Immune System Development

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Contents

Introduction

Lymphatic vessel development[1]
Developing Human Thymus (stage 22)

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

During prenatal development, maternal IgG antibodies are transferred from about week 13 (GA) across the placenta, from the maternal lacunae syncytiotrophoblast cell endosomes bind IgG through neonatal Fc receptors.

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

Some Recent Findings

  • The Nobel Prize in Physiology or Medicine 2011 Bruce A. Beutler and Jules A. Hoffmann for their discoveries concerning the activation of innate immunity and the other half to Ralph M. Steinman for his discovery of the dendritic cell and its role in adaptive immunity.
  • Regulation of lymphatic-blood vessel separation by endothelial Rac1.[2] "Sprouting angiogenesis and lymphatic-blood vessel segregation both involve the migration of endothelial cells, but the precise migratory molecules that govern the decision of blood vascular endothelial cells to segregate into lymphatic vasculature are unknown."
  • The development of intestinal lymphoid tissues at the interface of self and microbiota[3] "(postnatal) Intestinal lymphoid tissues face the challenging task of inducing adaptive immunity to pathogens, yet maintaining homeostasis with the enormous commensal microbiota. To that aim, the ancient partnership between self and flora has resulted in the generation of a unique set of lymphoid tissues capable of constant large-scale reformatting. A first set of lymphoid tissues, the mesenteric lymph nodes and Peyer's patches, are programmed to develop in the sterile environment of the fetus, whereas a second set of lymphoid tissues, the tertiary lymphoid tissues, are induced to form by the microbiota and inflammation."
  • Ordering human CD34+CD10-CD19+ pre/pro-B-cell and CD19- common lymphoid progenitor stages in two pro-B-cell development pathways.[4]"Here, we show a similar divergence in human B-cell development pathways between the Pax5(+)TdT(-) pre/pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway."
  • Epithelial cells in fetal intestine produce chemerin to recruit macrophages.[5] "Macrophages are first seen in the fetal intestine at 11-12 wk and rapidly increase in number during the 12- to 22-wk period of gestation. The development of macrophage populations in the fetal intestine precedes the appearance of lymphocytes and neutrophils and does not require the presence of dietary or microbial antigens."
  • Ontogeny of reticular framework of white pulp and marginal zone in human spleen: immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation. [6] "The reticular framework of the periarteriolar lymphoid sheath (PALS), lymph follicle (LF), and marginal zone (MZ) is thus heterogeneous in the fetal spleen, and the development of the heterogeneity is related to the ontogeny of the PALS, LF, and MZ."

Recent References | References

Spleen Development

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

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

D4 Dorsal Mesogastrium (stage 13)
Links: Spleen Development

Thymus Development

Stage 22 image 071.jpg The thymus has a key role in the development of an effective immune system as well as an endocrine function.

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

D4 Developing Thymus (stage 22)


Links: Thymus Development

Lymph Node Development

Lymph node cartoon 01.jpg

Links: Lymph Node Development


T Lymphocyte Development

A study of cord blood from 19 early second and third trimester fetuses (GA 18-36 weeks) and 16 term newborns (GA 37-42 weeks).[7]

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


Other Organs

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


Maternal Antibodies

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

During postnatal development, maternal antibodies are transferred by maternal milk across the neonatal gastrointestinal tract epithelium.


Links: Placenta Development | Milk

Additional Images

Histology

The images below are from adult immune Lymph Nodes.

Immune Cells

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


Adult Lymphocyte Histology

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

Adult Lymphocyte Motility Movies

Mouse adult lymph node 01.jpg Mouse adult lymph node 02.jpg Mouse adult lymph node 03.jpg Mouse adult lymph node 04.jpg Mouse adult lymph node 05.jpg Mouse adult lymph node 06.jpg
Transendothelial
migration
T cell zone T cell zone Sinus endothelial
barrier
Bi-directional traffic Cross the sinus
endothelial barrier
Quicktime | Flash Quicktime | Flash Quicktime | Flash Quicktime | Flash Quicktime | Flash Quicktime | Flash

References

  1. Friedemann Kiefer, Ralf H Adams Lymphatic endothelial differentiation: start out with Sox--carry on with Prox. Genome Biol.: 2008, 9(12);243 PMID:19138383 | PMC2646268 | Genome Biology
  2. Gabriela D'Amico, Dylan T Jones, Emma Nye, Karen Sapienza, Antoine R Ramjuan, Louise E Reynolds, Stephen D Robinson, Vassiliki Kostourou, Dolores Martinez, Deborah Aubyn, Richard Grose, Gareth J Thomas, Bradley Spencer-Dene, Daniel Zicha, Derek Davies, Victor Tybulewicz, Kairbaan M Hodivala-Dilke Regulation of lymphatic-blood vessel separation by endothelial Rac1. Development: 2009, 136(23);4043-53 PMID:19906871
  3. G Eberl, M Lochner The development of intestinal lymphoid tissues at the interface of self and microbiota. Mucosal Immunol: 2009, 2(6);478-85 PMID:19741595
  4. Eva Sanz, Norman Muñoz-A, Jorge Monserrat, Ana Van-Den-Rym, Pedro Escoll, Ismael Ranz, Melchor Alvarez-Mon, Antonio de-la-Hera Ordering human CD34+CD10-CD19+ pre/pro-B-cell and CD19- common lymphoid progenitor stages in two pro-B-cell development pathways. Proc. Natl. Acad. Sci. U.S.A.: 2010, 107(13);5925-30 PMID:20231472
  5. Akhil Maheshwari, Ashish R Kurundkar, Sadiq S Shaik, David R Kelly, Yolanda Hartman, Wei Zhang, Reed Dimmitt, Shehzad Saeed, David A Randolph, Charles Aprahamian, Geeta Datta, Robin K Ohls Epithelial cells in fetal intestine produce chemerin to recruit macrophages. Am. J. Physiol. Gastrointest. Liver Physiol.: 2009, 297(1);G1-G10 PMID:19443732
  6. 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 PMID:19255788
  7. Y Zhao, Z-P Dai, P Lv, X-M Gao Phenotypic and functional analysis of human T lymphocytes in early second- and third-trimester fetuses. Clin. Exp. Immunol.: 2002, 129(2);302-8 PMID:12165087

Reviews

Cara C Bertozzi, Paul R Hess, Mark L Kahn Platelets: covert regulators of lymphatic development. Arterioscler. Thromb. Vasc. Biol.: 2010, 30(12);2368-71 PMID:21071706

Hélène Maby-El Hajjami, Tatiana V Petrova Developmental and pathological lymphangiogenesis: from models to human disease. Histochem. Cell Biol.: 2008, 130(6);1063-78 PMID:18946678

David Zawieja Lymphatic biology and the microcirculation: past, present and future. Microcirculation: , 12(1);141-50 PMID:15804980

Young-Kwon Hong, Jay W Shin, Michael Detmar Development of the lymphatic vascular system: a mystery unravels. Dev. Dyn.: 2004, 231(3);462-73 PMID:15376314

Reina E Mebius Organogenesis of lymphoid tissues. Nat. Rev. Immunol.: 2003, 3(4);292-303 PMID:12669020


Articles

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Search August 2010 "Immune System Development" All (90551) Review (15955) Free Full Text (28278)


Search Pubmed: Immune System Development | Embryo Immune System Development


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