B and T lymphocytes are the mediators of immunity, but their function is under the control of dendritic cells. Dendritic cells in the periphery capture and process antigens, express lymphocyte co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses. They not only activate lymphocytes, they also tolerize T cells to antigens that are innate to the body (self-antigens), thereby minimizing autoimmune reactions. Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis. With knowledge comes the realization that these cells are a powerful tool for manipulating the immune system.

Dendritic cells and the control of immunity

WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

Inflammation and cancer

Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.

Immunobiology of Dendritic Cells

Interleukin-10 (IL-10), first recognized for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages, is a multifunctional cytokine with diverse effects on most hemopoietic cell types. The principal routine function of IL-10 appears to be to limit and ultimately terminate inflammatory responses. In addition to these activities, IL-10 regulates growth and/or differentiation of B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells. IL-10 plays a key role in differentiation and function of a newly appreciated type of T cell, the T regulatory cell, which may figure prominently in control of immune responses and tolerance in vivo. Uniquely among hemopoietic cytokines, IL-10 has closely related homologs in several virus genomes, which testify to its crucial role in regulating immune and inflammatory responses. This review highlights findings that have advanced our understanding of IL-10 and its receptor, as well as its in vivo function in health and disease.

Interleukin-10 and the interleukin-10 receptor.

The identification in the 1990's of the role of CTLA-4 and PD-1, two inhibitory receptors of T lymphocytes, in the control of the anti-tumor immune responses, led to the awarding of the Nobel Prize in Physiology or Medicine in 2018 to Dr. James Allison and Dr. Tasuku Honjo. These inhibitory receptors called immune checkpoints are essential to prevent any deleterious impact of on-going immune responses against pathogens or cancer cells on healthy tissues and, hence, guarantee the integrity of the host. These major discoveries have led James Allison and Tasuku Honjo to develop anti-CTLA-4 and anti-PD1/L-1 antibodies, respectively, in order to switch off these immune "brakes", making it possible to efficiently attack tumor cells. CTLA-4 regulates the amplitude of the early T-cell activation and inhibits the activity of CD28, a major activating co-receptor expressed by T cells. PD-1 is expressed by memory and effector T lymphocytes and is involved in the regulation of chronically activated cells, as observed during inflammatory processes. Immunotherapeutic treatments resulting from these discoveries have now a major place in the arsenal of anti-cancer therapies. This review presents firstly a synthesis of knowledge on CTLA-4, PD-1 and their ligands, their mechanisms of action and regulation and, secondly, an overview of biomarkers that have been associated with clinical response to anti-PD-1/PD-L1 and anti-CTLA-4 antibody therapies.

/pdf/the-biology-of-pd1-and-ctla-4-as-immunotherapeutic-targets-3vdctxr6p1.pdf

[The biology of PD1 and CTLA-4 as immunotherapeutic targets and the issue of biomarkers].

Following tissue injury, invading antigens are captured by dendritic cells (DC) which migrate to secondary lymphoid organs where they initiate immune responses that involve triads composed of T cells, B cells and DC. As both DC 1 and B cells 2 express functional CD40, we studied the effects of in vitro generated DC on B cells responses in a culture system where CD40-Ligand-transfected L cells are used as surrogate membranes of activated T cells.

Human dendritic cells can drive CD40-activated sIgD+ B cells to mount mucosal-type humoral response.

Uncertainties in production and assembly processes have a significant influence on performance. When one speaks about uncertainties, in most of the cases it implies machine breakdowns, defective items or different uncertainties in procurement. However, especially in manual production, each realistic model should also take into account and treat human related uncertainties. Unfortunately, in contrast to "standard" uncertainties, there are no statistical data credible enough to use in order to model them. In the present paper we demonstrate the application of Cognitive Reliability and Error Analysis Method (CREAM) in manual assembly. Through the knowledge of experts Cream permit to highlight the main cognitive errors, their impacts and to elicit these errors quantitatively.

https://hal.archives-ouvertes.fr/hal-00728558/document

Human error probabilities computation for manufacturing system simulation using CREAM

Nucleic acids encoding a membrane type matrix metalloprotease, from a mammal, reagents related thereto, including specific antibodies, and purified proteins are described. Methods of using said reagents and related diagnostic kits are also provided.

Mammalian matrix-type metalloprotease

The steel industry (SI) produces parts for different industrial markets, such as aeronautics and tools. The last few years have shown that the demand from these markets can be subject to variations, which can be drastic (e.g. consequences of the events of 11 September 2001 on the aeronautical industries) or more progressive. To cope in the best way with these unexpected changes, steel industries have to evaluate their ability to react, at a strategic decision level, to these changes. In particular, they need to adapt the long-term management of their resources in the best possible way. Although issues related to short-term perturbations appear in the literature, seldom seen are methodologies to analyse the long-term behaviour of manufacturing systems. In this article, we are concerned with the evaluation, using simulation, of the effect of unexpected variations in the demand of products on the firm performance, in order to determine in what extent the system may be disturbed, and whether or not it can cop...

Christophe Caux

Papers

[The biology of PD1 and CTLA-4 as immunotherapeutic targets and the issue of biomarkers].

Human dendritic cells can drive CD40-activated sIgD+ B cells to mount mucosal-type humoral response.

Human error probabilities computation for manufacturing system simulation using CREAM

Mammalian matrix-type metalloprotease

Analysing the impact of market variations in the steel industry: a simulation approach