Immune System Development

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Lymphatic vessel development cartoon
Lymphatic vessel development[1]

Developing Human Thymus (Carnegie stage 22)
Developing Human Thymus (stage 22)

Development of the immune system will also link to cardiovascular development notes (blood and vessel) and bone marrow development. Two organs which also relate to this system are the thymus and spleen, which have in the past been included in endocrine and gastrointestinal tract development respectively. There are now also movies showing lymphocyte (B and T cells) traffic within adult lymph nodes.

The maternal immune system also has specialised functions and cells associated with implantation, placenta and pregnancy.

  • During prenatal development, maternal IgG antibodies are transferred from about GA week 13 from maternal blood across the placenta. Placenta syncytiotrophoblast cell endosomes bind IgG, in maternal blood lacunae, through neonatal Fc receptors.
  • During early postnatal development, maternal IgA, IgM, IgG antibodies are transferred from breast milk into the infant gastrointestinal tract.
  • During postnatal development, the immune system matures.

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

Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development[2] "In a forward genetic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice for aberrant immune function, we identified mice with a syndromic disorder marked by growth retardation, diabetes, premature death, and severe lymphoid and myeloid hypoplasia together with diminished T cell-independent (TI) antibody responses. The causative mutation was in Pdia6, an essential gene encoding protein disulfide isomerase A6 (PDIA6), an oxidoreductase that functions in nascent protein folding in the endoplasmic reticulum. The immune deficiency caused by the Pdia6 mutation was, with the exception of a residual T cell developmental defect, completely rescued in irradiated wild-type recipients of PDIA6-deficient bone marrow cells, both in the absence or presence of competition. The viable hypomorphic allele uncovered in these studies reveals an essential role for PDIA6 in hematopoiesis, but one extrinsic to cells of the hematopoietic lineage. We show evidence that this role is in the proper folding of Wnt3a, BAFF, IL-7, and perhaps other factors produced by the extra-hematopoietic compartment that contribute to the development and lineage commitment of hematopoietic cells."

  • Paraxial Mesoderm Is the Major Source of Lymphatic Endothelium[3] " Endothelial cells (ECs), which line blood and lymphatic vessels, are generally described to come from the lateral plate mesoderm despite experimental evidence for a broader source of origin, including the paraxial mesoderm (PXM). Current dogma suggests that following specification from mesoderm, local environmental cues establish the distinct molecular and functional characteristics of ECs in different vascular beds. Here we present evidence to challenge this view, showing that lymphatic EC fate is imprinted during transition through the PXM lineage. We show that PXM-derived cells form the lymphatic endothelium of multiple organs and tissues, with a more restricted contribution to blood vessel endothelium. By deleting Prox1 specifically in PXM-derived cells, we show that this lineage is indispensable for lymphatic vessel development. Collectively, our data establish lineage history as a critical determinant of EC specialization, a finding with broad implications for our understanding of vascular development and heterogeneity."
  • Review - Key molecules in lymphatic development, function, and identification[4] "While both blood and lymphatic vessels transport fluids and thus share many similarities, they also show functional and structural differences, which can be used to differentiate them. Specific visualization of lymphatic vessels has historically been and still is a pivot point in lymphatic research. Many of the proteins that are investigated by molecular biologists in lymphatic research have been defined as marker molecules, i.e. to visualize and distinguish lymphatic endothelial cells (LECs) from other cell types, most notably from blood vascular endothelial cells (BECs) and cells of the hematopoietic lineage. Among the factors that drive the developmental differentiation of lymphatic structures from venous endothelium, Prospero homeobox protein 1 (PROX1) is the master transcriptional regulator. PROX1 maintains lymphatic identity also in the adult organism and thus is a universal LEC marker. Vascular endothelial growth factor receptor-3 (VEGFR-3) is the major tyrosine kinase receptor that drives LEC proliferation and migration. The major activator for VEGFR-3 is vascular endothelial growth factor-C (VEGF-C). However, before VEGF-C can signal, it needs to be proteolytically activated by an extracellular protein complex comprised of Collagen and calcium binding EGF domains 1 (CCBE1) protein and the protease A disintegrin and metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3)."
  • The Nobel Prize in Physiology or Medicine 2011 Bruce A. Beutler and Jules A. Hoffmann for their discoveries concerning the activation of innate immunity and the other half to Ralph M. Steinman for his discovery of the dendritic cell and its role in adaptive immunity.
More recent papers  
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  • The displayed list of references do not reflect any editorial selection of material based on content or relevance.
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More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Immune System Development | Lymphatic System Development | Thymus Development | Spleen Development | Lymph Node Development

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.

  • Tie1 is required for lymphatic valve and collecting vessel development[5] "Tie1 is a receptor tyrosine kinase with broad expression in embryonic endothelium. Reduction of Tie1 levels in mouse embryos with a hypomorphic Tie1 allele resulted in abnormal lymphatic patterning and architecture, decreased lymphatic draining efficiency, and ultimately, embryonic demise. ... Our findings reveal a fundamental role for Tie signaling during lymphatic vessel remodeling and valve morphogenesis and implicate it as a candidate gene involved in primary lymphedema."
  • Regulation of lymphatic-blood vessel separation by endothelial Rac1.[6] "Sprouting angiogenesis and lymphatic-blood vessel segregation both involve the migration of endothelial cells, but the precise migratory molecules that govern the decision of blood vascular endothelial cells to segregate into lymphatic vasculature are unknown."
  • The development of intestinal lymphoid tissues at the interface of self and microbiota[7] "(postnatal) Intestinal lymphoid tissues face the challenging task of inducing adaptive immunity to pathogens, yet maintaining homeostasis with the enormous commensal microbiota. To that aim, the ancient partnership between self and flora has resulted in the generation of a unique set of lymphoid tissues capable of constant large-scale reformatting. A first set of lymphoid tissues, the mesenteric lymph nodes and Peyer's patches, are programmed to develop in the sterile environment of the fetus, whereas a second set of lymphoid tissues, the tertiary lymphoid tissues, are induced to form by the microbiota and inflammation."
  • Ordering human CD34+CD10-CD19+ pre/pro-B-cell and CD19- common lymphoid progenitor stages in two pro-B-cell development pathways.[8] "Here, we show a similar divergence in human B-cell development pathways between the Pax5(+)TdT(-) pre/pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway."
  • Epithelial cells in fetal intestine produce chemerin to recruit macrophages.[9] "Macrophages are first seen in the fetal intestine at 11-12 wk and rapidly increase in number during the 12- to 22-wk period of gestation. The development of macrophage populations in the fetal intestine precedes the appearance of lymphocytes and neutrophils and does not require the presence of dietary or microbial antigens."
  • Ontogeny of reticular framework of white pulp and marginal zone in human spleen: immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation. [10] "The reticular framework of the periarteriolar lymphoid sheath (PALS), lymph follicle (LF), and marginal zone (MZ) is thus heterogeneous in the fetal spleen, and the development of the heterogeneity is related to the ontogeny of the PALS, LF, and MZ."

Spleen Development

Stage 13 image 074.jpg The human spleen arises in week 5 within the dorsal mesogastrium as proliferating mesenchyme overlying the dorsal pancreatic endoderm. Cells required for its hemopoietic function arise from the yolk sac wall and near dorsal aorta.

The spleen generates both red and white cells in the 2nd trimester. Note that many embryonic RBCs remain nucleated.

D4 Dorsal Mesogastrium (Carnegie stage 13)]]

Links: spleen

Thymus Development

Embryonic thymus The thymus has a key role in the development of an effective immune system as well as an endocrine function.

The thymus has two origins for the lymphoid thymocytes and the thymic epithelial cells. The thymic epithelium begins as two flask-shape endodermal diverticula that form from the third pharyngeal pouch and extend lateralward and backward into the surrounding mesoderm and neural crest-derived mesenchyme in front of the ventral aorta.

D4 Developing Thymus (stage 22)

Links: thymus

Lymph Node Development

Lymph node cartoon 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.
Links: Lymph Node Development

T Lymphocyte Development

A study of cord blood from 19 early second and third trimester fetuses (GA 18-36 weeks) and 16 term newborns (GA 37-42 weeks).[11]

  • Percentage of lymphocytes in fetal white blood cells was 79.3%, reducing to 40% by term birth
    • higher than that of adults.
  • Mononuclear cells (cord blood mononuclear cells (CBMC)
  • fetal mononuclear cells were unable to produce IL-2, IL-4 or IFN-gamma.
  • spontaneously secreted IL-10, IL-6 and TNF-alpha in vitro.
  • fail to respond to mitogen (PHA) or allogeneic stimulation in vitro.
    • Stimulation with PHA up-regulated the production of IL-10, IL-6 and TNF-alpha substantially.
    • CD3+ T cells in fetal (40.1%) and neonatal (42.4%)
    • lower than that of men (59.6%) and pregnant women (53.6%).
  • CD8+ T cells (9.5%)
  • gamma delta - T cells (0.5%)
  • NK cells (4.8%)

Gastrointestinal Tract

Intraepithelial Lymphocytes

Intraepithelial lymphocyte differentiation 02.jpg

Thymic and peripheral differentiation of natural and induced intraepithelial lymphocyte.[12]

See also Intraepithelial lymphocyte differentiation

Peyer's Patches

Peyer's patches appear and are continuously formed from 13.5 weeks (GA 15.5 wk) through to about 36 weeks in the gastrointestinal tract. Then between 15.5 and 20 weeks (GA17.5 wk to 22 wk) they develop the surface markers of lymphocytes in the mucosal immune system of the gut.[13] This developmental change is also occurring within the appendix lymphocyte markers: HLA - DR, CD19 (B cell population), CD9 (pre-B cells), CD3 T lymphocytes, CD4 helper / inducer lymphocytes, the CD8 suppressor / cytotoxic cells and lastly, the CD57 Natural Killer cells.

Links: gastrointestinal tract


Macrophages appear in the fetal intestine at 11-12 week GA and rapidly increase in number during the second trimester (12 to 22 week GA). Macrophage development also precedes the appearance of other immune cells (lymphocytes and neutrophils).[9]

Other Organs


The adult liver is a lymphoid organ with a predominantly innate immune system. NK cells are abundant in the normal liver (about one-third of intrahepatic lymphocytes), differs from other lymphoid organs and peripheral blood.

Maternal Antibodies

During prenatal development, maternal antibodies are transferred across the placenta to the fetus. Immunoglobulin G (IgG) is transferred across the syncytiotrophoblast cell layer is mediated by the Neonatal Fc receptor (FcRn). Once inside placental villi, immunoglobulins then need to enter fetal circulation by crossing the second cellular endothelial cell layer by an as yet unknown mechanism.

During postnatal development, maternal antibodies are transferred by maternal milk across the neonatal gastrointestinal tract epithelium by the Neonatal Fc receptor (FcRn). (See Neonatal Fc receptor review[14])

Links: placenta | milk

Additional Images


The images below are from adult immune Lymph Nodes.

Immune Cells

  • Human natural killer cells (NK) - originate from CD34(+) hematopoietic progenitor cells.

Adult Lymphocyte Histology

Lymphocyte EM Images: T and B Lymphocytes 1 TEM | T and B Lymphocytes 2 TEM | T Lymphocyte SEM | B lymphocyte 1 TEM | B lymphocyte 2 TEM | B lymphocyte 3 TEM | Plasma Cell TEM | T2 Lymphocyte 1 TEM | T2 Lymphocyte 2 TEM | lymphocyte rosettes | T lymphocyte 1 | T lymphocyte 2 | T lymphocyte 3 | T lymphocyte 4 | T lymphocyte 5 | T lymphocyte 6 | B lymphocyte | B lymphocytes TEM | Immune System Development | Blood


Adult Lymphocyte Motility

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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T cell zone Medullary sinus Sinus endothelial
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
Mouse adult thymus 11.jpg
 ‎‎Thymus 1
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  1. Kiefer F & Adams RH. (2008). Lymphatic endothelial differentiation: start out with Sox--carry on with Prox. Genome Biol. , 9, 243. PMID: 19138383 DOI.
  2. Choi JH, Zhong X, Zhang Z, Su L, McAlpine W, Misawa T, Liao TC, Zhan X, Russell J, Ludwig S, Li X, Tang M, Anderton P, Moresco EMY & Beutler B. (2020). Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development. J. Exp. Med. , 217, . PMID: 31985756 DOI.
  3. Stone OA & Stainier DYR. (2019). Paraxial Mesoderm Is the Major Source of Lymphatic Endothelium. Dev. Cell , , . PMID: 31130354 DOI.
  4. Jha SK, Rauniyar K & Jeltsch M. (2018). Key molecules in lymphatic development, function, and identification. Ann. Anat. , 219, 25-34. PMID: 29842991 DOI.
  5. Qu X, Zhou B & Scott Baldwin H. (2015). Tie1 is required for lymphatic valve and collecting vessel development. Dev. Biol. , 399, 117-28. PMID: 25576926 DOI.
  6. D'Amico G, Jones DT, Nye E, Sapienza K, Ramjuan AR, Reynolds LE, Robinson SD, Kostourou V, Martinez D, Aubyn D, Grose R, Thomas GJ, Spencer-Dene B, Zicha D, Davies D, Tybulewicz V & Hodivala-Dilke KM. (2009). Regulation of lymphatic-blood vessel separation by endothelial Rac1. Development , 136, 4043-53. PMID: 19906871 DOI.
  7. Eberl G & Lochner M. (2009). The development of intestinal lymphoid tissues at the interface of self and microbiota. Mucosal Immunol , 2, 478-85. PMID: 19741595 DOI.
  8. Sanz E, Muñoz-A N, Monserrat J, Van-Den-Rym A, Escoll P, Ranz I, Alvarez-Mon M & de-la-Hera A. (2010). Ordering human CD34+CD10-CD19+ pre/pro-B-cell and CD19- common lymphoid progenitor stages in two pro-B-cell development pathways. Proc. Natl. Acad. Sci. U.S.A. , 107, 5925-30. PMID: 20231472 DOI.
  9. 9.0 9.1 Maheshwari A, Kurundkar AR, Shaik SS, Kelly DR, Hartman Y, Zhang W, Dimmitt R, Saeed S, Randolph DA, Aprahamian C, Datta G & Ohls RK. (2009). Epithelial cells in fetal intestine produce chemerin to recruit macrophages. Am. J. Physiol. Gastrointest. Liver Physiol. , 297, G1-G10. PMID: 19443732 DOI.
  10. Satoh T, Sakurai E, Tada H & Masuda T. (2009). Ontogeny of reticular framework of white pulp and marginal zone in human spleen: immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation. Cell Tissue Res. , 336, 287-97. PMID: 19255788 DOI.
  11. Zhao Y, Dai ZP, Lv P & Gao XM. (2002). Phenotypic and functional analysis of human T lymphocytes in early second- and third-trimester fetuses. Clin. Exp. Immunol. , 129, 302-8. PMID: 12165087
  12. Cheroutre H, Lambolez F & Mucida D. (2011). The light and dark sides of intestinal intraepithelial lymphocytes. Nat. Rev. Immunol. , 11, 445-56. PMID: 21681197 DOI.
  13. Bhide SA, Wadekar KV & Koushik SA. (2001). Peyer's patches are precocious to the appendix in human development. Dev. Immunol. , 8, 159-66. PMID: 11589311
  14. Rath T, Baker K, Pyzik M & Blumberg RS. (2014). Regulation of immune responses by the neonatal fc receptor and its therapeutic implications. Front Immunol , 5, 664. PMID: 25601863 DOI.


Semo J, Nicenboim J & Yaniv K. (2016). Development of the lymphatic system: new questions and paradigms. Development , 143, 924-35. PMID: 26980792 DOI.

Kai-Larsen Y, Gudmundsson GH & Agerberth B. (2014). A review of the innate immune defence of the human foetus and newborn, with the emphasis on antimicrobial peptides. Acta Paediatr. , 103, 1000-8. PMID: 24861898 DOI.

Bertozzi CC, Hess PR & Kahn ML. (2010). Platelets: covert regulators of lymphatic development. Arterioscler. Thromb. Vasc. Biol. , 30, 2368-71. PMID: 21071706 DOI.

Maby-El Hajjami H & Petrova TV. (2008). Developmental and pathological lymphangiogenesis: from models to human disease. Histochem. Cell Biol. , 130, 1063-78. PMID: 18946678 DOI.

Zawieja D. (2005). Lymphatic biology and the microcirculation: past, present and future. Microcirculation , 12, 141-50. PMID: 15804980 DOI.

Hong YK, Shin JW & Detmar M. (2004). Development of the lymphatic vascular system: a mystery unravels. Dev. Dyn. , 231, 462-73. PMID: 15376314 DOI.

Mebius RE. (2003). Organogenesis of lymphoid tissues. Nat. Rev. Immunol. , 3, 292-303. PMID: 12669020 DOI.


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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 containing antigen-presenting cells, antigen, effector and memory T cells, and regulatory T cells.
  • 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) immature neutrophil 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.
  • bone marrow sinusoid - endothelial cells and no supporting cells vascular space supplied by arteriole and capillary vessels, interconnected by inter-sinusoidal capillaries, spanning throughout the bone marrow. Radially distributed around the draining central sinus (about 100 µm in diameter). Bone marrow sinusoids are unique and are not comparable with regular veins.
  • 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.
  • crypt - (tonsil crypt) tonsil squamous epithelium infold, with intraepithelial passages containing non-epithelial cells. Functions include: intimate contact between immune response effector cells, facilitate transport of antigens, synthesise secretory components, and contain a pool of immunoglobulins. PMID 7559106
  • 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 and pre-dendritic cells to enter a lymph node. The endothelial cells express ligands that bind lymphocytes, aiding their adhesion and subsequent transmigration into the lymph node. With inflammation, monocytes and NK cells can also enter here.
  • 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 released at mucosal surfaces and in secretions (saliva, tears, milk, and respiratory and intestinal secretions) and the most abundantly produced antibody (70%). PMID 22566964
  • 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, as in lingual tonsil, forms part of Waldeyer’s ring.
  • 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.
  • NAVL - (naval) mnemonic to remember the neurovascular bundle components Nerve Artery Vein Lymph found travelling together within organs and tissues.
  • 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.
  • PALS - acronym for PeriArterial Lymphoid Sheath in the spleen white pulp.
  • 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.
  • reticular fibres - reticular cells secrete this extracellular matrix protein, composed of type III collagen.
  • 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.
  • sinus - a larger vessel or space usually curved that may contain air, blood, or lymph. e.g. splenic medullary sinus, lymph node medullary sinus, sub-capsular sinus, trabecular sinus.
  • sinusoid - a tiny vessel with a tortuous path and many connections to similar vessels. e.g. hepatic and bone marrow sinusoids.
  • 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.
  • sphingosine-1-phosphate - (S1P) sphingolipid secreted into the extracellular space establishing a gradient acting through G protein-coupled receptors to attract lymphocytes out of lymphoid organs (lymph node, thymus, spleen) into the circulation.
  • 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 - (TD) largest and main lymphatic vessel, drains the lower body including the extremities and abdomen. Intra-thoracic tributaries include: intercostal, mediastinal, and bronchomediastinal trunks.

  • 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, thymosins) organ involved in the maturation (differentiation) of T lymphocytes (T-cells).
  • 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.
  • tonsillitis - a common bacterial infection of the palatine tonsils, occurring mostly in children and young adults and can also become recurrent tonsillitis.
  • 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 follicles, Malpighian bodies of the spleen, white nodules, 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. (2024, May 21) Embryology Immune System Development. Retrieved from

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