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      The mannose-binding lectin: a prototypic pattern recognition molecule

      review-article
      , , ,
      Current Opinion in Immunology
      Elsevier Ltd.

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          Abstract

          The innate immune system is comprised of a sophisticated network of recognition and effector molecules that act together to protect the host in the first minutes or hours of exposure to an infectious challenge. The mannose-binding lectin (MBL) is an evolutionary conserved circulating host defense protein that acts as a broad-spectrum recognition molecule against a wide variety of infectious agents. Target binding triggers the MBL pathway of complement activation. MBL can be considered conceptually as an ‘ante-antibody’ because it has a role in mammals during the lag period that is required to develop an antibody response against infectious agents. Additionally, there are MBL-like homologues in animals that lack adaptive immunity that activate a primitive complement system, and under these circumstances these MBL-like molecules play an analogous role to antibodies in higher animals. These molecules might be considered to be functional antecedents of antibodies. Recent work also indicates that MBL recognizes altered self-antigens, and as such MBL has a role that extends beyond a traditional role in first line host defense as it appears to play a role as a modulator of inflammation.

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          Most cited references60

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          Phylogenetic perspectives in innate immunity.

          The concept of innate immunity refers to the first-line host defense that serves to limit infection in the early hours after exposure to microorganisms. Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity.
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            Genetic dissection of immunity to mycobacteria: the human model.

            Humans are exposed to a variety of environmental mycobacteria (EM), and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. In addition, most of the world's population is occasionally exposed to human-borne mycobacterial species, which are less abundant but more virulent. Although rarely pathogenic, mildly virulent mycobacteria, including BCG and most EM, may cause a variety of clinical diseases. Mycobacterium tuberculosis, M. leprae, and EM M. ulcerans are more virulent, causing tuberculosis, leprosy, and Buruli ulcer, respectively. Remarkably, only a minority of individuals develop clinical disease, even if infected with virulent mycobacteria. The interindividual variability of clinical outcome is thought to result in part from variability in the human genes that control host defense. In this well-defined microbiological and clinical context, the principles of mouse immunology and the methods of human genetics can be combined to facilitate the genetic dissection of immunity to mycobacteria. The natural infections are unique to the human model, not being found in any of the animal models of experimental infection. We review current genetic knowledge concerning the simple and complex inheritance of predisposition to mycobacterial diseases in humans. Rare patients with Mendelian disorders have been found to be vulnerable to BCG, a few EM, and M. tuberculosis. Most cases of presumed Mendelian susceptibility to these and other mycobacterial species remain unexplained. In the general population leprosy and tuberculosis have been shown to be associated with certain human genetic polymorphisms and linked to certain chromosomal regions. The causal vulnerability genes themselves have yet to be identified and their pathogenic alleles immunologically validated. The studies carried out to date have been fruitful, initiating the genetic dissection of protective immunity against a variety of mycobacterial species in natural conditions of infection. The human model has potential uses beyond the study of mycobacterial infections and may well become a model of choice for the investigation of immunity to infectious agents.
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              The immune system evolved to discriminate infectious nonself from noninfectious self.

              Here, Charles Janeway argues that the requirement for two signals to initiate the adaptive immune response may reflect the evolutionary history of host defences. Early phases of host defence involve receptors and ligands that may have controlled immune responses prior to the development of clonally-distributed receptors encoded in rearranging genes. The former receptors persist in contemporary vertebrates both to trigger innate or nonclonal responses and to signal to lymphocytes that a particular antigen is associated with a microorganism.
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                Author and article information

                Contributors
                Journal
                Curr Opin Immunol
                Curr. Opin. Immunol
                Current Opinion in Immunology
                Elsevier Ltd.
                0952-7915
                1879-0372
                20 December 2005
                February 2006
                20 December 2005
                : 18
                : 1
                : 16-23
                Affiliations
                Laboratory of Developmental Immunology, Massachusetts General Hospital, Harvard Department of Pediatrics, 55 Fruit Street, Boston, MA 02114, USA
                Article
                S0952-7915(05)00207-4
                10.1016/j.coi.2005.11.014
                7126801
                16368230
                d3ea9c49-a4b3-473a-a907-d961b8b4b80b
                Copyright © 2005 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Immunology
                Immunology

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