Helminths, including nematodes, cestodes and trematodes, are complex parasitic organisms that infect at least one billion people globally living in extreme poverty. Helminthic infections are associated with severe morbidity particularly in young children who often harbor the highest burden of disease. While each helminth species completes a distinct life cycle within the host, several helminths incite significant lung disease. This impact on the lungs occurs either directly from larval migration and host immune activation or indirectly from a systemic inflammatory immune response. The impact of helminths on the pulmonary immune response involves a sophisticated orchestration and activation of the host innate and adaptive immune cells.  https://www.selleckchem.com/mTOR.html  The consequences of activating pulmonary host immune responses are variable with several helminthic infections leading to severe, pulmonary compromise while others providing immune tolerance and protection against the development of pulmonary diseases. Further delineation of the convoluted interface between helminth infection and the pulmonary host immune responses is critical to the development of novel therapeutics that are critically needed to prevent the significant global morbidity caused by these parasites.Recent evidence indicates that local immune responses and tissue resident memory T cells (TRM) are critical for protection against respiratory infections but there is little information on the contributions of upper and lower respiratory tract (URT and LRT) immunity. To provide a rational basis for designing methods for optimal delivery of vaccines to the respiratory tract in a large animal model, we investigated the distribution of droplets generated by a mucosal atomization device (MAD) and two vibrating mesh nebulizers (VMNs) and the immune responses induced by delivery of influenza virus by MAD in pigs. We showed that droplets containing the drug albuterol, a radiolabel (99mTc-DTPA), or a model influenza virus vaccine (S-FLU) have similar aerosol characteristics. 99mTc-DTPA scintigraphy showed that VMNs deliver droplets with uniform distribution throughout the lungs as well as the URT. Surprisingly MAD administration (1ml/nostril) also delivered a high proportion of the dose to the lungs, albeit concentrated in a small area. After MAD administration of influenza virus, antigen specific T cells were found at high frequency in nasal turbinates, trachea, broncho-alveolar lavage, lungs, tracheobronchial nodes, and blood. Anti-influenza antibodies were detected in serum, BAL and nasal swabs. We conclude that the pig is useful for investigating optimal targeting of vaccines to the respiratory tract.The loss of efferocytosis-the phagocytic clearance of apoptotic cells-is an initiating event in atherosclerotic plaque formation. While the loss of macrophage efferocytosis is a prerequisite for advanced plaque formation, the transcriptional and cellular events in the pre-lesion site that drive these defects are poorly defined. Transcriptomic analysis of macrophages recovered from early-stage human atherosclerotic lesions identified a 50-fold increase in the expression of GATA2, a transcription factor whose expression is normally restricted to the hematopoietic compartment. GATA2 overexpression in vitro recapitulated many of the functional defects reported in patient macrophages, including deficits at multiple stages in the efferocytic process. These findings included defects in the uptake of apoptotic cells, efferosome maturation, and in phagolysosome function. These efferocytic defects were a product of GATA2-driven alterations in the expression of key regulatory proteins, including Src-family kinases, Rab7 and components of both the vacuolar ATPase and NADPH oxidase complexes. In summary, these data identify a mechanism by which efferocytic capacity is lost in the early stages of plaque formation, thus setting the stage for the accumulation of uncleared apoptotic cells that comprise the bulk of atherosclerotic plaques.
  To study the clinical, serological and histologic features of primary Sjögren's syndrome (pSS) patients with early (young ≤35 years) or late (old ≥65 years) onset and to explore the differential effect on lymphoma development.
 
  From a multicentre study population of 1997 consecutive pSS patients, those with early or late disease onset, were matched and compared with pSS control patients of middle age onset. Data driven analysis was applied to identify the independent variables associated with lymphoma in both age groups.
 
  Young pSS patients (19%, n = 379) had higher frequency of salivary gland enlargement (SGE, lymphadenopathy, Raynaud's phenomenon, autoantibodies, C4 hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3% vs. 5.7%, p = 0.030, OR = 1.91, 95% CI 1.11-3.27), while old pSS patients (15%, n = 293) had more frequently dry mouth, interstitial lung disease, and lymphoma (6.8% vs. 2.1%, p = 0.011, OR = 3.40, 95% CI 1.34-8.17) compared to their middle-aged pSS controls, respectively. In young pSS patients, cryoglobulinemia, C4 hypocomplementemia, lymphadenopathy, and SGE were identified as independent lymphoma associated factors, as opposed to old pSS patients in whom SGE, C4 hypocomplementemia and male gender were the independent lymphoma associated factors. Early onset pSS patients displayed two incidence peaks of lymphoma within 3 years of onset and after 10 years, while in late onset pSS patients, lymphoma occurred within the first 6 years.
 
  Patients with early and late disease onset constitute a significant proportion of pSS population with distinct clinical phenotypes. They possess a higher prevalence of lymphoma, with different predisposing factors and lymphoma distribution across time.
 Patients with early and late disease onset constitute a significant proportion of pSS population with distinct clinical phenotypes. They possess a higher prevalence of lymphoma, with different predisposing factors and lymphoma distribution across time.Complement, as a central immune surveillance system, can be activated within seconds upon stimulation, thereby displaying multiple immune effector functions. However, in pathologic scenarios (like in tumor progression), activated complement can both display protective effects to control tumor development and passively promotes the tumor growth. Clinical investigations show that patients with several hematological malignancies often display abnormal level of specific complement components, which in turn modulates complement activation or deregulated cascade. In the past decades, complement-dependent cytotoxicity and complement-dependent cell-mediated phagocytosis were fully approved to display vital roles in monoclonal antibody-based immunotherapies, especially in therapies against hematological malignancies. However, tumor-mediated complement evasion presents a big challenge for such a therapy. This review aims to provide an integrative overview on the roles of the complement in tumor promotion, highlights complement mediated effects on antibody-based immunotherapy against distinct hematological tumors, hopefully provides a theoretical basis for the development of complement-based cancer targeted therapies.