Mini-symposium: Childhood TB in 2010 Immunology and pathogenesis of childhood TB Christine Jones, Elizabeth Whittaker, Alasdair Bamford, Beate Kampmann * Academic Department of Paediatrics, 2 nd Floor Wright-Fleming Institute, Imperial College London, St. Mary’s Campus, Norfolk Place, London W2 1PG INTRODUCTION Tuberculosis (TB) in children most commonly results from exposure to a household contact with active TB, and represents ongoing transmission of Mycobacterium Tuberculosis (Mtb) in the community. 1 Infants and young children have an increased risk of infection following exposure and progress more readily from infection to active TB disease; in the absence of intervention, infants have a 50-60% risk of disease in the first year following infection. 2,3 It could therefore be argued that the determining factor for the higher susceptibility to disease in children is prolonged, intimate contact between the child and the index case, which might lead to a larger inoculum of Mtb. However, there is little evidence to support this assumption, since the mycobacterial load in children is notoriously low, which lies at the root of the problem of bacteriological confirmation of primary TB. Young children more commonly present with disseminated disease and have an increased risk of death. 2 Even low bacillary loads in children can lead to acute and severe illness, be it respiratory or disseminated, especially in children younger than 2 years of age. The generally accepted assumption is therefore that qualitative and quantitative differences in the immune responses to Mtb infection between adults and children determine outcome. In the following review, we describe the multiple factors involved in containment of mycobacteria and review potential differences between responses in adults versus children. We have chosen to base this article primarily on studies conducted in the human host and - where available - in children. It is however obvious that crucial data on the impact of age on many of the cited factors are missing from the published literature, and we indicate where further studies would be warranted in this context. PATHOGENESIS - A BRIEF OVERVIEW A child in close contact with an infectious index case may inhale Mtb aerosolised in infected droplets. Should the bacilli be successful in traversing the physical and anatomical barriers encountered, Mtb bacilli are inhaled into the terminal alveoli. Once in the terminal alveoli, Mtb is readily phagocytosed by resident Paediatric Respiratory Reviews 12 (2011) 3–8 ARTICLE INFO Keywords: age antigen-presentation T cell populations mycobacteria EDUCATIONAL AIMS, RESEARCH DIRECTIONS Educational Aims  To discuss the range of immune mechanisms involved in the control of mycobacteria  To provide review of studies conducted in the human host and in children in particular  To illustrate the influence of age on immune function relevant to tuberculosis  To present the immune mechanisms involved as a continuum of responses rather than as strictly compartmentalised  To address the interplay of both host and mycobacterial factors in eliciting immune responses * Corresponding author. Tel.: +44 207 594 2063; Fax: +44 207 594 3894. E-mail addresses: christine.jones@imperial.ac.uk (C. Jones), e.whittaker@imper- ial.ac.uk (E. Whittaker), a.bamford@imperial.ac.uk (A. Bamford), b.kampmann@im- perial.ac.uk (B. Kampmann). Contents lists available at ScienceDirect Paediatric Respiratory Reviews 1526-0542/$ – see front matter ß 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.prrv.2010.09.006