Inflammatory Responses After Ischemic Stroke
AbstractIschemic stroke generates an immune response that contributes to neuronal loss as well as tissue repair. This is a complex process involving a range of cell types and effector molecules and impacts tissues outside of the CNS. Recent reviews address specific aspects of this response, but several years have passed and important advances have been made since a high-level review has summarized the overall state of the field. The present review examines the initiation of the inflammatory response after ischemic stroke, the complex impacts of leukocytes on patient outcome, and the potential of basic science discoveries t...
Source: Seminars in Immunopathology - June 29, 2022 Category: Pathology Source Type: research
Basic principles of neuroimmunology
AbstractThe brain is an immune-privileged organ such that immune cell infiltration is highly regulated and better tolerating the introduction of antigen to reduce risk of harmful inflammation. Thus, the composition and the nature of the immune response is fundamentally different in the brain where avoiding immunopathology is prioritized compared to other peripheral organs. While the principle of immune privilege in the central nervous system (CNS) still holds true, the role of the immune system in the CNS has been revisited over the recent years. This redefining of immune privilege in the brain is a result of the recent re...
Source: Seminars in Immunopathology - June 22, 2022 Category: Pathology Source Type: research
The immunology of Parkinson ’s disease
AbstractParkinson ’s disease (PD) is the second most common neurodegenerative disorder which affects 6.1 million people worldwide. The neuropathological hallmarks include the loss of dopaminergic neurons in the substantia nigra, the presence of Lewy bodies and Lewy neurites caused by α-synuclein aggregation, and n euroinflammation in the brain. The prodromal phase happens years before the onset of PD during which time many patients show gastro-intestinal symptoms. These symptoms are in support of Braak’s theory and model where pathological α‐synuclein propagates from the gut to the brain. Importantly, im mune respo...
Source: Seminars in Immunopathology - June 8, 2022 Category: Pathology Source Type: research
How genetic risk contributes to autoimmune liver disease
Abstract Genome-wide association studies (GWAS) for autoimmune hepatitis (AIH) and GWAS/genome-wide meta-analyses (GWMA) for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) have been successful over the past decade, identifying about 100 susceptibility loci in the human genome, with strong associations with the HLA locus and many susceptibility variants outside the HLA locus with relatively low risk. However, identifying causative variants and genes and determining their effects on liver cells and their immunological microenvironment is far from trivial. Polygenic risk scores (PRSs) based on cu...
Source: Seminars in Immunopathology - June 1, 2022 Category: Pathology Source Type: research
MAIT cells in liver inflammation and fibrosis
AbstractMucosal-associated invariant T cells or MAIT cells are an abundant cell type in humans and especially so in the liver. MAIT cells are a subset of T lymphocytes that sit at a bridge between innate and adaptive immunity, so-called innate-like or “unconventional” T cells. The specificity of their antigen receptor (T cell receptor or TCR) is for the conserved major histocompatibility complex (MHC)-related molecule MR1, which presents a modified bacterial metabolite from the vitamin B2 biosynthesis pathway – this allows them to respond i n the presence of many bacteria or yeast. MAIT cells also possess an array of...
Source: Seminars in Immunopathology - May 31, 2022 Category: Pathology Source Type: research
Challenges and opportunities in achieving effective regulatory T cell therapy in autoimmune liver disease
AbstractAutoimmune liver diseases (AILD) include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These immune-mediated liver diseases involve a break down in peripheral self-tolerance with largely unknown aetiology. Regulatory T cells (Treg) are crucial in maintaining immunological tolerance. Hence, Treg immunotherapy is an attractive therapeutic option in AILD. Currently, AILD do not have a curative treatment option and patients take life-long immunosuppression or bile acids to control hepatic or biliary inflammation. Clinical investigations using good manufacturing ...
Source: Seminars in Immunopathology - May 31, 2022 Category: Pathology Source Type: research
MAIT cells in liver inflammation and fibrosis
AbstractMucosal-associated invariant T cells or MAIT cells are an abundant cell type in humans and especially so in the liver. MAIT cells are a subset of T lymphocytes that sit at a bridge between innate and adaptive immunity, so-called innate-like or “unconventional” T cells. The specificity of their antigen receptor (T cell receptor or TCR) is for the conserved major histocompatibility complex (MHC)-related molecule MR1, which presents a modified bacterial metabolite from the vitamin B2 biosynthesis pathway – this allows them to respond i n the presence of many bacteria or yeast. MAIT cells also possess an array of...
Source: Seminars in Immunopathology - May 31, 2022 Category: Pathology Source Type: research
Challenges and opportunities in achieving effective regulatory T cell therapy in autoimmune liver disease
AbstractAutoimmune liver diseases (AILD) include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These immune-mediated liver diseases involve a break down in peripheral self-tolerance with largely unknown aetiology. Regulatory T cells (Treg) are crucial in maintaining immunological tolerance. Hence, Treg immunotherapy is an attractive therapeutic option in AILD. Currently, AILD do not have a curative treatment option and patients take life-long immunosuppression or bile acids to control hepatic or biliary inflammation. Clinical investigations using good manufacturing ...
Source: Seminars in Immunopathology - May 31, 2022 Category: Pathology Source Type: research
Immuno-pathogenesis of neuromyelitis optica and emerging therapies
AbstractNeuromyelitis optica (NMO) is an inflammatory disease that resembles MS in the relapsing clinical course of optic neuritis and myelitis. Two decades of studies have revealed that autoantibodies, reactive to the water channel protein aquaporin 4 (AQP4) are detected in the core group of patients. These autoantibodies play a crucial role in the inflammatory pathology of NMO, involving proinflammatory cytokines, chemokines, and various inflammatory cells such as Th17 cells. Anti-AQP4 antibody–positive NMO differs fundamentally from MS, particular ly in the responsiveness to therapies and the neuropathology accompan...
Source: Seminars in Immunopathology - May 30, 2022 Category: Pathology Source Type: research
