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MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VII Molecular Determinants of Microbial Immunity
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research
RODOLFO PAOLETTI, University of Milan
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Volume 451 GENE THERAPY IN CANCER
Edited by Peter Walden, Uwe Trefzer, Wolfram Sterry, and Farzin Farzaneh
Volume 452 MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VII: Molecular Determinants of Microbial Immunity
Edited by Sudhir Gupta, Alan Sher, and Rafi Ahmed
A Continuation Order Plan is available for this serieS. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher.
MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VII Molecular Determinants of Microbial Immunity
Edited by
Sudhir Gupta University of California, Irvine lrvine, California
Alan Sher National Institutes of Health Bethesda, Maryland
and
RafiAhmed Emory University Atlanta, Georgia
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Llbrary of Congrass Cataloglng-In-Publlcatlon Data
Mechantsms of lyaphocyte actlvatton and tm.une regulatton VII: molecular qetermtnants of mtcrobtal tmmuntty / edtted by Sudhtr Gupta. Alan Sher. and Raft Ahmed.
p. em. -- (Advanees tn expertmental medtetne and btology v. 452)
Ineludes btbltographteal referenees and index. ISBN 978-1-4615-5355-7 (eBook)
DOI 10.1007/978-1-4615-5355-7 1. Immune responsa--Regulatton--Congresses. 2. Natural t •• unlty
-Congresses. 3. Baetertal dtseases--I.munologteal aspeets--Congressas. 1. Gupta. Sudhtr. II. Sher. Alan. III. Ahmed. Raft. IV. Sertes. ORI86.M42 1998 616.07'95--dc21 98-40455
CIP
Proceedings ofthe Seventh International Conference on Lyrnphocyte Activation and Immune Regulation, held February 6 - 8, 1998, at Newport Beach, California
ISBN 978-1-4613-7443-5
© 1998 Springer Science+Business Media New York Origina11y published by Plenum Press, New York in 1998 Softcover reprint of the hardcover 1 st edition 1998
http://www.plenum.com
10987654321
AII rights reserved
No part ofthis book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher
ISBN 978-1-4613-7443-5
PREFACE
During the last decade, rapid progress has been made in the area of microbial immunity. New conceptual frameworks have emerged with regard to the processing and presentation of peptides and nonpeptide antigens from microbes, especially bacteria, to T cells in the context of classical MHC class I and nonconventional MHC I molecules. Experimental models have been instrumental in defining some of these pathways for generating protective immune responses against microbes, which form the basis for the design of new vaccines. New evidence has stressed the importance of innate immunity in microbial infections. The concept of dichotomy within T helper cells has revealed the role of these cell types in resistance and susceptibility to microbial-mediated pathology. These latest developments in microbial immunity are discussed in this volume.
Natural killer cell development is known to be regulated by the presence of MHC class I antigens. Receptors for MHC class I molecules on NK cells have been discovered. Interaction of these receptors with their specific ligands leads to inhibition of cytotoxicity. Vinay Kumar and colleagues review NK cell differentiation and ontogeny, and functions of NK cells in experimental animals. Lewis Lanier discusses the role of a newly discovered molecule, DAP 12, in KIR and other receptor-mediated signal transduction in NK cells. Eric Long describes the regulation of immune response by inhibitory receptors. Recent studies of the role of epithelial yo T cells, in addition to specific immune regulation, in innate immune response are discussed by Wendy Havran and associates.
The role ofCD4+ Thl and Th2 cells in the susceptibility and resistance to microbes, especially to protozoan, has been reviewed. Keats Nelms and colleagues provide an account of the molecular steps in signaling via IL-4 receptor and the biological significance of IL-4-IL-4R interactions. Richard Locksley et al. review the mechanisms, including the role of genetic factors, of the differentiation of naive T helper cells into cytokine effector cells. Thl responses confer resistance, whereas Th2 responses confer susceptibility to L. major. Jacques Louis and his colleagues discuss the effector functions of Thl cells and early events in the development of Th2 cells in murine model of L. major. Robert Coffman and Amy Beebe review the genetic control of T cell responses to L. major infection, and Edward Pearce and colleagues present data on the induction and function of Th2 cells during S. mansoni infection.
The general paradigm is that intracellular bacteria elicit Th I response; however, Stefan Kaufmann et al. have provided data, in experimental model systems, to suggest that IL-4 (Th2 response) is produced as an early response to several intracellular bacteria, followed by prolonged Thl response. Both CD4+ and CD8+ T cell responses are elicited in
v
vi Preface
response to M tuberculosis. Barry Bloom and his colleagues provide new data for the role of cytotoxic T cells in resistance to M. tuberculosis. Alan Sher and colleagues emphasize the role of dendritic cells in the initiation of host resistance to T. gondii. Michael Bevan, Rafi Ahmed, Christine Biron, and their colleagues discuss immune responses to viral infections. They present data regarding the role and dynamics of CD8+ T cells in infection with LCMV, and review endogenous innate cytokines during early viral infection and the role these cytokines play in promoting cell-mediated immunity.
During the last four years, major advances have been made in understanding the immunopathogenesis of HIV infection. Edward Berger reviews the discovery of chemokine receptors (co-receptors for HIV entry and tropism), expansion of co-receptor repertoire, and the molecular mechanisms underlying HIV fusion and tropism. Bruce Walker and associates discuss various HIV-I-specific responses in relation to progressive and nonprogressive HIV infection. In addition to the well-recognized role of neutralizing antibodies and cytotoxic T cells, they provide convincing evidence for the role of p24-specific T helper cells in the control of HIV infection. The SIV monkey model has provided most valuable information regarding mucosal transmission of HI V infection. Marian Neutra, using experimental model systems, shows local induction of specific IgG and secretory IgA response and demonstrates a role for M cells in pathogen entry. Norman Letvin and colleagues elucidate the development ofSIV-specific CD8+ T cells during primary SIV infection in monkeys.
Rapid understanding of the nature of determinants that dictate the immunogenicity and specificity of immune response has contributed to the area of vaccine development. Douglas Fearon discusses the role of non structural determinants of antigen in regulating B cell activation mediated by B cell co-receptors CDI9, CD21, and CD22. DNA vaccines, which differ from traditional vaccines, have been shown to elicit effective T cell and B cell responses and have been instrumental in evaluating mechanisms of induction of immune response. Margaret Liu and her colleagues review various types of DNA vaccines and the mechanisms for the generation of specific immune response. Louis Miller and associates discuss the status of vaccines against Falciparum malaria, and John Robbins and colleagues provide evidence for and highlight the fact that not all virulence factors are protective antigens in immunity to pertussis.
This book should be of interest primarily to researchers in immunology, microbiology, and vaccine development. It should also be of interest to academic pediatricians and internists specializing in infectious diseases and immunology.
The editors extend thanks to Miss Nancy 1. Doman for her excellent secretarial assistance.
Sudhir Gupta Alan Sher RafiAhmed
CONTENTS
INNATE DEFENSE MECHANISMS
1. Development of Self-Recognition Systems in Natural Killer Cells .......... . P. V. Sivakumar, N. S. Williams, I. 1. Puzanov, 1. D. Schatzle, M. Bennett,
and V. Kumar
2. Activating and Inhibitory NK Cell Receptors Lewis L. Lanier
13
3. Regulation ofImmune Responses by Inhibitory Receptors. . . . . . . . . . . . . . . . . . 19 Eric O. Long
4. Innate Functions of Epithelial yo T Cells ................................ 29 Wendy L. Havran, Yaping Chen, and Richard Boismenu
EFFECTOR CHOICE
5. Interleukin-4 Receptor Signalling Mechanisms and Their Biological Significance 37 Keats Nelms, Hua Huang, John Ryan, Achsah Keegan, and William E. Paul
6. Development of CD4+ Effector T Cells and Susceptibility to Infectious Diseases 45 Richard M. Locksley, Deborah 1. Fowell, Kanade Shinkai, Adil E. Wakil,
Dee Lacy, and Mark Bix
7. Anti-Leishmania Effector Functions of CD4+Thl Cells and Early Events Instructing Th2 Cell Development and Susceptibility to Leishmania major in BALB/c Mice .............................................. 53
Jacques A. Louis, Fatima Conceir;ao-Silva, Hayo Himmelrich, Fabienne Tacchini-Cottier, and Pascal Launois
8. Genetic Control of the T Cell Response to Leishmania major Infection. . . . . . . . 61 Robert L. Coffman and Amy M. Beebe
9. The Initiation and Function ofTh2 Responses during Infection with Schistosoma mansoni .......................................... 67
Edward 1. Pearce, Anne La Flamme, Elizabeth Sabin, and Laura Rosa Brunet
vii
viii Contents
REGULATION OF HOST RESISTANCE TO INTRACELLULAR PATHOGENS
10. Interleukin-4 Production in Response to Infection with Intracellular Bacteria. . . 75 Helen Collins, Inge E. A. Flesch, Masashi Emoto, and Stefan H. E. Kaufmann
11. Cytotoxic T Lymphocytes in Resistance to Tuberculosis ................... 85 Richard 1. Mazzaccaro, Steffen Stenger, Kenneth L. Rock,
Steven A. Porcelli, Michael B. Brenner, Robert L. Modlin, and Barry R. Bloom
12. The Role of Dendritic Cells in the Initiation of Host Resistance to Toxoplasma gondii . . .... ...... .... .. ... . .. . ........... .... .. .... .. . .. . ... 103
Alan Sher, Sara Hieny, Hugues Charest, Tanya Scharton-Kersten, Carmen Collazo, Ronald N. Germain, and Caetano Reis e Sousa
13. Dynamics of the CD8+ T Cell Response during Acute LCMV Infection. . . . . . . 111 Eric Butz and Michael 1. Bevan
14. In Vivo Dynamics of Anti-Viral CD8 T Cell Responses to Different Epitopes: An Evaluation of Bystander Activation in Primary and Secondary Responses to Viral Infection .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Kaja Murali-Krishna, John D. Altman, M. Suresh, David Sourdive, Allan Zajac, and Rafi Ahmed
15. Early Cytokine Responses to Viral Infections and Their Roles in Shaping Endogenous Cellular Immunity .................................. 143
Christine A. Biron, Leslie P. Cousens, Melanie C. Ruzek, Helen C. Su, and Thais P. Salazar-Mather
IMMUNOPATHOGENESIS OF HIV-l INFECTION
16. HIV Entry and Tropism: When One Receptor Is Not Enough. . . . . . . . . . . . . . . . 151 Edward A. Berger
17. Immune Control of HI V-I Replication. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Bruce D. Walker, Eric S. Rosenberg, Christine M. Hay, Nes1i Basgoz, and
OttoO. Yang
18. HIV Transmission and Immune Protection at Mucosal Surfaces Marian R. Neutra
169
19. The CD8+ T Lymphocyte Response during Primary SIVmac Infection ........ 177 Norman L. Letvin, Yasuhiro Yasutomi, Ling Shen, Keith A. Reimann,
Zheng Wei Chen, Jom E. Schmitz, and Marcelo J. Kuroda
NEW APPROACHES TO VACCINE DEVELOPMENT
20. Non-Structural Determinants ofImmunogenicity and the B Cell Co-Receptors, CDl9, CD21, and CD22 ....... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Douglas T. Fearon
Contents ix
21. DNA Vaccines: Mechanisms for Generation of Immune Responses . . . . . . . . . . . 187 M. A. Liu, T.-M. Fu, J. J. Donnelly, M. J. Caulfield, and J. B. Ulmer
22. Vaccines against the Blood Stages of Falciparum Malaria .................. 193 Louis H. Miller, Michael F. Good, and David C. Kaslow
23. Immunity to Pertussis: Not All Virulence Factors Are Protective Antigens 207 John B. Robbins, Rachel Schneerson, Dolores A. Bryla, Birger Trollfors,
John Taranger, and Teresa Lagergdrd
Index. . .. .. .. . .. .. . . . .. . . . . . . . ... .. .... .. . .. . . . . . . . ..... ... . . . . . . . . . .. 219
MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VII Molecular Determinants of Microbial Immunity