ABSTRACT
The present study was conducted to understand the aetiological link between tuberculosis (TB) and sarcoidosis. Sera from smear-positive TB subjects (n = 24), smear-negative TB subjects (n = 24), sarcoidosis patients (n = 24) and healthy controls (n = 24) were collected and circulating immune complexes were isolated. Sandwich ELISA was performed for detecting four highly specific mycobacterial regions of difference (RD) proteins (early secretory antigenic target 6 [ESAT6], 10 KDa culture filtrate protein [CFP10], 21 KDa CFP [CFP21] and mycobacterial protein from species TB [MPT 64]). Sensitivity and specificity was calculated, and receiver operating characteristic plots were plotted. Non-parametric Mann-Whitney U-test was used to calculate statistical significance. Seventy per cent of sarcoidosis patients showed the presence of immune complexes of mycobacterial RD proteins similar to that observed in the sera of smear-negative TB patients as opposed to antibody-based detection assay based on these RD proteins. Thus, immunoassays based on specific mycobacterial RD proteins also need to be developed and validated carefully to differentiate TB and sarcoidosis, a close mimic of smear-negative tuberculosis.
Subject(s)
Antigen-Antibody Complex/blood , Mycobacterium tuberculosis/immunology , Sarcoidosis/pathology , Tuberculosis, Pulmonary/pathology , Antibodies, Bacterial/blood , Antigens, Bacterial/blood , Case-Control Studies , Healthy Volunteers , Humans , Immunologic Factors/bloodABSTRACT
Bacillus Calmette-Guérin (BCG) remains the only available and most widely administered vaccine against Mycobacterium tuberculosis (Mtb), yet it fails to protect vaccinated individuals either from primary infection or reactivation of latent tuberculosis (TB). Despite BCG's variable efficacy against TB, the fact remains that BCG imparts protection in children against the disease, indicating that BCG possesses a wide protective antigenic repertoire. However, its failure to impart protection in adulthood can be linked to its failure to generate long-lived memory response and elicitation of an inadequate immune response against latency-associated antigens. Therefore, to improve the protective efficacy of BCG, a novel vaccination strategy is required. Consequently, in the present study, we have exploited the vaccination potential of liposomized α-crystalline 1 (Acr1L), a latency-associated antigen to induce enduring protective immunity against Mtb in BCG-primed animals. It is noteworthy that an increase in the multi-functional [interferon (IFN)-γ(hi) /tumour necrosis factor (TNF)-α(hi) ] CD4 and CD8 T cells were observed in BCG-primed and Acr1L-boosted (BCG-Acr1L) animals, compared to BCG alone. Further, substantial expansion of both central memory (CD44(hi) /CD62L(hi) ) and effector memory (CD44(hi) /CD62L(lo) ) populations of CD4 and CD8 T cells was noted. Importantly, BCG-Acr1L exhibited significantly better protection than BCG, as evidenced by a reduction in the bacterial burden and histopathological data of the lungs. In essence, BCG-Acr1L could be a potent future vaccination strategy to reinvigorate BCG potency.
Subject(s)
BCG Vaccine/immunology , Bacterial Proteins/immunology , Immunization, Secondary , Latent Tuberculosis/prevention & control , Mycobacterium tuberculosis/drug effects , alpha-Crystallins/immunology , Animals , BCG Vaccine/administration & dosage , BCG Vaccine/genetics , Bacterial Load/drug effects , Bacterial Proteins/genetics , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/microbiology , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/microbiology , CD8-Positive T-Lymphocytes/pathology , Female , Hyaluronan Receptors/genetics , Hyaluronan Receptors/immunology , Immunologic Memory/drug effects , Immunophenotyping , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , L-Selectin/genetics , L-Selectin/immunology , Latent Tuberculosis/immunology , Latent Tuberculosis/microbiology , Latent Tuberculosis/pathology , Liposomes/chemistry , Liposomes/immunology , Lung/drug effects , Lung/immunology , Lung/microbiology , Lung/pathology , Mice , Mycobacterium bovis/chemistry , Mycobacterium bovis/immunology , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/immunology , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/immunology , alpha-Crystallins/geneticsABSTRACT
The dependence of fission barriers on the excitation energy of the compound nucleus impacts the survival probability of superheavy nuclei synthesized in heavy-ion fusion reactions. In this work, we investigate the isentropic fission barriers by means of the self-consistent nuclear density functional theory. The relationship between isothermal and isentropic descriptions is demonstrated. Calculations have been carried out for 264Fm, 272Ds, ;{278}112, ;{292}114, and ;{312}124. For nuclei around ;{278}112 produced in "cold-fusion" reactions, we predict a more rapid decrease of fission barriers with excitation energy as compared to the nuclei around ;{292}114 synthesized in "hot-fusion" experiments. This is explained in terms of the difference between the ground-state and saddle-point temperatures. The effect of the particle gas is found to be negligible in the range of temperatures studied.
