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::Gestational age-dependent immune intolerance at the maternal-fetal interface might be a contributing factor to placental pathology and adverse pregnancy outcomes. Although the intrauterine setting is highly choreographed and considered to be a protective environment for the fetus, unscheduled inflammation might overwh...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00718
更新日期:2019-04-05 00:00:00
abstract::Dendritic cells (DCs) are the guardians of the immune system since they are located in the majority of peripheral tissues. In addition, they are crucial for the induction of an effective immune response based on their unique capacity to stimulate naive T cells. During co-evolution, the human pathogen herpes simplex vi...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01970
更新日期:2020-08-26 00:00:00
abstract::Over the past few decades, we have witnessed a decline in the rates of acute rejection without significant improvement in chronic rejection. Current treatment strategies principally target the adaptive immune response and not the innate response. Therefore, better understanding of innate immunity in transplantation an...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00918
更新日期:2020-05-28 00:00:00
abstract::Under non-inflammatory conditions HLA class II is predominantly expressed on hematopoietic cells. Therefore, donor CD4 T-cells after allogeneic stem cell transplantation (alloSCT) may mediate graft-vs.-leukemia reactivity without graft-vs.-host disease (GVHD). We analyzed immune responses in four patients converting f...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.03016
更新日期:2018-12-18 00:00:00
abstract::Modern animal and crop production practices are associated with the regular use of antimicrobials, potentially increasing selection pressure on bacteria to become resistant. Alternative approaches are needed in order to satisfy the demands of the growing human population without the indiscriminate use of antimicrobial...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02223
更新日期:2018-09-27 00:00:00
abstract::Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. In this study, we aimed to further characterize the role of macrophage-derived EVs in immune responses against hepatitis C virus (HCV) and the potential of polyunsaturated fatty acids (PUFAs) to modulate thi...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00723
更新日期:2018-04-12 00:00:00
abstract::Monocytes are critical defense components that play an important role in the primary innate immune response. The heterogeneous nature of monocytes and their ability to differentiate into either monocyte-derived macrophages or monocyte-derived dendritic cells allows them to serve as a bridge between the innate and adap...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01726
更新日期:2018-07-30 00:00:00
abstract::Strategies targeting T cells are the cornerstone of immunosuppression after solid organ transplantation. The transcription factor NF-κB is a key regulator of downstream T-cell activation and induction of inflammatory mediators; its full activation via antigen receptor engagement requires both the scaffold and the prot...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.576651
更新日期:2020-09-11 00:00:00
abstract::New approaches are needed to develop more effective interventions to prevent long-term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in this area. This manuscript outlines how our two groups are using m...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00385
更新日期:2015-08-03 00:00:00
abstract::Transfer of recipient regulatory T cells (Tregs) induces mixed chimerism and tolerance in an irradiation-free bone marrow (BM) transplantation (BMT) model involving short-course co-stimulation blockade and mTOR inhibition. Boosting endogenous Tregs pharmacologically in vivo would be an attractive alternative avoiding ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00821
更新日期:2017-07-19 00:00:00
abstract::This article describes the work I did in Bill Paul's lab as a postdoctoral fellow between 1979 and 1983, and to a lesser extent puts that work in the context of other work on B cell activation and antibody responses that was going on in Bill's lab at that time and shortly beforehand, including the discovery of interle...
journal_title:Frontiers in immunology
pub_type: 传,历史文章,杂志文章
doi:10.3389/fimmu.2018.00739
更新日期:2018-04-23 00:00:00
abstract::Although NGS technologies fuel advances in high-throughput HLA genotyping methods for identification and classification of HLA genes to assist with precision medicine efforts in disease and transplantation, the efficiency of these methods are impeded by the absence of adequately-characterized high-frequency HLA allele...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02294
更新日期:2018-10-04 00:00:00
abstract::Impressive clinical efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy for hematological malignancies have prompted significant efforts in achieving similar responses in solid tumors. The lack of truly restricted and uniform expression of tumor-associated antigens, as well as limited T cell persiste...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02268
更新日期:2018-11-19 00:00:00
abstract::Protein 4.1R, a member of the 4.1 family, functions as a bridge between cytoskeletal and plasma membrane proteins. It is expressed in T cells, where it binds to a linker for activation of T cell (LAT) family member 1 and inhibits its phosphorylation and downstream signaling events after T cell receptor triggering. The...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.03068
更新日期:2020-01-14 00:00:00
abstract::T cells are the main orchestrators of protective immunity in the stomach; however, limited information on the presence and function of the gastric T subsets is available mainly due to the difficulty in recovering high numbers of viable cells from human gastric biopsies. To overcome this shortcoming we optimized a cell...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00294
更新日期:2014-06-19 00:00:00
abstract::The mechanisms underlying pathophysiological regulation of tissue macrophage (Mφ) subsets remain poorly understood. From the expression of 207 Mφ genes comprising 31 markers for 10 subsets, 45 transcription factors (TFs), 56 immunometabolism enzymes, 23 trained immunity (innate immune memory) enzymes, and 52 other gen...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02612
更新日期:2019-11-14 00:00:00
abstract::Monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic MDSCs (G-MDSCs) have been found to be massively induced in TB patients as well in murine Mtb infection models. However, the interaction of mycobacteria with MDSCs and its role in TB infection is not well studied. Here, we investigated the role of Ca...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02826
更新日期:2019-12-03 00:00:00
abstract::We characterized five different vaccine candidates and a commercial vaccine in terms of safety, immunogenicity and using a systems vaccinology approach, with the aim to select novel vaccine candidates against Mycoplasma hyopneumoniae. Seven groups of six M. hyopneumoniae-free piglets were primo- and booster vaccinated...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01087
更新日期:2019-05-24 00:00:00
abstract::Migraine is a common, little understood, and debilitating disease. It is much more prominent in women than in men (~2/3 are women) but the reasons for female preponderance are not clear. Migraineurs frequently experience severe comorbidities, such as allergies, depression, irritable bowel syndrome, and others; many of...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00140
更新日期:2016-04-19 00:00:00
abstract::The progressive infiltration of immune cells is associated with the progression of melanoma. Specifically, Th17 cells in melanoma microenvironment have both antitumor and protumor effects. It is now necessary to understand the contradictory data associated with how Th17 cells play a role in melanoma. This review will ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00187
更新日期:2019-02-08 00:00:00
abstract::Under normal conditions our intestines are inhabited by trillions of diverse microorganisms composing the intestinal microbiota, which are mostly non-pathogenic anaerobic commensal bacteria vital for the maintenance of immune homeostasis. The composition and diversity of the intestinal microbiota can be disturbed by v...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.03179
更新日期:2019-01-17 00:00:00
abstract::Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with imm...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00069
更新日期:2012-04-17 00:00:00
abstract::Our immune system bears the tremendous task of mounting effective anti-microbial responses whilst maintaining immunoregulatory functions to avoid autoimmunity. In order to quickly respond to pathogens, Dendritic cells (DC) are armed with pattern recognition receptors (PRRs), allowing them to recognize highly conserved...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00094
更新日期:2013-04-22 00:00:00
abstract::Human papillomavirus (HPV) is the most common sexually transmitted virus. The high-risk HPV types (i.e., HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) are considered to be the main etiological agents of genital tract cancers, such as cervical, vulvar, vaginal, penile, and anal cancers, and of a subset of head and...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00188
更新日期:2020-02-18 00:00:00
abstract::In the past, lack of lineage markers confounded the classification of dendritic cells (DC) in the intestine and impeded a full understanding of their location and function. We have recently shown that the chemokine receptor XCR1 is a lineage marker for cross-presenting DC in the spleen. Now, we provide evidence that i...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00326
更新日期:2014-07-28 00:00:00
abstract::T follicular helper (Tfh) cells are the subset of CD4 T helper cells that are required for generation and maintenance of germinal center reactions and the generation of long-lived humoral immunity. This specialized T helper subset provides help to cognate B cells via their expression of CD40 ligand, IL-21, IL-4, and o...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00016
更新日期:2015-02-02 00:00:00
abstract:Background:Immunotherapies targeting CTLA-4 and PD-1 have elicited promising responses in a variety of cancers. However, the relatively low response rates warrant the identification of additional immunosuppressive pathways. V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitum...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.563044
更新日期:2020-10-29 00:00:00
abstract::The oral administration of Lacticaseibacillus rhamnosus CRL1505 differentially modulates the respiratory innate antiviral immune response triggered by Toll-like receptor 3 (TLR3) activation in infant mice, improving the resistance to Respiratory Syncytial Virus (RSV) infection. In this work, by using macrophages deple...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.568636
更新日期:2020-09-29 00:00:00
abstract::Alterations in the energy homeostasis contribute to sepsis-mediated multiple organ failure. The liver plays a central role in metabolism and participates to the innate immune and inflammatory responses of sepsis. Several clinical and experimental studies have suggested that females are less susceptible to the adverse ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00210
更新日期:2020-02-13 00:00:00
abstract::Emerging and re-emerging viruses pose a significant public health challenge around the world, among which RNA viruses are the cause of many major outbreaks of infectious diseases. As one of the early lines of defense in the human immune system, RIG-I-like receptors (RLRs) play an important role as sentinels to thwart ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01379
更新日期:2018-06-20 00:00:00