Talk:Immune System - Antibody Development
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Cite this page: Hill, M.A. (2019, July 23) Embryology Immune System - Antibody Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Immune_System_-_Antibody_Development
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<pubmed limit=5>Fetal Antibodies</pubmed>
<pubmed limit=5>Antibody Development</pubmed>
Neonatal Fc Receptor
<pubmed limit=5>Neonatal Fc Receptor</pubmed>
The natural autoantibody repertoire in newborns and adults: a current overview
Adv Exp Med Biol. 2012;750:198-212. doi: 10.1007/978-1-4614-3461-0_15.
Madi A, Bransburg-Zabary S, Kenett DY, Ben-Jacob E, Cohen IR. Source Faculty of Medicine, Tel Aviv University, Israel.
Antibody networks have been studied in the past based on the connectivity between idiotypes and anti-idiotypes-antibodies that bind one another. Here we call attention to a different network of antibodies, antibodies connected by their reactivities to sets of antigens-the antigen-reactivity network. The recent development of antigen microarray chip technology for detecting global patterns of antibody reactivities makes it possible to study the immune system quantitatively using network analysis tools. Here, we review the analyses of IgM and IgG autoantibody reactivities of sera of mothers and their offspring (umbilical cords) to 300 defined self-antigens; the autoantibody reactivities present in cord blood represent the natural autoimmune repertories with which healthy humans begin life and the mothers' reactivities reflect the development of the repertoires in healthy young adults. Comparing the cord and maternal reactivities using several analytic tools led to the following conclusions: (1) The IgG repertoires showed a high correlation between each mother and her newborn; the IgM repertoires of all the cords were very similar and each cord differed from its mother's IgM repertoire. Thus, different humans are born with very similar IgM autoantibodies produced in utero and with unique IgG autoantibodies found in their individual mothers. (2) Autoantibody repertoires appear to be structured into sets of reactivities that are organized into cliques-reactivities to particular antigens are correlated. (3) Autoantibody repertoires are organized as networks of reactivities in which certain key antigen reactivities dominate the network-the dominant antigen reactivities manifest a "causal" relationship to sets of other correlated reactivities. Thus, repertoires of autoantibodies in healthy subjects, the immunological homunculus, are structured in hierarchies of antigen reactivities.
The Contribution of FcRn Binding to Intestinal Uptake of IgG in Suckling Rat Pups and Human FcRn-Transgenic Mice
Am J Physiol Gastrointest Liver Physiol. 2012 Dec 6. [Epub ahead of print]
Kliwinski C, Cooper PR, Perkinson R, Mabus JR, Tam SH, Wilkinson TM, Giles-Komar J, Scallon B, Powers GD, Hornby PJ. Source 1Janssen Pharmaceutical.
Immunoglobulin G (IgG) is transcytosed across intestinal epithelial cells of suckling mammals by the neonatal Fc receptor (FcRn); however, the contribution of FcRn versus FcRn-independent uptake to serum IgG levels had not been determined in either rat pups or human (h)FcRn-expressing mice (Tg276 and Tg32). In isofluorane-anesthetized rodents, serum levels were determined after regional intestinal delivery of human monoclonal antibodies (hIgG) with either wild-type (WT) Fc sequences or variants engineered for different FcRn binding affinities. Detection of full-length hIgG was by immunoassay; intestinal hFcRn and hIgG localization was by immunocytochemistry. High (µg/mL) serum levels of hIgG were detected after proximal intestinal delivery (0.1-10 mg/kg) in 2-week-old rats. Human FcRn was visualized in epithelial cells of Tg276 mice but low serum hIgG levels (< 10 ng/mL) were obtained. In rat pups, intra-intestinal hIgG1 WT administration resulted in dose-related and saturable uptake, whereas uptake of a low FcRn-binding affinity variant was non-saturable. There were no differences in hIgG levels from systemic and hepatic portal vein serum samples, and intense hIgG immunostaining was noted in villi enterocytes and within lymphatic lacteal-like vessels. This study demonstrated that FcRn-mediated uptake in rat pups accounted for ~80% of serum hIgG levels, and IgG enters the circulation via the lymph and not the hepatic portal vein. The remaining uptake though the immature intestine is non-receptor mediated. Intestinal epithelial cell hFcRn expression occurred in Tg276 mice, but receptor-mediated transport of IgG was not observed. The suckling rat pup intestine is a mechanistic model of FcRn-IgG mediated transcytosis.
Network theory analysis of antibody-antigen reactivity data: the immune trees at birth and adulthood
PLoS One. 2011 Mar 8;6(3):e17445. doi: 10.1371/journal.pone.0017445.
Madi A, Kenett DY, Bransburg-Zabary S, Merbl Y, Quintana FJ, Tauber AI, Cohen IR, Ben-Jacob E. Source School of Physics and Astronomy, Tel Aviv University, Tel Aviv, Israel.
MOTIVATION: New antigen microarray technology enables parallel recording of antibody reactivities with hundreds of antigens. Such data affords system level analysis of the immune system's organization using methods and approaches from network theory. Here we measured the reactivity of 290 antigens (for both the IgG and IgM isotypes) of 10 healthy mothers and their term newborns. We constructed antigen correlation networks (or immune networks) whose nodes are the antigens and the edges are the antigen-antigen reactivity correlations, and we also computed their corresponding minimum spanning trees (MST)--maximal information reduced sub-graphs. We quantify the network organization (topology) in terms of the network theory divergence rate measure and rank the antigen importance in the full antigen correlation networks by the eigen-value centrality measure. This analysis makes possible the characterization and comparison of the IgG and IgM immune networks at birth (newborns) and adulthood (mothers) in terms of topology and node importance. RESULTS: Comparison of the immune network topology at birth and adulthood revealed partial conservation of the IgG immune network topology, and significant reorganization of the IgM immune networks. Inspection of the antigen importance revealed some dominant (in terms of high centrality) antigens in the IgG and IgM networks at birth, which retain their importance at adulthood.
Maternal autoimmune thyroid disease and the fetal immune system
Exp Clin Endocrinol Diabetes. 2011 Jul;119(7):445-50. doi: 10.1055/s-0031-1279741. Epub 2011 Jun 10.
Svensson J, Oderup C, Akesson C, Uvebrant K, Hallengren B, Ericsson UB, Arvastsson J, Danska JS, Lantz M, Cilio CM. Source Cellular Autoimmunity Unit, Department of Clinical Sciences, Lund University, Malmö University Hospital, Sweden.
OBJECTIVE: Several studies indicate that in utero exposure to maternal autoimmune diseases and transplacental passage of autoantibodies affect the risk of autoimmunity in the offspring, e. g., maternally derived GAD65 autoantibody correlates with decreased risk of type 1 diabetes, whereas thyroid peroxidase autoantibody (TPOAb) positivity at birth is associated with increased incidence of autoimmune thyroid disease later in life. The aim of this study was to identify immunological changes in children born to mothers with thyroid autoimmunity that may be related to in utero exposure to autoantibodies. DESIGN AND METHOD: Open label prospective analysis of cord blood lymphocytes and serum cytokines by Flow Cytometry in children born to mothers with autoimmune thyroiditis (AIT) (n=31) and to healthy mothers (n=76) and titers of thyroid autoantibodies were determined in cord blood and in maternal peripheral blood at delivery. RESULTS: We found an increase (almost 30%) in the frequency of cord blood natural killer (NK) cells (p=0.0016) and a minor increase in the subset of T cells expressing NK markers (p=0.028), in children born to AIT mothers. There were no detectable differences in the phenotype or frequency of cord blood memory/activated T cells, including CD4 (+)CD25 (+) T cells, between the 2 groups. The levels of pro-inflammatory cytokines TNF-α, IL-10, IL-12p70, IFN-γ and IL-1β were significantly decreased in offspring of AIT mothers as compared to healthy controls. CONCLUSIONS: Maternal thyroid autoimmunity and transplacental passage of autoantibodies against thyroid antigens may affect the generation or expansion of cells with NK activity and the secretion of inflammatory cytokines. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.