Table Of ContentStress, Immunity,
and Aging
IMMUNOLOGY SERIES
NOEL R. ROSE
Professor and Chairman
Department ofImmunology and
Infectious Diseases
The Johns Hopkins University
School ofHygiene and Public Health
Baltimore, Maryland
1. Mechanisms in Allergy: Reagin-Mediated Hypersensitivity
Edited by Lawrence Goodfriend, Alec Sehon, and Robert P. Orange
2. Immunopathology: Methods and Techniques
Edited by Theodore P. Zacharia and Sidney S. Breese, Jr.
3. Immunity and Cancer in Man: An Introduction
Edited by Arnold E Rei[
4. Bordetella pertussis: Immunological and Other Biological Activities
J. J. Munoz and R. K. Bergman
5. The Lymphocyte: Structure and Function (in two parts)
Edited by John J. Marchalonis
6. Immunology of Receptors
taited by B. Cinader
7. Immediate Hypersensitivity: Modern Concepts and Development
Edited by Michael K. Bach
8. Theoretical Immunology
Edited by George I. Bell, Alan S. Perelson. and George H. Pimbley, Jr.
9. Immunodiagnosis of Cancer (in two parts)
Edited by Ronald B. Herberman and K. Robert Mcintire
10. Immunologically Mediated Renal Diseases:
Criteria for Diagnosis and Treatment
Edited by Robert T. McCluskey and Giuseppe A. Andres
11. Clinical Immunotherapy
taited by Albert F. LoBug/io
12. Mechanisms of Immunity to Virus-Induced Tumors
Edited by John W. Blasecki
13. Manual of Macrophage Methodology: Collection, Characterization,
and Function
l:aited by Herbert B. Herscowitz, Howard T. Holden, Joseph A.
Bel/anti, and Abdul Ghajfar
14. Suppressor Cells in Human Disease
l:aited by James S. Goodwin
15. Immunological Aspects of Aging
l:aited by Diego Segre and Lester Smith
16. Cellular and Molecular Mechanisms of Immunologic Tolerance
Edited by Tomas Hraha and Milan Hasek
I 7. Immune Regulation: Evolution and Biological Significance
Edited by Laurens N Ruben and M. Eric Gershwin
IIi. Tumor Immunity in Prognosis: The Role of Mononuclear Cell Infiltration
Edited hy Stephen Haskill
19. Immunopharmacology and the Regulation of Leukocyte Function
Edited by David R. Webb
20. Pathogenesis and Immunology of Treponema! lnfecticn
Edited by Ronald F Schell and Daniel M. Musher
21. Macrophage-Mediated Antibody-Dependent Cellular Cytotoxicity
Edited by Hillel S. Koren
22. Molecular Immunology: A Textbook
Edited by M. Zouhair Atassi, Carel J. van Oss, and
Darryl R. Absolom
23. Monoclonal Antibodies and Cancer
Edited by George L. Wright, Jr.
24. Stress, Immunity, and Aging
Edited by Edwin L. Cooper
Other Volumes in Preparation
This book is dedicated to the memory
of two scientists who made valuable contributions
to the study of stress and immunity
A. F. Rasmussen, M.D., Ph.D.
( 1915-1984)
and
V. T. Riley, D.Sc.
( 1914-1982)
Stress, Immunity,
and
Aging
edited by
Edwin L. Cooper
School of Medicine
University of California, Los Angeles
Los Angeles, California
MARCEL DEKKER, INC. New York and Basel
Library of Congress Cataloging in Publication Data
Main entry under title:
Stress, immunity, and aging.
(Immunology series; v. 24)
Includes bibliographical references and index.
1. Stress (Physiology) -Addresses, essays, lectures.
2. Immunity-Addresses, essays, lectures. 3. Aging-
Addresses, essays, lectures. I. Cooper, Edwin Lowell,
[date]. II. Series. [DNLl\11: 1. Stress-complications.
2. Disease-Etiology. 3. Immunity. 4. Aging.
W1 IM53K v. 24 I QZ 160 S9146]
QP82.2.S8S88 1984 618.97'079 84-7076
ISBN 0-8247-7114-1
Copyright© 1984 by Marcel Dekker, Inc. All rights reserved.
Neither this book nor any part may be reproduced or transmitted in any
form or by any means, electronic or mechanical, including photocopying,
microfilming, and recording, or by any information storage and retrieval
system, without permission in writing from the publisher.
Marcel Dekker, Inc.
270 Madison Avenue, New York, New York 10016
Current printing (last digit):
10 9 8 7 6 5 4 3 2 1
Printed in the United States of America
Preface
The term "stress" brings to mind feelings of tension and urgency pro-
duced by fast, modern life-styles. When we talk about immunity, we
are prompted to think of the body's defense against infections, and
somehow we believe that lowered resistance due to stress affects the
efficiency of reacting against pathogens. Moreover, the less young
among us see connections between lowered resistance due to stress and
what may be a natural consequence of age. Each of these three topics
is a recognizable area worthy of a separate study, yet we have in this
text tried to join them together by probing how the various interactions
of the three might affect each other. How, then, are stress, immunity
and aging interrelated? Is it by interconnections via cells or cell prod-
ucts such as antibodies and hormones, or is it effected by a combination
of these intercommunicative components?
This book is divided into five parts. The Introduction and Chap. 1
contain two personal reminiscences of historical importance to research
on stress and infectious diseases, followed by Part I (introductory
chapters explaining to lay audiences basic features of the immune sys-
tem, the neuroendocrine system, and aspects of the environment) .
Basic aspects of the immune system are presented in Chap. 2, and
Chap. 3 deals with the neuroendocrine system, presumably the area
where central controls (for even the immune system?) may reside. This
chapter reminds us of the rather widely known example of how stress
and neuroendocrine effects can influence the immune system, that is,
the diminution of lymphocytes, prime movers in the body's immune sys-
tem. Chapter 4, the last chapter in Part I, a most provocative one, is
concerned with biorhythms and how these may affect the immune system.
Emphasized here are important environmental forces (e.g., sun, time)
iii
iv I Preface
that may affect the immune response, after having impinged first on
sensory receptors found within the nervous system.
Part II, entitled "The Aging Lymphocyte, Stress, and Immunity ,11
contains four chapters which present background and recent experi-
ments concerned with the effects of acute and/or chronic stressors on
different parameters of lymphocyte function. Stressors include electric
shock, mild restraint, repeated ether anesthesia, intermittent noise and
exposure to low ambient temperature in carefully monitored animal ex-
periments, and measurements of the effects of bereavement in humans.
A number of assays testing lymphocyte activity after stress were used,
revealing augmented mitogenic responses, reactions that mimic the mi-
totic changes lymphocytes undergo after challenge by antigen.
In Part Ill, four chapters cover work related to hormones, aging,
and the immune response. The general theme centers on multidirec-
tional interactions involving the brain-centered triad of stress, mood,
and emotion, and how these collide with other hormones, receptors, and
lymphocytes. One unusual area deals with the thymus and the repro-
ductive system. The thymus, since the early 1960s, has been shown
to strongly affect normal development of the immune system. Now, as
a producer of hormones, the thymus seems to be involved with aspects
of the development and function of the reproductive system. These
observations thus draw newer attention to the thymus which is important
to both the immune and neuroendocrine systems.
Five chapters in Part IV treat in depth the subjects of immunomodu-
lation, immunorestoration, stress, and disease. Once again, there is
in this, as in the previous chapters, an in-depth consideration of the
thymus but directed more to its influences on the immune response
through the effects of thymosin peptides and in turn, their effect on
the central nervous system. Various other roles are also of interest,
for example, those of neurotransmitters, hormones, and inflammatory
mediators on lymphocytes, macrophages, and granulocytes. As a pos-
sible revolutionary approach to modulation, another report considers
the effects of isoprinosine in reversing senescence and thereby main-
taining the immune system as it once was in young adults.
The last section (Part V) has two overview chapters which deal
specifically with perspectives on immunity, aging, and disease and the
prospects for immunorestoration in the treatment of immunodeficiency
arising from aging and stress. Beginning with ontogenetic development,
neonatal life, and puberty through adulthood and senescence, there
are reports of a progressive decline in the immune system as we age.
We are struck by evidence that prolonged lifespan can be induced by
dietary restriction which in turn increases certain lymphocyte functions
but decreases the incidence of spontaneous tumors. Left for the future
is the promise of more clarity after investigations go deeper into what
has been pointed out in the book: relationships between the neuro-
endocrine and immune systems and how aging may affect the interre-
latedness of these two systems.
Preface I v
Hardly a day or week passes without all of us being reminded ever
so naggingly of what life is like today, revealing a paradox. On the
one hand we enjoy the fruits of our labors, yet we are confronted, of-
ten bitterly, with all that we must plan, produce, and endure in order
to reap our harvest. Due to a relative amount of freedom and wealth,
we are almost insatiable in reaching and grasping-often with frenzy
and surely with stress. Indeed, the tales of fatigue leading to lowered
resistance, decline of youth, and perhaps even disease, are probably
not all hearsay. We are becoming more vulnerable to those ills, perhaps
psychosomatic, perhaps organic, which may result from bombarding the
interconnected immune and neuroendocrine systems by unacceptable
stimuli: the noise, visual pollution, and information explosion, produc-
ing damaging finite alterations to the body and to the spirit. That
similar conditions may be discerned in the senscent individual causes
us to ponder the possible effects of such stimuli on the presenscent
individual.
This often popular assumption that I have sketched, that is, that
lowered resistance and environmental pressures lead to alterations in
the body's immuno/defense system and aging, was the idea which
stimulated the production of this volume. This notion, coupled with ex-
perimental data, reinforced the urgency that leading authorities in
neuorendocrinology, immunology, and aging be brought together for
an intense exchange of information on interrelationships. The experts
expressed freely their new results and favorite hypotheses, but this
book is not a written version of their lectures. We left each other
assured that information is mounting, and that the gap is closing be-
tween speculation and hearsay and the results derived from repeatable
experiments. The workings of the immune and neuroendocrine systems
can affect each other, and it seems that the future challenge will be to
learn how they really interconnect and then to modify either system if
need to be to produce beneficial, not harmful, results.
We express appreciation to Newport Pharmaceuticals International,
Inc., and to its president, Alvin J. Glasky, Ph.D., whose assistance
helped to make this book possible.
Edwin L. Cooper
