Abstract:
:Here, we outline an overview of the mammalian immune system that updates and extends the classical clonal selection paradigm. Rather than focusing on strict self-not-self discrimination, we propose that the system orchestrates variable inflammatory responses that maintain the body and its symbiosis with the microbiome while eliminating the threat from pathogenic infectious agents and from tumors. The paper makes four points: The immune system classifies healthy and pathologic states of the body-including both self and foreign elements-by deploying individual lymphocytes as cellular computing machines; immune cells transform input signals from the body into an output of specific immune reactions.Rather than independent clonal responses, groups of individually activated immune-system cells co-react in lymphoid organs to make collective decisions through a type of self-organizing swarm intelligence or crowd wisdom.Collective choices by swarms of immune cells, like those of schools of fish, are modified by relatively small numbers of individual regulators responding to shifting conditions-such collective inflammatory responses are dynamically responsive.Self-reactive autoantibody and T-cell receptor (TCR) repertoires shared by healthy individuals function in a biological version of experience-based supervised machine learning. Immune system decisions are primed by formative experience with training sets of self-antigens encountered during lymphocyte development; these initially trained T cell and B cell repertoires form a Wellness Profile that then guides immune responses to test sets of antigens encountered later. This experience-based machine learning strategy is analogous to that deployed by supervised machine-learning algorithms. We propose experiments to test these ideas. This overview of the immune system bears clinical implications for monitoring wellness and for treating autoimmune disease, cancer, and allograft reactions.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Cohen IR,Efroni Sdoi
10.3389/fimmu.2019.00010subject
Has Abstractpub_date
2019-01-22 00:00:00pages
10issn
1664-3224journal_volume
10pub_type
杂志文章,评审abstract::Dendritic cells (DCs) are uniquely potent antigen presenting cells that acquire microbial products and prime adaptive immune responses against pathogens. Furthermore, DCs also play a key role in induction and maintenance of tolerance. Although numerous studies have assessed the diverse functions of DCs, many unanswere...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00161
更新日期:2012-06-18 00:00:00
abstract::The limited efficacy of seasonal influenza vaccines is usually attributed to ongoing variation in the major antigenic targets for protective antibody responses including hemagglutinin (HA) and neuraminidase (NA). Hence, vaccine development has largely focused on broadening antigenic epitopes to generate cross-reactive...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01207
更新日期:2020-06-19 00:00:00
abstract::Mucosal-associated invariant T (MAIT) cells, which are enriched in human blood and express a semi-invariant TCR chain, play important roles in conditions such as infectious diseases and cancer. The influence of age on levels and functional characteristics of circulating MAIT cells have not been fully addressed. Here w...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00260
更新日期:2019-02-19 00:00:00
abstract::Monoclonal antibody (mAb)-based therapeutics are the fastest growing class of human pharmaceuticals. They are typically IgG1 molecules with N-glycans attached to the N297 residue on crystallizable fragment (Fc). Different Fc glycoforms impact their effector function, pharmacokinetics, stability, aggregation, safety, a...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01554
更新日期:2017-11-13 00:00:00
abstract::Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on central nervous system (CNS) myelin. Although CD4(+) T cell function in MS pathology has been extensively studied, there is also strong evidence that CD8(+) T lymphocytes play a key role. Intriguingly, CD8(+) T cells accumula...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00541
更新日期:2015-10-22 00:00:00
abstract::Respiratory syncytial virus (RSV) remains the most common cause of lower respiratory tract infections in children worldwide. Development of a vaccine has been hindered by the risk of developing enhanced respiratory disease (ERD) upon natural exposure to the virus. Generation of higher quality neutralizing antibodies w...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01673
更新日期:2020-07-29 00:00:00
abstract::Significant advances in our understanding of neutrophil biology were made in the past several years. The exciting discovery that neutrophils deploy neutrophil extracellular traps (NETs) to catch pathogens paved the way for a series of additional studies to define the molecular mechanisms of NET generation and the biol...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00378
更新日期:2014-08-11 00:00:00
abstract::HIV infection profoundly affects many parameters of the immune system and ultimately leads to AIDS, yet which factors are most important for determining resistance, pathology, and response to antiretroviral treatment - and how best to monitor them - remain unclear. We develop a quantitative high-throughput sequencing ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2015.00644
更新日期:2016-01-11 00:00:00
abstract::The study of molecular host-parasite interactions is essential to understand parasitic infection and adaptation within the host system. As well, prevention and treatment of infectious diseases require a clear understanding of the molecular crosstalk between parasites and their hosts. Yet, large-scale experimental iden...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00212
更新日期:2019-02-13 00:00:00
abstract::IRF-7 mediates robust production of type I IFN via MyD88 of the TLR9 pathway in plasmacytoid dendritic cells (pDCs). Previous in vitro studies using bone marrow-derived dendritic cells lacking either Irf7 or Irf3 have demonstrated that only IRF-3 is required for IFN-β production in the TLR4 pathway. Here, we show that...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00640
更新日期:2020-04-16 00:00:00
abstract::Health-related quality of life (HRQoL) in common variable immunodeficiency diseases (CVID) was evaluated by different tools, which were mainly used to compare different schedules of immunoglobulins administration in cross-sectional or short-term longitudinal studies. We assessed the HRQoL and psychological status of C...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00605
更新日期:2014-11-26 00:00:00
abstract::Scavenger receptors are cell surface membrane-bound receptors that typically bind multiple ligands and promote the removal of endogenous proteins and pathogens. In this study, we characterized a novel scavenger receptor-like protein, namely, SpBark. SpBark was upregulated in hemocytes after challenges with bacteria, s...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01992
更新日期:2019-08-23 00:00:00
abstract::Piperlongumine (PL), a natural small molecule derived from the Piper longum Linn plant, has received growing interest as a prooxidative drug with promising anticancer properties. Yet, the influence of PL on primary human T cells remained elusive. Knowledge of this is of crucial importance, however, since T cells in pa...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01172
更新日期:2020-06-12 00:00:00
abstract::During the acute phase of Trypanosoma cruzi infection, macrophages can act as host cells for the parasites as well as effector cells in the early anti-parasitic immune response. Thus, the targeting of specific signaling pathways could modulate macrophages response to restrict parasite replication and instruct an appro...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00859
更新日期:2018-04-23 00:00:00
abstract::TNFAIP3 encodes the NF-κB regulatory protein A20. High-penetrance heterozygous mutations in TNFAIP3 cause a haploinsufficiency of A20 (HA20), inadequate inhibition of NF-κB pathway, and an early onset autoinflammatory disorder. However, the clinical phenotype of patients with HA20 varies greatly and clinical diagnoses...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01527
更新日期:2018-07-04 00:00:00
abstract::The T lymphocyte response initiates with the recognition of MHC/peptides on antigen presenting cells by the T cell receptor (TCR). After the TCR engagement, the proximal signaling pathways are activated for downstream cellular events. Among these pathways, the calcium-signaling flux is activated through the depletion ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00179
更新日期:2013-07-04 00:00:00
abstract::Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While in vitro macrophage models have been used to study diseases empirically, a systematic analysis of the transcriptome thereof is lacking. Here, we acquired gene expression data from eight commonly-used in vitro macrophage...
journal_title:Frontiers in immunology
pub_type: 杂志文章,meta分析
doi:10.3389/fimmu.2019.02887
更新日期:2019-12-11 00:00:00
abstract::The pathogenicity of group A Streptococcus (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely toxic in vivo. Recent ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.507092
更新日期:2020-12-08 00:00:00
abstract::pH is highly variable in different tissues and affects many enzymatic reactions in neutrophils. In response to calcium ionophores such as A23187 and ionomycin, neutrophils undergo nicotinamide adenine dinucleotide phosphate oxidase (NOX)-independent neutrophil extracellular trap (NET) formation (NETosis). However, how...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01849
更新日期:2018-01-09 00:00:00
abstract::Microvesicles (MVs) are membrane particles of 200-500 nm released by all cell types constitutively. MVs of myeloid origin are found increased in the cerebrospinal fluid (CSF) of patients suffering from neuroinflammatory disorders, although the factors triggering their production have never been defined. Here, we repor...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00204
更新日期:2018-02-07 00:00:00
abstract::Leprosy serology reflects the bacillary load of patients and multidrug therapy (MDT) reduces Mycobacterium leprae-specific antibody titers of multibacillary (MB) patients. The Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil (U-MDT/CT-BR) compared outcomes of regular 12 doses MDT/R-M...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00915
更新日期:2018-05-14 00:00:00
abstract::Defense peptides protect multicellular eukaryotes from infections. In biomedical sciences, a dominant conceptual framework refers to defense peptides as host-defense peptides (HDPs), which are bifunctional peptides with both direct antimicrobial and immunomodulatory activities. No HDP has been reported in plants so fa...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01825
更新日期:2020-08-21 00:00:00
abstract::T cells recognizing epitopes on the surface of mycobacteria-infected macrophages can impart protection, but with associated risk for reactivation to lung pathology. We aimed to identify antibodies specific to such epitopes, which carry potentials for development toward novel therapeutic constructs. Since epitopes pres...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.577815
更新日期:2020-10-02 00:00:00
abstract::The 5-year survival rate of primary anorectal malignant melanoma is less than 20%. Optimal treatment of this condition remains controversial regarding locally disease, and whether any preferential survival benefit arises from either abdominoperineal resection or wide local excision remains unknown. The majority of pat...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00797
更新日期:2018-04-19 00:00:00
abstract::In this study, we identified and characterized the potential of a high ratio of bicarbonate to CO2 and a moderately alkaline pH to render neutrophils prone to undergo neutrophil extracellular trap (NET) formation. Both experimental settings increased the rate of spontaneous NET release and potentiated the NET-inducing...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00583
更新日期:2016-12-09 00:00:00
abstract::The generation of antibodies against protein antigens (such as donor-specific HLA molecules) requires that T follicular helper cells (Tfh) provide help to B cells. Immunosuppressive (IS) armamentarium prevents T cell activation, yet a significant proportion of renal transplant patients develop donor-specific antibodie...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.03178
更新日期:2019-02-05 00:00:00
abstract::Antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infections has been designed to optimize CD4 T-cell survival and limit HIV replication. Cell types other than CD4 T cells such as monocytes/macrophage, dendritic cells, and granulocytes (collectively known as myeloid cells), are generally not consider...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00261
更新日期:2020-03-04 00:00:00
abstract:BACKGROUND:Subjects are considered infected with Trypanosoma cruzi when tested positive by at least two out of three serological tests, whereas a positive result in only one of up to three tests is termed "serodiscordant" (SD). Assessment of parasite-specific T-cell responses may help discriminate the uninfected from i...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01141
更新日期:2017-09-15 00:00:00
abstract::NOD-like receptors (NLRs) are a class of cytoplasmic pattern-recognition receptors. Although most NLRs play some role in immunity, their functions range from regulating antigen presentation (NLRC5, CIITA) to pathogen/damage sensing (NLRP1, NLRP3, NLRC1/2, NLRC4) to suppression or modulation of inflammation (NLRC3, NLR...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2013.00285
更新日期:2013-09-17 00:00:00
abstract::Background: Diarrhoea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). Objective: The aim of this study was to describe the prevalence and clinical presentation of chronic and recurrent diarrhoea in the Royal-Free-Hospital (RFH) London CVID cohort, including symptoms,...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01654
更新日期:2020-07-31 00:00:00