Self-tolerance: context dependent tuning of T cell antigen recognition.

Abstract:

:Physiological messages to cells are encoded in the magnitude, and in the time- and space-contingencies, of sets of stimuli. In particular, individual T cells continuously integrate antigenic and other signals and respond differentially to the rate of change in the level of stimulation, translated intracellularly into 'metabolic perturbations'. The organization of the immune response at the cell-population level in space and time is also conductive to discriminating the magnitude of 'system perturbations'. In this way, the immune system was 'designed' to respond in a characteristic explosive way mainly to episodes of infection and not to the continuous presence of self-antigens. T cells are selected to be moderately autoreactive, and the degree of autoreactivity that they express is continuously controlled through activation-threshold tuning. Their level of autoreactivity is maintained in a range that facilitates survival and self-renewal and is probably used in performing some immunoregulatory functions and possibly other physiological functions. Autoreactivity and outward-directed immunity are regulated simultaneously and interactively through the interplay of selection, tuning, controlled activation and feedback.

journal_name

Semin Immunol

journal_title

Seminars in immunology

authors

Grossman Z,Paul WE

doi

10.1006/smim.2000.0232

keywords:

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

197-203; discussion 257-344

issue

3

eissn

1044-5323

issn

1096-3618

pii

S1044-5323(00)90232-X

journal_volume

12

pub_type

杂志文章,评审
  • Exploiting Ca2+ signaling in T cells to advance cancer immunotherapy.

    abstract::Decades of basic research has established the importance of Ca2+ to various T cell functions, such as cytotoxicity, proliferation, differentiation and cytokine secretion. We now have a good understanding of how proximal TCR signaling initiates Ca2+ influx and how this influx subsequently changes transcriptional activi...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2020.101434

    authors: Meng X,Wu X,Zheng Y,Shang K,Jing R,Jiao P,Zhou C,Zhou J,Sun J

    更新日期:2020-06-01 00:00:00

  • Regulation of CD40 ligand expression and use of recombinant CD40 ligand for studying B cell growth and differentiation.

    abstract::Helper T cell activation leads to transient expression of a ligand for the B cell surface protein, CD40. CD40 ligand can deliver helper T cell-derived contact signals to B lymphocytes that drive B cell activation and proliferation. Regulation of expression of CD40 ligand is analogous to that of other helper T cell-der...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1006/smim.1994.1037

    authors: Kehry MR,Castle BE

    更新日期:1994-10-01 00:00:00

  • Hematopoiesis and models of immunodeficiency.

    abstract::This review focuses on recessive mutations at three loci whose gene products play critical roles in the development and regulation of the murine immune system. These mutations are: severe combined immunodeficiency (scid), osteopetrosis (op), and motheaten (me). The scid mutation blocks differentiation of functional T ...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:

    authors: Shultz LD

    更新日期:1991-11-01 00:00:00

  • The end-joining reaction in V(D)J recombination.

    abstract::V(D)J recombination consists of a DNA cleavage reaction catalysed by RAG1 and RAG2, followed by an end-joining reaction that utilizes the cell's double-strand break repair machinery. Genes essential for the end-joining reaction include: XRCC4 encoding a protein of unknown enzymatic function; XRCC5 and XRCC6 encoding 8...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1006/smim.1997.0070

    authors: Smider V,Chu G

    更新日期:1997-06-01 00:00:00

  • The complement system and adaptive immunity.

    abstract::The complement system covalently attaches C3d to microbial antigens which binds to CR2 on B lymphocytes, leading to a markedly enhanced adaptive immune response to that antigen. The enhancement is mediated by the cross-linking of the CR2-CD19 complex to mIg which augments the activation of several intracellular signal...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1006/smim.1998.0137

    authors: Fearon DT

    更新日期:1998-10-01 00:00:00

  • Heat shock proteins as antigens for gamma delta T cells.

    abstract::Recently, there have been a number of reports that gamma delta T cells are stimulated by heat shock, or stress, proteins. Although some alpha beta T cells are capable of recognizing heat shock proteins, we speculate that most or a group of gamma delta cells generally recognize this type of antigen. Recognition of heat...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:

    authors: O'Brien RL,Born W

    更新日期:1991-03-01 00:00:00

  • Development and function of tissue resident macrophages in mice.

    abstract::Macrophages are important for tissue development, homeostasis as well as immune response upon injury or infection. For a long time they were only seen as one uniform group of phagocytes with a common origin and similar functions. However, this view has been challenged in the last decade and revealed a complex diversit...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2016.03.017

    authors: Kierdorf K,Prinz M,Geissmann F,Gomez Perdiguero E

    更新日期:2015-12-01 00:00:00

  • The importance of lymphocyte trafficking in regulating blood lymphocyte levels during HIV and SIV infections.

    abstract::In humans, blood is commonly monitored to provide surrogates of disease progression and assess immune status. However, the varied, rapid and atypical alterations in lymphocyte subsets which may occur in blood in response to pathogens, are not predictive of changes in the bulk of the immune system. A hallmark of human ...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1006/smim.1999.0169

    authors: Rosenberg YJ,Janossy G

    更新日期:1999-04-01 00:00:00

  • Specificity in cancer immunotherapy.

    abstract::From the earliest days in the field of tumor immunology three questions have been asked: do cancer cells express tumor-specific antigens, does the immune system recognize these antigens and if so, what is their biochemical nature? We now know that truly tumor-specific antigens exist, that they are caused by somatic mu...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2008.07.001

    authors: Schietinger A,Philip M,Schreiber H

    更新日期:2008-10-01 00:00:00

  • The cellular origins of memory B cells.

    abstract::Recent evidence indicates that memory B cells may originate from a precursor cell subset that is distinct from AFC precursors. Most convincing is the finding that fractionation of naive peripheral B-cell populations on the basis of surface heat stable antigen (HSA) expression yields two populations; one greatly enrich...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1006/smim.1997.0075

    authors: Klinman NR

    更新日期:1997-08-01 00:00:00

  • Functions of caspase 8: the identified and the mysterious.

    abstract::Initially discovered as an initiator protease in apoptosis mediated by death receptors, caspase-8 is now known to have an apparently confounding opposing effect in securing cell survival. It is required to allow mouse embryo survival, and the survival of hematopoietic cells during their development and activation. Cla...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2014.03.005

    authors: Salvesen GS,Walsh CM

    更新日期:2014-06-01 00:00:00

  • Chemokines in rapid leukocyte adhesion triggering and migration.

    abstract::Leukocyte subsets are recruited from the blood to lymphoid and non-lymphoid tissues via a multi-step process that involves distinct adhesive and activation steps. Chemokines, a family of chemotactic cytokines that signal through G-protein-coupled receptors, play critical roles in regulating the leukocyte recruitment c...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1006/smim.2001.0345

    authors: Johnston B,Butcher EC

    更新日期:2002-04-01 00:00:00

  • Global virus outbreaks: Interferons as 1st responders.

    abstract::Outbreaks of severe virus infections with the potential to cause global pandemics are increasing. In many instances these outbreaks have been newly emerging (SARS coronavirus), re-emerging (Ebola virus, Zika virus) or zoonotic (avian influenza H5N1) virus infections. In the absence of a targeted vaccine or a pathogen-...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2019.101300

    authors: Wang BX,Fish EN

    更新日期:2019-06-01 00:00:00

  • Genetics and pathogenesis of multiple sclerosis.

    abstract::Multiple sclerosis (MS) is an idiopathic autoimmune neurodegenerative disease. Like many common diseases, MS has a genetic component; however, as with most complex diseases, the genetic architecture may be influenced by heterogeneity, incomplete penetrance, polygenic inheritance, and environmental factors. This clinic...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2009.08.003

    authors: Zuvich RL,McCauley JL,Pericak-Vance MA,Haines JL

    更新日期:2009-12-01 00:00:00

  • Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application.

    abstract::Periodontitis is a dysbiotic inflammatory disease leading to the destruction of the tooth-supporting tissues. Current therapies are not always effective and this prevalent oral disease continues to be a significant health and economic burden. Early clinical studies have associated periodontitis with elevated complemen...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2016.03.006

    authors: Hajishengallis G,Hajishengallis E,Kajikawa T,Wang B,Yancopoulou D,Ricklin D,Lambris JD

    更新日期:2016-06-01 00:00:00

  • Plasmacytoid dendritic cells in the skin: to sense or not to sense nucleic acids.

    abstract::Plasmacytoid dendritic cells (pDCs) are specialized sensors of viral nucleic acids that initiate protective immunity through the production of type I interferons (IFNs). Normally, pDCs fail to sense host-derived self-nucleic acids but do so when self-nucleic acids form complexes with endogenous antimicrobial peptides ...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2009.01.004

    authors: Conrad C,Meller S,Gilliet M

    更新日期:2009-06-01 00:00:00

  • Targeting antigens to antigen presenting cells.

    abstract::Antigen may be targeted to antigen presenting cells (APC) by conjugating the antigen to monoclonal antibodies directed against surface molecules on APC. By now several laboratories have shown that immunotargeting enhances humoral responses, depending upon the targeted ligand or cell type, with low doses of antigen and...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:

    authors: Fossum S,Berg SF,Mjaaland S

    更新日期:1992-08-01 00:00:00

  • Humoral immunity and antibody-mediated rejection in solid organ transplantation.

    abstract::The humoral arm of the immune system provides robust protection against extracellular pathogens via the production of antibody molecules that neutralize or facilitate the destruction of microorganisms. However, the humoral immune system also provides a significant barrier to solid organ transplantation due to the anti...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2011.08.021

    authors: Montgomery RA,Cozzi E,West LJ,Warren DS

    更新日期:2011-08-01 00:00:00

  • Harnessing dendritic cells in inflammatory skin diseases.

    abstract::The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune home...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2011.01.006

    authors: Chu CC,Di Meglio P,Nestle FO

    更新日期:2011-02-01 00:00:00

  • Regulation of lupus-related autoantibody production and clinical disease by Toll-like receptors.

    abstract::Autoantigens that contain DNA, RNA, or self-IgG are preferred targets for autoantibodies in systemic lupus erythematosus (SLE). B cells promote SLE pathogenesis by producing autoantibodies, activating autoreactive T cells, and secreting cytokines. We discuss how certain autoreactive B cells are selectively activated, ...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2006.12.005

    authors: Christensen SR,Shlomchik MJ

    更新日期:2007-02-01 00:00:00

  • Recognition and function of Valpha14 NKT cells.

    abstract::A novel lymphocyte lineage, V alpha 14 NKT cells, has recently been identified and appears to be distinct from conventional alphabeta T cells. V alpha 14 NKT cells express a single invariant V alpha 14 antigen receptor that is essential for their development. They recognize a glycolipid antigen (alpha -galactosylceram...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1006/smim.2000.0270

    authors: Taniguchi M,Nakayama T

    更新日期:2000-12-01 00:00:00

  • Cancer immunotherapy targeting neoantigens.

    abstract::Neoantigens are antigens encoded by tumor-specific mutated genes. Studies in the past few years have suggested a key role for neoantigens in cancer immunotherapy. Here we review the discoveries of neoantigens in the past two decades and the current advances in neoantigen identification. We also discuss the potential b...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2015.11.002

    authors: Lu YC,Robbins PF

    更新日期:2016-02-01 00:00:00

  • T cell metabolism and the immune response.

    abstract::As T cells respond to pathogens, they must transition from a quiescent, naïve state, to a rapidly proliferating, active effector state, and back again to a quiescent state as they develop into memory cells. Such transitions place unique metabolic demands on the differentiating cells. T cells meet these demands by alte...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2012.12.006

    authors: Verbist KC,Wang R,Green DR

    更新日期:2012-12-01 00:00:00

  • CD40 ligation in B cell activation, isotype switching and memory development.

    abstract::Interaction of CD40 on B cells with its ligand on activated T helper cells is crucial for the generation of mature T-dependent antibody responses. Experimental observations suggest that CD40 ligation acts at several points in B cell differentiation; however, it is not clear whether the consequences of ligation are dir...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1006/smim.1994.1039

    authors: Gray D,Siepmann K,Wohlleben G

    更新日期:1994-10-01 00:00:00

  • Germinal center structure and function: lessons from CD19.

    abstract::The germinal center is a critical locus in the production of protective immunity, but its function is poorly understood. Studies of mutant forms of CD19 revealed differences in signaling in different compartments inside the germinal center, and structural findings indicate a selective role in the interaction with foll...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2007.12.007

    authors: Carter RH,Myers R

    更新日期:2008-02-01 00:00:00

  • The role of B cells and humoral immunity in Mycobacterium tuberculosis infection.

    abstract::Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immun...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2014.10.005

    authors: Chan J,Mehta S,Bharrhan S,Chen Y,Achkar JM,Casadevall A,Flynn J

    更新日期:2014-12-01 00:00:00

  • PTX3 as a paradigm for the interaction of pentraxins with the complement system.

    abstract::Pentraxins are highly conserved components of the humoral arm of innate immunity. They include the short pentraxins C reactive protein (CRP) and serum amyloid P component (SAP), and the long pentraxin PTX3. These are soluble pattern-recognition molecules that are present in the blood and body fluids, and share the abi...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2013.05.002

    authors: Inforzato A,Doni A,Barajon I,Leone R,Garlanda C,Bottazzi B,Mantovani A

    更新日期:2013-02-01 00:00:00

  • Endoplasmic reticulum stress in the intestinal epithelium and inflammatory bowel disease.

    abstract::The unfolded protein response as a consequence of endoplasmic reticulum (ER) stress has recently been implicated as a novel mechanism that may lead to inflammatory bowel disease (IBD). Impairment of proper ER stress resolution in highly secretory Paneth and, to a lesser extent, goblet cells within the epithelium can p...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2009.01.001

    authors: Kaser A,Blumberg RS

    更新日期:2009-06-01 00:00:00

  • AIDing antibody diversity by error-prone mismatch repair.

    abstract::The creation of a highly diverse antibody repertoire requires the synergistic activity of a DNA mutator, known as activation-induced deaminase (AID), coupled with an error-prone repair process that recognizes the DNA mismatch catalyzed by AID. Instead of facilitating the canonical error-free response, which generally ...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2012.05.005

    authors: Chahwan R,Edelmann W,Scharff MD,Roa S

    更新日期:2012-08-01 00:00:00

  • Nutrient sensing, signal transduction and immune responses.

    abstract::Most cells in the body have a constant supply of nutrients, which are required to sustain cellular metabolism and functions. In contrast, cells of the immune system can encounter conditions with a limited nutrient supply during the course of an immune response. Cells of the immune system frequently operate in complex ...

    journal_title:Seminars in immunology

    pub_type: 杂志文章,评审

    doi:10.1016/j.smim.2016.09.001

    authors: Walls J,Sinclair L,Finlay D

    更新日期:2016-10-01 00:00:00