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Human Immunology of Tuberculosis

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  • Authors: Thomas J. Scriba1, Anna K. Coussens2, Helen A. Fletcher3
  • Editors: William R. Jacobs Jr.4, Helen McShane5, Valerie Mizrahi6, Ian M. Orme7
    Affiliations: 1: South African Tuberculosis Vaccine Initiative, Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; 2: Clinical Infectious Diseases Research Initiative, Division of Medical Microbiology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; 3: Immunology and Infection Department, London School of Hygiene and Tropical Medicine, London, United Kingdom; 4: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 5: University of Oxford, Oxford OX3 7DQ, United Kingdom; 6: University of Cape Town, Rondebosch 7701, South Africa; 7: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec February 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.TBTB2-0016-2016
  • Received 09 March 2016 Accepted 19 March 2016 Published 01 February 2017
  • Helen A. Fletcher, [email protected]
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  • Abstract:

    Immunology is a central theme when it comes to tuberculosis (TB). The outcome of human infection with is dependent on the ability of the immune response to clear or contain the infection. In cases where this fails, the bacterium replicates, disseminates within the host, and elicits a pathologic inflammatory response, and disease ensues. Clinical presentation of TB disease is remarkably heterogeneous, and the disease phenotype is largely dependent on host immune status. Onward transmission of to new susceptible hosts is thought to depend on an excessive inflammatory response causing a breakdown of the lung matrix and formation of lung cavities. But this varies in cases of underlying immunological dysfunction: for example, HIV-1 infection is associated with less cavitation, while diabetes mellitus comorbidity is associated with increased cavitation and risk of transmission. In compliance with the central theme of immunology in tuberculosis, we rely on detection of an adaptive immune response, in the form of interferon-gamma release assays or tuberculin skin tests, to diagnose infection with . Here we review the immunology of TB in the human host, focusing on cellular and humoral adaptive immunity as well as key features of innate immune responses and the underlying immunological dysfunction which associates with human TB risk factors. Our review is restricted to human immunology, and we highlight distinctions from the immunological dogma originating from animal models of TB, which pervade the field.

  • Citation: Scriba T, Coussens A, Fletcher H. 2017. Human Immunology of Tuberculosis. Microbiol Spectrum 5(1):TBTB2-0016-2016. doi:10.1128/microbiolspec.TBTB2-0016-2016.


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Immunology is a central theme when it comes to tuberculosis (TB). The outcome of human infection with is dependent on the ability of the immune response to clear or contain the infection. In cases where this fails, the bacterium replicates, disseminates within the host, and elicits a pathologic inflammatory response, and disease ensues. Clinical presentation of TB disease is remarkably heterogeneous, and the disease phenotype is largely dependent on host immune status. Onward transmission of to new susceptible hosts is thought to depend on an excessive inflammatory response causing a breakdown of the lung matrix and formation of lung cavities. But this varies in cases of underlying immunological dysfunction: for example, HIV-1 infection is associated with less cavitation, while diabetes mellitus comorbidity is associated with increased cavitation and risk of transmission. In compliance with the central theme of immunology in tuberculosis, we rely on detection of an adaptive immune response, in the form of interferon-gamma release assays or tuberculin skin tests, to diagnose infection with . Here we review the immunology of TB in the human host, focusing on cellular and humoral adaptive immunity as well as key features of innate immune responses and the underlying immunological dysfunction which associates with human TB risk factors. Our review is restricted to human immunology, and we highlight distinctions from the immunological dogma originating from animal models of TB, which pervade the field.

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Hypothesized stages of response to infection, beginning with elimination mediated by innate immune cells without induction of a long-lasting memory response; further stages of elimination may be mediated via acquired immune mechanisms. If antigen-specific effector memory persists, this can be measured via IFN-γ release assays (IGRA) or tuberculin skin test (TST) and may provide protection from infection for a variable period of time. If the acquired immunity does not eliminate the bacteria, then infection will persist over a range of bacterial states. Increasing bacterial load is hypothesized to correlate with progression to active TB. For all exposed individuals, the risk of developing TB is highest immediately following exposure and changes over time. The longitudinal risk of developing TB, predicted in the exposed individual, is presented (adapted from references 204 and 205 ).

Source: microbiolspec February 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.TBTB2-0016-2016
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The spectrum of pulmonary TB lesions that can be found in the same host and that represent different stages of disease. Primary TB is characterized by the hallmark circular granuloma with caseating necrosis which forms within the center, surrounded by a lymphocytic cuff. Conversely, post-primary TB is typically represented by a diverse range of pathologies. Acute post-primary lesions are composed of paucibacillary lobular pneumonia; these may either resolve (subacute dry), fibrose (chronic fibrosing) or necrose (acute caseating). Caseating granulomas in post-primary TB are distinct from the granulomas of primary TB in that they form around and in response to caseous necrosis of pneumonic lesions (post-primary granuloma) rather than necrosis occurring in the center of preformed lesions as occurs in primary TB. Cavities are formed from the dissolution of these caseating pneumonic lesions. Six stages are represented by a 19th century drawing and a 21st century photomicrograph of sections stained with hematoxylin and eosin or trichrome, imaged at 40 to 400×. (Reproduced from references 31 , 220 , and 221 ).

Source: microbiolspec February 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.TBTB2-0016-2016
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Role of antibodies in anti- () infection. Antibodies may directly bind to mycobacteria, triggering complement deposition and lysis of , or complement may mediate opsonophagocytosis of the organism. Alternatively, -bound antibody may enhance macrophage uptake through Fc receptor binding or activate NK cell activity through Fc receptor engagement. It is also possible for immune complexes to form between mycobacterial antigen and antibody. Abbreviations: FcγRIII, Fc gamma receptor III; IgA, immunoglobulin A; IgG, immunoglobulin G; LAM, lipoarabinomannan; MAC, membrane-attack complex. (From reference 37 with permission.)

Source: microbiolspec February 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.TBTB2-0016-2016
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Antibodies in infection

Source: microbiolspec February 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.TBTB2-0016-2016

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