Toll-Like Receptor Family Members and Their Ligands

Current Topics in Microbiology and Immunology

Book 270
Springer Science & Business Media
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On occasion, the innate immune system is referred to as the "primitive" immune system. Perhaps this has dissuaded immu nologists from analyzing it as energetically as they have analyzed the adaptive immune system during the past two decades. But while its phylogenetic origins are indeed ancient, and though it is "of the first type", there is nothing crude, nothing unsophisti cated, and nothing "inferior" about innate immunity. On the contrary, the innate immune system has had time to achieve a level of refinement that is nothing short of dazzling, and a modicum of respect is at long last due. Any immune system has two cardinal functions. It must destroy a broad range of pathogens, and it must spare the host. The adaptive immune system has applied a modular solution to these problems. Each cell of the adaptive immune system is prescreened to eliminate those that would produce untoward interactions with self; each cell is pre-programmed to recognize a foreign epitope that the host might one day encounter. Hence, the duties of each individual lymphocyte are quite circumscribed.
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Publisher
Springer Science & Business Media
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Published on
Dec 6, 2012
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Pages
192
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ISBN
9783642594304
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Best For
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Language
English
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Genres
Medical / General
Medical / Immunology
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Most lymphocytes recirculate throughout the body, migrating from blood through organized lymphoid tissues such as lymph nodes (LN) and Peyer's patches (PP), then to lymph and back to blood (GOWANS and KNIGHT 1964). Smaller numbers of lymphocytes migrate from blood to extranodal tissues such as pancreas and then through lymphatic vessels to LN (MACKAY et al. 1990). An important feature of this migration is the ability of lymphocytes to recognize and adhere to the surface of blood vessel endothelial cells before migrating through the vessel wall into surrounding tissue (CARLOS and HARLAN 1994; IMHOF and DUNON 1995; BUTCHER and PICKER 1996). Adhesion interactions of vascular endothelium with lymphocytes under flow or shear consist of at least four steps: (I) an initial transient sticking or rolling; (2) if the lymphocytes encounter appropriate activating or chemotactic factors in the local environment, rolling may be followed by a lymphocyte activation step that then leads to; (3) strong adhesion or sticking that may be followed by; (4) lym phocyte diapedesis into tissue (BUTCHER 1991; SHIMUZU et al. 1992; SPRINGER 1994; BARGATZE et al. 1995). Specific lymphocyte and endothelial adhesion molecules (AM) are involved in each step of this "adhesion cascade" (reviewed in CARLOS and HARLAN 1994; IMHOF and DUNON 1995; BUTCHER and PICKER 1996). This allows lymphocyte migration to be controlled at several different steps, leading to a combinatorial increase in specificity and sensitivity.
Severe sepsis and septic shock are the most serious compli cations of bacterial infections. Both gram-positive and gram negative bacteria can trigger these extreme inflammatory re sponses and, by so doing, cause substantial morbidity and mortality. In the United States alone, over 400 000 patients suffer from septicaemia each year, and approximately 100 000 of these patients die despite optimal intensive care and modern antimicrobial therapy. These dramatic figures have prompted intensive research to define the bacterial and host factors involved in the septic response. Scientists from many disciplines, including chem istry, physics, biology, medical microbiology, immunology, and pharmacology, have worked closely with clinicians to achieve rapid and profound progress. To translate this newly acquired knowledge into clinical practice, clinical trials have also been performed to evaluate numerous new therapeutic drugs. The disappointing results from these trials have underscored a major lesson, namely, that sepsis constitutes an extremely complex syndrome and that basic and clinical research must be greatly intensified in order to illuminate its molecular mechan isms. At this stage, the editors of the present volume of Current Topics in Microbiology and Immunology considered it would be rewarding to compile a volume summarizing our present basic and clinical knowledge on sepsis. Our particular gratitude extends to those international experts who have followed our invitation and elaborated on particular areas of the basic and clinical aspects of this field.
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