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. Lymph nodes lie 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.


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

  • Development of secondary lymphoid organs in relation to lymphatic vasculature[1] "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[2] "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."
More recent papers
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Search term: Lymph Node Embryology

<pubmed limit=5>Lymph Node Embryology</pubmed>

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.

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.[3]
  • 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.[4]

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[5]

The following data is from a recent article[6] and review[7] 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.

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
Page | Play
Mouse adult lymph node 04.jpg
 ‎‎Lymph Node 4
Page | Play
Transendothelial
migration
T cell zone Medullary sinus Sinus endothelial
barrier
Mouse adult lymph node 05.jpg
 ‎‎Lymph Node 5
Page | Play
Mouse adult lymph node 06.jpg
 ‎‎Lymph Node 6
Page | Play
Mouse adult lymph node 07.jpg
 ‎‎Lymph Node 7
Page | Play
Mouse adult lymph node 08.jpg
 ‎‎Lymph Node 8
Page | Play
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. <pubmed>24276888</pubmed>
  2. <pubmed>19060331</pubmed>
  3. <pubmed>19644499</pubmed>| PMC2785037 | Nat Rev Immunol.
  4. <pubmed>16533891</pubmed>| PMC2118258 | J Exp Med.
  5. <pubmed>15122201</pubmed>| Nat Rev Immunol.
  6. <pubmed>16273098</pubmed>
  7. <pubmed>18173372</pubmed>


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

<pubmed></pubmed>

Articles

<pubmed>165702</pubmed> <pubmed>1167215</pubmed>

Search Pubmed

Search Pubmed: Lymph Node Development | Lymphocyte Development

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Cite this page: Hill, M.A. (2024, March 29) 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 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G