Abstract：
:The adaptive immune system, which utilizes RAG-mediated recombination to diversify immune receptors, arose in ancestors of the jawed vertebrates approximately 500 million years ago. Homologs of immunoglobulins (Igs), T cell antigen receptors (TCRs), major histocompatibility complex (MHC) I and II, and the recombination activating genes (RAGs) have been identified in all extant classes of jawed vertebrates; however, no definitive ortholog of any of these genes has been identified in jawless vertebrates or invertebrates. Although the identity of the "primoridal" receptor that likely was interrupted by the recombination mechanism in the common ancestor of jawed vertebrates may never be established, many different families of genes that exhibit predicted characteristics of such a receptor have been described both within and outside the jawed vertebrates. Various model systems point toward a range of immune receptor diversity, encompassing many different families of recognition molecules, including non-diversified and diversified Ig-type variable (V) regions, as well as diversified VJ domains, whose functions are integrated in an organism's response to pathogenic invasion. The transition from the primordial antigen receptor to the monomeric Ig-/TCR-like domain and subsequent antigen-specific heterodimer likely involved progressive refinement of unique intermolecular associations in parallel with the acquisition of combinatorial diversity and antigen-specific recognition through somatic modification of the V region. RAG-mediated recombination and associated junctional diversification of both Ig and TCR genes occurs in all jawed vertebrates. In the case of Igs, somatic variation is expanded further through class switching, gene conversion, and somatic hypermutation. Various approaches, including both genomic and protein functional analyses, currently are being applied in jawless vertebrates, protochordates and other invertebrate deuterostome model systems in order to examine both RAG-mediated and alternative forms of antigen receptor diversification. Such studies have uncovered previously unknown mechanisms of generating receptor diversity.
journal_name
Semin Immunoljournal_title
Seminars in immunologyauthors
Eason DD,Cannon JP,Haire RN,Rast JP,Ostrov DA,Litman GWdoi
10.1016/j.smim.2004.08.001keywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
215-26issue
4eissn
1044-5323issn
1096-3618pii
S1044-5323(04)00034-Xjournal_volume
16pub_type
杂志文章,评审abstract：:The signalling mechanisms of the IL-2R remained an enigma until recent years. We now know that IL-2R are coupled to their own unique signalling pathways that complement rather than duplicate TCR signalling. The IL-2R beta- and gamma-chains are essential for signal coupling. Sequence comparisons indicate that portions ...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1006/smim.1993.1040
更新日期：1993-10-01 00:00:00
abstract：:In this review we discuss the changes that occur in the B lymphocyte compartment of mice and humans as they progress to old age, focusing on recent advances in this important area of research. Primary areas considered include increased morbidity and mortality in the elderly following infection, and decreased responsiv...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2012.04.004
更新日期：2012-10-01 00:00:00
abstract：:Protein tyrosine phosphatases (PTPs) are a family of enzymes that modulate the cellular level of tyrosine phosphorylation. Based on cellular location, they are classified as receptor like or intracellular PTPs. Structure and function studies have led to the understanding of the enzymatic mechanism of this class of enz...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1006/smim.2000.0209
更新日期：2000-02-01 00:00:00
abstract：:Signals from the precursor-B cell receptor (pre-BCR) are essential for selection and clonal expansion of pre-B cells that have performed productive immunoglobulin heavy chain V(D)J recombination. In the mouse, the downstream signaling molecules SLP-65 and Btk cooperate to limit proliferation and induce differentiation...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2005.10.002
更新日期：2006-02-01 00:00:00
abstract：:A growing amount of evidences indicates that inflammaging - the chronic, low grade inflammation state characteristic of the elderly - is the result of genetic as well as environmental or stochastic factors. Some of these, such as the accumulation of senescent cells that are persistent during aging or accompany its pro...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2018.10.009
更新日期：2018-12-01 00:00:00
abstract：:After decades of slow progress, the last years have seen a rapid acceleration of the development of adjuvanted vaccines which have lately been approved for human use. These adjuvants consist of different components, e.g. aluminium salts, emulsions such as MF59 and AS03, Toll-like receptor (TLR) agonists (CpG ormonopho...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2018.05.001
更新日期：2018-10-01 00:00:00
abstract：:Secondary, so-called costimulatory, signals are critically required for the process of T cell activation. Since landmark studies defined that T cells receiving a T cell receptor signal without a costimulatory signal, are tolerized in vitro, the investigation of T cell costimulation has attracted intense interest. Earl...
journal_title：Seminars in immunology
pub_type： 杂志文章
doi：10.1016/j.smim.2011.04.002
更新日期：2011-08-01 00:00:00
abstract：:The Ly49 and Nkrp1 loci encode structurally and functionally related cell surface proteins that positively or negatively regulate natural killer (NK) cell-mediated cytotoxicity and cytokine production. Yet despite their clear relatedness and genetic linkage within the NK gene complex (NKC), these two multi-gene famili...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2008.05.004
更新日期：2008-12-01 00:00:00
abstract：:Apoptosis of activated lymphocytes is critical to immune homeostasis. The cell surface receptor Fas is an important mediator of lymphocyte apoptosis; defective Fas expression causes accumulation of lymphocytes and autoimmune disease in mice. Apoptosis defects due to mutations of Fas have also been found in a rare huma...
journal_title：Seminars in immunology
pub_type： 杂志文章
doi：10.1006/smim.1996.0056
更新日期：1997-02-01 00:00:00
abstract：:Ten seven-transmembrane-domain G protein-coupled receptors have been identified that are functional HIV-1, HIV-2 and SIV coreceptors. However, the specific structures these receptors have in common that enable them to mediate HIV entry are unknown. Structure-function analyses have revealed that the determinants of cor...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1006/smim.1998.0130
更新日期：1998-06-01 00:00:00
abstract：:Advancing age is accompanied by profound changes in immune function; some are induced by the loss of critical niches that support development of naïve cells (e.g. thymic involution), others by the intrinsic physiology of long-lived cells attempting to maintain homeostasis, still others by extrinsic effects such as oxi...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2012.04.007
更新日期：2012-10-01 00:00:00
abstract：:A humoral immune response in the form of autoantibodies to tumor antigens occurs early during tumor development. Identification of antigens that induce an autoantibody response restricted to a cancer type has the potential to yield markers useful for early detection. A multitude of strategies are currently available f...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2020.101388
更新日期：2020-02-01 00:00:00
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
更新日期：1994-10-01 00:00:00
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
更新日期：2014-12-01 00:00:00
abstract：:The recombination activating genes 1 and 2 (Rag1 and Rag2) encode the key enzyme that is required for the generation of the highly diversified antigen receptor repertoire central to adaptive immunity. The longstanding model proposed that this gene pair was acquired by horizontal gene transfer to explain its abrupt app...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2009.11.004
更新日期：2010-02-01 00:00:00
abstract：:The BLyS family of receptors includes two cytokines, BLyS and APRIL; and three receptors, BR3, BCMA and TACI. Together, these regulate the size and composition of peripheral B cell pools. The multiplicity of ligand-receptor sets, in conjunction with differential receptor expression, alternative binding partners and di...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2006.07.001
更新日期：2006-10-01 00:00:00
abstract：:Follicular dendritic cells (FDCs) were identified decades ago by their ability to retain immune complexes and more recent findings indicate that they are a source of B cell attractants and trophic factors. New imaging studies have shown that B cells closely associate with their dendritic processes during migration. He...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2007.12.001
更新日期：2008-02-01 00:00:00
abstract：:The OX-40 receptor (OX-40R) is a transmembrane protein found on the surface of activated CD4(+) T cells. When engaged by an agonist such as anti-OX-40 antibody or the OX-40 ligand (OX-40L) during antigen presentation to T cell lines, the OX-40R generates a costimulatory signal that is as potent as CD28 costimulation. ...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1006/smim.1998.0146
更新日期：1998-12-01 00:00:00
abstract：:Lymph nodes (LNs) represent the principal site where antigen-specific memory T- and B-cell responses are primed and differentiated into memory and effector cells. During chronic viral infections such as HIV, these lymphoid tissues undergo substantial structural changes. These changes are mostly caused by an imbalanced...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2008.07.008
更新日期：2008-06-01 00:00:00
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
更新日期：2013-02-01 00:00:00
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
更新日期：2011-08-01 00:00:00
abstract：:Studies on oral immunotherapy (OIT) have been increasing worldwide. Nevertheless, some concerns exist with this treatment. The rate of long-term sustained unresponsiveness is quite low; moreover, the desensitization or sustained unresponsiveness does not equate to tolerance. Furthermore, adverse reactions are frequent...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2017.07.008
更新日期：2017-04-01 00:00:00
abstract：:The frontiers of cancer immunotherapy are extending in terms of both the range of cancer types that can potentially be targeted and the types of therapeutics that are in clinical development. The use of adoptive cellular therapy (ACT) and its derivative, chimeric antigen receptor (CAR) T cells, is currently limited to...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2015.11.003
更新日期：2016-02-01 00:00:00
abstract：:Metazoan parasites typically induce a type 2 immune response, characterized by T helper 2 (Th2) cells that produce the cytokines IL-4, IL-5 and IL-13 among others. The type 2 response is host protective, reducing the number of parasites either through direct killing in the tissues, or expulsion from the intestine. Typ...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2014.06.003
更新日期：2014-08-01 00:00:00
abstract：:Celiac disease (CD) is an increasingly common disease of the small intestine that occurs in genetically susceptible subjects by ingestion of cereal gluten proteins. Gluten is highly abundant in the modern diet and well tolerated by most individuals. In CD, however, an erroneous but highly specific, adaptive immune res...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2015.11.001
更新日期：2015-09-01 00:00:00
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
更新日期：2007-02-01 00:00:00
abstract：:Humans are continuously exposed to a high number of diverse pathogens that induce different types of immune responses. Primary pathogen-specific immune responses generate multiple subsets of memory T cells, which provide protection against secondary infections. In recent years, several novel T cell subsets have been i...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2013.10.012
更新日期：2013-11-15 00:00:00
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
更新日期：2011-02-01 00:00:00
abstract：:Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonar...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2014.09.003
更新日期：2014-12-01 00:00:00
abstract：:Natural killer (NK) cells have traditionally been classified as a cellular component of the innate immune system, given their ability to rapidly produce effector cytokines and kill infected or transformed cells without prior exposure. More recently, NK cells have been shown to possess features of adaptive immunity suc...
journal_title：Seminars in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.smim.2017.08.012
更新日期：2017-06-01 00:00:00
