Immune modulating agents

572 Pages·1998·101.5 MB·English

by  Thomas F. Kresina

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Laura Williams Cheever, RachelA nn,
Jennifer Lynn, and Rebecca Marie
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In recent years,t he fie1 of immunology has expanded significantlwy ith the identifi-
cation of numerous bi ogical response modifiers. Elucidation of these molecules in
the systemic responses of the immune system has rapidly followed. Thus, networks
or immune response pathways have been identified and consistently depicted in
immunological texts and slide presentations as a complex array of arrows, inscrip-
napnst ia, d t hcwio na nr y t esx t tth oe ancielen nt dars. I ~ ~ u n e
du~~tinAgge nts a es the complexity of the sys unree s ponse and
providesa c omprehend escription of immunem odulatinga gentsi nt hec ontext
of disease and therapy. The initial chapters deal with the identificatioofn b iological
response modifiers and the interactions of these molecules with cells, tissues, and
organs.
The first eight chapters deal with the immune mediators as individual compo-
nents of immunologically bas d systemic pathways. Initiallyt,h e general rules of the
immune system are outlined. n this context, specificv ersus nonspecific immunity is
presenteda long with cognatea ndn oncognat nei n teractionsC. ytokinesa nd
immunomodulatoriyn terventionas r e listed. odry e gulationc ,e llulasr i gnal
transductiona, ndc ytokinep athwaysa rei n t d in Chapter 2. A serological
property of antibodiesa nd cellularr eceptors,i diotypy,a ndi tsr olei ni mmune
regulation pathways are presented in Chapter 3. Chapter 4 presents the pathways
for stem cells to differentiate into cells of the immune system. This chapter intro-
duces thei mportance of regulatoryg rowthf actorsf orc ellulard ifferentiation.
Chapter 5 introduces the complex interaction etween the neuroendocrine system
andt hec omponents of thei mmune system. diators betweent hese systems in-
clude growtha nd lactogen hormone family, hormones and factorosf the hypothala-
us-pituitary-adrenal axis, thyroid hormones, steroid sex hormones, and vitamin
.
Chapter 6 completes the picture of growth hormones and immune modulation
by describing the immune modulatory aspectos f transforming growth factors.
Chapters 7 and 8 create a transition to immune modulation in disease states.
Chapter 7 presents aspects of a growing field based on ourp resent-day lifestyle. The
role of psychological stress and immune competencei s addressed. This is followed
i
by the use of an immunological mediator, interleukin 12, as an adjuvant to modu-
late the systemici mmuner esponses, i.e., the use of an immune mediator as a
vaccine to boost normal immuner esponses.
This topic progresses in Chapter 9 into the description of cytokine pathways
induced in infectious pathogens. Chapter 9 initiates a series of 10 chapters focused
on immune modulation in disease states. Following a description of the ability of
the host to defend against infectious pathogens with either T helpelr or 2 cytokine
profile and how these immune response profiles could also be deleterious to the
host, cellular immune responses to infectious pathogens are described. Chapter 10
details antigen presentation through the class I pathway and cytolytic T cells in the
context of viral infection. Chapter 11 focuses this discussion on the changes in the
cellular immune T cell repertoire on infection with the human immunodeficiency
virus, These changes are eloquently portrayed by flow cytometry analysis. Addi-
tional regulation of T cells is presented in Chapter 12: idiotypic networks are de-
scribed that modulate T cell-mediatedh epatic granulomatous inflammation in-
duced by an infectious pathogen. The discussion of immunoregulation of disease
then broadens to include immune modulation through human monoclonal antibod-
ies (Chapter 13), immune modulation as a function of nutritional states (Chapter
14), immune modulation in gastrointestinal disease (Chapter 15), sepsis (Chapter
16), cancer (Chapter 17), and immune modulation and the neuroendocrine system
(Chapter 18). Each of these chapters provides a unique focus on the immunsey stem
in the context of systemic infections anddis ease.
The remaining eight chapters present immune modulationi n the form of both
accepted and experimental therapies. Thus, the book concludes with an emphasis
on immune modulation in the therapy of disease. An important aspect of new
experimental therapies is the reduction of side effects through a reduction in sys-
temic interactions. Thus, a review of targeted antigen delivery systems for experi-
mental therapies is presented in Chapter 19. Chapter 20 presents immune modula-
tion in gene therapy. In this exciting new field, cytokine gene therapy and cellular
adoptive therapy is described. Chapters 21 and 22 return to the human immunodefi-
ciency virus and present apoptosis pathways and immune-based therapies for hu-
man immunodeficiency virus infection. Chapter 23 provides a descri~tiono f the
novel observation of microchimerism in immune-mediated allograft acceptance in
organ transplantation. As the last disease-based chapter, Chapter 24 provides a
review of immune modulation and therapy in arthritis, followed by a presentation
of vaccination via mucosal- and oral-induced immune modulation (Chapter 25).
The book closes with the use of immune modulating agents in the performance of
human clinical trials.
Thus, Z ~ ~ ~uo ~~ uel ~ Agteint~s gis a comprehensive, current manual of
pathways and individual agents that describe and affect the immune response. As
such, this book is a unique referencet hat summarizes current state-of-the-art immu-
nological paradigms related to clinically relevant immune modulation.
Thomas F. Kresina
Preface V
Contributors X
1. The Immune System and Immune Modulation 1
Fran~oiHs irsch and Guido Kroemer
2. Molecular Mechanisms Controlling ImmunoglobulinE Responses 21
Rachel L. Miller and PauBl . Rothman
3. Idiotypes and T Cell Selection 35
Bjarne Bogen, Zlatko DembiC, andS iegfried Weiss
4. In Vivo Modulation of Lymphohemopoietic Stem Cell Populations
with Cytokines 55
Gerald de Haan and Gary Van Zant
5. Hormones as Immune Modulating Agents 75
Istvan Berczi and Eva Nagy
6. Transforming Growth Factor-@A: Cytokine Paradigm 121
~ichelle FRr,a zier- Jessen, Nancy McCartney-Francis,
and Sharon M. Wahl
~ i i
iii IlS
7. Psychological Stress and Immune Competence 145
~lizabeth AB.a chen, Anna L. ~arslanSdt,e phen
and Sheldon Cohen
8. Interleukin 12: A Potent Vaccine Adjuvant for Promoting
Cellular Immunity and Modulating HumoralI mmunity 161
Stanley F. Wolf
9. Cytokine Immunomodulation of InfectiousD iseases 169
Joseph F. Urban, Jr., Fred Douglass Finkelman, ?'ere2
Shea-Donohue, and William C. Cause
10. lating Cytolytic Responses to Infectious Pathogens 187
ca Pogue Caley and Jeffrey A. Frelinger
11. Im~unologyof 1: Cells in AIDS: Dynamics Revealed by
ht-Color Flow Cytometry 209
*
rio Roederer, Ste~henC . De Rosa, Leonore A. Herzenberg,
and Leonard A. Herzenberg
12. Immunomodulation of Schistosomal-Induced Inflammation 22 1
Thomas F. Kresina
13. noclonAa ln tibodies and Me odulatioinn
Sitci hs,i stosomiasis, Iann fde ction 237
Tho~aFs: Kresina, Carry A. Neil, and Steven K. H. Foung
14. Nutrition and Immunity 255
Srinivas ~endulurain d ~anjiKtu rnar ~handra
15. Immunomodulating Agents in Gastrointestinal Disease 267
Samir A. Shah, Athos Bousvaroas,n d A. Christopher Stevens
16. Immune Modulation in Sepsis 301
Janet M. J. Hammond and Peter D. Potgieter
17. Int~rleukin6 : Role in the Pathogenesis of Cancer 345
Ofoniel ~art~nez-~aza
i
l$, Neuroendocrine-Induced Immune Modulation and Autoimmunity 363
Terence Smith and Adrian K. Hewson
rt
19. Antigen Delivery Systems Used to Induce Immunomodulation 385
.
~ahiruIl. Khan, Ian G. Tucker, and Joan P. Opdebeeck
20. Immunomodulation in Gene Therapeutics 42 1
lock, Susan S. Rich, Shu-Hsia Chen, and Savio L. C. Woo
21. Cytokines, Apoptosis, and Immune Therapyi n HIV Infection 439
Jer6me Estaquier and Jean-Claude Ameisen
22. ost-Directed and Immune-Based Therapies for Human
deficiency Virus Infection 457
Valdez, ~ichael MLe. derman, Bharat Ramratnam,
and ~ i m ~ tPh. yF lani~an
23. Transplantation Tolerance, Microchimerism, and the
Two-way Paradigm 483
Thomas E. Starzl,A nthony J. Dernetris, ~oriko ~urase,
Massimo Trucco, Angus W. ~homson, AbduSl. Rao, and John J. Fung
24. Immunomodulation of Cytokines and TC ells by Biologicals
Arthritis Rheumatoid in 507
~avindeNr .M aini and arc Feldmann
25. Immunomodulation at Mucosal Surfaces: Prospects for the
DevelopmeAon f nt tiinfectioaun sd Antiin~ammatoryV accines 529
Cecil Czerkinsky and Jan Ho~mgren
26. New Statistical Designs for Clinical Trials of Immunomodulating Agents 539
R~chardS imon
Index 551