Josephsendawson0829

Mucosal barriers are active sites that encounter a bombardment of antigenic stimuli derived from both the commensal flora and a variety of pathogens, as well as from environmental insults. As such, the ability to mount appropriate innate immune responses is an important first line of defense that confers protection to the host. Central to innate immunity are innate lymphoid cells (ILCs), which were first described a decade ago, and represent a family of heterogeneous cells driven by specific transcription factors and exhibit distinct cytokine profiles that are shared with their CD4+ T-helper cell counterparts. ILCs are particularly enriched at mucosal surfaces, and the tissue microenvironment and cytokine milieu in which ILCs reside are critical factors that drive the behavior and overall function of these cells. In fact, ILCs situated at mucosal barriers must be able to temper their response to a constant exposure of environmental antigens, but also promptly react to pathogens or signals that are potentially harmful to the host. In this context, the ability of ILCs to readily transdifferentiate in response to their dynamic surroundings has become a vigorous area of research, and defining specific mechanism(s) of ILC plasticity is at the advent of discovery. This review will summarize what is currently known regarding the network of cytokines and regulatory elements that enable ILCs to readily transform, based on the range of diverse signals and signal gradients they encounter that lead to either protective or pathogenic function(s), with focus on the gut mucosal immune system.The search for tumor-specific antigens (TSAs) has considerably accelerated during the past decade due to the improvement of proteogenomic detection methods. This provides new opportunities for the development of novel antitumoral immunotherapies to mount an efficient T cell response against one or multiple types of tumors. learn more While the identification of mutated antigens originating from coding exons has provided relatively few TSA candidates, the possibility of enlarging the repertoire of targetable TSAs by looking at antigens arising from non-canonical open reading frames opens up interesting avenues for cancer immunotherapy. In this review, we outline the potential sources of TSAs and the mechanisms responsible for their expression strictly in cancer cells. In line with the heterogeneity of cancer, we propose that discrete families of TSAs may be enriched in specific cancer types.

CD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of anti-CD19 scFv are derived from murine antibody sequences. However, about 10-20% of B-ALL patients exhibit primary resistance to murine-based CD19CAR-T (CD19mCAR-T). Herein, we report that a humanized selective CD19CAR-T (CD19hsCAR-T) may offer a solution to this problem.

A 10-year old boy was diagnosed with high-risk B-ALL in Mar., 2013, and relapsed in Oct., 2018, after he underwent haplo-identical hematopoietic stem cell transplantation (HSCT) in 2017. The patient then received haplo-identical CD19mCAR-T infusions twice following induction chemotherapy with Vincristine, Dexamethasone and Asparaginase (VDL), but no response was observed. We further treated this patient with CD19hsCAR-T following chemotherapy with Vindesine, Idarubicin, Dexamethasone, and Pegylated Asparaginase (VDLD) plus bortezomib. The patient achieved minimal residual disease-negative (MRDneg) complete remission with incomplete hematopoietic recovery (CRi), and remained in CRi for more than 8 months with manageable side effect. The patient, unfortunately, died of unidentified pulmonary infection on Jan. 25 2020.

CD19hsCAR-T may have the potential to induce remission in patients who are primarily refractory to CD19mCAR-T.

CD19hsCAR-T may have the potential to induce remission in patients who are primarily refractory to CD19mCAR-T.

The risk of cardiovascular events in patients with Rheumatoid Arthritis (RA) is disproportionately heightened as a result of systemic inflammation. The relative effect of autoimmune-associated citrullination on the structure and thrombotic potential of fibrin(ogen) remains unknown. We therefore compared indices of vascular function, inflammation, coagulation and fibrin clot composition in RA patients with healthy controls and evaluated parameter association with disease presence.

Blood samples were collected from 30 RA patients and 30 age- and gender-matched healthy volunteers. Levels of serum amyloid A (SAA), c-reactive protein (CRP), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) was measured using a sandwich immunoassay. Whole blood coagulation was assessed using Thromboelastography (TEG

). Fibrin clot networks and fiber structure was investigated using Scanning Electron Microscopy. The detection and quantification of citrullination in formetrol plasma and plasma is more accessible than synovial fluid. Citrullinated fibrinogen could play a role as a determinant of thrombotic risk in RA patients.Vi-polysaccharide conjugate vaccines are efficacious against cases of typhoid fever; however, an absolute correlate of protection is not established. In this study, we investigated the leukocyte response to a Vi-tetanus toxoid conjugate vaccine (Vi-TT) in comparison with a plain polysaccharide vaccine (Vi-PS) in healthy adults subsequently challenged with Salmonella Typhi. Immunological responses and their association with challenge outcome was assessed by mass cytometry and Vi-ELISpot assay. Immunization induced significant expansion of plasma cells in both vaccines with modest T follicular helper cell responses detectable after Vi-TT only. The Vi-specific IgG and IgM B cell response was considerably greater in magnitude in Vi-TT recipients. Intriguingly, a significant increase in a subset of IgA+ plasma cells expressing mucosal migratory markers α4β7 and CCR10 was observed in both vaccine groups, suggesting a gut-tropic, mucosal response is induced by Vi-vaccination. The total plasma cell response was significantly associated with protection against typhoid fever in Vi-TT vaccinees but not Vi-PS.