scholarly journals Immune system development varies according to age, location, and anemia in African children

2020 ◽  
Vol 12 (529) ◽  
pp. eaaw9522 ◽  
Author(s):  
Danika L. Hill ◽  
Edward J. Carr ◽  
Tobias Rutishauser ◽  
Gemma Moncunill ◽  
Joseph J. Campo ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Cell ◽  
System Development ◽  
High Titer ◽  
Geographical Location ◽  
Cell Types ◽  
Iron Bioavailability ◽  
Immune System Development

Children from low- and middle-income countries, where there is a high incidence of infectious disease, have the greatest need for the protection afforded by vaccination, but vaccines often show reduced efficacy in these populations. An improved understanding of how age, infection, nutrition, and genetics influence immune ontogeny and function is key to informing vaccine design for this at-risk population. We sought to identify factors that shape immune development in children under 5 years of age from Tanzania and Mozambique by detailed immunophenotyping of longitudinal blood samples collected during the RTS,S malaria vaccine phase 3 trial. In these cohorts, the composition of the immune system is dynamically transformed during the first years of life, and this was further influenced by geographical location, with some immune cell types showing an altered rate of development in Tanzanian children compared to Dutch children enrolled in the Generation R population–based cohort study. High-titer antibody responses to the RTS,S/AS01E vaccine were associated with an activated immune profile at the time of vaccination, including an increased frequency of antibody-secreting plasmablasts and follicular helper T cells. Anemic children had lower frequencies of recent thymic emigrant T cells, isotype-switched memory B cells, and plasmablasts; modulating iron bioavailability in vitro could recapitulate the B cell defects observed in anemic children. Our findings demonstrate that the composition of the immune system in children varies according to age, geographical location, and anemia status.

scholarly journals Toll-Like Receptor Signaling in the Establishment and Function of the Immune System

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1374
Author(s):  
Jahnavi Aluri ◽  
Megan A. Cooper ◽  
Laura G. Schuettpelz
Keyword(s):  
Immune System ◽  
Immune Cell ◽  
System Development ◽  
Cell Types ◽  
Tlr Signaling ◽  
Inborn Errors ◽  
Immune System Dysfunction ◽  
Immune System Development ◽  
And Function ◽  
Immune Defects

Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the development and function of the immune system. TLR signaling promotes the earliest emergence of hematopoietic cells during development, and thereafter influences the fate and function of both primitive and effector immune cell types. Aberrant TLR signaling is associated with hematopoietic and immune system dysfunction, and both loss- and gain-of- function variants in TLR signaling-associated genes have been linked to specific infection susceptibilities and immune defects. Herein, we will review the role of TLR signaling in immune system development and the growing number of heritable defects in TLR signaling that lead to inborn errors of immunity.

scholarly journals The Influence of Aging and Sex Hormones on Expression of Growth Hormone-Releasing Hormone in the Human Immune System1

2001 ◽  
Vol 86 (7) ◽  
pp. 3157-3161
Author(s):  
O. Khorram ◽  
M. Garthwaite ◽  
T. Golos
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Mrna Expression ◽  
Postmenopausal Women ◽  
Cell Line ◽  
Immune Cell ◽  
Hormone Replacement ◽  
Men And Women

GHRH is a neuropeptide that has also been localized to the immune system. The physiological function of GHRH in the immune system has not been elucidated. This study was conducted to determine whether immune GHRH expression is altered in certain pathological states, such as immune cell tumors, and whether gender, aging, and alterations in the sex steroid milieu influence the expression of this peptide in immune cells. Using double color flow cytometry, GHRH protein was found to be expressed in less than 2% of peripheral blood mononuclear cells (PBMC). Monocytes and B and T cells all expressed GHRH protein, although a greater percentage of T cells compared with B cells and monocytes expressed GHRH (5- to 7-fold). Semiquantitative RT-PCR was used to quantify GHRH messenger ribonucleic acid (mRNA) in PBMC and several immune cell-derived tumors. PBMC and granulocytes expressed low levels of GHRH mRNA with relatively higher levels of expression in monocytes. The tumor cell lines CEMX 174 (B/T cells), HUT 78 (T cells), WIL2-N (B cells), U937 (monocytes/macrophages), and JM 1 (pre-B cell lymphoma) all showed greater expression of GHRH mRNA relative to PBMC. However, two cell lines, CCRF-SB, a B lymphoblastoid cell line, and HL-60, a promyelocytic cell line, expressed GHRH mRNA at similar levels as PBMC. A significant decrease in the percentage of lymphocytes (CD45+ cells) expressing GHRH protein was found in age-advanced men and women compared with young men and women. This decline was noted in B cells (CD20+) and monocytes (CD14+), but not in T cells (CD3+). GHRH mRNA expression in PBMC derived from postmenopausal women was lower than that from premenopausal women. However, no differences in PBMC GHRH mRNA expression were found in young and old men. Although in older men there were fewer peripheral lymphocytes that express GHRH protein, these cells secreted significantly more GHRH in vitro than cells from postmenopausal women with no hormone replacement therapy (HRT), but similar levels as cells from women receiving HRT. PBMC from women receiving HRT secreted more GHRH in vitro than cells from women receiving no hormone replacement. This study demonstrates that the expression of immune GHRH is dynamic, and therefore likely to be regulated. Increased expression of GHRH in certain immune tumors suggests that GHRH may be mitogenic under certain conditions and therefore play a role in the pathogenesis of select immune cell tumors. Collectively, these results suggest a role for GHRH as a local immune modulator and in the pathophysiology of immunosenescence and immune cell tumors.

scholarly journals Mother-fetus immunogenetic dialogue as a factor of progeny immune system development

2019 ◽  
Vol 22 (8) ◽  
pp. 1009-1019
Author(s):  
L. A. Gerlinskaya ◽  
A. V. Varlachev ◽  
G. I. Krotov ◽  
G. V. Kontsevaya ◽  
M. P. Moshkin
Keyword(s):  
Molecular Weight ◽  
Immune System ◽  
Breast Milk ◽  
System Development ◽  
Large Body ◽  
Micro Rna ◽  
Surrogate Mothers ◽  
Immune System Development ◽  
Pass Through

Despite the advances in medicine, about 4 million children under the age of 6 months die annually around the world due to infection, which is 450 deaths per hour (UNISEF, 2009). The degree of development of the immune system of children born in time is determined by many factors, including the immunogenetic similarity or difference of mother and fetus organisms, which, in turn, is due to the genotypes of mating pairs, as well as the selection of surrogate mothers duringin vitrofertilization. From our review of the literature, it follows that immunogenetic interactions of mother and fetus organisms, which occur at all stages of pre- and postnatal development, have a signifcant effect on the resistance of offspring to infections and allergens. Before implantation, the mother’s immune responses are formed under the influence of semen fluid antigens, leukocytes and cytokines, as well as under the influence of the genes of the major histocompatibility complex, which are expressed in embryos at the stage of two cells. After implantation, transplacental transfer of immunoglobulins and immunocompetent cells becomes of immunomodulating importance. It is important to emphasize that, although substances with a high molecular weight usually do not pass through the placenta, this rule does not apply to immunoglobulin G (IgG), which, with a molecular weight of about 160 kDa, overcomes the transplacental barrier due to binding to the fetal Fc receptor. The level of IgG in newborns usually correlates with the level of maternal antibodies. During the period of natural feeding, the immune protection of newborns is provided by the mechanisms of innate immunity and the factors of humoral immunity of mothers. It has been shown that immunoglobulins from the milk of many animal species are transferred through the neonatal intestinal epithelium to the blood. Since breast milk contains large amounts of various immunoactive components, including proteins, cytokines, hormones, immunoglobulins, exosomes containing micro-RNA, and viable immune cells, the immunomodulating effects of breast milk persist even after elimination of maternal immunoglobulins from the blood of the offspring, up to maturation. Analysis of a large body of experimental data shows that the study of mechanisms of “motherfetus” and “mother-newborn” interactions are the basis of a knowledge base needed to fnd means of life-long directed modulation of the descendants’ immune status.

scholarly journals Authentic Patient-Derived Hepatitis C Virus Infects and Productively Replicates in Primary CD4+and CD8+T LymphocytesIn Vitro

2017 ◽  
Vol 92 (3) ◽  
Author(s):  
Georgia Skardasi ◽  
Annie Y. Chen ◽  
Tomasz I. Michalak
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocytes ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Hcv Rna ◽  
Biophysical Properties

ABSTRACTAccumulated evidence indicates that immune cells can support the replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to which individual immune cell types support HCV propagation and on characteristics of virus assembly. We investigated the ability of authentic, patient-derived HCV to infectin vitrotwo closely related but functionally distinct immune cell types, CD4+and CD8+T lymphocytes, and assessed the properties of the virus produced by these cells. The HCV replication system in intermittently mitogen-stimulated T cells was adapted to infect primary human CD4+or CD8+T lymphocytes. HCV replicated in both cell types although at significantly higher levels in CD4+than in CD8+T cells. Thus, the HCV RNA replicative (negative) strand was detected in CD4+and CD8+cells at estimated mean levels ± standard errors of the means of 6.7 × 102± 3.8 × 102and 1.2 × 102± 0.8 × 102copies/μg RNA, respectively (P< 0.0001). Intracellular HCV NS5a and/or core proteins were identified in 0.9% of CD4+and in 1.2% of CD8+T cells. Double staining for NS5a and T cell type-specific markers confirmed that transcriptionally competent virus replicated in both cell types. Furthermore, an HCV-specific protease inhibitor, telaprevir, inhibited infection in both CD4+and CD8+cells. The emergence of unique HCV variants and the release of HCV RNA-reactive particles with biophysical properties different from those of virions in plasma inocula suggested that distinct viral particles were assembled, and therefore, they may contribute to the pool of circulating virus in infected patients.IMPORTANCEAlthough the liver is the main site of HCV replication, infection of the immune system is an intrinsic characteristic of this virus independent of whether infection is symptomatic or clinically silent. Many fundamental aspects of HCV lymphotropism remain uncertain, including the degree to which different immune cells support infection and contribute to virus diversity. We show that authentic, patient-derived HCV productively replicatesin vitroin two closely related but functionally distinct types of T lymphocytes, CD4+and CD8+cells. The display of viral proteins and unique variants, the production of virions with biophysical properties distinct from those in plasma serving as inocula, and inhibition of replication by an antiviral agent led us to ascertain that both T cell subtypes supported virus propagation. Infection of CD4+and CD8+T cells, which are central to adaptive antiviral immune responses, can directly affect HCV clearance, favor virus persistence, and decisively influence the development and progression of hepatitis C.

scholarly journals Long Chain Polyunsaturated Fatty Acids Docosahexaenoic Acid and Arachidonic Acid Supplementation in the Suckling and the Post-weaning Diet Influences the Immune System Development of T Helper Type-2 Bias Brown Norway Rat Offspring

2021 ◽  
Vol 8 ◽  
Author(s):  
Dhruvesh Patel ◽  
Marnie Newell ◽  
Susan Goruk ◽  
Caroline Richard ◽  
Catherine J. Field
Keyword(s):  
Immune System ◽  
Immune Cell ◽  
System Development ◽  
Maternal Diet ◽  
Brown Norway ◽  
Norway Rat ◽  
Adaptive Immune ◽  
Immune System Development ◽  
Brown Norway Rat

Background: Dietary long chain polyunsaturated fatty acids (LCPUFA) such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) play an important role in the development of the infant immune system. The role of LCPUFA in the T helper type 2 (Th2) biased immune system is unknown. We aimed to understand the effect of feeding LCPUFA during suckling and post-weaning on immune system development in Th2 bias Brown Norway rat offspring.Methods: Brown Norway dams were randomly assigned to nutritionally adequate maternal diet throughout the suckling period (0–3 weeks), namely, control diet (0% ARA, 0% DHA; n= 8) or ARA + DHA (0.45% ARA, 0.8% DHA; n = 10). At 3 weeks, offspring from each maternal diet group were randomized to either a control (0% ARA, 0% DHA; n = 19) or ARA+DHA post-weaning (0.5% ARA, 0.5% DHA; n = 18) diet. At 8 weeks, offspring were killed, and tissues were collected for immune cell function and fatty acid composition analyses.Results: ARA + DHA maternal diet resulted in higher (p &lt; 0.05) DHA composition in breast milk (4×) without changing ARA levels. This resulted in more mature adaptive immune cells in spleen [T regulatory (Treg) cells and B cells], mesenteric lymph nodes (MLN, lower CD45RA+), and Peyer's patches (PP; higher IgG+, B cells) in the ARA+DHA group offspring at 8 weeks. ARA+DHA post-weaning diet (3–8 weeks) resulted in 2 × higher DHA in splenocyte phospholipids compared to control. This also resulted in higher Th1 cytokines, ~50% higher TNF-α and IFNγ, by PMAi stimulated splenocytes ex vivo, with no differences in Th2 cytokines (IL-4, IL-13, and IL-10) compared to controls.Conclusion: Feeding dams a diet higher in DHA during the suckling period resulted in adaptive immune cell maturation in offspring at 8 weeks. Providing ARA and DHA during the post-weaning period in a Th2 biased Brown Norway offspring model may support Th1 biased immune response development, which could be associated with a lower risk of developing atopic diseases.

Lactobacillus brevis strain 1E1 administered to piglets through milk supplementation prior to weaning maintains intestinal integrity after the weaning event

2011 ◽  
Vol 2 (1) ◽  
pp. 35-45 ◽  
Author(s):  
S. Gebert ◽  
E. Davis ◽  
T. Rehberger ◽  
C. Maxwell
Keyword(s):  
Immune System ◽  
Gastrointestinal Tract ◽  
Immune Cell ◽  
System Development ◽  
Lactobacillus Brevis ◽  
Neonatal Piglets ◽  
Progressive Development ◽  
Immune System Development ◽  
Lactation Phase ◽  
Cell Phenotypes

Early colonisation in the gastrointestinal tract by commensal microbes influences the progressive development and maturity of digestive and immune system functionality in the neonate. Application of strategically selected direct-fed microbials to neonatal pigs may provide an opportunity to dictate a portion of the intestinal microbial community and exert a beneficial influence on these developmental processes. Experiments were conducted to determine the effects of early administration of Lactobacillus brevis strain 1E1 to neonatal piglets (n=224) via a milk supplement system on gastrointestinal microbial counts, villous architecture, and immune cell phenotypes during the lactation phase and after weaning. Pigs administered the direct-fed microbial had lower Escherichia coli counts in the jejunum and ileum (P<0.05), and lower coliform counts in the jejunum compared to unsupplemented pigs (P<0.05). The villous height:crypt depth ratio was greater in the ileum at 9 days of age when pigs were provided L. brevis 1E1 compared to unsupplemented pigs (P<0.05), as well as in the duodenum of pigs supplemented with L. brevis 1E1 at 22 days of age (P<0.05). The number of leukocytes expressing CD2 (P<0.05), CD4 (P=0.07) and MHC-II (P=0.07) was lower in the jejunum of pigs administered L. brevis 1E1 compared to unsupplemented pigs, however direct-fed microbial treatment had no effect on the number of leukocytes expressing CD8, CD25 or SWC3. These data demonstrate that early colonisation of the porcine gastrointestinal tract with L. brevis strain 1E1 during the lactation phase influences the progression of intestinal structure, immune system development, and pathogen establishment, indicating a relationship between early microbial colonisation and development of intestinal maturity and integrity.

scholarly journals NFIL3 mutations alter immune homeostasis and sensitise for arthritis pathology

2018 ◽  
Vol 78 (3) ◽  
pp. 342-349 ◽  
Author(s):  
Susan Schlenner ◽  
Emanuela Pasciuto ◽  
Vasiliki Lagou ◽  
Oliver Burton ◽  
Teresa Prezzemolo ◽  
...  
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Types ◽  
Monozygotic Twin ◽  
Preclinical Model ◽  
Potential Contribution ◽  
Mutant Form ◽  
Single Cell Sequencing

ObjectivesNFIL3 is a key immunological transcription factor, with knockout mice studies identifying functional roles in multiple immune cell types. Despite the importance of NFIL3, little is known about its function in humans.MethodsHere, we characterised a kindred of two monozygotic twin girls with juvenile idiopathic arthritis at the genetic and immunological level, using whole exome sequencing, single cell sequencing and flow cytometry. Parallel studies were performed in a mouse model.ResultsThe patients inherited a novel p.M170I in NFIL3 from each of the parents. The mutant form of NFIL3 demonstrated reduced stability in vitro. The potential contribution of this mutation to arthritis susceptibility was demonstrated through a preclinical model, where Nfil3-deficient mice upregulated IL-1β production, with more severe arthritis symptoms on disease induction. Single cell sequencing of patient blood quantified the transcriptional dysfunctions present across the peripheral immune system, converging on IL-1β as a pivotal cytokine.ConclusionsNFIL3 mutation can sensitise for arthritis development, in mice and humans, and rewires the innate immune system for IL-1β over-production.

scholarly journals Hemoglobin drives inflammation and initiates antigen spread and nephritis in lupus

2020 ◽  
Author(s):  
Hritika Sharma ◽  
Anjali Bose ◽  
Uma Kumar ◽  
Rahul Pal
Keyword(s):  
T Cells ◽  
B Cells ◽  
Inflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Peripheral Blood Mononuclear ◽  
Autoantibody Production

AbstractHemoglobin (Hb) has well-documented inflammatory effects and is normally efficiently scavenged; clearance mechanisms can be overwhelmed during conditions of erythrocyte lysis, a condition that may occur in systemic lupus erythematosus. Whether Hb is preferentially inflammatory in lupus and additionally induces autoreactivity against prominent autoantigens was assessed. Peripheral blood mononuclear cells derived from SLE patients secreted higher levels of lupus-associated inflammatory cytokines when incubated with Hb, effects negated by haptoglobin. Hb (more particularly, ferric Hb) triggered the preferential release of lupus-associated cytokines from splenocytes, B cells, CD4 T cells, CD8 T cells and plasmacytoid dendritic cells isolated from aging NZM2410 mice, and also had mitogenic effects on B cells. Ferric Hb activated multiple signaling pathways which were differentially responsible for the generation of specific cytokines; inflammatory signaling also appeared to be cell-context dependent. Pull-downs, followed by mass spectrometry, revealed interactions of Hb with several lupus-associated autoantigens; co-incubation of ferric Hb with apoptotic blebs (structures which contain packaged autoantigens, believed to trigger lupus autoreactivity) revealed synergies (in terms of cytokine release and autoantibody production in vitro) that were also restricted to the lupus genotype. Infusion of ferric Hb into NZM2410 mice led to enhanced release of lupus-associated cytokines, the generation of a spectrum of autoantibodies, and enhanced-onset glomerulosclerosis. Given that the biased recognition of ferric Hb in a lupus milieu, in concert with lupus-associated autoantigens, elicits the generation of inflammatory cytokines from multiple immune cell types and stimulates the generation of potentially pathogenic autoantibodies, neutralization of Hb could have beneficial effects.

scholarly journals Chronic heat stress delays immune system development and alters serotonin signaling in pre-weaned dairy calves

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252474
Author(s):  
Marcela G. Marrero ◽  
Bethany Dado-Senn ◽  
Sena L. Field ◽  
Guan Yang ◽  
John P. Driver ◽  
...  
Keyword(s):  
Heat Stress ◽  
Immune System ◽  
Interleukin 6 ◽  
System Development ◽  
Late Gestation ◽  
Dairy Calves ◽  
Cell Counts ◽  
Immune System Development ◽  
Developmental Windows

Exposure to heat stress can alter the development and immune system function in dairy calves. Serotonin is an immunomodulatory biogenic amine that functions as a neurotransmitter and as a stress-response mediator. Our objectives were to characterize the patterns of serum serotonin concentrations and the pattern of serotonin-related genes expressed by immune cells of calves exposed to chronic heat stress or heat stress abatement during early life, and to explore whether these might relate to immune system development. Dairy calves were exposed to chronic heat stress (HS; n = 6) or heat stress abatement (cooling, CL; n = 6) across the prenatal (late gestation, last 46 d) and postnatal (from birth to weaning, 56 d) developmental windows. Blood samples were collected to harvest serum (weekly, from d 1 to 49), to isolate of circulating leukocyte mRNA (at 1, 21 and 42 d of age) and characterize immune cell populations by flow cytometry (at 21 and 47 d of age). Calves exposed to chronic heat stress pre- and postnatally had lower red blood cell counts and lower circulating serotonin, immunoglobulin G, and B-lymphocytes compared to CL calves. Circulating blood leukocyte mRNA expression of serotonin receptors -1A, -1F, -4 and -5 was greater, while heat shock protein 70 and immune-related genes (i.e., TBX21, TLR4, and TGFβ) were lower in HS relative to CL calves. Peripheral blood leukocytes from all calves secreted serotonin and interleukin-6 after in-vitro lipopolysaccharide stimulation. However, the HS calves produced more serotonin and less interleukin-6 than CL calves when activated in-vitro. Together, our data suggest that providing heat stress abatement to dairy calves across prenatal and postnatal developmental windows might modulate the serotonin synthesis pathway in ways that may benefit humoral immunity against microbial pathogens.

scholarly journals The Aging of γδ T Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1181 ◽  
Author(s):  
Weili Xu ◽  
Zandrea Wan Xuan Lau ◽  
Tamas Fulop ◽  
Anis Larbi
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Cell ◽  
Γδ T Cells ◽  
Cell Types ◽  
Developed Countries ◽  
Common Denominator ◽  
Age Related ◽  
The Relationship ◽  
Diverse Interactions

In the coming decades, many developed countries in the world are expecting the “greying” of their populations. This phenomenon poses unprecedented challenges to healthcare systems. Aging is one of the most important risk factors for infections and a myriad of diseases such as cancer, cardiovascular and neurodegenerative diseases. A common denominator that is implicated in these diseases is the immune system. The immune system consists of the innate and adaptive arms that complement each other to provide the host with a holistic defense system. While the diverse interactions between multiple arms of the immune system are necessary for its function, this complexity is amplified in the aging immune system as each immune cell type is affected differently—resulting in a conundrum that is especially difficult to target. Furthermore, certain cell types, such as γδ T cells, do not fit categorically into the arms of innate or adaptive immunity. In this review, we will first introduce the human γδ T cell family and its ligands before discussing parallels in mice. By covering the ontogeny and homeostasis of γδ T cells during their lifespan, we will better capture their evolution and responses to age-related stressors. Finally, we will identify knowledge gaps within these topics that can advance our understanding of the relationship between γδ T cells and aging, as well as age-related diseases such as cancer.

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