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- Volume 10, 1992
Annual Review of Immunology - Volume 10, 1992
Volume 10, 1992
- Review Articles
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Specialization, Tolerance, Memory, Competition, Latency, and Strife among T Cells
Vol. 10 (1992), pp. 1–13More LessOver the last four decades much insight has been gained into the working of T cells. This survey offers an interpretation of regulatory T-cell function in terms of epitope linkage and the need to free B cells of responsibility for self-tolerance. These functions dictate specialized forms of antigen presentation, by separate populations of dendritic cells. Tolerance induction among T cells occurs at a threshold of antigen concentration which is close to that required for positive stimulation, as would be expected for the efficient workingo f the immunsey stem. Certain self-proteins, especially those located on cell surfaces, also induce tolerance among B cells, thus reducing the danger of activating latent epitopes. Memory among T cells is attributed to two components, one of hyperreactivity of activated cells, and the other of clonal expansion. Examples of competition and buffering between T-cell activities are given. A brief discussion of autoimmune disease focusses on the importance of disease remission, protective HLA genes, and immunoinhibitory genes in animal models. The mechanism underlying all three may be a balance between competing subsets of T cells.
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Sequences and Factors: A Guide to MHC Class-II Transcription
Vol. 10 (1992), pp. 13–49More LessThe expression of the class-II antigens of the major histocompatibility complex is tissue-specific, developmentally regulated in cells of the B lineage, and inducible by cytokine. Some of the molecular mechanisms that account for this regulation have recently been elucidated. DNA sequences upstream of human and mouse class-II genes that are critical for the transcription of these genes have been identified through transfection studies and transgenic analysis. Furthermore, a number of transcription factors that bind to important promoter motifs have recently been isolated. Examination of the class-II promoter in vivo both in the normal state and in patients with bare lymphocyte syndrome has further increased our understanding of class-II regulation.
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Peripheral T Cell Tolerance
Vol. 10 (1992), pp. 51–69More LessThe most efficient way to ensure self-tolerance in the T-cell repertoire is by intrathymic deletion of self-reactive clones. Antigens not present intrathymically may, however, influence the peripheral T-cell pool in various ways. They may of course activate T cells, provided that these have the correct specificity and affinity and that the antigens are presented in sufficient amounts on professional antigen-presenting cells. They may be ignored by T cells if some of these conditions are not met. In some forms, the antigen may be toleragenic for mature T cells. If the antigens persist in an immunogcnic form, unresponsiveness may eventually be imposed as the end result of a powerful immune response. Extrathymic self-antigenic components are generally encountered early in development, and the way in which these influence peripheral T lymphocytes has been studied by transgenic technology. They may be ignored by T cells if they are sequestered from the immune system, or if they are present in low amounts or on nonprofessional antigen-presenting cells which lack the appropriate accessory molecules or signals needed to activate the relevant T-cell subset. On the other hand, some of these self-antigens readily induce anergy in peripheral T cells, which may or may not involve downregulation of antigen receptors and coreceptors. Tolerance in the T-cell repertoire is therefore achieved not only by intrathymic deletion of self-reactive clones but also by several postthymic mechanisms
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The Human T Cell Receptor in Health and Disease
Vol. 10 (1992), pp. 71–96More LessThe T cell antigen receptor (TCR) recognizes antigen in the form short peptides bound to a major histocompatibility (MHC) molecule. This review provides a synopsis of the current state of knowledge of the structure and function of the receptor and its possible role in human disease. Analysis of the T cell receptor usage of T-cell lines and clones recognizing the same peptide-MHC complex is beginning to shed light onto the structural basis of the TCR-peptide-MHC complex. Also, it is now apparent that there are two mechanisms by which the TCR can interact with the MHC molecule, either through classical peptide interactions or through superantigens. Finally, we review the role of specific TCRs in human disease. Current evidence in this area is difficult to interpret; however, it is likely that TCR-mediatedi sease susceptibility exists, and its basis at either a germline or somatic level will soon be clarified.
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Antigen Receptors on B Lymphocytes
Vol. 10 (1992), pp. 97–121More LessRecent studies on the structure of the B cell antigen receptor demonstrate that the membrane-bound and antigen-binding immunoglobulin molecules are noncovalently associated with a heterodimer of two novel transmembrane proteins. The B cell antigen receptor is thus a multicomponent receptor complex whose structural features are similar to those of the T cell antigen receptor complex. Cross-linking of the B cell antigen receptor results in rapid tyrosine phosphorylation of substrate proteins. This suggests that the B cell receptor belongs to a subgroup of the tyrosine kinase receptor family with a noncovalently associated src-like tyrosine kinase.
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Roles of alphabeta and gammadelta T Cell Subsets in Viral Immunity
Vol. 10 (1992), pp. 123–151More LessThe current status of T-cell subset involvement in viral immunity is summarized for experimental studies in mice. The immunobiology of the normal host response is discussed, with particular reference to lymphocytic choriomeningitis (LCM) and influenza. The general impression is that CD8+ cytotoxic T lymphocytes, CD4+ TH1 cells, γ interferon, and IL-2 are of major importance, with these different components of the immune system interacting to promote an optimal response. However, experiments with a variety of virus systems indicate that there is considerable plasticity, at least in young, adult mice. Other mechanisms often compensate if a key lymphocyte subset is absent throughout the development of the immune response. Influenza-infected mice depleted of either CD4+ or CD8+ T cells clear virus and recover, though the latter may not be true for the elimination of LCM Virus. Emerging information on the involvement of γδ T cells in viral pneumonia is summarized, but there is as yet no understanding of the biological significance (if any) of these lymphocytes in viral immunity. The point is made that αβ T-cell memory to viruses is long-lived, and the need for antigen persistence to maintain such memory is questioned.
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Immunological Aspects of Demyelinating Diseases
Vol. 10 (1992), pp. 153–187More LessPrimary demyelination in the central nervous system results from damage to the myelin sheath or oligodendroglia and can be produced by a variety of mechanisms, including metabolic disturbances, toxicities, infection, and autoimmunity. The major human demyelinating disease affecting the central nervous system is multiple sclerosis (MS). Although the etiology MS is not known, existing data indicate that both genetic and environmental factors contribute to pathogenesis. Experimental allergic encephalomyelitis (EAE) is induced by immunization of genetically susceptible animals with myelin proteins. This is mediated by autoimmune T cells. Characterization of MHC restriction, fine specificity of antigen recognition, and T cell receptor (TCR) usage by encephalitogenic T cells has resulted in highly specific immunotherapies. Both HLA and TCR genes have been linked to susceptibility for MS which is widely believed to be mediated by T cells that recognize an as yet unidentified autoantigen. Because of the advances in the understanding and treatment of EAE, recent research in MS has been focused on the characterization of cellular immune responses against myelin components. The results of these studies are reviewed and the potential implications of these findings for the pathogenesis and future therapy of MS are examined.
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Murine Natural Killer Cells and Marrow Graft Rejection
Y. Y. L. Yu, V. Kumar, and M. BennettVol. 10 (1992), pp. 189–213More LessRejection of bone marrow transplants in lethally irradiated mice differs from rejection of solid tissue grafts in several respects. The genetic laws that govern rejection of solid tissue grafts often fail with hemopoietic grafts. For example, F1 hybrids between two H-2 disparate strains of mice often reject parental bone marrow cells (BMC), and conversely, marrow cells of F1 hybrids (H-2 heterozygous) are usually not rejected by either parent or an unrelated allogeneic recipient. Thus, unlike the classical MHC antigens, the hemopoietic histocompatibility (Hh) antigens relevant marrow graft rejection are inherited in a recessive pattern. The major Hh (Hh-1) locus maps within the mouse H-2 complex between the H-2S and H-2D regions, and it can therefore be dissociated from the class-I MHC genes. Nevertheless, it is possible that class-I MHC antigens play a role in the formation or expression of Hh-1 antigens. Three models that explain the possible relationship between class-I MHC and Hh-1 genes and the noncodominant pattern of inheritance of Hh antigens are presented. The effector cells responsible for resisting BMC grafts are different from those responsible for rejection of solid tissue grafts. Three cell types, natural killer cells (CD3-, NK1.1+), cytotoxic T cells (CD3+, CD8+), and T cells with natural killer cell markers (CD3+, NK1.1+) have been implicated in the rejection of BMC grafts. Involvement of these cell types is reviewed and the relative roles played by each are discussed. Evidence supporting the existence of Hh-1 specific subsets of NK cells is presented.
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Molecular Approaches to Analysis of X-Linked Immunodeficiencies
Vol. 10 (1992), pp. 215–238More LessAlthough the X-linked immunodeficiencies—X-linked agammaglobulinemia (XLA), X-linked severe combined immunodeficiency (XSCID), Wiskott-Aldrich syndrome (WAS), X-linked lymphoproliferative syndrome and X-linked hyper IgM syndrome—have been mapped to loci distributed throughout the X chromosome, they have several features in common that suggest that they might be members of a gene family: (i) all are maintained in the population at approximately the same gene frequency; (ii) expression of each defect is limited to the hematopoieticsy stem; (iii) atypical forms of each disorder have been described; and (iv) obligate carriers of these disorders are normal by all immunologic criteria. The failure of carriers of XLA, XSCID, and WAS to show signs of their gene defects can be explained by the preferential use of the normal, nonmutant X as the active X in the cell lineages affected by the gene defects. These three disorders also share an additional feature; in boys with XLAX, SCID, or WAS there is asynchronous expression of cell surface markers of differentiation or activation. If some or all of the genes that are abnormal in the X-linked immunodeficiencies are members of a gene family, then isolation of one gene may lead to the others.
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In Vitro Antibodies: Strategies for Production and Application
Vol. 10 (1992), pp. 239–265More LessThe approaches to the production of antibodies (Ab) using the techniques of genetic engineering and expression are reviewed. Genetic engineering facilitates the production of proteins tailormade for an intended use. Bacterial and mammalian expression systems are commonly used for the production of Ab and Ab-like molecules. While genomic or cDNA cloning can be used to obtain the relevant variable regions, PCR-based cloning approaches facilitate the acquisition of additional binding specificities. Large numbers of different chimeric Abs with murine variable regions joined to constant regions from human and other species have been expressed and found to exhibit the expected binding specificities and effector functions. These molecules have been used to study the structural basis of effector functions such as complement activation and Fc receptor binding, and potentially they may be used as therapeutic agents. Carbohydrate has been shown to influence both variable and constant region function. Single-chain Abs and fusion proteins with Ab binding specificities joined to nonimmunoglobulin sequences provide a source of Ab-like molecules with novel properties, and genetically engineered Ab-like molecules provide a source of useful antigens. Combinatorial libraries produced in bacteriophage present an alternative to hybridomas for the production of Abs with desired combining specifities. Issues of the immunogenicity of the recombinant molecules are addressed.
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Apoptosis and Programmed Cell Death in Immunity
Vol. 10 (1992), pp. 267–293More LessDeath of some cells in the mammalian body is clearly programmed. In the immune system there are many examples of programmed cell death, during development of lymphocytes as well as at later stages, after interaction with antigen. Many of these examples display the morphology of apoptosis: They undergo shrinkage and zeiosis, the nucleus collapses, and chromatin is cleaved into nucleosomal fragments. The cell is rapidly recognized by phagocytes and disposed of without releasing its contents. In some but not all cases of apoptosis, new macromolecular synthesis is required. Cytotoxic T cells induce changes in their targets that are morphologically apoptotic. The mechanism ofapoptosis is currently under active investigation.
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Cytokine Receptors and Signal Transduction
Vol. 10 (1992), pp. 295–331More LessCytokinesp lay a vital role in coordinating immune and inflammatory responses. Unlike growth factor receptors with a tyrosine kinase, cytokine receptors have no intrinsic tyrosine kinase activity. Based on their structure, cytokinere ceptors are classified into several groups. High affinity receptors for IL-2, IL-3, IL-5, IL-6, and GM-CSF are composed of at least two distinct subunits, α and β. The α subunits are primary cytokine binding proteins, and the β subunits are required for formation of high affinity binding sites as well as for signal transduction. The GM-CSF, IL-3, and IL-5 receptors appear to share the same β subunit in human, and therefore cross-talk among these cytokines may occur at the receptor level. High affinity receptors presumably are linked to various signal transduction pathways that lead to different cytokine functions. Differential expression of the cytokine receptors as well as reorganization of intracellular signalling pathways are critical for development of hemopoietic cells.
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Previous Volumes
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Volume 42 (2024)
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Volume 41 (2023)
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Volume 40 (2022)
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Volume 39 (2021)
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Volume 38 (2020)
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Volume 37 (2019)
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Volume 36 (2018)
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Volume 35 (2017)
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Volume 34 (2016)
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Volume 33 (2015)
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Volume 32 (2014)
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Volume 31 (2013)
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Volume 30 (2012)
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Volume 29 (2011)
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Volume 28 (2010)
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Volume 27 (2009)
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Volume 26 (2008)
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Volume 25 (2007)
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Volume 24 (2006)
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Volume 23 (2005)
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Volume 22 (2004)
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Volume 21 (2003)
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Volume 20 (2002)
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Volume 19 (2001)
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Volume 18 (2000)
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Volume 17 (1999)
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Volume 16 (1998)
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Volume 15 (1997)
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Volume 14 (1996)
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Volume 13 (1995)
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Volume 12 (1994)
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Volume 11 (1993)
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Volume 10 (1992)
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Volume 9 (1991)
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Volume 8 (1990)
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Volume 7 (1989)
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Volume 6 (1988)
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Volume 5 (1987)
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Volume 4 (1986)
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Volume 3 (1985)
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Volume 2 (1984)
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Volume 1 (1983)
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Volume 0 (1932)