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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.
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."
Comparative endocrinology helps to find the roots of homeostatic
regulation in organisms. In this context, many years ago a series
of experiments were done, which demonstrated the hormonal regula
tion also on the invertebrate level. The mechanisms are partly
similar, partly different, from those found in vertebrates. The new
receptor era of mammalian endocrinology stimulated research on
invertebrate hormone receptors, and sophisticated methods are
applied also to determine hormones. The experiments demonstrated
the existence and even similar function of these structures and
signaling molecules. However, data on hormones and receptors at the
lowest level of metazoan life and the highest level of protozoan
life were not at our disposal. About two decades ago, first
observations on the presence of hormone receptors reacting to
vertebrate hormones in protozoa were made. Since the early 1980s we
know that hormone-like molecules similar to those of higher
vertebrates are present also in unicellular organisms. The presence
of some second messengers in Tetrahymena was recognized. Since
then, the research has been extended and many structures -
previously believed to be solely vertebrate characteristics, such
as opiate receptors, similar to mammalian ones - were found in
unicellular organisms. These observations justified the assumption
of a complete endocrine system at protozoan level, where -
considering the unicellularit- this seemed to be not required.
However, it became clear that the roots of endocrine communication
date back at least 2 billion years."
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.
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.
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