Talk:Immune System Development
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Cite this page: Hill, M.A. (2026, August 17) Embryology Immune System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Immune_System_Development |
Note much of the current immune research refers to the postnatal or adult system.
2012
Development of murine hepatic NK cells during ontogeny: comparison with spleen NK cells
Clin Dev Immunol. 2012;2012:759765. Epub 2011 Dec 6.
Wu X, Chen Y, Wei H, Sun R, Tian Z. Source Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China.
Abstract
The phenotype of developing liver NK cells (CD3(-)NK1.1(+)) was investigated during mouse ontogeny comparing with spleen NK cells. The highest percentage of hepatic CD27(-)CD11b(-) NK cells occurred at the fetal stage. After birth, the percentage of CD27(-)CD11b(-)NK cells in both the liver and spleen gradually decreased to their lowest level at 6 weeks. More CD27(+)CD11b(-)NK cells were detected in the liver than that in spleen from week 1 to 6. Expression of NKG2A on liver NK cells was decreased but still much higher than that of spleen NK cells after 1 week. The NKG2D expression on liver NK cells increased to its highest level and was significantly higher than on spleen NK cells till 4 weeks. During mouse ontogeny, weaker expression of NKp46 and CD2 and stronger expression of CD69, CD11c, 2B4, and CD73 were observed on liver NK cells. Furthermore, neonatal liver NK cells express higher IFN-γ and perforin than adult .These results suggest that the maturation process of NK cells is unique in the livers, and liver microenvironments might play critical roles to keep NK cells in an immature status.
- The liver is a lymphoid organ with a predominantly innate immune system [31, 32]. NK cells are abundant in the normal liver, accounting for approximately one-third of intrahepatic lymphocytes, which differs from other lymphoid organs and peripheral blood.
PMID 22203859
31 Hepatology. 2008 Feb;47(2):729-36. Liver: An organ with predominant innate immunity. Gao B, Jeong WI, Tian Z. Source Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. bgao@mail.nih.gov Abstract Blood circulating from the intestines to the liver is rich in bacterial products, environmental toxins, and food antigens. To effectively and quickly defend against potentially toxic agents without launching harmful immune responses, the liver relies on its strong innate immune system. This comprises enrichment of innate immune cells (such as macrophages, natural killer, natural killer T, and gammadelta T cells) and removal of waste molecules and immunologic elimination of microorganisms by liver endothelial cells and Kupffer cells. In addition, the liver also plays an important role in controlling systemic innate immunity through the biosynthesis of numerous soluble pathogen-recognition receptors and complement components. CONCLUSION: The liver is an organ with predominant innate immunity, playing an important role not only in host defenses against invading microorganisms and tumor transformation but also in liver injury and repair. Recent evidence suggests that innate immunity is also involved in the pathogenesis of liver fibrosis, providing novel therapeutic targets to treat such a liver disorder. PMID 18167066
Annu Rev Immunol. 2009;27:147-63. The liver as a lymphoid organ. Crispe IN. Source David H. Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Research, University of Rochester Medical Center, Rochester, New York 14642, USA. nick_crispe@urmc.rochester.edu Abstract The liver receives blood from both the systemic circulation and the intestine, and in distinctive, thin-walled sinusoids this mixture passes over a large macrophage population, termed Kupffer cells. The exposure of liver cells to antigens, and to microbial products derived from the intestinal bacteria, has resulted in a distinctive local immune environment. Innate lymphocytes, including both natural killer cells and natural killer T cells, are unusually abundant in the liver. Multiple populations of nonhematopoietic liver cells, including sinusoidal endothelial cells, stellate cells located in the subendothelial space, and liver parenchymal cells, take on the roles of antigen-presenting cells. These cells present antigen in the context of immunosuppressive cytokines and inhibitory cell surface ligands, and immune responses to liver antigens often result in tolerance. Important human pathogens, including hepatitis C virus and the malaria parasite, exploit the liver's environment, subvert immunity, and establish persistent infection. PMID 19302037
2011
2010
Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans
Science. 2010 Dec 17;330(6011):1695-9.
Mold JE, Venkatasubrahmanyam S, Burt TD, Michaëlsson J, Rivera JM, Galkina SA, Weinberg K, Stoddart CA, McCune JM.
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94143-1234, USA. Erratum in:
Science. 2011 Feb 4;331(6017):534. Comment in:
Science. 2010 Dec 17;330(6011):1635-6.
Abstract
Although the mammalian immune system is generally thought to develop in a linear fashion, findings in avian and murine species argue instead for the developmentally ordered appearance (or "layering") of distinct hematopoietic stem cells (HSCs) that give rise to distinct lymphocyte lineages at different stages of development. Here we provide evidence of an analogous layered immune system in humans. Our results suggest that fetal and adult T cells are distinct populations that arise from different populations of HSCs that are present at different stages of development. We also provide evidence that the fetal T cell lineage is biased toward immune tolerance. These observations offer a mechanistic explanation for the tolerogenic properties of the developing fetus and for variable degrees of immune responsiveness at birth.
PMID 21164017
Platelets: covert regulators of lymphatic development
Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2368-71. Epub 2010 Nov 11.
Bertozzi CC, Hess PR, Kahn ML. Department of Medicine and Cardiovascular Institute, University of Pennsylvania, Philadelphia Pa 19104, USA.
Abstract
The field of platelet biology has rapidly expanded beyond the classical role of platelets in preventing blood loss and orchestrating clot formation. Despite the lack of transcriptional ability of these anuclear cell fragments, platelet function is now thought to encompass such diverse contexts as tissue repair, immune activation, primary tumor formation, and metastasis. Recent studies from multiple groups have turned the spotlight on an exciting new role for platelets in the formation of lymphatic vessels during embryonic development. Genetic experiments demonstrate that podoplanin, a transmembrane protein expressed on lymphatic endothelial cells, engages the platelet C-type lectin-like receptor 2 (CLEC-2) when exposed to blood, leading to SYK-SLP-76-dependent platelet activation. When components of this pathway are disrupted, aberrant vascular connections form, resulting in blood-lymphatic mixing. Furthermore, platelet-null embryos manifest identical blood-lymphatic mixing. The identification of platelets as the critical cell type mediating blood-lymphatic vascular separation raises new questions in our understanding of lymphatic development and platelet biology.
PMID 21071706
2003
Organogenesis of lymphoid tissues
Nat Rev Immunol. 2003 Apr;3(4):292-303. Mebius RE. Source Department of Molecular Cell Biology, VU University Medical Center, v.d. Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. r.mebius.cell@med.vu.nl Erratum in Nat Rev Immunol. 2003 Jun;3(6):509.
Abstract
The development of lymphoid organs depends on the correct expression of several molecules within a defined timeframe during ontogeny. Although this is an extremely complex process, with each secondary lymphoid tissue requiring subtly different signals, a common framework for lymphoid development is beginning to emerge. Drawing on studies of lymph nodes, Peyer's patches and nasal-associated lymphoid tissue, an integrative model of lymphoid-tissue development, involving adhesion molecules, cytokines and chemokines, which emphasizes the role of interactions between CD3-CD4+CD45+ 'inducer' cells and VCAM1+ICAM1+ stromal 'organizer' cells is presented.
PMID 12669020
2002
Phenotypic and functional analysis of human T lymphocytes in early second- and third-trimester fetuses
Clin Exp Immunol. 2002 Aug;129(2):302-8.
Zhao Y, Dai ZP, Lv P, Gao XM. Source Department of Obstetrics & Gynaecology, People's Hospital, Peking University, Beijing, China.
Abstract
This study was undertaken to investigate the phenotypic and functional status of T lymphocytes of human fetuses from early second- to third-trimester. Cord blood samples were obtained from 19 healthy human fetuses (gestation weeks: 18-36), by cordocentesis, and 16 term newborns (gestation weeks 37-42). Maternal and unrelated male blood samples were also taken as controls. Percentage of lymphocytes in fetal white blood cells was 79.3%, reducing to 40% by term birth, much higher than that of adults. Cord blood mononuclear cells (CBMC), prepared by density gradient centrifugation followed by lysis of erythrocytes, were stained using PE- or FITC-labelled monoclonal Abs and analysed by flow cytometry. The frequencies of CD3+ T cells in fetal (40.1%) and neonatal (42.4%) CBMC were significantly lower than that of men (59.6%) and pregnant women (53.6%). Proportions of CD8+ T cells (9.5%), gammadelta-T cells (0.5%) and NK cells (4.8%) in fetal CBMC were also lower than that of neonates (except gammadelta-T cells) and adults. A negative linear correlation (r = -0.609) between the ratio of CD4+/CD8+ T cells in fetal blood and gestation age could also be established. Fetal CBMC showed vigorous spontaneous proliferation but failed to respond to mitogen (PHA) or allogeneic stimulation in vitro. The fetal mononuclear cells were unable to produce IL-2, IL-4 or IFN-gamma, but spontaneously secreted IL-10, IL-6 and TNF-alphain vitro. Stimulation with PHA up-regulated the production of IL-10, IL-6 and TNF-alpha substantially.
PMID 12165087
2001
Slow, programmed maturation of the immunoglobulin HCDR3 repertoire during the third trimester of fetal life
Blood. 2001 Nov 1;98(9):2745-51.
Schroeder HW Jr, Zhang L, Philips JB 3rd. Source Division of Developmental and Clinical Immunology, Department of Medicine, University of Alabama at Birmingham, 35294, USA. harry.schroeder@cc.uab.edu
Abstract
The mean distribution of lengths in the third complementarity-determining region of the heavy chain (HCDR3) serves as a measure of the development of the antibody repertoire during ontogeny. To determine the timing and pattern of HCDR3 length maturation during the third trimester of pregnancy, the mean distribution of HCDR3 lengths among variable-diversity-joining-constant-mu (VDJC(mu)) transcripts from the cord blood was analyzed from 138 infants of 23 to 40 weeks' gestation, including 3 sets of twins, 2 of which were of dizygotic origin. HCDR3 maturation begins at the start of the third trimester; follows a slow, continuous expansion over a 5-month period; and is unaffected by race or sex. The range and mean distribution of lengths may vary in dizygotic twins, indicating individual rates of development. The mean HCDR3 length distribution in 10 premature infants with documented bacterial sepsis was then followed for 2 to 12 weeks after their first positive blood culture. HCDR3 spectrotype analysis demonstrated oligoclonal B-cell activation and expansion after sepsis, but maturation of the repertoire was not accelerated even by the systemic exposure to external antigen represented by bacteremia. Antibody repertoire development appears to be endogenously controlled and adheres to an individualized developmental progression that probably contributes to the relative immaturity of the neonatal immune response.
PMID 11675347
Dynamics of immunoglobulins at the feto-maternal interface
Rev Reprod. 1999 May;4(2):81-9.
Saji F, Samejima Y, Kamiura S, Koyama M. Source Department of Gynecology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. Abstract Transplacental transport of maternal immunoglobulin G (IgG) to the developing fetus is extremely important in the protection of the newborn from infection. Although the exact mechanisms of the selective and active transfer of IgG across the placental barrier are not fully understood, receptors for the Fc part of IgG (FcgammaRs) in the placenta are believed to play a key role. Several known Fc receptors, FcgammaRI, FcgammaRII, FcgammaRIII and FcRn (neonatal FcR), demonstrate heterogeneous expression patterns in placenta. Immunohistochemical analysis shows the expression of FcgammaRI on Hofbauer cells in stromal tissue, FcbetaRII on Hofbauer cells and fetal blood endothelium, FcgammaRIII on Hofbauer cells and trophoblasts, and FcRn on syncytiotrophoblasts and endothelial cells. Recent studies provide evidence for important associations among these receptors and transcytosis of IgG, as well as scavenger mechanisms for clearing immune complexes in the placenta during pregnancy.
PMID 10357095
