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From molecules to populations and back In biology, the most vigorous organisms often ensue from a union of two disparate, pure lines. In science, too, laws of hybrid vigor seem to operate at the interface between two disciplines, an interface that often proves to be fertile ground for germinating concepts and new outlooks. The fringes of research into the major histocompatibility complex (Mhc) have provided such an interface several times in the past and the encounters have invigorated fields such as transplantation biology, cellular immunology, and immunogenetics. In the last few years, a new interface has been emerging between Mhc and evolutionary genetics, and particularly the branch of evolutionary genetics dealing with molecular evolution. Mhc research relies upon molecular evolutionary genetics, with its grand superstructure of mathematical formulations, to come to grips with the events leading to and maintaining the Mhc polymorphism. Without the armament of rigorous statistical procedures developed by evolutionary geneticists, the intricate relationships among Mhc genes cannot be resolved. It will undoubtedly be a molecular geneticist who is the final arbiter in the dispute concerning the nature of the selection pressure molding the Mhc genes. And it is doubtful whether the true function of Mhc can ever be comprehended without the vantage point afforded by the elucidation of its evolutionary history.
This book presents an authoritative collection of HLA phenotyping and genotyping techniques to be used at the bench level and as a reference. It includes detailed methodologies, notes on the interpretation of tests, reference material, and appendices.
A comprehensive guide to the HLA (Human Leukocyte Antigen) system for immunologists and clinicians, this book contains up-to-date information on the MHC (Major Histocompatibility Complex) and its role in the immune response and in various diseases. The book explores the biological significance and role of the HLA system in organ and haematopoietic stem cell transplantation management. This volume is an invaluable guide to the full spectrum of HLA-related science while also serving as a conceptual and technical resource for those involved in HLA-related research and in clinical or surgical practice. In addition, it will be a primary point of contact for individuals working in other areas who suddenly find that their research is drawing them into the complexities of HLA genetics.
Zoologists have categorized primates into a single order, and no one doubts today that they share a common ancestry. Humans and Old and New World non human primate species, from the lemurs of Madagascar to the African anthro poid apes, represent diverging branches of an evolutionary common trunk. Along with species-specific characters, all primates have retained a number of ancestral traits, relics of their common origin. The comparative study of these species-specific and ancestral traits makes it possible to reconstruct the evolu tionary pathways of humans and nonhuman primates. The discovery of the human blood groups and, later, of the Major Histocom patibility Complex (MHC) had a seminal effect on the field of human genetics, providing the first sound examples of mendel ian polymorphisms. The use of blood group and MHC alleles as genetic markers in biological anthropology gen erated a conceptual revolution and persuaded researchers to begin to think in terms of populations and not only intems of typology. The counterparts of these human red and white cell antigens were found and studied in nunhuman primates, and progress in this field is summarized in this book.
Immunologic privilege of the cornea and anterior chamber has, in most cases, been believed to be a sufficient guarantee for survival of the donor cornea. If this failed, it was thought that adjunctive immunomodulating agents would compensate. But the question of how to care for better tolerance and safer long-term survival of corneal grafts after withdrawal of a potent immunomodulating shield still remained unanswered. The answer is human leukocyte antigens (HLA) matching. In this volume, immunological and clinical aspects are discussed by renowned clinical and experimental immunologists as well as experienced keratoplasty surgeons. These experts conclude that HLA matching is, in fact, a valuable adjunct for long-term survival of corneal grafts not only in those at high risk but notably also in patients at normal risk. This volume opens new pathways towards the successful application of HLA matching to keratoplasty surgeons, experimental and clinical immunologists and cornea bank officers, at the same time acting as an aid to ophthalmologists when finding the basis to adequately advise their keratoplasty patients.
This important book uses selected molecules expressed on erythrocytes, lymphocytes, platelets and granulocytes to illustrate how genetic polymorphisms and variations in these molecules can affect their structure and function in mature human blood cells. The examples described tend to have a clinical association. Human blood group antigens and HLA antigens are classic examples of genetic polymorphism and they are important in blood transfusion and organ transplantation, respectively. In common with the blood group antigens, the polymorphic and variant antigens on platelets and granulocytes can be targets for antibodies in feto-maternal antigen incompatibility and transfusion reactions. Certain inherited haemolytic anaemias can be attributed to some of the polymorphic and variant forms of erythrocyte anion transport protein, spectrin, and glucose-6-phosphate dehydrogenase which exhibit abnormal structural or functional properties. Similarly, the study of cytokine gene polymorphism can provide a further understanding of the immune/inflammatory diseases and allogeneic transplantation./a
To interpret the laboratory results. To distinguish the normal from the abnormal and to understand the merits and demerits of the assays under study. The book attempts to train a laboratory medicine student to achievesound knowledge of analytical methods and quality control practices, tointerpret the laboratory results, to distinguish the normal from the abnormaland to understand the merits and demerits of the assays under study.
The human leukocyte antigen (HLA) or tissue types are the products of a rapidly developing field of knowledge within the last 20 years. In the early stages of the research many investigators suspected the existence of a complex series of transplantation antigens, but it was widely believed that these antigens would not be well-defined even in this century. Yet in the last two decades as many as 124 different HLA antigens determined by at least 7 very closely linked genes located on the short arm of chromosome 6 have been identified and subsequently agreed upon by an international nomenclature committee. 1 Extensive international collaboration fueled by the potential clinical application of these antigens to clinical transplantation has advanced the field rapidly. There were nine inter national histocompatibility workshops held during this period. Although iden tification of HLA antigens was of primary clinical importance in transplantation 2 and of great basic interest in human genetics and anthropology, a rather un expected bonus has been the determination that HLA antigens are associated with disease susceptibility to a greater extent than any other known genetic marker in man. In the past, many genetic polymorphisms have been suspected to be associated with diseases. The most extensively studied markers are blood groups, enzymes, and serum proteins. A comprehensive account of published studies, totalling approximately 1,000, of these markers is available in a book by Mourant et al.
Rossi's Principles of Transfusion Medicine is the most comprehensive and practical reference on transfusion science and medicine available. It features brand new chapters on the measurement of cell kinetics, obstetric transfusion practice, cord blood, transfusion alternatives and regenerative medicine. Produced jointly with AABB, the world's leading association in the fields of blood banking and transfusion medicine, it now has two companion CD-ROMs-one containing interactive case studies and one containing PDFs of all 66 chapters.