Thymus Development

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Introduction

Embryonic origins of the endocrine organs of the neck
Adult thymus location

The thymus has a key role in the development of an effective immune system as well as an endocrine function. In the adult thymus, specialised microenvironments allow the production of self-tolerant T cells from immature precursors.

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. The immune system T cells are essential for responses against infections and much research concerns the postnatal development of T cells within the thymus.

History - Stieda in 1881[1] was the first to observe that the thymus gland originated from a visceral (pharyngeal) pouch (third pharyngeal pouch endoderm). More recently there was discussion of possible surface ectoderm (third pharyngeal cleft ectoderm) contribution, but mouse tracing studies have discounted this contribution.[2]

The mature thymus epithelium has two main cell types: cortical thymic epithelial (cTECs) and medullary thymic epithelial cells (mTECs) or stromal cells. These thymic stromal cells provide signals for T cell differentiation.

The thymic medulla phagocytes negatively selects auto reactive CD4+ and CD8+ thymocytes, eliminate T cells bearing autoreactive T cell antigen receptors (TCRs). This process to prevent autoimmunity is also known as "negative selection", see adult thymus T cell elimination movie.


Endocrine Links: Introduction | BGD Lecture | Science Lecture | Pineal | Hypothalamus‎ | Pituitary | Thyroid | Parathyroid | Thymus‎ | Pancreas‎ | Adrenal‎ | Gonad‎ | Placenta‎ | Other Tissues | Stage 22 | Abnormalities | Hormones | Category:Endocrine


Immune Links: Introduction | Blood | Spleen | Thymus | Lymphatic | Lymph Node | Antibody | Med Lecture - Lymphatic Structure | Med Practical | Immune Movies | Vaccination | Bacterial Infection | Abnormalities | Category:Immune
Historic Embryology
1912 Development of the Lymphatic System | 1918 Gray's Lymphatic Images | 1916 Pig Lymphatics | 1919 Chicken Lymphatic | 1922 Pig Stomach Lymphatics | Historic Disclaimer

Some Recent Findings

Mouse Thymus gene expression[3]
  • Fetal thymus size in human pregnancies reveals inverse association with regulatory T cell frequencies in cord blood[4] "Thymus size was measured with four ultrasound techniques. The approaches with lowest coefficient of variation (thymus transverse diameter, 3 vessel edge) were used to longitudinally assess fetal and thymus growth in 137 cases at four time points between a gestational age (GA) of 13 and 37 weeks. Cord blood at birth was analyzed by flow-cytometry to evaluate the frequency of regulatory T (Treg) cells. We observed an inverse correlation between fetal thymus size at GA 23-25 weeks and cord blood Treg cells (r=0.37, p=0.01). Thymus growth occurs in a linear fashion throughout pregnancy and can be reliably measured using ultrasound. Our findings of an inverse correlation between thymus growth and Treg cells in cord blood suggests a link between fetal growth, thymus development and immune-status at birth."
  • Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse[5] "Previous studies have shown that the Hoxa3 null mutant lacks third pharyngeal pouch derivatives, the thymus and parathyroids by E18.5, and organ-specific markers are absent or downregulated during initial organogenesis. Our current analysis of the Hoxa3 null mutant shows that organ-specific domains did undergo initial patterning, but the location and timing of key regional markers within the pouch, including Tbx1, Bmp4 and Fgf8, were altered. Expression of the parathyroid marker Gcm2 was initiated but was quickly downregulated and differentiation failed; by contrast, thymus markers were delayed but achieved normal levels, concurrent with complete loss through apoptosis. To determine the cell type-specific roles of Hoxa3 in third pharyngeal pouch development, we analyzed tissue-specific mutants using endoderm and/or neural crest cell (NCC)-specific Cre drivers. Simultaneous deletion with both drivers resulted in athymia at E18.5, similar to the null. By contrast, the individual tissue-specific Hoxa3 deletions resulted in small, ectopic thymi, although each had a unique phenotype. Hoxa3 was primarily required in NCCs for morphogenesis. In endoderm, Hoxa3 temporally regulated initiation of the thymus program and was required in a cell-autonomous manner for parathyroid differentiation. Furthermore, Hoxa3 was required for survival of third pharyngeal pouch-derived organs, but expression in either tissue was sufficient for this function." Developmental Signals - Homeobox
  • Dynamics of thymus organogenesis and colonization in early human development[6] "The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. ... In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyngeal pouch, as in the mouse, in contrast to previous suggestions."
  • Thymus organogenesis[7]"A new study in the jawless fish, lampreys, indicates the existence of a primitive thymus in these surviving representatives of the most ancient vertebrates, providing strong evidence of co-evolution of T cells and thymus."
  • Modulation of Bmp4 signalling in the epithelial-mesenchymal interactions that take place in early thymus and parathyroid development in avian embryos[8] "Epithelial-mesenchymal interactions are crucial for the development of the endoderm of the pharyngeal pouches into the epithelia of thymus and parathyroid glands. ...Furthermore, mesenchymal-derived Bmp4 appears to be essential to promote early stages of endoderm development during a short window of time, irrespective of the mesenchymal source. In vivo studies using the quail-chick system and implantation of growth factor soaked-beads further showed that expression of Bmp4 by the mesenchyme is necessary during a 24 h-period of time. After this period however, Bmp4 is no longer required and another signalling factor produced by the mesenchyme, Fgf10, influences later differentiation of the pouch endoderm. "
More recent papers
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  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

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Search term: Thymus Embryology

Katalin Sándor, Anna Pallai, Edina Duró, Pascal Legendre, Isabelle Couillin, Tibor Sághy, Zsuzsa Szondy Adenosine produced from adenine nucleotides through an interaction between apoptotic cells and engulfing macrophages contributes to the appearance of transglutaminase 2 in dying thymocytes. Amino Acids: 2016; PubMed 27236567

Joanna Kabat-Koperska, Agnieszka Kolasa-Wołosiuk, Bartosz Wojciuk, Iwona Wojciechowska-Koszko, Paulina Roszkowska, Barbara Krasnodębska-Szponder, Edyta Paczkowska, Krzysztof Safranow, Edyta Gołembiewska, Bogusław Machaliński, Kazimierz Ciechanowski Changes in the immune system of female Wistar rats after exposure to immunosuppressive treatment during pregnancy. Scand. J. Immunol.: 2016; PubMed 27007325

Theodoros Petridis, Dimitra Giannakopoulou, Vassiliki Stamatopoulou, Katerina Grafanaki, Christos G Kostopoulos, Helen Papadaki, Christina J Malavaki, Nikos K Karamanos, Stathianna Douroumi, Dionysios Papachristou, George E Magoulas, Dionissios Papaioannou, Denis Drainas Investigation on Toxicity and Teratogenicity in Rats of a Retinoid-Polyamine Conjugate with Potent Anti-Inflammatory Properties. Birth Defects Res. B Dev. Reprod. Toxicol.: 2016; PubMed 26762583

Roger Colobran, Elena Álvarez de la Campa, Pere Soler-Palacín, Andrea Martín-Nalda, Ricardo Pujol-Borrell, Xavier de la Cruz, Mónica Martínez-Gallo Clinical and structural impact of mutations affecting the residue Phe367 of FOXP3 in patients with IPEX syndrome. Clin. Immunol.: 2015; PubMed 26748374

Aleksandar Rašković, Nebojša Pavlović, Maja Kvrgić, Jan Sudji, Gorana Mitić, Ivan Čapo, Momir Mikov Effects of pharmaceutical formulations containing thyme on carbon tetrachloride-induced liver injury in rats. BMC Complement Altern Med: 2015, 15(1);442 PubMed 26683486

Development Overview

Stage 13 Embryo pharyngeal arches showing 3rd pharyngeal pouch

The thymus and parathyroid are derived from 3rd pharyngeal pouches.

Development is a series of epithelial/mesenchymal inductive interactions between neural crest-derived arch mesenchyme and pouch endoderm. There is also the possibility that the surface ectoderm of 3rd pharyngeal clefts participates in thymus development.

Thymic epithelial cells (TECs) are derived from the endoderm of the third pharyngeal pouch.

Hassall's bodies form between 6 and 10 lunar months in humans. They appear after lymphopoiesis has been established and the cortex, medulla and the cortico-medullary junction are able to select of T lymphocytes undergoing progressive maturation. (Text modified from Bodey and Kaiser, 1997)

Experimental studies have shown that a neural crest contribution is also required during early thymic organogenesis.

Week 8

Late embryonic thymus development.

Stage 22 image 200.jpg Human- Stage 22 thymus 01.jpg
Image shows general position of the developing thymus in entire embryo cross-section. The developing thymus is shown in the midline, located behind the sternum (right) and in front of the oesophagus and trachea. Selected high power image of thymus from complete cross-section above.


Links: Carnegie stage 22

Fetal

Gray1178.jpg Fetal thymus.jpg
Fetal thymus anatomy Fetal thymus histology]]
Fetal thymus weight growth graph.jpg

Human Fetal Thymus Weight Growth

Overall Size Changes with age
  • birth 10-15 g
  • puberty 30-40 g
  • after puberty - involution
    • Replaced by adipose tissue
    • middle-aged 10 g

Thymus Anatomy

  • Superior mediastinum, anterior to heart
  • Bilobed lymphoepithelial organ
    • Contains reticular cells but no fibers
  • Stem lymphocytes
    • proliferate and differentiate
    • forms long-lived T- lymphocytes

Mouse Model

These two figure and descriptions are from a recent review.[9]

Structure and function Mouse model thymus development
Thymus structure and function cartoon01.jpg Mouse model thymus development 01.jpg
Cartoon shows the thymus histological regions (cortex and medulla) each contains several different thymic epithelial cell (TEC) subtypes. Cartoon gives embryonic timing, key events and genes for prenatal mouse thymus development.


Mouse Thymus Gene Expression Pattern

Data from review.[9]

  • Hoxa3 (homeobox A3) - Early E9.5–E10.5, third cleft surface ectoderm.
  • Pax1 (paired box gene 1) Early E9.5–E10.5, all pharyngeal pouch endoderm. Late, progressively restricted to a minor population of cells in the adult cortex
  • Pax9 (paired box gene 9) Early E9.5–E10.5, all pharyngeal pouch endoderm.
  • Eya1 (eyes absent 1 homologue ) - Early E9.5–E10.5, all pharyngeal pouch endoderm, cleft ectoderm and neural crest cell mesenchyme organogenesis. Late N.D.
  • Foxn1 (forkhead box N1) - Early E11.25, the thymus domain of third pouch (high level of expression); hair follicles and the epidermis from about E14.5. 
Late all thymic epithelial cells.
Links: Mouse Development | Homeobox | FGF | Fox | Pax

Thymus Cell Types

T cell maturation requires interaction with thymic epithelial cells (TECs) in different regions of the thymus lobule

  • cortex - (cortical thymic epithelial cells, cTECs)
  • medulla - (medullary thymic epithelial cells, mTECs).
Thymus Histology: Fetal Thymus overview | Fetal Thymus Medulla | Fetal Thymus Cortex | Adult Thymus | unlabeled fetal overview | unlabeled fetal medulla |unlabeled fetal thymic corpuscle |unlabeled fetal cortex | unlabeled adult overview | Category:Thymus | Immune System Development

T Cells

T Cells (T lymphocytes) undergo maturation within the thymus.

  1. T cell progenitors enter the thymus at the cortex/medulla border via post–capillary venules
  2. migrate toward the capsule in response to chemokine signalling.
  3. In the cortex, thymocytes undergo positive selection by cTECs then migrate to the medulla
  4. In the medulla, thymocytes are screened for reactivity to tissue-restricted self antigens expressed by mTECs.
  5. Mature T cells exit the thymus via blood or lymphatic vessels in response to a sphingosine-1-phosphate (S1P) gradient.


  • cortex and medulla - more numerous (denser) in cortex
  • majority of them developing T-lymphocytes (= thymic lymphocytes or thymocytes)

The following images are electron micrographs of T Lymphocyte (T cell) at different stages.

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

Thymic Epithelial Cells

Thymic epithelial cells (TECs) Reticuloendothelial cells, reticular cells.

T cell maturation occurs through interaction with thymic epithelial cells (TECs) in different microenvironment and regions of the thymus lobule

  • cortex - (cortical thymic epithelial cells, cTECs)
  • medulla - (medullary thymic epithelial cells, mTECs)

These cells also ensheathe cortical capillaries, form an epitheloid layer (form blood-thymus barrier)

  • abundant, eosinophilic, large, ovoid and light nucleus 1-2 nucleoli

Thymus Macrophages

These Macrophages (phagocytes) are derived from the same lineage as monocytes in the bone marrow.

  • located in cortex and medulla
  • histologically difficult to distinguish from reticular cells in (Stain - Haematoxylin Eosin)

Click Here to play on mobile device

Movie shows how dying thymocytes are efficiently cleared by phagocytes.[10]

Examples of cell death in situ during negative selection.

Purified CD4+CD8+ F5 thymocytes labeled with SNARF and Hoechst were introduced into LysM-GFP thymic slices then treated with 1 nM specific peptide for 30 min.

The incubation was continued for the indicated times and the slices were imaged by time-lapse two-photon microscopy.

The arrowheads point to dy|}ing thymocytes. Scale bars are 5 µm.

Mouse adult thymus 11.jpg

Mouse adult thymus 11.jpg
 ‎‎Thymus 1
Page | Play

Fetal/Young Thymus

Thymus histology 06.jpg

Thymus - young 01.jpg Thymus - young 02.jpg
Young medulla Young cortex

Thymic corpuscle

Hassall’s corpuscle - Mass of concentric epithelioreticular cells

Thymus Involution

Thymus adult.jpg

Adult Thymus Histology

A postnatal process defined as a decrease in the size, weight and activity of the gland with advancing age.
  • After puberty much of the parenchyma of the thymus is replaced by adipose tissue.
  • particularly cortical lymphoid tissue.
  • initially proceeds rapid but slows down in adulthood.
  • Increase in size of thymic corpuscles.
  • process is called involution
  • under the control of steroid hormones

In a recent review[11], thymic involution was described as a result of high levels of circulating sex hormones, in particular during puberty, and a lower population of precursor cells from the bone marrow and finally changes in the thymic microenvironment.

Hassall's Bodies

Fetal thymus showing Hassall's body

Hassall's bodies, also called Hassall's corpuscles

  • form between 6 and 10 lunar months in humans.
  • appear after lymphopoiesis has been established and the cortex, medulla and the cortico-medullary junction are able to select of T lymphocytes undergoing progressive maturation.
  • within the thymus their number increases until puberty, then decreases.
  • features are named after Arthur Hill Hassall (1817-1894) a British physician and chemist.

Function

Thymus Hassall's corpuscle.jpg

Hassall's corpuscles express thymic stromal lymphopoietin (TSLP), suggesting that Hassall's corpuscles have a critical role in dendritic-cell-mediated secondary positive selection of medium-to-high affinity self-reactive T cells, leading to the generation of CD4(+)CD25(+) regulatory T cells within the thymus.[12]

Thymic stromal lymphopoietin is an epithelial cell-derived cytokine expressed in several tissues (skin, gut, lungs, and thymus) that signals through a TSLP receptor (TSLPR). This receptor is a heterodimer of the IL-7 receptor alpha chain and the TSLPR chain.

Disease Association

There has been one report showing changes in Hassall's bodies morphology associated with congenital heart defects.[13]

Histology

Thymus Histology: Fetal Thymus overview | Fetal Thymus Medulla | Fetal Thymus Cortex | Adult Thymus | unlabeled fetal overview | unlabeled fetal medulla |unlabeled fetal thymic corpuscle |unlabeled fetal cortex | unlabeled adult overview | Category:Thymus | Immune System Development

The developing fetal thymus shown below is from a 20 week gestational age (GA), 18 week post-fertilization age, or second trimester stage of development.

Molecular Development

Most molecular data based upon mouse development timing and expression.

Mouse Thymus gene expression[3]
Mouse Thymus E9.5 and E10.5[3]
Mouse Thymus E11[3]


Data from review.[9]

  • Hoxa3 (homeobox A3) - Early E9.5 to E10.5, third cleft surface ectoderm.
  • Pax1 (paired box gene 1) Early E9.5 to E10.5, all pharyngeal pouch endoderm. Late, progressively restricted to a minor population of cells in the adult cortex
  • Pax9 (paired box gene 9) Early E9.5 to E10.5, all pharyngeal pouch endoderm.
  • Eya1 (eyes absent 1 homologue ) - Early [[Category:Mouse E9.5|E9.5 to E10.5, all pharyngeal pouch endoderm, cleft ectoderm and neural crest cell mesenchyme organogenesis. Late N.D.
  • Foxn1 (forkhead box N1) - Early E11.25, the thymus domain of third pouch (high level of expression); hair follicles and the epidermis from about E14.5. 
Late all thymic epithelial cells.

Foxg1 and Isl1

Transcription factors that appear to have a role in early thymic epithelial cell (TEC) differentiation

Foxn1

Cited2

Cited2 deletion in the mouse is embryonic lethal with cardiovascular malformations, adrenal agenesis, cranial ganglia fusion, exencephaly, and left-right patterning defects.[14]

"Examination of Lmo4-deficient embryos revealed partially penetrant cardiovascular malformations and hypoplastic thymus. Examination of Lmo4;Cited2 compound mutants indicated that there is a genetic interaction between Cited2 and Lmo4 in control of thymus development. Our data suggest that this may occur, in part, through control of expression of a common target gene, Tbx1, which is necessary for normal thymus development."

Eva and Six

Both Eva and Six have been implicated in thymus development.[15]

  • Eya - human homolog of the Drosophila 'eyes absent' (Eya) gene.
  • Six - vertebrate genes which are homologs of the Drosophila 'sine oculis' (so) gene.

Growth Factors

Adult thymus functions are regulated by a range of factors i, including a range of peptides:

  • ghrelin
  • leptin
  • nerve growth factor
  • interleukins


References

  1. Stieda L (1881) Untersuchungen über die Entwickelung der Glandular Thymus, Glandular Thyreoidea, und Glandular carotidica. Leipzig, Engelmann p38.
  2. Julie Gordon, Valerie A Wilson, Natalie F Blair, Julie Sheridan, Alison Farley, Linda Wilson, Nancy R Manley, C Clare Blackburn Functional evidence for a single endodermal origin for the thymic epithelium. Nat. Immunol.: 2004, 5(5);546-53 PubMed 15098031
  3. 3.0 3.1 3.2 3.3 Qiaozhi Wei, Brian G Condie A focused in situ hybridization screen identifies candidate transcriptional regulators of thymic epithelial cell development and function. PLoS ONE: 2011, 6(11);e26795 PubMed 22087235 | PLoS One.
  4. Anke Diemert, Isabel Hartwig, Mirja Pagenkemper, Ryoko Mehnert, Gudula Hansen, Eva Tolosa, Kurt Hecher, Petra Arck Fetal thymus size in human pregnancies reveals inverse association with regulatory T cell frequencies in cord blood. J. Reprod. Immunol.: 2015, 113;76-82 PubMed 26851722
  5. Jena L Chojnowski, Kyoko Masuda, Heidi A Trau, Kirk Thomas, Mario Capecchi, Nancy R Manley Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse. Development: 2014, 141(19);3697-708 PubMed 25249461
  6. Alison M Farley, Lucy X Morris, Eric Vroegindeweij, Marianne L G Depreter, Harsh Vaidya, Frances H Stenhouse, Simon R Tomlinson, Richard A Anderson, Tom Cupedo, Jan J Cornelissen, C Clare Blackburn Dynamics of thymus organogenesis and colonization in early human development. Development: 2013, 140(9);2015-26 PubMed 23571219
  7. Qing Ge, Yong Zhao Evolution of thymus organogenesis. Dev. Comp. Immunol.: 2011, 39(1-2);85-90 PubMed 22266420
  8. Hélia Neves, Elisabeth Dupin, Leonor Parreira, Nicole M Le Douarin Modulation of Bmp4 signalling in the epithelial-mesenchymal interactions that take place in early thymus and parathyroid development in avian embryos. Dev. Biol.: 2012, 361(2);208-19 PubMed 22057081
  9. 9.0 9.1 9.2 C Clare Blackburn, Nancy R Manley Developing a new paradigm for thymus organogenesis. Nat. Rev. Immunol.: 2004, 4(4);278-89 PubMed 15057786 | Nat Rev Immune.
  10. Ivan Lilyanov Dzhagalov, Katherine Grace Chen, Paul Herzmark, Ellen A Robey Elimination of self-reactive T cells in the thymus: a timeline for negative selection. PLoS Biol.: 2013, 11(5);e1001566 PubMed 23700386 | PLoS Biol. | PLoS Biol. Immunobiology Collection
  11. Victor Appay, Delphine Sauce, Martina Prelog The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals. Aging (Albany NY): 2010, 2(2);78-81 PubMed 20354268
  12. Norihiko Watanabe, Yi-Hong Wang, Heung Kyu Lee, Tomoki Ito, Yui-Hsi Wang, Wei Cao, Yong-Jun Liu Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature: 2005, 436(7054);1181-5 PubMed 16121185
  13. I Varga, V Pospisilova, V Jablonska, V Sisovsky, P Galfiova, S Polak, M Adamkov Thymic Hassall's bodies of children with congenital heart defects. Bratisl Lek Listy: 2010, 111(10);552-7 PubMed 21125801
  14. Anna C Michell, José Bragança, Carol Broadbent, Bradley Joyce, Angela Franklyn, Jürgen E Schneider, Shoumo Bhattacharya, Simon D Bamforth A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2. Dev. Dyn.: 2010, 239(7);1988-94 PubMed 20549734
  15. Dan Zou, Derek Silvius, Julie Davenport, Raphaelle Grifone, Pascal Maire, Pin-Xian Xu Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1. Dev. Biol.: 2006, 293(2);499-512 PubMed 16530750

Reviews

Thomas Boehm, Jeremy B Swann Thymus involution and regeneration: two sides of the same coin? Nat. Rev. Immunol.: 2013, 13(11);831-8 PubMed 24052146

Julie Gordon, Nancy R Manley Mechanisms of thymus organogenesis and morphogenesis. Development: 2011, 138(18);3865-78 PubMed 21862553

Thomas Boehm Thymus development and function. Curr. Opin. Immunol.: 2008, 20(2);178-84 PubMed 18403191

Wilson Savino The thymus is a common target organ in infectious diseases. PLoS Pathog.: 2006, 2(6);e62 PubMed 16846255

Georg Holländer, Jason Gill, Saulius Zuklys, Norimasa Iwanami, Cunlan Liu, Yousuke Takahama Cellular and molecular events during early thymus development. Immunol. Rev.: 2006, 209;28-46 PubMed 16448532

Thomas Boehm, Conrad C Bleul, Michael Schorpp Genetic dissection of thymus development in mouse and zebrafish. Immunol. Rev.: 2003, 195;15-27 PubMed 12969307

J Sen Signal transduction in thymus development. Cell. Mol. Biol. (Noisy-le-grand): 2001, 47(1);197-215 PubMed 11292256


Articles

Adrienne E Calder, Melanie N Hince, Jarrod A Dudakov, Ann P Chidgey, Richard L Boyd Thymic involution: where endocrinology meets immunology. Neuroimmunomodulation: 2011, 18(5);281-9 PubMed 21952680

A Cromi, F Ghezzi, R Raffaelli, V Bergamini, G Siesto, P Bolis Ultrasonographic measurement of thymus size in IUGR fetuses: a marker of the fetal immunoendocrine response to malnutrition. Ultrasound Obstet Gynecol: 2009, 33(4);421-6 PubMed 19306477

Yaron Zalel, Ronni Gamzu, Shlomo Mashiach, Reuven Achiron The development of the fetal thymus: an in utero sonographic evaluation. Prenat. Diagn.: 2002, 22(2);114-7 PubMed 11857615


Search PubMed: Thymus Development | Thymus Embryology

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Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Sudler, MT. The Development of the Nose and of the Pharynx and its Derivatives in Man. (1902) Amer. J. Anat 1:391–416. Thymus Gland

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.
  • 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) historically named after a structure called the bursa of Fabricius in birds, a source of antibody-producing lymphocytes. These cells develop in the bone marrow. (More? Electron micrographs of nonactivate and activated lymphocytes)
  • BALT - Bronchus Associated Lymphoid Tissue
  • 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.
  • Cell-mediated immunity - the immune function of T lymphocytes.
  • "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.
  • CD4+ - (T helper cells) refers to T lymphocytes that express CD4 (glycoprotein of the immunoglobulin superfamily) on their surface. These cells can be infected by human immunodeficiency virus (HIV).
  • CD8+ - (cytotoxic T cells) refers to T lymphocytes that express CD8 (glycoprotein of the immunoglobulin superfamily) on their surface.
  • "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.
  • 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.
  • GALT - Gut Associated Lymphatic Tissue consisting of Peyer’s patches, isolated lymphoid follicles and mesenteric lymph nodes.
  • haemopoiesis (hemopoiesis) formation of blood cells.
  • Hassall's corpuscle - thymic corpuscle.
  • 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. Their endothelial cells express ligands that bind lymphocytes, aiding their adhesion and subsequent transmigration into the lymph node.
  • 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.
  • immunodeficiency - when one or more components of the immune system is defective. (More? Immunobiology - immunodeficiency)
  • immunoglobulin - (antibody, Ab) protein produced by plasma cells.
  • intraepithelial lymphocyte (IEL) immune cells residing in the gastrointestinal tract epithelium. image - Intraepithelial lymphocyte differentiation
  • involution - in the thymus refers to the replacement, mainly in the cortex, of cells by adipose tissue. (More? PubMed- thymus involution) | Cancer Medicine - Thymomas and Thymic Tumors)
  • 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 the epithelium of 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.
  • 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.
  • macrophage - a large highly motile white blood cell which engulfs foreign material (bacteria etc) and both degenerating cells and cell fragments. Differentiates from a monocyte and found in many different tissues and locations. Current theory suggests tissue macrophage is also derived from resident stem cell population in many tissues. More? Immunobiology - Defects in phagocytic cells are associated with persistence of bacterial infection)
  • 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.
  • Memory Cell - effector T cell (lymphocyte)
  • mesenteric lymph nodes - Part of GALT as well as being involved in gut-draining. image - mesenteric lymph nodes
  • 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.
  • 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)
  • 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.
  • red pulp - spleen region, organized as cell cords (splenic cords, cords of Billroth) and vascular sinuses.
  • sentinel lymph node - the hypothetical first lymph node or group of nodes reached by metastasizing cancer cells from a primary tumour.
  • splenic sinusoids - enlarged spleen capillary 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.
  • 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) 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)
  • 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.
  • 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. (2016) Embryology Thymus Development. Retrieved July 25, 2016, from https://embryology.med.unsw.edu.au/embryology/index.php/Thymus_Development

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© Dr Mark Hill 2016, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G