Cardiovascular System - Spleen Development
|Embryology - 26 Feb 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Development Overview
- 4 Spleen Development Movies
- 5 Adult Spleen
- 6 Histology
- 7 Molecular
- 8 Abnormalities
- 9 References
- 10 Terms
- 11 Glossary Links
The spleen is located on the left side of the abdomen and has a role initially in blood and then immune system development. The spleen's haematopoietic function (blood cell formation) is lost with embryo development and lymphoid precursor cells migrate into the developing organ. Vascularization of the spleen arises initially by branches from the dorsal aorta. Mesoderm within the dorsal mesogastrium form a long strip of cells adjacent to the forming stomach above the developing pancreas.
The human spleen arises in week 5 within the dorsal mesentery 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.
|Immune Links: Introduction | Blood | Spleen | Thymus | Lymphatic | Lymph Node | Antibody | Med Lecture - Lymphatic Structure | Med Practical | Immune Movies | Vaccination | Bacterial Infection | Abnormalities | Category:Immune|
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
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.
Jonathan K H Tan, Takeshi Watanabe Stromal Cell Subsets Directing Neonatal Spleen Regeneration. Sci Rep: 2017, 7;40401 PubMed 28067323
Marie-Therese Khairallah, Jacob Astroski, Sarah K Custer, Elliot J Androphy, Craig L Franklin, Christian L Lorson SMN deficiency negatively impacts red pulp macrophages and spleen development in mouse models of Spinal Muscular Atrophy. Hum. Mol. Genet.: 2017; PubMed 28062667
Cindy Colson, Estelle Aubry, Maryse Cartigny, Amélie-Anne Rémy, Hélène Franquet, Xavier Leroy, Géraldine Kéchid, Christine Lefèvre, Rémi Besson, Martine Cools, Anne Françoise Spinoit, Charles Sultan, Sylvie Manouvrier, Pascal Philibert, Jamal Ghoumid Short report: SF1 and spleen development: new heterozygous mutation, literature review and consequences for NR5A1-mutated-patient's management. Clin. Genet.: 2016; PubMed 28032338
Guoxi Li, Yinli Zhao, Jie Wang, Bianzhi Liu, Xiangli Sun, Shuang Guo, Jianxin Feng Transcriptome profiling of developing spleen tissue and discovery of immune-related genes in grass carp (Ctenopharyngodon idella). Fish Shellfish Immunol.: 2016; PubMed 27965162
Elisa Lenti, Diego Farinello, Kazunari K Yokoyama, Dmitry Penkov, Laura Castagnaro, Giovanni Lavorgna, Kenly Wuputra, Lisa L Sandell, Naomi E Butler Tjaden, Francesca Bernassola, Nicoletta Caridi, Anna De Antoni, Michael Wagner, Katja Kozinc, Karen Niederreither, Francesco Blasi, Diego Pasini, Gregor Majdic, Giovanni Tonon, Paul A Trainor, Andrea Brendolan Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development. J. Clin. Invest.: 2016; PubMed 27214556
| Embryonic Carnegie stage data from a recent study of the Kyoto Collection embryos.
|D4 Dorsal Mesogastrium (stage 13)|
D4 Dorsal Mesogastrium (stage 13)
F1 Developing Human Spleen (stage 22)
F2 Developing Human Spleen (stage 22)
F3 Developing Human Spleen (stage 22)
- week 15 (17 GA) - alpha-smooth muscle actin (alpha-SMA)-positive reticulum cells scattered around the arterioles.
- week 18 to 21 (20 - 23 GA) - alpha-SMA-positive reticulum cells increase in number and began to form a reticular framework. An accumulation of T and B lymphocytes occurred within the framework, and a primitive white pulp was observed around the arterioles.
- week 22 (24 GA) - antigenic diversity of the reticular framework was observed, and T and B lymphocytes were segregated in the framework. T lymphocytes were sorted into the alpha-SMA-positive reticular framework, and the periarteriolar lymphoid sheath (PALS) was formed around the arteriole. B lymphocytes aggregated in eccentric portions to the PALS and formed the lymph follicle (LF). The reticular framework of the LF was alpha-SMA-negative.
- week 24 (26 GA) - marginal zone appeared in the alpha-SMA-positive reticular framework around the white pulp.
(Note - weeks above are approximate post-conception PC corrected from gestational age GA)
Reticular framework of white pulp and marginal zone.
- "The antigenic heterogeneity of the reticular framework of the white pulp (WP) and marginal zone (MZ) is well documented in the human adult spleen. The ontogeny of the WP and MZ of human fetal spleens was examined with special reference to the heterogeneity of the reticular framework. In the spleen of the 17th gestational week (gw), alpha-smooth muscle actin (alpha-SMA)-positive reticulum cells were scattered around the arterioles. From the 20th to 23rd gw, alpha-SMA-positive reticulum cells increased in number and began to form a reticular framework. An accumulation of T and B lymphocytes occurred within the framework, and a primitive WP was observed around the arterioles. At the 24th gw, antigenic diversity of the reticular framework was observed, and T and B lymphocytes were segregated in the framework. T lymphocytes were sorted into the alpha-SMA-positive reticular framework, and the periarteriolar lymphoid sheath (PALS) was formed around the arteriole. B lymphocytes aggregated in eccentric portions to the PALS and formed the lymph follicle (LF). The reticular framework of the LF was alpha-SMA-negative. MZ appeared in the alpha-SMA-positive reticular framework around the WP at the 26th gw. The PALS, LF, and MZ developed with gestational time. The reticular framework of the PALS, LF, and 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 Movies
| This animation shows the development of the lesser sac associated with the rotation of the stomach and growth of the liver.
This cross-sectional view of the abdomen viewed from above, with dorsal (back) top and ventral (front) bottom of animation.
Later the retroperitoneal position of the developing kidneys is also shown either side of the dorsal (thoracic) aorta.
|Gastrointestinal Tract Movies|
Adult Spleen and ligamentous attachments.
- Spleen Development: Adult Histology | Overview Red and White Pulp | Overview Red and White Pulp | Cords and Sinuses | Reticular Fibre overview | Reticular Fibre detail | unlabeled red and white pulp | unlabeled red pulp and macrophages | unlabeled white pulp germinal centre | unlabeled reticular fibre | unlabeled white pulp reticular | unlabeled red pulp reticular | Structure cartoon | Cartoon and stain | Category:Spleen | Histology Stains | Immune System Development
The spleen of wild-type (A) embryos is observed as a brown stripe next to the stomach (black arrowhead).
A subpopulation of splanchnic mesoderm cells in mice expresses this basic helix-loop-helix (bHLH) transcription factor early in spleen organogenesis. This transcription factor is also expressed in mesenchymal cells that encapsulate the epithelial primordia of internal organs.
Capsulin also known as Epicardin, Podocyte-Expressed 1, POD1, TRANSCRIPTION FACTOR 21; TCF21
- Links: OMIM
Congenital absence of the spleen is usually accompanied by complex cardiac malformations, malposition and maldevelopment of the abdominal organs, and abnormal lobation of the lungs. There are a range of other spleen anatomical development abnormalities, some of which have no effect and others are very rare.
Can be due to left/right patterning abnormality or failure of early spleen differentiation.
Clinically no significant efects in most patients, occur as single or multiple and generally found in autopsy or as an an incidental finding. Thought to occur due to a failure of primordia fusion within the dorsal mesogastrium.
Rare resulting from abnormal fusion of the splenic and gonadal primordia during prenatal development. On the left side and more common in male and adhesion to the gonad, epididymis or ductus deferens and then follows the caudal descent with the gonad. Failure of complete descent can also result in associated intraabdominal cryptorchism.
- continuous - orthotopic spleen connects to the gonad with a cord of fibrous or splenic tissue.
- discontinuous - no connection between the orthotopic spleen and gonad.
(More? Testis Development)
A very rare abnormality where the spleen can be found anatomically located in a range of places in the abdominal or thoracic cavity.
Connexin-43 involved with abnormal spleen development (cardiac and lung also).
- Aya Endo, Saki Ueno, Shigehito Yamada, Chigako Uwabe, Tetsuya Takakuwa Morphogenesis of the spleen during the human embryonic period. Anat Rec (Hoboken): 2014; PubMed 25403423
- Takashi Satoh, Eiichi Sakurai, Hiroshi Tada, Tomoyuki Masuda 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.: 2009, 336(2);287-97 PubMed 19255788
- Amir Asayesh, James Sharpe, Robert P Watson, Jacob Hecksher-Sørensen, Nicholas D Hastie, Robert E Hill, Ulf Ahlgren Spleen versus pancreas: strict control of organ interrelationship revealed by analyses of Bapx1-/- mice. Genes Dev.: 2006, 20(16);2208-13 PubMed 16912273
- Birte Steiniger, Norbert Ulfig, Manfred Risse, Peter J Barth Fetal and early post-natal development of the human spleen: from primordial arterial B cell lobules to a non-segmented organ. Histochem. Cell Biol.: 2007, 128(3);205-15 PubMed 17624541
- Danielle L Drayton, Shan Liao, Rawad H Mounzer, Nancy H Ruddle Lymphoid organ development: from ontogeny to neogenesis. Nat. Immunol.: 2006, 7(4);344-53 PubMed 16550197
- L A Lettice, L A Purdie, G J Carlson, F Kilanowski, J Dorin, R E Hill The mouse bagpipe gene controls development of axial skeleton, skull, and spleen. Proc. Natl. Acad. Sci. U.S.A.: 1999, 96(17);9695-700 PubMed 10449756 | PMC22272 | PNAS
- C W Roberts, J R Shutter, S J Korsmeyer Hox11 controls the genesis of the spleen. Nature: 1994, 368(6473);747-9 PubMed 7908720
- T N Dear, W H Colledge, M B Carlton, I Lavenir, T Larson, A J Smith, A J Warren, M J Evans, M V Sofroniew, T H Rabbitts The Hox11 gene is essential for cell survival during spleen development. Development: 1995, 121(9);2909-15 PubMed 7555717
- J Lu, P Chang, J A Richardson, L Gan, H Weiler, E N Olson The basic helix-loop-helix transcription factor capsulin controls spleen organogenesis. Proc. Natl. Acad. Sci. U.S.A.: 2000, 97(17);9525-30 PubMed 10944221
Mark F Cesta Normal structure, function, and histology of the spleen. Toxicol Pathol: 2006, 34(5);455-65 PubMed 17067939
Danielle L Drayton, Shan Liao, Rawad H Mounzer, Nancy H Ruddle Lymphoid organ development: from ontogeny to neogenesis. Nat. Immunol.: 2006, 7(4);344-53 PubMed 16550197
Miriam Shapiro-Shelef, Kathryn Calame Regulation of plasma-cell development. Nat. Rev. Immunol.: 2005, 5(3);230-42 PubMed 15738953
Rainer H Straub Complexity of the bi-directional neuroimmune junction in the spleen. Trends Pharmacol. Sci.: 2004, 25(12);640-6 PubMed 15530642
Pere-Ramon Balliu, Juan Bregante, Maria-Carmen Pérez-Velasco, Miguel Fiol, Consuelo Galiana, Manuel Herrera, Jaime Mulet Splenic haemorrhage in a newborn as the first manifestation of wandering spleen syndrome. J. Pediatr. Surg.: 2004, 39(2);240-2 PubMed 14966753
A Chadburn The spleen: anatomy and anatomical function. Semin. Hematol.: 2000, 37(1 Suppl 1);13-21 PubMed 10676919
P A Lane The spleen in children. Curr. Opin. Pediatr.: 1995, 7(1);36-41 PubMed 7728201
Search NCBI Bookshelf: Spleen Development
Search PubMed: Search August 2006 "Spleen Development" 13,401 reference articles of which 450 were reviews.
- 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 cell - (B-cell, B lymphocyte) historically named after a structure called the bursa of Fabricius in birds, a source of antibody-producing lymphocytes. These immune cells develop in the bone marrow. (More? Electron micrographs of nonactivate and activated lymphocytes)
- 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.
- 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.
- fibroblastic reticular cell - (FRC) specialized myofibroblasts that form the structural mesenchymal network "sponge" within lymphoid tissue, through which T cells, B cells, dendritic cells (DCs), plasma cells and macrophages move and interact.
- 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 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.
- 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.
- 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)
- 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.
- 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)
- T cell activation - (T lymphocyte activation)The activation process begins with T-cells searching for and encountering antigen-bearing dendritic cells within lymph nodes.
- 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).
- 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).
- 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. 2017 Embryology Cardiovascular System - Spleen Development. Retrieved February 26, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Cardiovascular_System_-_Spleen_Development
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G