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Immunotherapy with genetically engineered immune cell products is a transformative treatment modality with potential applications in various fields of medicine. A prime example is chimeric antigen receptor (CAR)-modified T cells in hematology and oncology, and the advent of CAR T cell therapies to treat infectious diseases, autoimmune disorders, and cardiovascular diseases. The medical need and demand from patients and caregivers require radical innovations to accelerate and improve pre-clinical development and clinical translation, provision of gene-transfer vectors, and immune cell product manufacturing as well as a critical reflection and discussion on ethical and socioeconomic aspects. T...
The receptors of the TNFRSF (TNFRs) are of overwhelming importance in the regulation of the immune system but are also involved in the induction of apoptotic cell death or cell survival and proliferation, making them excellent therapeutic targets for cancer but also other diseases. TNFRSF members provide crucial co-stimulatory signals to many if not all immune effector cells. Each co-stimulatory TNFR has a distinct expression profile and a unique functional impact on various types of cells and at different stages of the immune response. For example, the two receptors of TNF, TNF receptor-1 (TNFR1) and TNF receptor-2 (TNFR2), regulate the interaction of the various types of immune cells and a...
Interferons (IFN) belong to the family of cytokines and have been described first in the late 1950s as an inhibitory factor of viral replication. Since then, the impact of interferon has been greatly expanded and its function comprises a role not only in different types of infection, cancer and autoimmunity but importantly also in immunehomeostasis. IFN have important anti-viral effects but it is becoming more and more evident that they are true immunomodulators and have an important impact on the development and maintenance of innate and adaptive immunity.
The tumor necrosis factor/receptor [TNF/TNFR] superfamily consists of more than 20 transmembrane proteins with conserved N-terminal cysteine-rich domains [CRDs] in the extracellular ligand binding region. Members have wide tissue distribution and play important roles in biological processes such as lymphoid and neuronal development, innate and adaptive immune response, and cellular homeostasis. The chapters of this book address some of the most interesting functions of the TNF/TNFR superfamily.
Long-lasting T cell immunity is delivered by an array of individual T lymphocytes expressing clonally distributed and highly specific antigen receptors recognizing an almost infinite number of antigens that might enter in contact with the host. Following antigen-specific priming in lymphnodes, naïve CD4 and CD8 T lymphocytes proliferate generating clones of effector cells that migrate to peripheral tissues and deliver unique antigen-specific effector functions. Moreover, a proportion of these effector lymphocytes survive as memory T cells that can be rapidly mobilized upon new exposure to the same antigen, even years after their primary induction. Innate immune cells play crucial roles in t...
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The macrophage (or “big eater”) is often considered the first cell type to encounter the causative agent of Tuberculosis (TB), Mycobacterium tuberculosis, upon entry to the lung. Once inside the macrophage the tubercle bacillus can survive and even replicate where many other invading pathogens perish. Recent research suggests the bacilli adapts within this hostile environment, treating the macrophage like a Trojan horse. Indeed, cutting-edge techniques have revealed that the degree of bacterial heterogeneity and resistance to antibiotics changes within the macrophage. M. tuberculosis spends most of its life cycle within the macrophage and has adopted specific mechanisms to survive, egres...