Tuberculosis: Immunity

Abstract

For centuries, tuberculosis has been recognised as one of the most dangerous diseases on the planet, and in the twenty‐first century, this situation has not changed. In fact, both in the context of prevention by vaccination and treatment by chemotherapy, it has proven very difficult to halt the continued global epidemic of this deadly disease – a situation further compounded by the concomitant HIV epidemic. The immune response to tuberculosis involves both innate and acquired immune responses. Should an infection established an integrated response involving antigen‐specific T lymphocytes and macrophages ensues (‘TH1 response’) that involves the formation of a cellular barrier (‘granuloma’) that is controlled by cytokines and chemokines. As the infection becomes contained, the effector immune response contracts and is gradually replaced by T cells capable of an accelerated memory response to further exposure.

Key Concepts

  • Immunity to tuberculosis is cell mediated.
  • The central even involves the interaction between antigen‐specific T cells and infected macrophages.
  • The response is complex and involves multiple soluble mediators including cytokines and chemokines.
  • The primary containment device involves the formation of a structure called the granuloma.
  • Contraction of effector immunity is followed by the emergence of still poorly understood memory immunity.

Keywords: tuberculosis; immunity; T cells; granuloma; TH1 immunity; memory T cells

Figure 1. The ‘pulmonary interstitial model’ of tuberculosis infection favoured by my laboratory. After active erosion through the alveolar epithelium, local inflammation in the interstitium causes the influx of tissue fluid, which in turn allows the influx of macrophages, DC and neutrophils from the surround tissues and from the blood. DC picks up bacilli and transports them to lymph nodes, triggering T‐cell immunity. In the guinea pig (and we suspect in humans), neutrophils, being short‐lived, die and/or degranulate, establishing small foci of necrosis that coalesce to form the central necrosis in the granuloma that is the hallmark of human disease.
Figure 2. TH1 immunity to tuberculosis. Specialised macrophages (‘dendritic cells’) roam the lung tissues and encounter bacilli in the interstitium. Either locally or more likely after carriage to the draining lymph node, these dendritic cells present antigens to antigen‐specific T cells. These cells respond to IL‐12 and other signals from the infected macrophages, and upon recognition by their receptor of specific antigen presented in the context of class‐II MHC molecules, the T cell releases IFNγ which activates the macrophage to express its anti‐microbial functions. This includes the production of reactive oxygen species (ROS) and nitric oxide.
Figure 3. The gradual development of the granulomatous response in mice. Large aggregates of lymphocytes (mostly CD4 T cells and also some smaller groups of B cells) become spread over large fields of epithelioid macrophages. In the mouse, little or no necrosis is usually seen. Haematoxylin and eosin staining.
Figure 4. Distribution of T cells in the mouse granuloma. CD4 cells are distributed across the structure, while CD8 cells tend to be more distributed across the periphery of the granuloma. Immunohistochemical staining; target cells are red.
Figure 5. A primary granuloma in guinea pigs. Most of the structures consist of necrotic tissue, in which dystrophic calcification is often seen (dark black material). On the edge of the lesion is a strip or rim of eosinophilic material and beyond that a thin region containing scattered lymphocytes. Haematoxylin and eosin staining.
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Further Reading

Basaraba RJ and Orme IM (2010) Pulmonary tuberculosis in the guinea pig. In: Leong FY, Dartois V and Dick T, (eds). A Color Atlas of Comparative Pathology of Pulmonary Tuberculosis. Baton Rouge: CRC Press.

Cooper AM and Torrado E (2012) Protection versus pathology in tuberculosis: recent insights. Current Opinion in Immunology 24: 431–437.

McShane H, Jacobs WR, Fine PE, et al. (2012) BCG: myths, realities, and the need for alternative vaccine strategies. Tuberculosis (Edinb) 92: 283–288.

Srivastava S, Ernst JD and Desvignes L (2014) Beyond macrophages: the diversity of mononuclear cells in tuberculosis. Immunological Reviews 262: 179–192.

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Orme, Ian M(Apr 2015) Tuberculosis: Immunity. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020184.pub2]