Evanspritchard8997

This brief state-of-the-art review touches on novel engineering of smart nanomaterials, their binding with therapeutic agents, on demand delivery of drugs, image guided target delivery, biocompatibility, and theranostic applications in biomedical research. Developing green or organic approaches using micro-nanogel particles for theranostic and prophylactic applications in a variety of diseases, including HIV and degenerative medicine, are proposed.This article is about my amazing immunological journey for more than a decade with Eli Sercarz as an achaarya, which in Sanskrit means enlightened mentor. My training and routine interactions with colleagues not only at Eli's laboratory but at University of California at Los Angeles, La Jolla Institute for Immunology, Torrey Pines Institute for Molecular Studies, and University of California, San Diego School of Medicine were instrumental in my continued quest to understand how activation of autoimmune inflammatory cells results in pathology and how inflammatory responses are controlled to keep us healthy. I briefly outline different aspects of immune principles related to the immune response to a self-antigen myelin basic protein (MBP) that induces experimental autoimmune encephalomyelitis, a prototype for multiple sclerosis, and how a coordinated interactive network of regulatory T cells (Tregs) CD4+ (CD4 Tregs) and CD8+ (CD8 Tregs) control the anti-MBP response to maintain immune homeostasis. Eli was my mentor, collaborator, and friend, an incredible human being, and dear member of our extended family. CC-122 in vivo This article is written in his memory with unconditional gratitude.This article is a tribute to Eli Sercarz and draws on his proposal of a hierarchical order of T-cell determinants in antigen presentation and T-cell activation. Here I revisit the concept of dominance and crypticity in the context of lymphocyte cooperation in the generation of the adaptive immune response, with emphasis on Th-Th cooperation. The remarks made in this article serve as a basis for a reassessment of the unresponsiveness of self-tumor antigens and how to leverage cryptic T-cell determinants operationally to generate antitumor T-cell immunity.The contribution of Eli E. Sercarz to immunology and immunopathology has been remarkable and achieved many milestones in the understanding of the processes of the mechanisms fine-tuning immune responses. A part of his work was dedicated to the study of the deep complexity of the lymphocyte T cell repertoire and its importance during the physiologic development and disease, such as clonal heterogeneity of T cell responses. Starting from these studies, under his mentoring, we had the opportunity to implement the spectratyping method and apply it to human and experimental autoimmune diseases, obtaining intriguing results. The open question of this brief review is the possible role of this fine and complex technique, the immunoscope analysis, in the era of the big data and omics.The autoimmune disease multiple sclerosis (MS) is driven by T cells that are reactive to self-antigens of the brain and spinal cord. Many drugs have been developed to treat MS, but we believe that immune-specific targeting of pathogenic T cells may be a better approach for treatment. This type of therapy identifies specific components of the self-reactive T-cell repertoire that would undergo similar natural selection criteria as those found in driver genes in cancer genesis. In the context of autoimmunity, we propose that a focused subpopulation of T cells "drive" disease and could be found in higher frequency and become over-represented during disease induction and subsequent MS relapses. In addition, identification of other key signatures of driver T cells is important. One such marker could be interleukin (IL)-17- producing T cells. Here, we discuss the use of experimental autoimmune encephalomyelitis (EAE) animal models (that mimic many pathologic mechanisms involved in MS) to identify possible driver clones of this autoimmunity within the set of T cells expressing the IL-17 cytokine. EAE can be induced by myelin injection-associated proteins in adjuvants. The disease model in the Swiss/Jackson laboratory mouse strain represents the most common form of MS in humans relapsing remitting MS. Finally, we discuss the concept of using IL-17 as a marker for pathogenic T cells, combined with identifying their T-cell receptor V repertoire, which could provide targeted approaches designed to neutralize driver T cells for MS immunotherapy.Eli Sercarz pioneered epitope recognition by T cells. Studying mice, he made the seminal observation decades ago that epitope dominance is so unpredictable with mixed MHC haplotypes that he coined it aleatory, for dice-like. Accordingly, for every individual there is a unique potential epitope space that is defined by the polymorphic and polygenic MHC molecules (restriction elements) expressed. Of this potential epitope space, some peptides will elicit stronger T cell responses than others, bringing about the actually realized epitope space. The selection of the actually recognized peptides from the potential epitope space is random, however, resulting in unique epitope dominance and hierarchy patterns in individuals. Engaging in brute-force epitope scans, which permit the assessment of the entire potential epitope space at the highest possible resolution, we observe aleatory epitope recognition in human CD8 cell responses to viruses. Because the selection of peptide has fundamental implications for successful T cell immune monitoring, we dedicate this article to Eli Sercarz in a special issue of Critical Reviews™ in Immunology in his honor.Macrophages are cells of the myeloid lineage with important roles not only in immune regulation and tissue repair, but also in pathological states such as autoimmune disease and cancer. A plethora of macrophage subtypes exist with distinct phenotypes and functions, not least within the tumor microenvironment (TME) of solid tumors. The abundant macrophages located within the TME are often referred to as tumor-associated macrophages (TAMs). TAMs may be pro-inflammatory with antitumor properties, or may have pro-tumor functions such as angiogenesis. Typically, TAMs are endowed with pro-tumor phenotypes, which has led to strategies to deplete or reprogram TAMs within the TME. Although historically recognized as professional antigen presenting cells (APCs), macrophages are often considered inferior in their abilities to process and present antigens in comparison with dendritic cells (DCs). Notwithstanding, this review gives an overview of the potential accessory role that macrophages might have in antigen processing and presentation to T cells within the TME, with implications for the design of novel immunotherapies.