The immunological footprint of Mycobacterium tuberculosis T-cell epitope recognition

Aerosols containing Mycobacterium tuberculosis (MTB) generated from the cough of patients with active pulmonary tuberculosis are the source of MTB infection. About 70% of individuals exposed to infected aerosols do not get infected, depending on the intensity and duration of MTB exposure. Only 40% of the rest of the individuals (about 10% of those originally exposed) develop primary tuberculosis, whereas the remaining 60% contain the infection with generation of a robust immune response leading to latent tuberculosis, which is regarded as a spectrum rather than a single entity. The mechanisms involved in this natural protection are not yet well understood. There is an increasing need to integrate all disparate observations into a coherent systems biology approach for a comprehensive understanding: we need to decipher the nature of success and failure in MTB infection in humans. New advances in cellular immunology will aid in achieving that goal. We review here the nature of MTB peptide generation, antigen presentation, and detection of major histocompatibility complex class I and II-presented T-cell epitopes. Cross-sectional thinking from lessons learned in the context of the major efforts to develop vaccines will help to dissect biologically relevant mechanisms that need to be translated into the clinical context of MTB infection with the aim to (1) better understand clinically relevant T-cell responses in individuals protected from tuberculosis disease and develop markers of immune protection and vaccine take, (2) characterize the nature of the immune response in individuals who are not able to contain MTB infection, and ultimately (3) characterize markers to gauge response to therapy.     

Arterial pulse wave velocity in relation to carotid intima-media thickness, brachial flow-mediated dilation and carotid artery distensibility: the Cardiovascular Risk in Young Finns Study and the Health 2000 Survey

ObjectiveIncreased arterial pulse wave velocity (PWV) is a strong predictor of cardiovascular events and mortality. The data regarding the relationships between PWV and other indices of vascular damage is limited and partly controversial. We conducted the present study to examine PWV in relation to non-invasive measures of early atherosclerosis (brachial flow-mediated dilation [FMD], carotid intima-media thickness [IMT]) and local arterial stiffness (carotid artery distensibility [Cdist]).MethodsThe study population consisted of 1754 young adults (aged 30–45 years, 45.5% males) participating in the Cardiovascular Risk in Young Finns Study (YFS), and of 336 older adults (aged 46–76 years, 43.2% males) participating in the Health 2000 Survey. FMD was measured only in the YFS cohort. FMD, IMT and Cdist were assessed by ultrasound, and PWV was measured using the whole-body impedance cardiography device.ResultsIn young adults, FMD and IMT were not associated with PWV independently of cardiovascular risk factors. Moreover, FMD status was not found to modulate the association between cardiovascular risk factors and PWV. In older adults, PWV and IMT were directly and independently associated (β = 1.233, p = 0.019). In both cohorts, PWV was inversely related with Cdist, and this relation remained significant (p < 0.04) in models adjusted for cardiovascular risk factors.ConclusionsThe current findings suggest that PWV reflects a different aspect of vascular damage than FMD or IMT in young adults, whereas in older adults the information provided by PWV and IMT may be, to some extent, similar as regards subclinical vascular damage. The present observations also suggest that PWV and Cdist represent, at least in part, a similar adverse vascular wall process.