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During the last 5 years, major advances have been made in our understanding of the pathogenesis of human immunodeficiency virus (HIV) disease and in the development of new potent antiviral agents. With regard to HIV pathogenesis, several recent observations have not only changed our perspectives of HIV disease, but have been critical for the design of therapeutic strategies.
Immunological memory has fascinated microbiologists and immunologists for decades as one of the new frontiers to conquer to better understand the response to pathogens, cancer and vaccination. Over the past decade, attention has turned to the intrinsic properties of the memory T cells themselves, as it has become clear that the eradication of both infected cells and tumors requires T cells. This book is an attempt to capture the wave of discoveries associated with these recent studies. Its chapters represent a wide collection of topics related to memory T cells by laboratories that have invested their skills and knowledge to understand the biology and the principles upon which memory T cells are generated, maintained and expanded upon re-encounter with antigen. Ultimately, these studies are all aimed at a better understanding of the function of memory T cells in protection against disease.
Naïve T cells get activated upon encounter with their cognate antigen and differentiate into a specific subset of effector cells. These T cells are themselves plastic and are able to re-differentiate into another subset, changing both phenotype and function. Differentiation into a specific subset depends on the nature of the antigen and of the environmental milieu. Notably, certain nutrients, such as vitamins A and D, sodium chloride, have been shown to modulate T cell responses and influence T cell differentiation. Parasite infection can also skew Th differentiation. Similarly, the gut microbiota regulates the development of immune responses. Lastly, the key role of metabolism on T cells has also been demonstrated. This series of articles highlights some of the multiple links existing between environmental factors and T cell responses.
Mathematical biomedicine is a rapidly developing interdisciplinary field of research that connects the natural and exact sciences in an attempt to respond to the modeling and simulation challenges raised by biology and medicine. There exist a large number of mathematical methods and procedures that can be brought in to meet these challenges and this book presents a palette of such tools ranging from discrete cellular automata to cell population based models described by ordinary differential equations to nonlinear partial differential equations representing complex time- and space-dependent continuous processes. Both stochastic and deterministic methods are employed to analyze biological phenomena in various temporal and spatial settings. This book illustrates the breadth and depth of research opportunities that exist in the general field of mathematical biomedicine by highlighting some of the fascinating interactions that continue to develop between the mathematical and biomedical sciences. It consists of five parts that can be read independently, but are arranged to give the reader a broader picture of specific research topics and the mathematical tools that are being applied in its modeling and analysis. The main areas covered include immune system modeling, blood vessel dynamics, cancer modeling and treatment, and epidemiology. The chapters address topics that are at the forefront of current biomedical research such as cancer stem cells, immunodominance and viral epitopes, aggressive forms of brain cancer, or gene therapy. The presentations highlight how mathematical modeling can enhance biomedical understanding and will be of interest to both the mathematical and the biomedical communities including researchers already working in the field as well as those who might consider entering it. Much of the material is presented in a way that gives graduate students and young researchers a starting point for their own work.
In an effort to go beyond immune-based therapies, researchers are now considering the implications of apoptosis dysregulation during HIV-induced immunodeficiency. This work provides the first comprehensive compendium of the progress made in understanding the process of cell death related to HIV and the potential breakthroughs in treatment that offer much promise. Combining the work of more than two-dozen top researchers, this seminal volume provides clinicians and researchers with an excellent reference, while also serving as an incubator to stimulate future research. It explains the fundamental biology involved with apoptosis, explains its clinical impact in HIV, and examines the newest therapeutic approaches.
Infection with the human immunodeficiency virus is characterized by the destruction of the host immune system as also reflected by a progressive loss of CD4-positive T-cells. This finally results in the host's incapacity to deal with opportunistic infections and the immune surveillance of tumors, a clinical status known as the Acquired Immunodeficiency Syndrome (AIDS). The book AIDS Pathogenesis provides the reader with a complete overview of the clinical course of HIV-1 infection. It describes the clinical aspects of primary infection, the different clinical outcomes of HIV-1 infection, and strategies for anti-viral treatment. In addition, more fundamental aspects of HIV-1 infection are reviewed. These include the biology of the virus and the novel insights in AIDS pathogenesis. Not only is the significance of an HIV-specific cellular and humoral immune response discussed, but also the possible incapacity of the adult human host to deal with T-cell destruction. Finally, the book discusses the currently used laboratory markers that allow for monitoring of the clinical course of infection.