Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-2pzkn Total loading time: 0 Render date: 2024-06-06T18:07:41.669Z Has data issue: false hasContentIssue false

Chapter 3 - The Development of the Human Immune System

from Section I - Developmental Hematology

Published online by Cambridge University Press:  30 January 2021

By
Amy E. O’Connell ,
Angela E. Rivers  and
William B. Slayton
Edited by
Pedro A. de Alarcón ,
Eric J. Werner ,
Robert D. Christensen  and
Martha C. Sola-Visner
Pedro A. de Alarcón
Affiliation:
University of Illinois College of Medicine
Eric J. Werner
Affiliation:
Children's Hospital of the King's Daughters
Robert D. Christensen
Affiliation:
University of Utah
Martha C. Sola-Visner
Affiliation:
Harvard University, Massachusetts
Get access

Summary

Neonates frequently suffer from life threatening infections. Immaturity of the immune system increases the vulnerability to infection, and the preterm and term neonatal immune system has specific deficiencies relative to that of an older child or adult [1, 2]. During pregnancy, the physical barrier of the placenta and the maternal immune system protect the developing human fetus from infection. However, maternal infections such as rubella, almost eradicated in developed nations through vaccination [3], or the zika virus, an emerging pathogen [4, 5], can ravage the developing embryo and fetus, leading to life-long disabilities. Furthermore, immaturity of natural barrier systems such as skin, bronchial epithelium and the lining of the gastrointestinal tract compound the weaknesses of the immune system of the premature infant [6, 7]. The importance of interactions between the developing immune system, epithelial barriers, and the microbiome to protect the preterm neonate from infection and promote health is increasingly recognized [8, 9]. Ethical and political concerns limit our ability to study the embryological development of the human immune system to the same depth [10, 11].

Type
Chapter
Information
Neonatal Hematology
Pathogenesis, Diagnosis, and Management of Hematologic Problems
 , pp. 25 - 42
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Collins, A, Weitkamp, JH, Wynn, JL. Why are preterm newborns at increased risk of infection? Arch Dis Child Fetal Neonatal Ed 2018;103:F391–F394.Google Scholar
Simon, AK, Hollander, GA, McMichael, A. Evolution of the immune system in humans from infancy to old age. Proc Biol Sci 2015;282:20143085.Google ScholarPubMed
Meissner, HC, Reef, SE, Cochi, S. Elimination of rubella from the United States: a milestone on the road to global elimination. Pediatrics 2006;117:933–5.CrossRefGoogle ScholarPubMed
May, M, Relich, RF. A comprehensive systems biology approach to studying zika virus. PLoS One 2016;11:e0161355.CrossRefGoogle ScholarPubMed
Mehta, R, Soares, CN, Medialdea-Carrera, R, et al. The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series. PLoS Negl Trop Dis 2018;12:e0006212.Google Scholar
Narendran, V, Visscher, MO, Abril, I, et al. Biomarkers of epidermal innate immunity in premature and full-term infants. Pediatr Res 2010;67:382–6.Google Scholar
Whitsett, JA. Review: The intersection of surfactant homeostasis and innate host defense of the lung: lessons from newborn infants. Innate Immun 2010;16:138–42.Google Scholar
Collado, MC, Cernada, M, Neu, J, et al. Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants. Pediatr Res 2015;77:726–31.Google Scholar
Tamburini, S, Shen, N, Wu, HC, et al. The microbiome in early life: implications for health outcomes. Nat Med 2016;22:713–22.Google Scholar
Cefalo, RC, Berghmans, RL, Hall, SP. The bioethics of human fetal tissue research and therapy: moral decision making of professionals. Am J Obstet Gynecol 1994;170:12–19.Google Scholar
Reardon, S. Trump administration launches sweeping review of fetal-tissue research. Nature 2018;562:16–17.Google Scholar
Dudley, DJ, Wiedmeier, S. The ontogeny of the immune response: perinatal perspectives. Semin Perinatol 1991;15:184–95.Google ScholarPubMed
Haddad, R, Guimiot, F, Six, E, et al. Dynamics of thymus-colonizing cells during human development. Immunity 2006;24:217–30.CrossRefGoogle ScholarPubMed
Zlotoff, DA, Schwarz, BA, Bhandoola, A. The long road to the thymus: The generation, mobilization, and circulation of T-cell progenitors in mouse and man. Semin Immunopathol 2008;30:371–82.CrossRefGoogle Scholar
Westra, ER, Swarts, DC, Staals, RH, et al. The CRISPRs, they are a-changin’: How prokaryotes generate adaptive immunity. Annu Rev Genet 2012;46:311–39.Google Scholar
Dishaw, LJ, Cannon, JP, Litman, GW, et al. Immune-directed support of rich microbial communities in the gut has ancient roots. Dev Comp Immunol 2014;47:36–51.CrossRefGoogle ScholarPubMed
Rohlfing, K, Stuhlmann, F, Docker, MF, et al. Convergent evolution of hemoglobin switching in jawed and jawless vertebrates. BMC Evol Biol 2016; 16:30.Google Scholar
Buchmann, K. Evolution of innate immunity: Clues from invertebrates via fish to mammals. Front Immunol 2014;5:459.Google Scholar
Beck, G, Habicht, GS. Immunity and the invertebrates. Sci Am 1996;275:60–3, 66.Google Scholar
Orkin, SH. Molecular genetics of chronic granulomatous disease. Annu Rev Immunol 1989;7:277–307.Google Scholar
Segal, AW, Jones, OT, Webster, D, et al. Absence of a newly described cytochrome b from neutrophils of patients with chronic granulomatous disease. Lancet 1978;2:446–9.Google Scholar
Yoshida, LS, Saruta, F, Yoshikawa, K, et al. Mutation at histidine 338 of gp91(phox) depletes FAD and affects expression of cytochrome b558 of the human NADPH oxidase. J Biol Chem 1998;273:27879–86.Google Scholar
Sharp, JG, Crouse, DA, Purtilo, DT. Ontogeny and regulation of the immune system. Arch Pathol Lab Med 1987;111:1106–13.Google ScholarPubMed
Dishaw, LJ, Litman, GW. Invertebrate allorecognition: The origins of histocompatibility. Curr Biol 2009;19:R286–8.Google Scholar
Fagan, MB, Weissman, IL. Sequence and characterization of two HSP70 genes in the colonial protochordate Botryllus schlosseri. Immunogenetics 1996;44:134–42.Google Scholar
Fagan, MB, Weissman, IL. Linkage analysis of HSP70 genes and historecognition locus in botryllus schlosseri. Immunogenetics 1998;47:468–76.Google Scholar
Parrinello, N. Cytotoxic activity of tunicate hemocytes. Prog Mol Subcell Biol 1996;15:190–217.Google Scholar
Hirano, M, Guo, P, McCurley, N, et al. Evolutionary implications of a third lymphocyte lineage in lampreys. Nature 2013;501:435–8.CrossRefGoogle ScholarPubMed
Potts, KS, Sargeant, TJ, Markham, JF, et al. A lineage of diploid platelet-forming cells precedes polyploid megakaryocyte formation in the mouse embryo. Blood 2014; 124:2725–9.Google Scholar
Tober, J, Maijenburg, MW, Speck, NA. Taking the leap: runx1 in the formation of blood from endothelium. Curr Top Dev Biol 2016;118:113–62.CrossRefGoogle ScholarPubMed
Bockamp, EO, McLaughlin, F, Gottgens, B, et al. Distinct mechanisms direct SCL/tal-1 expression in erythroid cells and CD34 positive primitive myeloid cells. J Biol Chem 1997;272:8781–90.Google Scholar
Endoh, M, Ogawa, M, Orkin, S, et al. SCL/tal-1-dependent process determines a competence to select the definitive hematopoietic lineage prior to endothelial differentiation. EMBO J 2002;21:6700–8.Google Scholar
Robertson, SM, Kennedy, M, Shannon, JM, et al. A transitional stage in the commitment of mesoderm to hematopoiesis requiring the transcription factor SCL/tal-1. Development 2000;127:2447–59.Google Scholar
Stanulovic, VS, Cauchy, P, Assi, SA, et al. LMO2 is required for TAL1 DNA binding activity and initiation of definitive haematopoiesis at the haemangioblast stage. Nucleic Acids Res 2017;45:9874–88.Google Scholar
Zhu, H, Traver, D, Davidson, AJ, et al. Regulation of the lmo2 promoter during hematopoietic and vascular development in zebrafish. Dev Biol 2005;281:256–69.Google Scholar
Kingsley, PD, Malik, J, Fantauzzo, KA, et al. Yolk sac-derived primitive erythroblasts enucleate during mammalian embryogenesis. Blood 2004;104:19–25.CrossRefGoogle ScholarPubMed
Palis, J. Primitive and definitive erythropoiesis in mammals. Front Physiol 2014;5:3.Google Scholar
Enzan, H. Electron microscopic studies of macrophages in early human yolk sacs. Acta Pathol Jpn 1986;36:49–64.Google Scholar
Gomez Perdiguero, E, Klapproth, K, Schulz, C, et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 2015;518:547–51.Google Scholar
Beaudin, AE, Boyer, SW, Perez-Cunningham, J, et al. A transient developmental hematopoietic stem cell gives rise to innate-like B and T cells. Cell Stem Cell 2016;19:768–83.Google Scholar
Beaudin, AE, Forsberg, EC. To B1a or not to B1a: Do hematopoietic stem cells contribute to tissue-resident immune cells? Blood 2016;128:2765–9.Google Scholar
Dieterlen-Lievre, F. On the origin of haemopoietic stem cells in the avian embryo: an experimental approach. J Embryol Exp Morphol 1975;33:607–19.Google Scholar
Bertrand, JY, Giroux, S, Golub, R, et al. Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin. Proc Natl Acad Sci USA 2005;102:134–9.Google Scholar
Choi, K, Kennedy, M, Kazarov, A, et al. A common precursor for hematopoietic and endothelial cells. Development 1998;125:725–32.CrossRefGoogle ScholarPubMed
Cumano, A, Dieterlen-Lievre, F, Godin, I. Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura. Cell 1996;86:907–16.Google Scholar
Cumano, A, Godin, I. Ontogeny of the hematopoietic system. Annu Rev Immunol 2007; 25:745–85.Google Scholar
Tavian, M, Robin, C, Coulombel, L, et al. The human embryo, but not its yolk sac, generates lympho-myeloid stem cells: Mapping multipotent hematopoietic cell fate in intraembryonic mesoderm. Immunity 2001;15:487–95.Google Scholar
de Bruijn, M, Dzierzak, E. Runx transcription factors in the development and function of the definitive hematopoietic system. Blood 2017;129:2061–9.Google Scholar
Draper, JE, Sroczynska, P, Tsoulaki, O, et al. RUNX1B expression is highly heterogeneous and distinguishes megakaryocytic and erythroid lineage fate in adult mouse hematopoiesis. PLoS Genet 2016;12:e1005814.Google Scholar
Kamikubo, Y. Genetic compensation of RUNX family transcription factors in leukemia. Cancer Sci 2018;109:2358–63.Google Scholar
Yoder, MC. Inducing definitive hematopoiesis in a dish. Nat Biotechnol 2014;32:539–41.Google Scholar
Boiers, C, Carrelha, J, Lutteropp, M, et al. Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells. Cell Stem Cell 2013;13:535–48.Google Scholar
Gekas, C, Dieterlen-Lievre, F, Orkin, SH, et al. The placenta is a niche for hematopoietic stem cells. Dev Cell 2005;8:365–75.Google Scholar
Gordon-Keylock, S, Sobiesiak, M, Rybtsov, S, et al. Mouse extraembryonic arterial vessels harbor precursors capable of maturing into definitive HSCs. Blood 2013;122:2338–45.Google Scholar
Lin, Y, Yoder, MC, Yoshimoto, M. Lymphoid progenitor emergence in the murine embryo and yolk sac precedes stem cell detection. Stem Cells Dev 2014;23:1168–77.Google Scholar
Medvinsky, A, Dzierzak, E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 1996;86:897–906.CrossRefGoogle ScholarPubMed
Muller, AM, Medvinsky, A, Strouboulis, J, et al. Development of hematopoietic stem cell activity in the mouse embryo. Immunity 1994;1 291–301.CrossRefGoogle ScholarPubMed
Hadland, BK, Varnum-Finney, B, Mandal, PK, et al. A common origin for B-1a and B-2 lymphocytes in clonal pre-hematopoietic stem cells. Stem Cell Reports 2017;8:1563–1572.Google Scholar
Zhang, Y, Gao, S, Xia, J, et al. Hematopoietic hierarchy: An updated roadmap. Trends Cell Biol 2018;28:976–86.Google Scholar
Ignatz, M, Sola-Visner, M, Rimsza, LM, et al. Umbilical cord blood produces small megakaryocytes after transplantation. Biol Blood Marrow Transplant 2007;13:145–50.Google Scholar
Slayton, WB, Wainman, DA, Li, XM, et al. Developmental differences in megakaryocyte maturation are determined by the microenvironment. Stem Cells 2005;23:1400–8.Google Scholar
Hiwarkar, P, Hubank, M, Qasim, W, et al. Cord blood transplantation recapitulates fetal ontogeny with a distinct molecular signature that supports CD4(+) T-cell reconstitution. Blood Adv 2017;1:2206–16.Google Scholar
Tavassoli, M. Embryonic and fetal hemopoiesis: an overview. Blood Cells 1991;17:269–81; discussion 282–6.Google Scholar
Fukuda, T. Fetal hemopoiesis. I. Electron microscopic studies on human yolk sac hemopoiesis. Virchows Arch B Cell Pathol 1973;14:197–213.Google Scholar
Luckett, WP. Origin and differentiation of the yolk sac and extraembryonic mesoderm in presomite human and rhesus monkey embryos. Am J Anat 1978;152:59–97.Google Scholar
Barcena, A, Kapidzic, M, Muench, MO, et al. The human placenta is a hematopoietic organ during the embryonic and fetal periods of development. Dev Biol 2009;327:24–33.Google Scholar
Barcena, A, Muench, MO, Kapidzic, M, et al. A new role for the human placenta as a hematopoietic site throughout gestation. Reprod Sci 2009;16:178–87.Google Scholar
Kelemen, E, Janossa, M. Macrophages are the first differentiated blood cells formed in human embryonic liver. Exp Hematol 1980;8:996–1000.Google Scholar
Fomin, ME, Beyer, AI, Muench, MO. Human fetal liver cultures support multiple cell lineages that can engraft immunodeficient mice. Open Biol 2017;7:170108.Google Scholar
Yurasov, S, Kollmann, TR, Kim, A, et al. Severe combined immunodeficiency mice engrafted with human T cells, B cells, and myeloid cells after transplantation with human fetal bone marrow or liver cells and implanted with human fetal thymus: a model for studying human gene therapy. Blood 1997;89:1800–10.Google Scholar
Charbord, P, Tavian, M, Humeau, L, et al. Early ontogeny of the human marrow from long bones: an immunohistochemical study of hematopoiesis and its microenvironment. Blood 1996;87:4109–19.Google Scholar
Kelemen, E, Calvo, W, Fliedner, TM. Atlas of Human Hematopoietic Development (New York: Springer-Verlag, 1979).CrossRefGoogle Scholar
Slayton, WB, Juul, SE, Calhoun, DA, et al. Hematopoiesis in the liver and marrow of human fetuses at 5 to 16 weeks post-conception: quantitative assessment of macrophage and neutrophil populations. Pediatr Res 1998;43:774–82.CrossRefGoogle Scholar
Slayton, WB, Li, Y, Calhoun, DA, et al. The first-appearance of neutrophils in the human fetal bone marrow cavity. Early Hum Dev 1998;53:129–44.Google Scholar
Haynes, BF, Denning, SM, Singer, KH, et al. Ontogeny of T-cell precursors: A model for the initial stages of human T-cell development. Immunol Today 1989;10:87–91.Google Scholar
Haynes, BF, Martin, ME, Kay, HH, et al. Early events in human T cell ontogeny. Phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues. J Exp Med 1988;168:1061–80.Google Scholar
MacDonald, TT, Spencer, J. Ontogeny of the gut-associated lymphoid system in man. Acta Paediatr Suppl 1994;83:3–5.Google Scholar
Hinchliffe, D. Development of the Vertebrate Limb (Oxford: Clarendon Press, 1980).Google Scholar
Hofman, FM, Danilovs, J, Husmann, L, et al. Ontogeny of B cell markers in the human fetal liver. J Immunol 1984;133:1197–201.Google Scholar
Naito, K, Takahashi, H, Kojima, M. Ontogenic Development of Kupffer Cells (Amsterdam: Elsevier Biomedical Press, 1982).Google Scholar
Guilliams, M, De Kleer, I, Henri, S, et al. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J Exp Med 2013;210:1977–92.Google Scholar
Schulz, C, Gomez Perdiguero, E, Chorro, L, et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 2012;336:86–90.Google Scholar
Hoeffel, G, Chen, J, Lavin, Y, et al. C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 2015;42:665–78.Google Scholar
Orlikowsky, TW, Spring, B, Dannecker, GE, et al. Expression and regulation of B7 family molecules on macrophages (MPhi) in preterm and term neonatal cord blood and peripheral blood of adults. Cytometry B Clin Cytom 2003;53:40–7.Google ScholarPubMed
Marodi, L. Deficient interferon-gamma receptor-mediated signaling in neonatal macrophages. Acta Paediatr Suppl 2002;91:117–9.Google Scholar
Kraft, JD, Horzempa, J, Davis, C, et al. Neonatal macrophages express elevated levels of interleukin-27 that oppose immune responses. Immunology 2013;139:484–93.Google Scholar
Cuenca, AG, Joiner, DN, Gentile, LF, et al. TRIF-dependent innate immune activation is critical for survival to neonatal gram-negative sepsis. J Immunol 2015;194:1169–77.Google Scholar
Chelvarajan, RL, Collins, SM, Doubinskaia, IE, et al. Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens. J Leukoc Biol 2004;75:982–94.CrossRefGoogle ScholarPubMed
Olin, A, Henckel, E, Chen, Y, et al. Stereotypic immune system development in newborn children. Cell 2018;174:1277–92 e14.Google Scholar
Christensen, RD, Hill, HR. Rothstein G: granulocytic stem cell (CFUc) proliferation in experimental group B streptococcal sepsis. Pediatr Res 1983;17:278–80.Google Scholar
Christensen, RD. Rothstein G: Pre- and postnatal development of granulocytic stem cells in the rat. Pediatr Res 1984;18:599–602.Google Scholar
Makoni, M, Eckert, J, Anne Pereira, H, et al. Alterations in neonatal neutrophil function attributable to increased immature forms. Early Hum Dev 2016;103:1–7.Google Scholar
Prosser, A, Hibbert, J, Strunk, T, et al. Phagocytosis of neonatal pathogens by peripheral blood neutrophils and monocytes from newborn preterm and term infants. Pediatr Res 2013;74:503–10.CrossRefGoogle ScholarPubMed
Henkart, P, Yue CC: The role of cytoplasmic granules in lymphocyte cytotoxicity. Prog Allergy 1988;40:82–110.Google Scholar
Strauss-Albee, DM, Liang, EC, Ranganath, T, et al. The newborn human NK cell repertoire is phenotypically formed but functionally reduced. Cytometry B Clin Cytom 2017;92:33–41.Google Scholar
Lopez, C. Immunology and Pathogenesis of Persistent Virus Infections (Washington, DC: American Society of Microbiology, 1988).Google Scholar
Yu, JC, Khodadadi, H, Malik, A, et al. Innate immunity of neonates and infants. Front Immunol 2018;9:1759.Google Scholar
Eberl, G, Colonna, M, Di Santo, JP, et al. Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science 2015;348:aaa6566.Google Scholar
Bernink, JH, Peters, CP, Munneke, M, et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol 2013;14:221–9.Google Scholar
Fuchs, A, Vermi, W, Lee, JS, et al. Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-gamma-producing cells. Immunity 2013;38:769–81.Google Scholar
Moro, K, Yamada, T, Tanabe, M, et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 2010;463:540–4.Google Scholar
Neill, DR, Wong, SH, Bellosi, A, et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 2010;464:1367–70.Google Scholar
Cella, M, Fuchs, A, Vermi, W, et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 2009;457:722–5.CrossRefGoogle ScholarPubMed
Luci, C, Reynders, A, Ivanov, II, et al. Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin. Nat Immunol 2009;10:75–82.Google Scholar
Sanos, SL, Bui, VL, Mortha, A, et al. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol 2009;10:83–91.Google Scholar
Satoh-Takayama, N, Vosshenrich, CA, Lesjean-Pottier, S, et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 2008;29:958–70.Google Scholar
Miller, D, Motomura, K, Garcia-Flores, V, et al. Innate lymphoid cells in the maternal and fetal compartments. Front Immunol 2018;9:2396.Google Scholar
Bank, U, Deiser, K, Finke, D, et al. Cutting edge: Innate lymphoid cells suppress homeostatic T cell expansion in neonatal mice. J Immunol 2016;196:3532–6.Google Scholar
Colten, HR, Goldberger, G. Ontogeny of serum complement proteins. Pediatrics 1979;64:775–80.CrossRefGoogle ScholarPubMed
Ballow, M, Fang, F, Good, RA, et al. Developmental aspects of complement components in the newborn. The presence of complement components and C3 proactivator (properdin factor B) in human colostrum. Clin Exp Immunol 1974;18:257–66.Google ScholarPubMed
Grumach, AS, Ceccon, ME, Rutz, R, et al. Complement profile in neonates of different gestational ages. Scand J Immunol 2014;79:276–81.Google Scholar
Adkins, B, Mueller, C, Okada, CY, et al. Early events in T-cell maturation. Annu Rev Immunol 1987;5:325–65.Google Scholar
Haynes, BF. The role of the thymic microenvironment in promotion of early stages of human T cell maturation. Clin Res 1986;34:422–31.Google Scholar
Germain, RN, Margulies, DH. The biochemistry and cell biology of antigen processing and presentation. Annu Rev Immunol 1993;11:403–50.CrossRefGoogle ScholarPubMed
Kingsley, G, Pitzalis, C, Waugh, AP, et al. Correlation of immunoregulatory function with cell phenotype in cord blood lymphocytes. Clin Exp Immunol 1988;73:40–5.Google Scholar
Bruning, T, Daiminger, A, Enders, G. Diagnostic value of CD45RO expression on circulating T lymphocytes of fetuses and newborn infants with pre-, peri- or early post-natal infections. Clin Exp Immunol 1997;107:306–11.Google Scholar
Paganelli, R, Cherchi, M, Scala, E, et al. Activated and “memory” phenotype of circulating T lymphocytes in intrauterine life. Cell Immunol 1994;155:486–92.Google Scholar
Durandy, A, De Saint Basile, G, Lisowska-Grospierre, B, et al. Undetectable CD40 ligand expression on T cells and low B cell responses to CD40 binding agonists in human newborns. J Immunol 1995;154:1560–8.Google Scholar
Granberg, C, Hirvonen, T. Cell-mediated lympholysis by fetal and neonatal lymphocytes in sheep and man. Cell Immunol 1980;51:13–22.Google Scholar
Granberg, C, Manninen, K, Toivanen P: Cell-mediated lympholysis by human neonatal lymphocytes. Clin Immunol Immunopathol 1976;6:256–63.Google Scholar
Hayakawa, S, Ohno, N, Okada, S, et al. Significant augmentation of regulatory T cell numbers occurs during the early neonatal period. Clin Exp Immunol 2017;190:268–79.Google Scholar
Xu, L, Tanaka, S, Bonno, M, et al. Cord blood CD4(+)CD25(+) regulatory T cells fail to inhibit cord blood NK cell functions due to insufficient production and expression of TGF-beta1. Cell Immunol 2014;290:89–95.Google Scholar
Prince, LR, Maxwell, NC, Gill, SK, et al. Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease. PLoS One 2014;9:e103059.Google Scholar
Charrier, E, Cordeiro, P, Cordeau, M, et al. Post-transcriptional down-regulation of Toll-like receptor signaling pathway in umbilical cord blood plasmacytoid dendritic cells. Cell Immunol 2012;276:114–21.CrossRefGoogle ScholarPubMed
Wilson, CB, Penix, L, Melvin, A, et al. Lymphokine regulation and the role of abnormal regulation in immunodeficiency. Clin Immunol Immunopathol 1993;67:S25–32.Google Scholar
Lawton, AR, Cooper, MD. B cell ontogeny: Immunoglobulin genes and their expression. Pediatrics 1979;64:750–7.Google Scholar
Gathings, WE, Lawton, AR, Cooper, MD. Immunofluorescent studies of the development of pre-B cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol 1977;7:804–10.Google Scholar
Coffman, RL, Seymour, BW, Lebman, DA, et al. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev 1988;102:5–28.Google Scholar
Waddick, KG, Uckun, FM. CD5 antigen-positive B lymphocytes in human B cell ontogeny during fetal development and after autologous bone marrow transplantation. Exp Hematol 1993;21:791–8.Google Scholar
Cooper, MD. Current concepts. B lymphocytes. Normal development and function. N Engl J Med 1987;317:1452–6.Google Scholar
Gathings, WE, Kubagawa, H, Cooper, MD. A distinctive pattern of B cell immaturity in perinatal humans. Immunol Rev 1981;57:107–26.Google Scholar
Lucey, DR, Clerici, M, Shearer, GM. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev 1996;9:532–62.Google Scholar
Ghilardi, N, Ouyang, W. Targeting the development and effector functions of TH17 cells. Semin Immunol 2007;19:383–93.Google Scholar
Nesin, M, Cunningham-Rundles, S. Cytokines and neonates. Am J Perinatol 2000;17:393–404.Google Scholar
Malhotra, I, Ouma, J, Wamachi, A, et al. In utero exposure to helminth and mycobacterial antigens generates cytokine responses similar to that observed in adults. J Clin Invest 1997;99:1759–66.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×