scholarly journals Prenatal development of human immunity

Science ◽  
2020 ◽  
Vol 368 (6491) ◽  
pp. 600-603 ◽  
Author(s):  
Jong-Eun Park ◽  
Laura Jardine ◽  
Berthold Gottgens ◽  
Sarah A. Teichmann ◽  
Muzlifah Haniffa
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Immune Cells ◽  
Large Scale ◽  
Prenatal Development ◽  
Emergent Properties ◽  
Human Immune System ◽  
Human Immunity ◽  
Human Immune ◽  
Anatomical Space

The blood and immune systems develop in parallel during early prenatal life. Waves of hematopoiesis separated in anatomical space and time give rise to circulating and tissue-resident immune cells. Previous observations have relied on animal models, which differ from humans in both their developmental timeline and exposure to microorganisms. Decoding the composition of the human immune system is now tractable using single-cell multi-omics approaches. Large-scale single-cell genomics, imaging technologies, and the Human Cell Atlas initiative have together enabled a systems-level mapping of the developing human immune system and its emergent properties. Although the precise roles of specific immune cells during development require further investigation, the system as a whole displays malleable and responsive properties according to developmental need and environmental challenge.

scholarly journals The Immune System as Drug Target

2013 ◽  
Vol 5 ◽  
pp. III.S12145
Author(s):  
Darren R. Flower
Keyword(s):  
Immune System ◽  
Drug Targets ◽  
Adaptive Immune System ◽  
Therapeutic Interventions ◽  
Human Immune System ◽  
Adaptive Immune ◽  
Histocompatibility Complex ◽  
Human Immunity ◽  
Human Immune ◽  
Adaptive Immune Systems

The immune system is perhaps the largest yet most diffuse and distributed somatic system in vertebrates. It plays vital roles in fighting infection and in the homeostatic control of chronic disease. As such, the immune system in both pathological and healthy states is a prime target for therapeutic interventions by drugs–-both small-molecule and biologic. Comprising both the innate and adaptive immune systems, human immunity is awash with potential unexploited molecular targets. Key examples include the pattern recognition receptors of the innate immune system and the major histocompatibility complex of the adaptive immune system. Moreover, the immune system is also the source of many current and, hopefully, future drugs, of which the prime example is the monoclonal antibody, the most exciting and profitable type of present-day drug moiety. This brief review explores the identity and synergies of the hierarchy of drug targets represented by the human immune system, with particular emphasis on the emerging paradigm of systems pharmacology.

scholarly journals Comprehensive multi-omics single-cell data integration reveals greater heterogeneity in the human immune system

2021 ◽  
Author(s):  
Congmin Xu ◽  
Junkai Yang ◽  
Astrid Kosters ◽  
Benjamin R Babcock ◽  
Peng Qiu ◽  
...  
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Types ◽  
Cell Receptor ◽  
Surface Proteins ◽  
Cell Type ◽  
Human Immune System ◽  
Receptor Repertoire ◽  
Human Immune

Single-cell transcriptomics enables the definition of diverse human immune cell types across multiple tissue and disease contexts. Still, deeper biological understanding requires comprehensive integration of multiple single-cell omics (transcriptomic, proteomic, and cell receptor repertoire). To improve the identification of diverse cell types and the accuracy of cell-type classification in our multi-omics single-cell datasets, we developed SuPERR-seq, a novel analysis workflow to increase the resolution and accuracy of clustering and allow for the discovery and characterization of previously hidden cell subsets. We show that by incorporating information from cell-surface proteins and immunoglobulin transcript counts, we accurately remove cell doublets and prevent widespread cell-type misclassification. This approach uniquely improves the identification of heterogeneous cell types in the human immune system, including a novel subset of antibody-secreting cells in the bone marrow.

scholarly journals A comprehensive logic-based model of the human immune system to study the dynamics responses to mono- and coinfections

2020 ◽  
Author(s):  
Bhanwar Lal Puniya ◽  
Robert Moore ◽  
Akram Mohammed ◽  
Rada Amin ◽  
Alyssa La Fleur ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Computational Models ◽  
Single Infection ◽  
Human Immune System ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Human Immune

AbstractThe human immune system, which protects against pathogens and diseases, is a complex network of cells and molecules. The effects of complex dynamical interactions of pathogens and immune cells on the immune response can be studied using computational models. However, a model of the entire immune system is still lacking. Here, we developed a comprehensive computational model that integrates innate and adaptive immune cells, cytokines, immunoglobulins, and nine common pathogens from different classes of virus, bacteria, parasites, and fungi. This model was used to investigate the dynamics of the immune system under two scenarios: (1) single infection with pathogens, and (2) various medically relevant pathogen coinfections. In coinfections, we found that the order of infecting pathogens has a significant impact on the dynamics of cytokines and immunoglobulins. Thus, our model provides a tool to simulate immune responses under different dosage of pathogens and their combinations, which can be further extended and used as a tool for drug discovery and immunotherapy. Furthermore, the model provides a comprehensive and simulatable blueprint of the human immune system as a result of the synthesis of the vast knowledge about the network-like interactions of various components of the system.

scholarly journals Gene Expression Analysis Reveals Age and Ethnicity Signatures Between Young and Old Adults in Human PBMC

2021 ◽  
Author(s):  
Yang Hu ◽  
Yudai Xu ◽  
Lipeng Mao ◽  
Wen Lei ◽  
Jan Jian Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Human Immune System ◽  
Immune Systems ◽  
Network Analyses ◽  
Age Related ◽  
Human Immune

Abstract Background: Human immune system functions over an entire lifetime, yet how and why the immune system becomes less effective with age are not well understood. Therefore, the aim of this study is to exploit a large-scale population-based strategy to systematically identify genes and pathways differentially expressed as a function of chronological age. Despite the importance of age and race in shaping immune cell numbers and functions, it is unclear whether Asian and Caucasian immune systems go through similar gene expression changes throughout their lifespan, and to what extent these aging-associated variations are shared among ethnicities. Results: Here, we characterize peripheral blood mononuclear cells transcriptome from 19 healthy adults of RNA-seq data and 153 healthy subjects of micoarray data with 21~90 years of age using the weighted gene correlation network analyses (WGCNA). These data reveal a set of insightful gene expression modules and representative gene biomarkers for human immune system aging from Asian and Caucasian ancestry, respectively. Among them, the aging-specific modules may show an age-related gene expression variation spike around early-seventies. In addition, we find the top hub genes including NUDT7, CLPB, OXNAD1 and MLLT3 are shared between Asian and Caucasian aging related modules and further validated in human PBMCs from different age groups. Conclusion: Overall, our findings reveal how age and race differentially affect the immune systems between Asian and Caucasian, as well as discovered a common genetic variant that greatly impacts normal PBMC aging between Asian and Caucasian.

scholarly journals Computational Modeling of Microabscess Formation

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Alexandre Bittencourt Pigozzo ◽  
Gilson Costa Macedo ◽  
Rodrigo Weber dos Santos ◽  
Marcelo Lobosco
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Computational Modeling ◽  
Bacterial Infection ◽  
Computational Model ◽  
Immune Cells ◽  
Bacterial Infections ◽  
Distinct Pattern ◽  
Human Immune System ◽  
Human Immune

Bacterial infections can be of two types: acute or chronic. The chronic bacterial infections are characterized by being a large bacterial infection and/or an infection where the bacteria grows rapidly. In these cases, the immune response is not capable of completely eliminating the infection which may lead to the formation of a pattern known as microabscess (or abscess). The microabscess is characterized by an area comprising fluids, bacteria, immune cells (mainly neutrophils), and many types of dead cells. This distinct pattern of formation can only be numerically reproduced and studied by models that capture the spatiotemporal dynamics of the human immune system (HIS). In this context, our work aims to develop and implement an initial computational model to study the process of microabscess formation during a bacterial infection.

COVIEdb: A database for potential immune epitopes of coronaviruses

2020 ◽  
Author(s):  
Jingcheng Wu ◽  
Wenfan Chen ◽  
Jingjing Zhou ◽  
Wenyi Zhao ◽  
Shuqing Chen ◽  
...  
Keyword(s):  
Immune System ◽  
Large Scale ◽  
Vaccine Development ◽  
Protein Sequences ◽  
T Cell Epitopes ◽  
Human Immune System ◽  
The World ◽  
Human Immune ◽  
Human Coronaviruses ◽  
Novel Coronavirus

Abstract2019 novel coronavirus (2019-nCoV) has caused large-scale pandemic COVID-19 all over the world. It’s essential to find out which parts of the 2019-nCoV sequence are recognized by human immune system for vaccine development. And for the prevention of the potential outbreak of similar coronaviruses in the future, vaccines against immunogenic epitopes shared by different human coronaviruses are essential. Here we predict all the potential B/T-cell epitopes for SARS-CoV, MERS-CoV, 2019-nCoV and RaTG13-CoV based on the protein sequences. We found YFKYWDQTY in ORF1ab protein, VYDPLQPEL and TVYDPLQPEL in spike (S) protein might be pan-coronavirus targets for vaccine development. All the predicted results are stored in a database COVIEdb (http://biopharm.zju.edu.cn/coviedb/).

Dissecting the human immune system with single cell RNA sequencing technology

2019 ◽  
Vol 107 (4) ◽  
pp. 613-623 ◽  
Author(s):  
Gang Xu ◽  
Yang Liu ◽  
Hanjie Li ◽  
Lei Liu ◽  
Shuye Zhang ◽  
...  
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Rna Sequencing ◽  
Sequencing Technology ◽  
Human Immune System ◽  
Single Cell Rna Sequencing ◽  
Human Immune

scholarly journals Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
J. M. Spatz ◽  
M. Hughes Fulford ◽  
A. Tsai ◽  
D. Gaudilliere ◽  
J. Hedou ◽  
...  
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Cell Mass ◽  
Deep Understanding ◽  
Immune Defense ◽  
Mass Cytometry ◽  
Human Immune System ◽  
Functional Responses ◽  
Human Immune

AbstractExposure to microgravity (µG) during space flights produces a state of immunosuppression, leading to increased viral shedding, which could interfere with long term missions. However, the cellular mechanisms that underlie the immunosuppressive effects of µG are ill-defined. A deep understanding of human immune adaptations to µG is a necessary first step to design data-driven interventions aimed at preserving astronauts’ immune defense during short- and long-term spaceflights. We employed a high-dimensional mass cytometry approach to characterize over 250 cell-specific functional responses in 18 innate and adaptive immune cell subsets exposed to 1G or simulated (s)µG using the Rotating Wall Vessel. A statistically stringent elastic net method produced a multivariate model that accurately stratified immune responses observed in 1G and sµG (p value 2E−4, cross-validation). Aspects of our analysis resonated with prior knowledge of human immune adaptations to µG, including the dampening of Natural Killer, CD4+ and CD8+ T cell responses. Remarkably, we found that sµG enhanced STAT5 signaling responses of immunosuppressive Tregs. Our results suggest µG exerts a dual effect on the human immune system, simultaneously dampening cytotoxic responses while enhancing Treg function. Our study provides a single-cell readout of sµG-induced immune dysfunctions and an analytical framework for future studies of human immune adaptations to human long-term spaceflights.

scholarly journals Using single-cell technologies to map the human immune system — implications for nephrology

2019 ◽  
Vol 16 (2) ◽  
pp. 112-128 ◽  
Author(s):  
Benjamin J. Stewart ◽  
John R. Ferdinand ◽  
Menna R. Clatworthy
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Human Immune System ◽  
Cell Technologies ◽  
Human Immune

Should we Try to Alleviate Immunosenescence and Inflammaging - Why, How and to What Extent?

2019 ◽  
Vol 25 (39) ◽  
pp. 4154-4162 ◽  
Author(s):  
Jacek M. Witkowski ◽  
Ewa Bryl ◽  
Tamas Fulop
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Malignant Neoplasm ◽  
Human Beings ◽  
Therapeutic Approaches ◽  
Human Immune System ◽  
Immune Systems ◽  
Human Immune

With advancing age, immune responses of human beings to external pathogens, i.e., bacteria, viruses, fungi and parasites, and to internal pathogens - malignant neoplasm cells - become less effective. Two major features in the process of aging of the human immune system are immunosenescence and inflammaging. The immune systems of our predecessors co-evolved with pathogens, which led to the occurrence of effective immunity. However, the otherwise beneficial activity may pose problems to the organism of the host and so it has builtin brakes (regulatory immune cells) and - with age - it undergoes adaptations and modifications, examples of which are the mentioned inflammaging and immunosenescence. Here we describe the mechanisms that first created our immune systems, then the consequences of their changes associated with aging, and the mechanisms of inflammaging and immunosenescence. Finally, we discuss to what extent both processes are detrimental and to what extent they might be beneficial and propose some therapeutic approaches for their wise control.

Sign in / Sign up

Export Citation Format

Share Document