W.E.G. Müller - Böcker

Studies have identified important families of proteins (denoted: heat shock or stress proteins, Hsps) which display an enhanced expression in response to heat shock or other physiological stresses. Besides the characterization of the genes encoding Hsp and the mechanisms of their induction, recent studies have concentrated on the function of these proteins. It was shown that the expression of Hsp protects the cell against different types of aggressions. In addition,Hsp can regulate essential biochemical processes in unstressed cells. For example, members of the Hsp60 and Hsp70 families act as ATP-binding proteins allowing the folding of nascent or denatured proteins as well as the assembly or disassembly of protein complexes. These observations have led to the discovery of the molecular chaperone concept (Ellis and Hemmingsen 1989). Amongst the proteins whose expression is up-regulated by heat shock or other types of stresses are the small stress proteins also denoted (sHsps, sHsp or sHSP). Small stress proteins encompass a large numbers of related proteins which are represented in virtually all organisms, including prokary- otes.These polypeptides share a structural domain, often referred to as the a-crystallin domain, common to the lens protein alpha-crystallin (Ingolia and Craig 1982;Wistow 1985). In addition to being increased in response to several types of stresses, the Hsp level is also upregulated during development and correlates with the differentiation and oncogenic status of the cell. In spite of the fact that sHsp can confer cellular protection against stresses,their molecular function has remained enigmatic for years.

Biological response modifiers are increasingly used in viral and cancer therapy. Since alterations of the immune system are the primary symptoms of HIV infection, especially therapies directed towards the modulation of the immune response have been under intense evaluation. This volume summarizes current knowledge of the interferon-based natural antiviral protection system including 2',5'-oligoadenylate and double-stranded RNA. It will also help to develop further a solid scientific rationale for the practical use of heterologous immunomodulators in the clinics.

The biological bases of invertebrate immune responses have interested scientists for decades, from the first relevant observation by E. Metchnikoff in 1882, who discovered phagocytosis while studying starfish larvae. Invertebrate immunology first began to be appre­ ciated as an important field in the late 1960s and 1970s. However, in the following years there was much controversy regarding the question: do invertebrates offer insight into the origin of the sophisticated immune responses of the vertebrates? There are several reasons why progress in research on invertebrate immune competence has been painfully slow. One of the main impediments to the progress, as compared to the fast development of knowledge in the vertebrate systems, was the fact that most of the studies concentrated on "whole organism" assays, mainly on grafting tissues between allogeneic partners. Only in the last few years have more and more aspects of invertebrate immunity been investigated on the cellular, biochemical and molecular levels. These studies led to discoveries of novel defense reactions, new pathways of effector mechanisms which are elicited after recognition of "nonself', and complex, sometimes highly polymorphic genetic elements that control invertebrate immune reactions. The importance of invertebrate immunity for understanding "immunology" as a whole, despite the conflicting models and hypotheses, is now much more recognized than before. Although most of the 20 phyla belonging to the inver­ tebrates have different modes of life, body organizations, habitats occupied, and biochemical patterns, they show striking aspects of exceptional precision for discriminating between self and nonself.

Apoptosis plays a central role in the regulation of cell proliferation. Disruption of this control mechanism may cause serious human diseases such as encephalomyelitis and cancer. Thus, understanding of the molecular mechanisms of apoptotic cell death should lead to fundamental advances in the therapy of these diseases.