocities up to 30 μm/min. (move more slowly in the medullary region near the hilus of the lymph node than in the paracortex)

B cells - 6 μm/min in the follicle diffuse cortex, peak velocities up to 20 μm/min.

Both cortical T cells and follicular B cells move in random directions following "guide cells".

Lymphocyte Guide Cells

FDC - Follicular Dendritic Cells, may guide B cells in the follicle.

FRC - Fibroblastic Reticular Cells, may guide T cells in the follicle.

Subcapsular Space

The subcapsular region is not only the initial entry site for lymph flow into the node, but has also been shown to have important immune functions associated with cells located in this space.

  • Macrophages - clear lymph-borne viruses and present them to antiviral B cells.[17] This has also been recently demonstrated in the mouse model.[2]
  • Memory B cells - have been shown to be reactivated in subcapsular proliferative foci of lymph nodes.[18]


Lymphocyte Movies

Adult Mouse Lymphocyte Motility
Mouse adult lymph node 01.jpg
 ‎‎Lymph Node 1
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Mouse adult lymph node 02.jpg
 ‎‎Lymph Node 2
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Mouse adult lymph node 03.jpg
 ‎‎Lymph Node 3
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Mouse adult lymph node 04.jpg
 ‎‎Lymph Node 4
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Transendothelial
migration
T cell zone Medullary sinus Sinus endothelial
barrier
Mouse adult lymph node 05.jpg
 ‎‎Lymph Node 5
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Mouse adult lymph node 06.jpg
 ‎‎Lymph Node 6
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Mouse adult lymph node 07.jpg
 ‎‎Lymph Node 7
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Mouse adult lymph node 08.jpg
 ‎‎Lymph Node 8
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Bi-directional traffic Cross the sinus
endothelial barrier
T and B cell motility T and B cell coupling
Mouse Immune Movies: Transendothelial migration | T cell zone | Medullary sinus | Sinus endothelial barrier | Bi-directional traffic | cross the sinus endothelial barrier | T and B cell motility | T and B cell coupling | T cell Elimination | Immune System Development | Mouse Development


References

  1. Onder L & Ludewig B. (2018). A Fresh View on Lymph Node Organogenesis. Trends Immunol. , 39, 775-787. PMID: 30150089 DOI.
  2. 2.0 2.1 Moran I, Grootveld AK, Nguyen A & Phan TG. (2019). Subcapsular Sinus Macrophages: The Seat of Innate and Adaptive Memory in Murine Lymph Nodes. Trends Immunol. , 40, 35-48. PMID: 30502023 DOI.
  3. Khaksary-Mahabady M, Khazaeel K, Pourmahdi Borujeni M & Yazdanjoo B. (2018). Morphometric development of sheep (Ovis aries) lymph nodes in fetal period. Vet Res Forum , 9, 121-128. PMID: 30065800 DOI.
  4. Huang SS, Li YW, Wu JL, Johnson FE & Huang JS. (2018). Development of the LYVE-1 gene with an acidic-amino-acid-rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity. J. Cell. Physiol. , 233, 2681-2692. PMID: 28833090 DOI.
  5. Gentek R & Bajénoff M. (2017). Lymph Node Stroma Dynamics and Approaches for Their Visualization. Trends Immunol. , 38, 236-247. PMID: 28214099 DOI.
  6. van de Pavert SA & Mebius RE. (2014). Development of secondary lymphoid organs in relation to lymphatic vasculature. Adv Anat Embryol Cell Biol , 214, 81-91. PMID: 24276888 DOI.
  7. Vondenhoff MF, van de Pavert SA, Dillard ME, Greuter M, Goverse G, Oliver G & Mebius RE. (2009). Lymph sacs are not required for the initiation of lymph node formation. Development , 136, 29-34. PMID: 19060331 DOI.
  8. Fletcher AL, Acton SE & Knoblich K. (2015). Lymph node fibroblastic reticular cells in health and disease. Nat. Rev. Immunol. , 15, 350-61. PMID: 25998961 DOI.
  9. Fletcher AL, Acton SE & Knoblich K. (2015). Lymph node fibroblastic reticular cells in health and disease. Nat. Rev. Immunol. , 15, 350-61. PMID: 25998961 DOI.
  10. Alvarenga HG & Marti L. (2014). Multifunctional roles of reticular fibroblastic cells: more than meets the eye?. J Immunol Res , 2014, 402038. PMID: 24829927 DOI.
  11. Liu K & Nussenzweig MC. (2010). Origin and development of dendritic cells. Immunol. Rev. , 234, 45-54. PMID: 20193011 DOI.
  12. Hervouet C, Luci C, Bekri S, Juhel T, Bihl F, Braud VM, Czerkinsky C & Anjuère F. (2014). Antigen-bearing dendritic cells from the sublingual mucosa recirculate to distant systemic lymphoid organs to prime mucosal CD8 T cells. Mucosal Immunol , 7, 280-91. PMID: 23801305 DOI.
  13. Mueller SN & Germain RN. (2009). Stromal cell contributions to the homeostasis and functionality of the immune system. Nat. Rev. Immunol. , 9, 618-29. PMID: 19644499 DOI.
  14. Macpherson AJ & Smith K. (2006). Mesenteric lymph nodes at the center of immune anatomy. J. Exp. Med. , 203, 497-500. PMID: 16533891 DOI.
  15. Miyasaka M & Tanaka T. (2004). Lymphocyte trafficking across high endothelial venules: dogmas and enigmas. Nat. Rev. Immunol. , 4, 360-70. PMID: 15122201 DOI.
  16. Wei SH, Rosen H, Matheu MP, Sanna MG, Wang SK, Jo E, Wong CH, Parker I & Cahalan MD. (2005). Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinuses. Nat. Immunol. , 6, 1228-35. PMID: 16273098 DOI.
  17. Junt T, Moseman EA, Iannacone M, Massberg S, Lang PA, Boes M, Fink K, Henrickson SE, Shayakhmetov DM, Di Paolo NC, van Rooijen N, Mempel TR, Whelan SP & von Andrian UH. (2007). Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature , 450, 110-4. PMID: 17934446 DOI.
  18. Moran I, Nguyen A, Khoo WH, Butt D, Bourne K, Young C, Hermes JR, Biro M, Gracie G, Ma CS, Munier CML, Luciani F, Zaunders J, Parker A, Kelleher AD, Tangye SG, Croucher PI, Brink R, Read MN & Phan TG. (2018). Memory B cells are reactivated in subcapsular proliferative foci of lymph nodes. Nat Commun , 9, 3372. PMID: 30135429 DOI.


Textbook

Immunobiology 5th edition The Immune System in Health and Disease Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik.

Part I. An Introduction to Immunobiology and Innate Immunity

Part III. The Development of Mature Lymphocyte Receptor Repertoires

Reviews

Onder L & Ludewig B. (2018). A Fresh View on Lymph Node Organogenesis. Trends Immunol. , 39, 775-787. PMID: 30150089 DOI.

Kuper CF, van Bilsen J, Cnossen H, Houben G, Garthoff J & Wolterbeek A. (2016). Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies. Reprod. Toxicol. , 64, 180-90. PMID: 27282947 DOI.

Hartiala P & Saarikko AM. (2016). Lymphangiogenesis and Lymphangiogenic Growth Factors. J Reconstr Microsurg , 32, 10-5. PMID: 25665098 DOI.

Articles

Bailey RP & Weiss L. (1975). Light and electron microscopic studies of postcapillary venules in developing human fetal lymph nodes. Am. J. Anat. , 143, 43-58. PMID: 165702 DOI.

Bailey RP & Weiss L. (1975). Ontogeny of human fetal lymph nodes. Am. J. Anat. , 142, 15-27. PMID: 1167215 DOI.

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Search Pubmed: Lymph Node Development | Lymphocyte Development

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Terms

Immune Development

  • adenoid - (Greek " +-oeides = in form of) in the form of a gland, glandular; the pharyngeal tonsil.
  • afferent lymph - vessel carrying lymph towards a node.
  • acquired immune deficiency syndrome - (AIDS) note this is now better described as "advanced HIV disease", decrease in the number of CD4 T cells. (More? Immunobiology - AIDS)
  • anastomose - joining of two tubes or structures together.
  • Antibody mediated immunity - the immune function of plasma cells (active B lymphocytes) secreting antibody which binds antigen.
  • antibodies - mammals have five classes (IgA, IgD, IgE, IgG, and IgM)
  • antigen - any substance that is recognised by the immune system and stimulates antibody production.
  • appendix - is a gut-associated lymphoid tissue (GALT) located at the beginning of the colon. The anatomy is as a finger-like structure that arises from the cecum. The length (2.5-13 cm) is longer in both infants and children and also has more abundant lymphatic tissue in early life. The wall structure is similar to the small intestine (though with no villi), nor plicae circularis. Lymph nodules surround the lumen of the gastrointestinal tract and extend from the mucosa into the submucosa.
  • B lymphocyte - (B cell, B-cell)
  • BALT - (Bronchus Associated Lymphoid Tissue) immune tissue associated with the respiratory tract.
  • band cell - (band neutrophil or stab cell) seen in bone marrow smear, a cell undergoing granulopoiesis, derived from a metamyelocyte, and leading to a mature granulocyte. Also occasionally seen in circulating blood.
  • cecum - (caecum, Latin, caecus = "blind") within the gastrointestinal tract a pouch that connects the ileum with the ascending colon of the large intestine.
  • cell - has a specific cell biology definition, but is often used instead of "lymphocyte" when describing B and T cells.
  • "clockface" - a term used to describe the appearance of plasma cell nuclei due to the clumping of the chromatin at the nucleus periphery. More clearly seen in tissue plasma cells that the bone marrow smear, where they are sometimes confused with the basophilic erythroblasts. Image - plasma cell
  • CD - (cluster of differentiation) identifies immunological surface markers on cells. Positive (+) generally means that the substance is expressed/identified, while negative (-) means that it is missing/not identified.
  • CD4+ - (T helper cells) refers to T lymphocytes that express CD4 (cluster of differentiation 4, a glycoprotein of the immunoglobulin superfamily) on their surface, associated with helper/inducer function. These cells can be infected by human immunodeficiency virus (HIV).
  • CD4/CD8 ratio - clinical measurement of different immune cell types (ratios between 1.5 to 2.5 are considered normal). Viral infections such as HIV, cytomegalovirus, Epstein-Barr virus, and influenza virus, associated with an inversion of the ratio.
  • CD8+ - (cytotoxic T cells) refers to T lymphocytes that express CD8 (glycoprotein of the immunoglobulin superfamily) on their surface, associated with cytotoxic/suppressor activity.
  • "clockface" - a term used to describe the appearance of plasma cell nuclei due to the clumping of the chromatin at the nucleus periphery. More clearly seen in tissue plasma cells that the bone marrow smear, where they are sometimes confused with the basophilic erythroblasts.
  • cords of Billroth - spleen cellular columns located in red pulp. surrounded by splenic sinusoids. Cords contain reticular cells, macrophages, lymphocytes, plasma cells and erythrocytes.
  • cortex - outer layer, used in association with medulla (innner layer or core) a general description that can be applied to describing an organ with a layered structure.
  • cortical Thymic Epithelial Cell - (cTEC, types I - IV) support and antigen presenting cells located in the cortex regions of the thymus required for positive and negative selection of maturing T cells. See also medullary epithelial cell.
  • dendritic cell - (DC, antigen-presenting cell, APC) cells that present antigens and induce a primary immune response in resting naïve T lymphocytes. Originate from the same common progenitor as monocytes (PMID 20193011). In 2011 Ralph M. Steinman received half the Nobel Prize half of the award to to Ralph M. Steinman for his discovery of the dendritic cell and its role in adaptive immunity.
  • Effector cells - the immune functioning (active) B and T lymphocytes.
  • Efferent lymph - vessel carrying lymph away from a node.
  • fibroblastic reticular cell - (FRC) specialized myofibroblasts that form the structural mesenchymal network "sponge" within lymphoid tissue that regulate immune cell migration, activation, and survival. Immune T cells, B cells, dendritic cells (DCs), plasma cells and macrophages move and interact.
  • follicular dendritic cell - (FDC) in B cell follicles of secondary lymphoid organs, cells interspersed within the stromal cell network function: Primary - help B cells to cluster. Secondary - in GC long-term retention of intact antigen and support B cell survival.
  • GALT - Gut Associated Lymphatic Tissue consisting of Peyer’s patches, isolated lymphoid follicles and mesenteric lymph nodes.
  • germinal centre - (GC) centre of B cell follicles of secondary lymphoid organs, where antigen-activated B-cell clones expand and undergo immunoglobulin gene hypermutation and selection.
  • haemopoiesis (hemopoiesis) formation of blood cells.
  • high endothelial venule - (HEV) the specialised post-capillary venous region that enables blood lymphocytes to enter a lymph node. These specialised post-capillary venules enables blood lymphocytes to enter a lymph node. The endothelial cells express ligands that bind lymphocytes, aiding their adhesion and subsequent transmigration into the lymph node.
  • humoral immune response - production of antibody by plasma cells derived from B lymphocytes (B cells).
  • IEL - Intraepithelial Lymphocyte are T lymphocytes located in the gastrointestinal tract epithelium. Natural IELs (previously ‘type b’ IELs) acquire activated phenotype during development in the thymus in the presence of self antigens. Induced IELs (previously ‘type a’ IELs) progeny of conventional T cells activated post-thymically in response to peripheral antigens.
  • IgA - the main class of antibody in secretions (saliva, tears, milk, and respiratory and intestinal secretions).
  • IgD - the immunoglobulin B cell starts to produce as a cell-surface molecule after leaving the bone marrow.
  • IgE - bind Fc receptors (surface of mast cells in tissues and basophils in the blood) release of potent pro inflammatory molecules mediators of allergic reactions.
  • IgG - the major class of immunoglobulin in the blood.
  • IgM - the first class of antibody made by a developing B cell, which may switch to making other classes of antibody.
  • immunoglobulin - (antibody, Ab) protein produced by plasma cells.
  • immunosenescence - in ageing and disease, refers to a weaker immune responses producing a progressive deterioration and increased susceptibility to infectious diseases, neoplasia, and autoimmune diseases.
  • innate lymphoid cells - (ILCs) subset of lymphocytes that lack antigen-specific receptors, are located in peripheral tissues and abundant at barrier surfaces, decrease in number with age. PMID 29924974
  • Kupffer cells - stellate macrophage cells located in the liver sinusoids, named after Karl Wilhelm von Kupffer (1829 - 1902) a German anatomist who originally identified these cells. (More? Liver Development)
  • lacteal - term used to describe the lymphatic vessels of the small intestine.
  • lamina propria - a layer of loose connective tissue found underneath an epithelium, together with the epithelium described as mucosa.
  • Langerhans cell - (LC, dendritic cell) Antigen-presenting immune cell found mainly in the basal/suprabasal layers of adult skin and mucosa. Cells lie in the basal/suprabasal layers of stratified epidermal and mucosal tissues. First in the innate antiviral immune defines and can migrate to lymph nodes and induce a T cell–mediated adaptive immune response. (More? Integumentary | Immune System Development)
  • Leukocyte - (Greek, lukos = clear, white) white blood cell.
  • lingual - related to the tongue.
  • lymph node - connective tissue encapsulated lymphoid organ (1mm - 2cm in size), positioned in the pathway of lymph vessels. (More? Lymph Node Development)
  • lymphangion - the functional unit of a lymph vessel that lies between two semilunar (half moon-shaped) valves.
  • lymphangiogenesis - formation of new lymph vessels from pre-existing lymphatic structures. During embryogenesis and in adult tissues as reaction to inflammation or injury.
  • M cell - (microfold cell) found in the follicle-associated epithelium of the Peyer's patch. Function to transport gut lumen organisms and particles to immune cells across the epithelial barrier.
  • MALT - Mucosa Associated Lymphoid Tissue.
  • medulla - inner layer or core, used in association with cortex (outer layer) a general description that can be applied to describing an organ with a layered structure.
  • medullary Thymic Epithelial Cell - (mTEC, types I-VII) support and antigen presenting cells located in the medullary regions of the thymus, required for central tolerance (negative selection) of maturing T cells (PMID 11375064). See also cortical thymic epithelial cell.
  • Memory Cell - effector T cell (lymphocyte)
  • Mononuclear Phagocytic System - (MPS, Lymphoreticular System, Reticuloendothelial System, RES) Consists of circulating monocytes in the peripheral blood and non-circulating (fixed) tissue macrophages (MΦ) located in tissues and organs.
  • negative selection - T cells bearing autoreactive T cell antigen receptors (TCRs) are eliminated during their development in the thymus, protects against autoimmunity.
  • normoblast - seen in bone marrow smear, a developing erythroblast (red blood cell) that still retains a nucleus.
  • nude mice - (nu/nu) mice which are congenitally hairless and athymic, therefore they do not reject tissue and tumor grafts.
  • parenchyma - (Greek = enkeim "to pour in") cells forming the functional cells of an organ or tissue. These cells carry out the function of the organ at a cellular level, and are not the structural cells, connective tissue, extracellular matrix (stromal).
  • periarterial lymphoid sheath - (PALS) in the spleen the white pulp that surrounds the central arteries. (T-lymphocytes,macrophages and plasma cells)
  • pharyngeal pouch III - origin of endodermal component of the thymus (also formed from neural crest). Pharyngeal arches
  • Plasma Cell - active B cell (lymphocyte) which is secreting antibody. Located in either bone marrow or peripheral lymphoid tissues, these cells have and increased cytoplasmic volume (due to increase rough endoplasmic reticulum) in comparison to the inactive (non-secreting) lymphocyte.
  • primary follicle - follicle that does not contain germinal centre, secondary follicles do germinal centre.
  • red pulp - spleen region, organized as cell cords (splenic cords, cords of Billroth) and vascular sinuses.
  • regulatory T cells - (Tregs) maintain self tolerance and suppress pathological immune responses by control of immune response to non-self antigens.
  • right lymphatic duct - drains most of the right upper quadrant. See also thoracic duct.
  • secondary follicle - contain germinal centre, primary follicle does not contain germinal centre.
  • sentinel lymph node - the hypothetical first lymph node or group of nodes reached by metastasizing cancer cells from a primary tumour.
  • splenic capillary sheaths - in spleen around capillary endothelium and consist of three main cell types: CD271+ stromal capillary sheath cells, CD68+CD163− macrophages and recirculating B-lymphocytes. Sheaths may; 1. allow interaction among sheath macrophages and B-lymphocytes, 2. attract recirculating B-lymphocytes from the open circulation of the red pulp to start migration into white pulp follicles. 30356180
  • splenic sinusoids - enlarged splenic spaces located in red pulp and surrounding cords of Billroth.
  • stroma - (Greek = "a cover, table-cloth, bedding") tissue forming the framework/support of an organ or tissue. That is the structural cells which form connective tissue and secrete extracellular matrix, rather than the functional cells (parenchymal). All organs can therefore be functionally divided into these 2 components, stromal/parenchymal.
  • Subcapsular sinus (=marginal sinus) space lying under the connective tissue capsule which receives lymph from afferent lymphatic vessels.
  • T cell - (T-cell, T lymphocyte) named after thymus, where they develop, the active cell is responsible for cell-mediated immunity (killer T cells and helper T cells). Cells express T-cell receptor on surface and directly kill virally or bacterially infected cells. These cells can themselves be infected by HIV. (More? Electron micrographs of nonactivate and activated lymphocytes)
  • TEC - (Thymic Epithelial Cell) thymus support and antigen presenting cells further divided anatomically and functionally into medullary TEC (mTEC, types I-VII, for central tolerance) and cortical epithelial cell (cTEC, types I-IV, positive and negative selection) populations (see PMID 28800929 PMID 30308217).
  • T cell activation - (T lymphocyte activation)The activation process begins with T-cells searching for and encountering antigen-bearing dendritic cells within lymph nodes.
  • thoracic duct - largest lymphatic vessel, drains the lower body including the extremities and abdomen.
  • Thymic corpuscle - (Hassall's corpuscle) a mass of concentric epithelioreticular cells found in the thymus. The number present and size tend to increase with thymus age. (see classical description of Hammar, J. A. 1903 Zur Histogenese und Involution der Thymusdriise. Anat. Anz., 27: 1909 Fiinfzig Jahre Thymusforschung. Ergebn. Anat. Entwickl-gesch. 19: 1-274.)
  • thymic epitheliocytes - reticular cells located in the thymus cortex that ensheathe the cortical capillaries, creating and maintain the microenvironment necessary for the development of T-lymphocytes in the cortex.
  • T helper cells - (helper T-cells) (Th cells, CD4+) refers to T lymphocytes that when mature express CD4 (glycoprotein of the immunoglobulin superfamily) on their surface.
  • T lymphocyte - (T cell, T-cell) regulate cell-mediated immunity.
  • thymus - an immune/endocrine (thymic hormone) organ involved in the maturation of T lymphocytes (T-cells). Thymus Development
  • tonsils - lymph nodules embedded in the mucus membranes located at the back of the mouth and top of the throat. The overlying epithelium helps identify the location.
  • vermiform appendix - see appendix, anatomical region containing gut-associated lymphoid tissue located within the gastrointestinal tract at the beginning of the colon. The anatomy is as a finger-like structure that arises from the cecum. The length (2.5-13 cm) is longer in both infants and children and also has more abundant lymphatic tissue in early life. The wall structure is similar to the small intestine (though with no villi), nor plicae circularis. Lymph nodules surround the lumen of the gastrointestinal tract and extend from the mucosa into the submucosa.
  • VDJ recombination - (variable, diversity and joining gene segments) genetic recombination event that occurs in immune cell maturation in primary lymphoid organs, B cells ((bone marrow) and T cells (thymus).
  • Waldeyer’s ring - ring of lymphoid tissue in the pharyngeal wall: palatine tonsils, nasopharyngeal tonsil (adenoid) and lingual tonsil. First described in 1884 by von Waldeyer-Hartz.
  • white pulp - (Malpighian bodies of the spleen, splenic lymphoid nodules) spleen lymphoid region, organized as lymphoid sheaths with both T-cell and B-cell compartments, around the branching arterial vessels (resembles lymph node structure).


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Cite this page: Hill, M.A. (2019, February 17) Embryology Lymph Node Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Lymph_Node_Development

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G