The Molecular Basis of Cellular Defence Mechanisms: v. 204 (Novartis Foundation Symposia)

Much of the defence of the body against invading microorganisms has been delegated to two sets of haemopoietic cells?the T and B lymphoid cells, and the granulocytes and monocyte/macrophages. These have in common their ancestral origin from multipotential haemopoietic stem cells and the need to be produced continuously throughout life. This biology requires complex programmes of controlled cell division, differentiation, commitment and maturation, the molecular nature of which have been established in some detail. While there are unique features of the regulations of each of the four lineages, there is much in common in the manner in which corresponding processes are controlled by a group of interacting regulatory glycoproteins. Based largely on the use of clonal in vitro cultures, the regulators involved have been cloned and active recombinant regulators mass-produced. The membrane receptor complexes mediating the cellular actions of these regulators have been identified and at least some details of the intracellular signalling pathways established. In the case of the granulocyte-macrophage regulators, the colony stimulating factors (CSFs), successful documentation of their effectiveness in enhancing host resistance to model infections has led to their widespread clinical use. However, the biology of the regulatory process indicates that these regulators are designed to operate in combination. The availability of more than twenty of these regulators in mass-produced recombinant form offers exciting prospects for their use in appropriate combinations for intelligent clinical intervention in diseases ranging from infections to cancer, provided only that the daunting logistical problem posed by current testing requirements can be resolved. In parallel to these exciting developments, the enormously large and fertile field of lymphokine research has grown up. Whereas the molecular regulators of haemopoiesis, the CSFs, come generally within the purview of haematologists, the lymphokines are the ?property? of the immunologists. Despite the conceptual similarities in the two fields, and despite the fact that CSFs have actions on the immune system and some interleukins have actions of haemopoiesis, meetings where experts from the two fields get together are still very rare. This book contains the detailed discussions of a group of experts from both fields.