Springer-Verlag Cell Communication In Nervous And Immune System.pdf

Eckart D. Gundelﬁnger, Constanze I. Seidenbecher,

Burkhart Schraven (Eds.)

Cell Communication

in Nervous

and Immune System

With 28 Figures, 8 in Color, and 3 Tables

123

Professor Dr. Eckart D. Gundelﬁnger

Dr. Constanze I. Seidenbecher

Leibniz Institut für Neurobiologie

Abteilung Neurochemie und Molekularbiologie

Brenneckestr. 6

39118 Magdeburg

Germany

gundelﬁnger@ifn-magdeburg.de

Professor Dr. Burkhart Schraven

Institut für Immunologie

Otto-von-Guericke-Universität Magdeburg

Leipzigerstrasse 44

3120 Magdeburg

burkhart.schraven@medizin.uni-magdeburg.de

ISSN 0080-1844

ISBN-10 3-540-36828-0 Springer Berlin Heidelberg New York

ISBN-13 978-3-540-36828-1 Springer Berlin Heidelberg New York

Library of Congress Control Number: 2006932575

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Preface

Signal exchange between cells is a key feature of life from humble monads

to human beings. Appropriate communication is of particular importance

between cells of multi-cellular organisms. Various basic mechanisms of cell–

cell communication have evolved during phylogenesis, which were subject

to organ, tissue and cell type-speciﬁc adaptation. These mechanisms range

from long-distance communication via hormones to more and more local pro-

cesses, e.g. via cytokines, chemokines or neuromodulators/neurotransmitters,

and eventually direct physical interactions of molecules anchored at cell sur-

faces. Accordingly, highly specialized transient or stable cell–cell contact sites

have evolved that mediate signaling between cells. With few exceptions (e.g.

lipophilic hormones, gases) intercellular communication depends on speciﬁc

signal detection devices at the cell surface coupled to a signal transduction

apparatus that mediates the signal transfer across the cell membrane and acti-

vates intracellular effector systems, which generate intracellularly decipherable

signals.

Prime examples for tissues of intensely communicating cells are the nervous

and the immune systems. Although at the ﬁrst glance these systems appear very

different, both have developed sophisticated mechanisms for the formation of

memory, though of quite different quality and signiﬁcance for the organism.

Memory formation in the immune system serves the recognition and tolerance

oftheorganism’sowncellsandtissuesaswellastheeffectiverecognitionofand

defense from invading pathogens. It is based on a complex network of cellular

communication and signaling processes between cells of this “dispersed” organ

and with target cells. Brain mechanisms of learning and memory, on the other

hand, are indispensable for survival of an organism in its natural and social

environment. They are based on the function and plasticity of the probably

most complex cell junction: the chemical synapse. However, other cell–cell

connections, such as gap junctions or specialized neuron-glia interaction sites,

play an essential part in brain performance and plasticity.

This collection of reviews, contributed by internationally recognized im-

munologists and molecular and cellular neurobiologists, juxtaposes cellular

communication devices and signaling mechanisms in the immune and the

nervous system and discusses mechanisms of interaction between the two sys-

tems, the signiﬁcance of which has only been fully appreciated in recent years.

Preface

Thus messengers produced by one of the two systems, such as cytokines or

neuropeptides, can modulate cellular communication in the other system as

well. Moreover, the central nervous system (CNS) has long been considered

an immune-privileged organ lacking the classical immune response. Based

on recent studies this view had to be revised and reﬁned, and the particular

role of the immune system in neuropathological as well as in neuroprotective

and neurorepair processes has been recognized. This implies that the poten-

tially harmful effects of the immune system in the CNS have to be tightly

controlled by precise communication between cells of neural and immune

systems.

The ﬁrst four review articles deal with chemical synapses of the CNS. This

highly sophisticated asymmetric cell–cell contact is designed for particular

communication between neurons via chemical substances, the neurotrans-

mitters. Neurotransmitters are stored in little membranous containers, i.e.

synaptic vesicles, and released from the presynaptic cell in response to incom-

ing electrical signals in a regulated manner. Different postsynaptic devises

have evolved to detect excitatory (the ﬁrst chapter) or inhibitory (the second

chapter) transmitters and transduce the signals into the postsynaptic cell. Also

the site of regulated neurotransmitter release from the presynaptic neuron—

the active zone—is a complex molecular machine that organizes the synaptic

vesicle cycle (the third chapter). The gap between the pre- and the postsynap-

tic membranes, the synaptic cleft, is a specialized extracellular compartment

arranged by various cell adhesion molecules and components of the extracel-

lular matrix that is thought to contribute importantly to synaptic assembly and

plasticity (the fourth chapter).

Though known for more than 50 years, the electrical synapses have had

a shadowy existence for a long time and only during recent years have their

identity and their physiological relevance been studied in more detail. The

ﬁfth chapter discusses the role of gap junctions that form electrical synapses

in the CNS. The next chapter discusses another intriguing cell–cell contact site

that determines the capacity and efﬁcacy of the vertebrate nervous system is

the neuron-glia interaction at the so-called nodes of Ranvier, which facilitates

rapid propagation of electrical signals along myelinated axons.

Also within the immune system the term “synapse” has been meanwhile

well established. Here, the so-called immunological synapse describes the

molecular and biophysical events that occur when immunocompetent cells

interact with each other at the beginning of the adaptive immune response.

T-cells, the major components of the adaptive immune system are by them-

selves incapable of detecting complete bacteria or viruses. Rather, the major

structure on the T-cell surface that initiates T-cell activation, the T-cell receptor

(TCR) only recognizes small, 9 to 12 amino acid-long bacterial or viral (anti-

genic) peptides. These have to be generated by particular immunocompetent

cells, which have collectively been termed antigen presenting cells (APCs).

Although it is well known that B-cells, dendritic cells and macrophages rep-

Preface

VII

resentthemajortypesofAPCsthatactivateT-cells,itisstillunclearwhether,

for example, endothelial cells, which are spread throughout the whole body,

are also capable of presenting antigens to T-cells, at least in particular organs

such as the liver, or under particular conditions such as inﬂammation. These

questions are addressed in the seventh chapter, which also discusses the im-

munological consequences of the interaction between T-cells and endothelial

cells.

Importantly, the mere generation of antigenic peptides is not sufﬁcient to

activate T-cells. This is due to the fact that the TCR only signals when anti-

genic peptides are presented to the T-cell by APCs in conjunction with self-

molecules, the so-called major histocompatibility complex (MHC) molecules.

The detection of antigen/MHC by the TCR occurs at the beginning of the

immune response at the interface between the T-cell and the APC and this

ﬁrst physical contact between the two cells induces the formation of the im-

munological synapse. Consequently, the immunological synapse is a highly

dynamic structure that changes its morphology and molecular composition

during the initial phase of the immune response. During the past decade nu-

merous groups have begun to dissect the molecular events that either regulate

the formation of the immunological synapse or occur after immunological

synapse formation by applying sophisticated microscopic and biochemical

techniques. As a result, several models of the molecular composition and the

function of the immunological synapse have evolved. The eighth and ninth

chapters focus on the biophysics and the morphological changes of the im-

munological synapse under different conditions of stimulation and further

discuss the role of the immunological synapse during T-cell activation. While

these two articles primarily deal with the dynamics of APC/T-cell interactions

and the morphological changes of the immunological synapse on the micro-

scopic level, the following two chapters focus on the signaling events that

regulate particular aspects of immunological synapse formation and T-cell

activation. The ﬁrst of these discusses alterations of the cytoskeleton and the

second the regulation of intimate membrane contacts via adhesion molecules

and integrins.

The ﬁnal two chapters shed some light on the communication between

the immune and the nervous system and the control of immune responses in

the nervous system. To gain access to the CNS, immune cells have to cross

the blood–brain barrier provided by composed of endothelial cells. How this

process is mediated and controlled under physiological and pathological con-

ditions is discussed in the penultimate chapter. Endocannabinoids, the endoge-

nous ligands for the “Marihuana” receptors, seem to be intricately involved in

the neural control of the immune system. The current view of how the CNS

endocannabinoid system contributes to the immune surveillance is discussed

in the ﬁnal chapter.

This book is dedicated to our colleague Werner Hoch, who intended to

contribute an article on the neuromuscular junction, the supposedly best-

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