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Immunohematology aims at predicting by in vitro assays the in vivo compatibility of blood, cells, and tissues in the setting of transfusion and transplantation medicine. Immunohematology therefore focuses on aspects of blood cell antigen typing, and on the detection and characterization of humoral and cellular immune responses to blood cell antigens. Progress in immunohematology in the past has been defined mainly by the application of state-of-the-art techniques in order to enhance the level of certitude with which to predict the degree of in vivo compatibility. Thus, serological techniques to type blood cell antigens have been supplemented by approaches derived from the methodological spectrum of molecular biology, and high throughput screening techniques such as cDNAor oligonucleotide-based microarray formats are likely to complete the spectrum of immunohematological techniques during the coming years. The concept of compatibility is dependent on the specificity of immune responses. According to the current understanding widely present within the immunohematology community, specificity is defined by structural components of single cells, single antibodies, and their interaction. However, beyondgenome biology indicates strongly that the specificity of functional modules of the immune system contributes to the overall outcome of immune responses. Thus, specificity – and thereby compatibility – may be defined by functional aspects of the immune system in its respective condition as much as by structural components of immune cells and immune receptors. Such an altered concept of compatibility might have far reaching consequences for our understanding of tolerance to blood cell antigens with regard to autoimmune responses as well as with regard to alloimmune responses. It requires the understanding of regulatory mechanisms that determine the proper recognition of self and non-self antigens in the context of complex dynamic interactions at the cellular and humoral level of the immune system. Current concepts on immune regulation start to take into account the inherent complexity of biological systems. Future directions of immunohematological research might shift the focus of efforts from applying advances of compatibility testing at an exclusively structural level towards a functional understanding of compatibility, taking into account current concepts on immune regulation. The present issue and the follow-up issue of TRANSFUSION MEDICINE AND HEMOTHERAPY present a series of reviews highlighting the current understanding of immune interactions that contribute to the outcome of immune responses, and that may be of relevance for the functional understanding of the phenomenon ‘compatibility’ in immunohematology. In the first review, Arthur Silverstein, USA, introduces the topic of this issue by providing an overview on the development of concepts on the understanding of the immune response in the historical context since the end of the 19th century, and demonstrates how the clarification of cellular and molecular regulatory mechanisms became one of the central interests of current immunobiology [1]. The current knowledge in immunobiology of diverse biological components and the data that are emerging from highthroughput screening technologies call for the need to understand how the individual genes, proteins, signaling pathways and molecular networks are integrated and how they govern the behavior of cells, tissues and physiological systems, allowing to dynamically maintain the organism’s homeostasis. Systems analysis is regarded as an emerging interdisciplinary field of systems biology which relies upon the extensive use of a range of mathematical modeling tools, allowing the integration of various regulation levels. Gennady Bocharov, Russia, presents the methodology of systems analysis, and comprehensively reviews the application of systems analysis to complex regulatory phenomena in biology [2]. Jacques F.A.P. Miller, Australia, summarizes basic principles of immunological tolerance, depicting T lymphocytes and B

Current Concepts on Immune Regulation: Impact on Scientific and Clinical Aspects of Immunohematology