UMLS:C0029713 - FACTA Search

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Query: UMLS:C0029713 (immaturity)
4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neonatal B cells have been considered immature because of their impaired capacity to produce immunoglobulins in response to polyclonal activators in vitro. Here we demonstrate that cord blood mononuclear cells (MNC) produce normal levels of IgE in vitro when cultured in the presence of interleukin-4 (IL-4), indicating that the B cells are mature in their capacity to switch to IgE-producing cells. However, in contrast to adult peripheral blood T cells, cord blood T cells failed to produce detectable levels of IL-4 upon activation by phytohaemagglutinin (PHA) concanavalin A (Con A) or combinations of PHA and the phorbol ester TPA. Interferon-gamma (IFN-gamma) production by cord blood T cells following activation by Con A or PHA was also strongly reduced. However, high levels of IFN-gamma, significantly higher than those produced by adult T cells, were synthesized in response to combinations of PHA and TPA, indicating that IFN-gamma production by cord blood T cells is not intrinsically defective. In contrast, cord blood T cells produced levels of IL-2 that were significantly higher than those obtained by adult T cells tested in parallel. Collectively, our data indicate that the minimal levels of IgE production measured in cord blood (less than 1 U/ml) are not due to immaturity of the cord blood B cells, but may be associated with the failure of cord blood T cells to produce detectable levels of IL-4, which has been shown to be responsible for induction of IgE synthesis both in vitro and in vivo.
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PMID:Cord blood B cells are mature in their capacity to switch to IgE-producing cells in response to interleukin-4 in vitro. 211 17

Mature basophils can be differentiated from other blood born cells by their morphology, metachromatically staining granules, histamine content, and the presence on their surfaces of high-affinity IgE receptors. The identification of basophil-like cells arising in mixed human bone marrow cultures, however, is made more difficult because of their immaturity and the morphologic alterations due to in vitro culture. Identification of IgE receptors on individual cells in cell preparations which could simultaneously be examined for their histochemical properties would facilitate the study of basophil growth and differentiation. Because this was difficult using existing techniques, we developed an IgE staphylococcal protein A rosetting assay which allows the identification of cells bearing high-affinity IgE receptors and permits the same cells to be examined by a variety of staining techniques. We then examined the appearance of basophil-like cells bearing IgE receptors in cultures of human bone marrow and correlated this data with measurements of IgE receptor number and affinity. The percentage of total cells grown in the presence of human recombinant IL-3 (rIL-3) that rosetted with Staphylococcus aureus increased from 2 +/- 0.5% at 1 week of culture to 7 +/- 2% at 2 weeks, 14 +/- 5% at 3 weeks, and 18 +/- 5% at 4 weeks. Using 125I-labeled IgEPS, the number of IgE receptors per rosetting basophil-like cell was calculated to be 7.3 x 10(4) at 2 weeks, 6.8 x 10(4) at 3 weeks, and 3.9 x 10(4) receptors per rosette positive basophil-like cell at 4 weeks. Finally, the rate of dissociation of IgE from these cultured cells was found to be 4.0 +/- 1.3 x 10(-5) s-1, indicating that IgE bound to IgE receptors on cultured basophil-like cells with high affinity.
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PMID:A staphylococcal protein A rosetting assay for the demonstration of high affinity IgE receptors on rIL-3-dependent human basophil-like cells grown in mixed cell cultures. 252 16

Adverse clinical reactions to food associated with disturbed immunologic function (food allergy) affect 1-3% of the population and vary from life-threatening to a minor inconvenience. They must be differentiated from reactions caused by toxins, pharmacologic agents, enzyme deficiences and non-specific release of inflammatory mediator substances. Enteric absorption of food protein antigens which may occur despite an array of gastrointestinal protective mechanisms normally induces both a protective immune response and immunologic tolerance. Quantitative changes in absorption related to deficient protective mechanisms or excessive antigen load may contribute to the development of an allergic immune response and explain the greater incidence of food allergy in infants and children. Important factors include immunologic immaturity, enhanced macromolecular mucosal transport, intrauterine and neonatal malnutrition, breast feeding and infection. Double-blind food challenge tests remain as the most definitive diagnostic yardstick but carefully standardized skin tests may be helpful if interpreted in the context of the clinical history. Despite the association of food allergy with food antigen specific IgE hypersensitivity, immune complex formation and lymphocyte sensitization the pathophysiological changes which result in symptoms remain obscure. Recent advances have clarified many aspects of our knowledge of food allergy but inevitably have raised many more questions for future study.
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PMID:Food allergy. 638 38

IgG, IgA, and IgE production by newborn B cells is limited both in vivo and in vitro in various activation conditions, whereas IgM production is readily detectable. It has been suggested that the Ig heavy chain switch inability could be the consequence of T and B cell immaturity. As the interaction between CD40 (expressed on B cells) and its ligand CD40-L (expressed on activated T cells) triggers a key signal required for isotype switching, we studied the expression and function of these two components in normal fetuses, newborns, and infants, compared with adults. CD40-L expression was not inducible in 28 of 30 specimens of newborn cord-blood T cells following incubation with PMA and ionomycin, whereas activation markers such as CD69 were inducible. CD40-L expression was triggered by activation of T cells from infants > 3 wk of age. Surprisingly, T cells from 19- to 28-wk-old fetuses also expressed CD40-L following activation. CD40-L expression on newborn T lymphocytes was induced on T cell lines generated in the presence of PHA and maintained with IL-2 following further stimulation with PMA and ionomycin. CD40-L mRNA transcripts and intracytoplasmic protein expression following activation of newborn T cells were strongly decreased, leading to undetectable protein membrane detection. These results point to a possible transcriptional down-regulation of CD40-L expression by neonatal T lymphocytes. In addition, fetal and cord-blood B cells were poorly able to switch to IgG or IgA by stimulation with CD40 agonists (Ab or soluble CD40-L) in the presence of IL-4 or IL-10 as also detected with surface IgD+ adult B cells. Both phenomena could contribute to the neonatal Ig switch inability, although distinct underlying regulatory mechanisms are probably involved, as suggested by different in vivo time courses.
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PMID:Undetectable CD40 ligand expression on T cells and low B cell responses to CD40 binding agonists in human newborns. 753 Jul 39

Job' syndrome and IgA immunodeficiency are a rare dysfunction of the immune system. In this work, we reported a case of a young woman who had recurrent episodes of bacterial infections in the urinary tract and genital, generalized erythematous eczematous patches and stomatitis of oral mucosa and fever. During the hospitalization, laboratory data showed high immunoglobulin IgE and low IgA levels. The T-lymphocyte presented a reduction of CD8+ cells. Tests of granulocyte function have showed a global deficit in the in vitro and in vivo chemotaxis. The correlation between these two clinic conditions is not completely clarified but it is possible to hypothesize that CD8+ lymphocytes produce an inhibition factor of chemotaxis. Job' syndrome is characterized by a selective reduction of CD8+ cells subpopulation which have an immunoregulatory function on the production of IgE by plasmacells. In the ipoIgA, an intrinsic inability of B-IgA cells to proliferate and to differentiate produce a defect in the IgA production. In these two clinic disorders there is an effective dysfunction of immune system. It is possible to hypothesize that an effective defect of CD8+ cells and an immaturity of B-cells may coexist in our patient. That justifies an abnormal production of Ig and a defect in granulocyte chemotaxis.
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PMID:[Job syndrome (hyper-IgE) and hypo-IgA. A rare association of immunodeficiencies]. 872 83

The newborn immune system differs quantitatively and functionally from that of adults. Development of the immune system has important implications for childhood diseases. The immaturity of the immune system in the first years of life may contribute to failure of tolerance induction and in the development of allergic disease. T cell function is diminished, especially the capacity to produce cytokines; production of interferon (IFN)-gamma, and IL-4 is strongly reduced. IFN-gamma has been found to be even lower in cord blood of newborns with a family history of atopy. Differences in other cell types (natural killer cells, antigen-presenting cells, and B cells) could also play a role in the development of allergic disease. Current data suggest that irregularities in IgE synthesis, helper T cell subsets (Th1, Th2, CD45RA, and CD45RO), cytokines (IL-4, IFN-gamma), and possibly other cell types may play a role in the development of allergy in childhood. Moreover, the role of cell surface molecules, like co-stimulatory molecules (CD28, CD40L), activation markers (CD25), and adhesion molecules (LFA-1/ICAM-1, VLA-4/ VCAM-1) is also discussed. These variables are modulated by genetic (relevant loci are identified on chromosome 5q, 11q, and 14) and environmental forces (allergen exposure, viral infections, and smoke). The low sensitivity of current predictive factors for the development of allergic diseases, such as cord blood IgE levels, improves in combination with family history and by measurement of in vitro responses of lymphocytes and skin reactivity to allergens. New therapeutic approaches are being considered on the basis of our current understanding of the immunopathology of allergic disease, for instance cytokine therapy and vaccination with tolerizing doses of allergen or peptides.
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PMID:Development of immune functions related to allergic mechanisms in young children. 886 70

Human neonates are generally deficient in their ability to generate humoral immunity. This deficiency is thought to reflect physiologic immaturity of T and B cell function and lack of previous exposure to exogenous Ags. To determine whether neonatal humoral immunity can be modified by maternal helminth infection during pregnancy, we assessed Ig production by cord blood lymphocytes from healthy newborns of mothers living in an area of Kenya where schistosomiasis, bancroftian filariasis, and geohelminth infections are endemic. Twelve of 40 and 17 of 39 cord blood lymphocyte preparations from healthy newborns in Coast Province, Kenya, spontaneously made polyclonal IgE (range, 0.15-21 ng/ml) and IgG (1.6-10.1 ng/ml) in vitro. In vitro IgE synthesis by cord blood lymphocytes (CBL) was, on the average, 10-fold less than that of PBMC of Kenyan mothers (1.1-98 ng/ml) and was undetectable for CBL from newborns delivered in the United States. Schistosome and filarial Ags stimulated a 3- to > 100-fold increase in the production of polyclonal IgE and parasite-specific IgG Abs by lymphocytes from 10 of 40 and 6 of 39 Kenyan newborns, respectively. CBL observed to have helminth Ag-driven B cell responses were more likely to be from newborns of schistosome- or filaria-infected mothers than from uninfected mothers (p < 0.05). These data indicate that the human fetus can be sensitized in utero to produce helminth-specific B cells and that neonatal B cells are intrinsically capable of IgE and IgG production.
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PMID:B cell sensitization to helminthic infection develops in utero in humans. 953 21

The synthesis of IgE class antibodies takes place in plasma cells after activation of B lymphocytes by two different signals. The presence of interleukin-4 (IL-4) in the microenvironment and intimate contact between B and T cells through the CD-40 molecule and its specific ligand (CD-40L) are necessary. Lymphocyte activation also can be induced by mast cells. IgE does not cross the placenta, but fetuses are capable of synthesizing it. We attempted to identify children at high risk of atopy by determining IgE in umbilical cord blood. The system was not entirely satisfactory because many other factors are involved, but it demonstrated that intrauterine sensitization can occur. IgE-mediated allergy is conditioned by the predominance of Th2 lymphocytes (secretors of IL-4, IL-5, and IL-10) over Th1 lymphocytes (secretors of IL-12 and IFN gamma). This imbalance is physiological in the fetus and Th1 stimulation causes miscarriage. At birth, the functional predominance of Th2 continues, probably because of the immaturity of the dendritic antigen-presenting cells. An irregular maturation process takes place in the following months; for instance, while the intestinal mucosa tends towards tolerance and matures more rapidly, the respiratory mucosa tends toward the Th1 response and is slower. It is likely that sensitization during fetal and neonatal life is interesting because it generates type Th2 memory cells that can predispose toward atopic responses in the future.
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PMID:[Synthesis and modulation of IgE in the newborn infant]. 967 88

The contribution of cord blood B lymphocytes to the immune response has been under considerable investigation. Cord blood B cells produce almost no antibodies except of the immunoglobulin (Ig)M isotype, indicating immaturity of the cells or the environment they reside in. The aim of this study was to investigate the number of circulating IgA-, IgM-, IgG-, and IgE-producing cells in cord blood in comparison to adult peripheral blood using the ELISPOT method. Moreover, we studied the effect of transformation with the Epstein-Barr virus (EBV) on the proportion of cells producing different isotypes with or without interleukin (IL)-4. Cord blood had IgM-producing cells circulating predominantly, but also some IgA- and IgG-producing cells, whereas adult peripheral blood contained high amounts of circulating IgA-producing cells and some IgM- and IgG-producing cells. No circulating IgE-producing cells were found in either group. Transformation by EBV caused significant expansion of IgA-, IgM-, and IgG-producing cells in adult peripheral blood, but almost only of IgM-producing cells in cord blood. A low but detectable expansion of IgA- and IgG-producing cells was found. Cells producing IgE were still not found, even after EBV transformation. However, EBV transformation in the presence of IL-4 increased the numbers of IgE-producing cells significantly both in cord blood and adult peripheral blood. These findings indicate that cord blood contains some circulating IgA- and IgG-producing cells that are expanded to some extent after EBV infection. They also indicate that cord blood B cells have a similar capacity for IgE production to adult peripheral blood B cells when appropriately stimulated.
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PMID:Immunoglobulin-secreting cells in cord blood: effects of Epstein-Barr virus and interleukin-4. 1040 47

Latex is a substance that is extracted from the plant Hevea Brasiliensis, and world production is 6 million metric tons per year. After gathering it undergoes a series of processes in which ammonia, vulcanization-accelerating additives or anti-oxidants are added. All of this may constitute the antigenic load that latex contains. It is used in medicine for gloves, drainage tubes, dental implants and a growing number of products from condoms to sport products or automobile components. Over fifteen different allergenic bands have been described, with molecular weights of between 2 and 100 kDa. In a joint study, USA-Finland identified three antigenic bands that predominate according to the population type studied (2). In children with spina bifida, congenital urogenital abnormalities or those submitted to multiple surgical interventions, the band of 27 kDa is predominant. This antigen has not been detected in adult serum, which suggests that contact with the antigen is through the mucous membranes and the sensitization is triggered from here. The incidence of allergy to latex in the general population is not known, but it seems to be lower than 1%. Turjanmaa (1) establishes a frequency of 0.125% (1/800) in patients submitted to general surgery. The incidence of sensitization to latex varies according to the population studied. Among the population considered to be at risk are the workers of the health environment, where the incidence is between 2.6 and 16.9%, whereas in the general population the percentage is around 1%. Sensitivity to latex is of great importance in patients suffering from spina bifida, in whom an incidence of between 28 and 67% has been found. We present our experience in a group of children attending our service for the first time for diverse reasons of supposed allergic etiology. The objective is to determine the incidence of sensitization to latex according to the diagnostic methodology [cutaneous test or by determination of specific IgE (CAP)]; according to the type of patient (atopic or non-atopic), the direct relationship with latex material and the role that can be played by a history of surgical intervention. In our experience with 282 children studied in our pediatric allergology service using diverse methods, the incidence of allergy to latex is 3.19%. Nevertheless, if we analyze this percentage we observe that if the diagnosis is based exclusively on cutaneous tests, it is only 1.08%; if to establish a diagnosis we used exclusively the determination of specific IgE (CAP) we would label 7. 2% of our children as allergic. Atopy is a factor that facilitates sensitization. In our sample, the incidence among the atopic population is 4.4%, though this percentage may vary between 1.69% and 9.5% depending on the methodology used. There are several hypotheses for explaining these discrepancies in the diagnostic tests. Although there do not seem to be differences regarding the ammonia content of the different lots, it seems that the differential factor could lie in the type of extract and in whether it is commercial or a natural latex extract. It could be a consequence of the existence of a prophyllin, so it has not been ruled out that a part of the IgE is an antiprophyllin. The presence of different epitopes would mean that each of them has the ability to produce its own specific IgE, though the RAST/CAP was not able to differentiate them and identified them as whole. The rate of allergy to latex in a group of children suffering from myelomeningocele is 80%. At a paediatric level, sensitization to latex is influenced by the means of contact, the duration of the exposure to the antigen and the fact that the exposure occurs early, which in the case of children with myelomeningocele is associated with the immaturity of the defence mechanism of the mucous membranes.
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PMID:Prevalence of allergy to latex in the pediatric population. 1043 Oct 98

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