Chapter 11 : Human Immunology of Tuberculosis

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Immunity to is an interplay between the innate and adaptive immune response, both cellular and humoral. This interplay is not static but changes over time as we grow, age, and respond to our environment. Animal models enable examination of individual components of the immune response at distinct time points during the course of infection. This has enabled identification and understanding of key immune mechanisms for control. However, rational development of interventions, such as more effective vaccines and other host-directed therapies, has to take into consideration the enormous heterogeneity of the interactions between with human innate and adaptive immune responses, which are profoundly influenced by genetic variation, environment, and comorbidities.

Citation: Scriba T, Coussens A, Fletcher H. 2017. Human Immunology of Tuberculosis, p 213-237. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0016-2016
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Figure 1

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 and ).

Citation: Scriba T, Coussens A, Fletcher H. 2017. Human Immunology of Tuberculosis, p 213-237. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0016-2016
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Figure 2

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 , and ).

Citation: Scriba T, Coussens A, Fletcher H. 2017. Human Immunology of Tuberculosis, p 213-237. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0016-2016
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Figure 3

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 with permission.)

Citation: Scriba T, Coussens A, Fletcher H. 2017. Human Immunology of Tuberculosis, p 213-237. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0016-2016
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