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The pathogenesis of cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is dictated mainly by the immune-mediated-tissue inflammation developed. The understanding of the immunological mechanisms that generate tissue damage or resolution of lesions is the key to the development of effective vaccine protocols and proper therapeutic schemes. It is clear that the specific immune response mediated by T cells is responsible for the beneficial outcome of the disease, however, the roles of CD4+ T, CD8+ T, NK and NKT cell subpopulations in immunopathogenesis of CL need to be elucidated. Peripheral blood cells from patients before, during and after the antimonial therapy, as well as healthy individuals (HI) were cultured with (LbAgS) or without (NS) L. braziliensis antigens (LbAg). Afterwards, the frequencies of LbAg-specific-cytotoxic CD8+ T, CD4+ T, NK and CD3+CD56+ NKT cells, as well as their activation and exhaustion profiles, were defined by flow cytometry. We observed higher frequencies of CD8+ T, NK and CD3+CD56+ NKT cells and lower frequencies of CD4+ T lymphocytes in LbAgS cell cultures from patients before treatment. The specific response to LbAg resulted in an expansion of cytotoxic-activated CD4+ T, CD8+ T, and NK cells, before and during treatment, indicating specificity in the response by these cells against L. braziliensis. Furthermore, comparing the differences of frequencies of cytotoxic-activated CD4+T, CD8+T, and NK cells, among before and during treatment patients and HI groups, we conclude that these cell populations are in charge of immune response elicited by antimonial therapy. Interestingly, we also observed that NK cells were induced by LbAg to an exhaustion profile during all clinical stages of the disease. The increased antigen-specific activation and cytotoxic activity are in line with the strong inflammatory response described in this disease, a likely cause of tissue damage. These findings reinforce the involvement of these distinct cytotoxic-activated cell populations in the immunopathogenesis of CL, showing a character of specificity in this immune response.

Background: Coronal malalignment of the lower extremity is closely related to the onset and progression of osteoarthritis. Restoring satisfactory alignment after tibial osteotomy improves the long-term success of this conservative surgery. The purpose of our study was to determine (1) if there is a difference between two-dimensional (2D) and 3D measurements of the hip-knee-ankle (HKA) angle between the mechanical axes of the femur and the tibia, (2) which parameter most affects 2D-3D HKA measurement, and (3) the percentage of patients who are at risk of error in HKA measurement., Methods: We reviewed imaging studies of the consecutive patients referred to us for hip or knee pain between June and October 2013. Patients with previous pelvis or lower extremity surgery were excluded., Results: In 51 % (95/186) of lower extremities examined, the 3D method showed more valgus than the 2D method, and in 49 % (91/186), the 3D method showed more varus. In 12 % of extremities (23/186), the knee varus or valgus alignment was completely opposite in 3D images compared to 2D images. Having more than 7° of flexum/recurvatum alignment increased error in 2D HKA measurement by 5.7°. This was calculated to be 0.15° per 1° increase in femoral torsion and 0.05° per 1° increase in tibial torsion. Approximately 20 % of patients might be at risk of error in HKA angle measurement in 2D imaging studies., Conclusions: Orthopaedic surgeons should assess lower extremity alignment in standing position, with enough exposure of the extremity to find severe alignment or rotational deformities, and consider advanced 3D images of those patients who have them. Otherwise, HKA angle can be measured with good accuracy with 2D techniques., Level of Evidence: Level-III diagnostic.