Description:
The book summarises the current understanding of the Nervous - Endocrine and Immune systems with emphasis on shared mediators and receptors and functional interaction. In addition to the fundamental physiological and pathophysiological mechanisms, which are presented in detail, some clinically relevant subjects are also presented, such as inflammation, asthma and allergy, autoimmune disease, immunodeficiency and the acute phase response.
 

	A comprehensive presentation of neuroimmune biology.
	Introduces the subject matter to the uninformed reader.
	Contains basic information, theoretical considerations and up-to-date  clinical chapters.
	The clinical chapters will be helpful to practising physicians.

Audience:

Neurologists, psychologists, psychiatrists, immunologists, endocrinologists, physiologists, practising clinicians, veterinarians, animal scientists.

Contents:

Foreword:
Istvan Berczi, Andor Szentivanyi

Preface:
Istvan Berczi, Andor Szentivanyi

Part I: The nervous system, receptors, ligands and signal transduction
 

Acknowledgements.

I.Introduction

Introduction 
Andor Szentivanyi, Istvan Berczi, Harry Nyanteh, Allan Goldman 

History
Andor Szentivanyi, Istvan Berczi, Harry Nyanteh, Allan Goldman

The discovery of immune neuroendocrine circuitry - A generation of progress.
Andor  Szentivanyi, Istvan Berczi, Harry Nyanteh, Allan Goldman

II.The Nervous System - A historical perspective.

Altered effector responses.
Andor Szentivanyi, Istvan Berczi, Harry Nyanteh, Allan Goldman

Some evolutionary morphoregulatory and functional aspects of the immune-neuroendocrine circuitry.
Andor Szentivanyi, Istvan Berczi, Harry Nyanteh, Allan Goldman

Virus associated immune and pharmacologic mechanisms in disorders of respiratory and cutaneous atopy.
Andor Szentivanyi, Istvan Berczi, Harry Nyanteh, Allan Goldman

III.Receptors, ligands and signaling

Adhesion molecules
Istvan Berczi, Andor Szentivanyi

Immunoglobulins
Istvan Berczi, Andor Szentivanyi

Growth and lactogenic hormones, insulin-like growth factor and insulin.
Istvan Berczi, Andor Szentivanyi

The hypothalamus-pituitary-adrenal axis and opioid peptides.
Istvan Berczi, Andor Szentivanyi

The hypothalamus-pituitary-thyroid axis.
Istvan Berczi, Andor Szentivanyi

Nerve growth factror, leptin and neuropeptides.
Istvan Berczi, Andor Szentivanyi

Cytokines and chemokines.
Istvan Berczi, Andor Szentivanyi

Steroid hormones.
Istvan Berczi, Eva Nagy, Edward Baral, Andor Szentivanyi 

Regulatory enzymes.
Istvan Berczi, Edris Sabbadini

Part II; Neuroimmune Functiona and the Neuroimmune Regulatory Network

IV.  Neuroimmune function 

A. Physiology

Immunocompetence
Istvan Berczi, Andor Szentivanyi

Antigen presentation.
Istvan Berczi, Andor Szentivanyi

Immune reactions.
Istvan Berczi, Andor Szentivanyi

The hypothalamus-pituitary-adrenal (HPA) axis: A major mediator of the adaptive responses to stress. K.Eddie. Gabry, George Chrousos, Philip W. Gold 

Immunoregulation by innervation.
Dwight Nance, Brian MacNeil

B. Pathophysiology

Inflammation in the airways.
Peter Barnes

Defensins: antimicrobial peptides with a broad spectrum of biological activity.
Elena A. Korneva, Vladimir N. Kokryakov

The acute phase response.
Istvan Berczi, Andor Szentivanyi

Autoimmune disease. 
Istvan Berczi, Andor Szentivanyi

Immunodeficiency
Istvan Berczi, Andor Szentivanyi

V. Immune-Neuroendocrine Circuitry

The immune-neuroendocrine circuitry.
Istvan Berczi, Andor Szentivanyi

(Article used with permission, NIB 2003,3 vii-viii)
Preface:

     This volume of Neuroimmune Biology (NIB), and the entire series, have several unique features that are worthy of consideration. Remarkably, the fundamental concepts outlined by the ingenious thinkers and experimentalists of early Physiology and Medicine, Claude Bernard, Pavlov, Cannon and Selye, are being extended in these books by facts and concepts more than ever before. For instance, it is discussed that the concept of homeostasis may now be extended to pathophysiological conditions. It is also clear that Palov’s thesis of conditioning clearly applies to the immune system as it has been presented in relation to the stress response and to the conditioning of immune reactions (NIB Volume 1.) The “fight or flight” concept of Cannon and the “general adaptation syndrome” of Selye have now been related to the acute phase response. It is now clear that the neuroimmune regulatory network coordinates physiological and pathophysiological reactions in higher animals. The health, disease, growth and development, the biology of reproduction, aging and lifespan of animals/man depend to a large extent on the function of this systemic regulatory network.

     The simplest animals, sponges, show self-recognition, as demonstrated by their ability to re-aggregate with their own kind after dispersion and by the rejection of tissue grafts from a foreign sponge species. This fundamental form of self-recognition has long been thought to be the basic characteristics of the immune system. In actual fact, this recognition is the pre-requisite of evolution from unicellular to multi-cellular organisms.  Adhesion molecules serve as the basis of this organization in the absence of the nervous and endocrine systems. These non-diffusible regulatory molecules maintained their dominant role in tissue organization, the regulation of cell growth and differentiation as well as function also in higher animals. However, during evolution a remarkably complex and very efficient system, the Neuroimmune system, has been superimposed on this cell-to-cell mediated regulation.  The result is the Neuroimmune Regulatory Network, with its incredible complexity, precision and efficiency. The central nervous system of man and higher animals is more powerful than the best man-made computer and is still not understood in sufficient detail. The endocrine system harbors the secret of life itself, which remains to be elucidated. The immune system is better than the best biochemist, as it is capable of recognizing instantaneously chemical structure and to synthesize specific reagents (antibodies) to it.  Much of immune function remains to be clarified.

     In recent years much evidence was produced and important conceptual developments occurred with regards to the function of the neuroimmune interaction. Now it is apparent that in addition to the hypothalamus - pituitary-adrenal axis (HPA), the sympathetic nervous system is very much involved in immunoregulation. It seems clear that the HPA axis and the sympathetic nervous system are equal partners in the profound suppression of the adaptive immune system, and in promoting natural immune mechanisms, which is characteristic of the acute phase response (APR). This gives new emphasis to the long-standing, by now historical,  observations that the sympathetic nervous system plays a key role in the regulation of immune function and of inflammatory diseases and that the beta-adrenergic receptor is fundamental to this regulatory process. Mutant beta-adrenergic receptors have now been linked to inflammatory disease as discussed in the introductory chapters. It is now apparent, that the ultimate center of immunoregulation is the hypothalamus, which has the power to control immune and inflammatory reactions both by neural and endocrine mechanisms. This allows for an overall systemic control as well as for local regulation that can be customized to the specific local requirements of the tissues and cells involved. In health the  hypothalamus maintains immune homeostasis and the homeostasis of the entire organism by securing a homeostatic neuroimmune milieu.   In acute febrile illness the homeostatic milieu has to be reset in the interest of survival. It should be apparent to the reader of the relevant chapters that the essence of the acute phase response is to suppress the adaptive immune system and to mobilize maximally the natural immune resources of the host in a highly organized fashion in the interest of host survival. This immunoconversion is achieved by switching to an allostatic neuroendocrine milieu, in which immune derived cytokines, the sympathetic nervous system and the HPA axis play fundamental regulatory roles. Again, the ultimate coordinator of APR is the hypothalamus.

     The prevailing view today is that high levels of IgE antibodies cause allergy and frequently asthma as well. It is widely held that the excessive levels of IgE antibodies are solely responsible for allergic inflammatory diseases in man. However, as discussed in the introductory chapters, human IgE antibodies could not transfer allergic disease to monkeys and it was not possible to induce asthma of non-immune origin experimentally. These facts indicate that IgE functions only to deliver the initial signal, that triggers mediator release from the appropriate cells, and that the overall reactivity of these cells is regulated by a different mechanism. Indeed in mice and rats histamine production and release from bone marrow cells was clearly shown to be under the control of the hypothalamus [1].

     The early, by now historical, are reviewed in the introduction of this volume in order to re-emphasize the emerging importance of the sympathetic nervous system and of the hypothalamus in NIB. In actual fact this historical introduction is also an up to date presentation of a much neglected but potentially very important area. Indeed this history remains highly relevant to our current understanding of NIB.

 Neither a scientific, polemic, nor a historical analysis is comparable to this Volume, which describes the origins, the underlying forces and trends, the principal events, findings, the vital participants, their associates, and witnesses, from the standpoint of their perspectives and vision of the immunological revolution of our times.  It hopes to extend the reader's perspective beyond the confines of simplistic formulas that have been used many times to explain immune function.

    These chapters written by the participants as well as the witnesses are based on broad knowledge, insight, and personal experiences in this phase of the development of Neuroimmune Biology.  Thus emerges a rare and penetrating view of the immunological revolution.

Istvan Berczi and Andor Szentivanyi

LITERATURE:
Szentivanyi A, Berczi I, Pitak D, Goldman A. Studies of the hypothalamic regulation of histamine synthesis. In New foundation of Biology, Neuroimmune Biology Volume 1,  Berczi I, Gorczynski R, Editors, Elsevier, 2001; pp. 47-55