Handbook of Human Immunology

HUM AN

IMMUNOLOGY

Handbook of

Second Edition

CRC_1984_FM.indd i 1/16/2008 6:21:32 PM

CRC_1984_FM.indd ii 1/16/2008 6:21:32 PM

CRC Press is an imprint of the

Taylor & Francis Group, an informa business

Boca Raton London New York

HUM AN

IMMUNOLOGY

Edited by

Maurice R. G. O’Gorman, Ph.D.

The Children's Memorial Hospital

Chicago, Illinois

Albert D. Donnenberg, Ph.D. Hillman Cancer Center

Pittsburgh, Pennsylvania

Handbook of

Second Edition

CRC_1984_FM.indd iii 1/16/2008 6:21:33 PM

Cover art by Yoju from the original artwork “Ao ni Aru Saibo”-525A. Copyright Yoju’s Studio. Used

with permission.

CRC Press

Taylor & Francis Group

6000 Broken Sound Parkway NW, Suite 300

Boca Raton, FL 33487-2742

© 2008 by Taylor & Francis Group, LLC

CRC Press is an imprint of Taylor & Francis Group, an Informa business

No claim to original U.S. Government works

Printed in the United States of America on acid-free paper

10 9 8 7 6 5 4 3 2 1

International Standard Book Number-13: 978-0-8493-1984-6 (Hardcover)

This book contains information obtained from authentic and highly regarded sources. Reprinted

material is quoted with permission, and sources are indicated. A wide variety of references are

listed. Reasonable efforts have been made to publish reliable data and information, but the author

and the publisher cannot assume responsibility for the validity of all materials or for the conse￾quences of their use.

Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced,

transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or

hereafter invented, including photocopying, microfilming, and recording, or in any information

storage or retrieval system, without written permission from the publishers.

For permission to photocopy or use material electronically from this work, please access www.

copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC)

222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that

provides licenses and registration for a variety of users. For organizations that have been granted a

photocopy license by the CCC, a separate system of payment has been arranged.

Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and

are used only for identification and explanation without intent to infringe.

Library of Congress Cataloging-in-Publication Data

Handbook of human immunology / editors, Maurice R. G. O’Gorman and Albert

D. Donnenberg -- 2nd ed.

p. ; cm.

“A CRC title.”

Includes bibliographical references and index.

ISBN 978-0-8493-1984-6 (alk. paper)

1. Immune system. 2. Immunology. I. O’Gorman, Maurice R. G. II.

Donnenberg, Albert David. III. Title.

[DNLM: 1. Immunity. 2. Immune System Diseases. 3. Immunologic

Techniques. 4. Immunologic Tests. QW 540 H236 2008]

QR181.H27 2008

616.07’9--dc22 2007035313

Visit the Taylor & Francis Web site at

http://www.taylorandfrancis.com

and the CRC Press Web site at

http://www.crcpress.com

CRC_1984_FM.indd iv 1/16/2008 6:21:33 PM

v

Contents

Preface ......................................................................................................................ix

Editors .......................................................................................................................xi

Contributors ........................................................................................................... xiii

Chapter 1 Overview of Immunity .........................................................................1

James D. Folds

Chapter 2 Statistics of Immunological Testing ...................................................29

Albert D. Donnenberg

Chapter 3 Human Immunoglobulins ..................................................................63

Robert G. Hamilton

Chapter 4 The Complement System ................................................................. 107

Patricia C. Giclas

Chapter 5 Cellular Immunology: Monitoring of Immune Therapies ............... 137

Theresa L. Whiteside

Chapter 6 Understanding Clinical Flow Cytometry ......................................... 181

Albert D. Donnenberg and Vera S. Donnenberg

Chapter 7 Leukemia and Lymphoma Immunophenotyping

and Cytogenetics .............................................................................. 221

Maria A. Proytcheva

Chapter 8 Guidelines for the Use of Flow Cytometry in the

Management of Patients Infected with the Human

Immunodefi ciency Virus Type-1 and the Acquired

Immunodefi ciency Syndrome .......................................................... 257

Maurice R.G. O’Gorman

CRC_1984_FM.indd v 1/16/2008 6:21:33 PM

vi Contents

Chapter 9 Role of Flow Cytometry in the Diagnosis and Monitoring

of Primary Immunodefi ciency Disease ............................................267

Maurice R.G. O’Gorman

Chapter 10 Detection and Characterization of the T-Cell

Receptor Repertoire ......................................................................... 313

Gulbu Uzel

Chapter 11 Human Leukocyte Differentiation Antigens, Cluster

of Differentiation: Past, Present, and Future .................................... 319

Maurice R.G. O’Gorman

Chapter 12 Immunologic Diagnosis of Autoimmunity ......................................369

Noel R. Rose

Chapter 13 Autoimmune and Immune-Mediated Diseases

of the Gastrointestinal Tract ............................................................. 383

Stefano Guandalini, Mala Setty, and Bana Jabri

Chapter 14 Serologic Testing for Infectious Diseases ........................................ 421

John L. Schmitz

Chapter 15 Molecular Techniques Applied to Infectious Diseases .................... 441

Jennifer S. Goodrich and Melissa B. Miller

Chapter 16 Cytokines: Regulators of Immune Responses and Key

Therapeutic Targets .......................................................................... 495

Barbara Detrick, Chandrasekharam N. Nagineni,

and John J. Hooks

Chapter 17 Measuring Human Cytokines .......................................................... 517

Holden T. Maecker

Chapter 18 The Human Major Histocompatibility Complex and

DNA-Based Typing of Human Leukocyte Antigens

for Transplantation ........................................................................... 541

Susana G. Marino, Andrés Jaramillo,

and Marcelo A. Fernández-Viña

CRC_1984_FM.indd vi 1/16/2008 6:21:33 PM

Contents vii

Chapter 19 Relevance of Antibody Screening and Crossmatching

in Solid Organ, Hematopoietic Stem Cell Transplantation,

and Blood Transfusion .....................................................................565

Chee L. Saw, Denise L. Heaney, Howard M. Gebel,

and Robert A. Bray

Chapter 20 Functional Assessment of Immunosuppression: Monitoring

Posttransplant Alloreactivity with Flow Cytometric Mixed

Lymphocyte Cocultures ................................................................... 589

Chethan Ashok Kumar, Ali Abdullah, Alison Logar,

Patrick Wilson, Anjan Talukdar, Nydia Chien,

Mandal Singh, and Rakesh Sindhi

Index .....................................................................................................................599

CRC_1984_FM.indd vii 1/16/2008 6:21:33 PM

CRC_1984_FM.indd viii 1/16/2008 6:21:33 PM

ix

Preface

Since the publication of the fi rst edition of the Handbook of Human Immunology in

1997, major scientifi c achievements have contributed directly to an increased under￾standing of the complexities of the human immune system in health and disease.

Whether directly as a result of the sequencing of the entire human genome or as a

result of the technological advancements in the completion of the latter, several new

components of the immune system have been revealed, and new technologies for

their measurement and evaluation have been developed. In the past decade, the num￾ber of recognized clusters of differentiation (CD) on the surface of leukocytes and

associated cells has more than doubled; an entire new chemokine and chemokine

receptor nomenclature system has been established; the number of “lymphokines”

(now greater than 30) and humanized monoclonal antibody therapy have become a

staple of our pharmacologic armamentarium (to mention only a few of the signifi -

cant immunological developments of the past decade). The discovery of all of these

immune system components has been accompanied by the development of new and

improved methods for their detection as well as the recognition of the roles that these

components play in health and disease. These major breakthroughs are refl ected in

the present edition of the Handbook of Human Immunology.

There are six new chapters for a total of 20 (compared to 14 in the previous

edition) written by 12 new authors covering all the major components of the innate

and adaptive human immune system, descriptions of the specifi c human conditions

characterized by their assessment, the specifi c technologies and methods currently

used for their measurement, and fi nally the relevance and potential pitfalls involved

in the interpretation of their specifi c measurements.

As in the past, the book is introduced with an overview of the immune system,

which is immediately followed by a new, practical, and fun-to-read chapter on “Statistics

of Immunological Testing” that is invaluable both in interpreting test results and also

in the validation of new tests and the development of reference ranges. Throughout

this edition, readers will fi nd “normal ranges” including serum immunoglobulins,

complement components, cytokines, and new to this edition—age-associated normal

ranges for lymphocyte subsets. The fi rst edition’s chapter on fl ow cytometry has been

expanded into six completely revised chapters including a thorough treatise on general

fl ow cytometry principles and practice, quality control and theory, leukemia and lym￾phoma immunophenotyping analyses along with cytogenetic abnormalities, an update

on CD4 measurement guidelines in HIV-infected persons and two new chapters cover￾ing (1) the fl ow cytometry–based diagnosis of primary immunodefi ciency disease and

(2) a history of the human leukocyte differentiation antigen workshops (now renamed

the human cell differentiation antigen workshops) along with two comprehensive and

very informative tables on CD.

The chapters on clinical laboratory disease monitoring include laboratory meth￾ods for monitoring new biological therapies in the context of clinical trials and routine

practice, an entire chapter devoted specifi cally to the immunological assessment of

CRC_1984_FM.indd ix 1/16/2008 6:21:33 PM

x Preface

gastrointestinal diseases, and a global review of the laboratory assessment of auto￾immune disease. Infectious disease monitoring is discussed from the serological

perspective, as well as the timely review of the technology and applications of new

and now well-established molecular techniques. Finally, the laboratory’s role in bone

marrow and solid organ transplant is presented from the perspectives of antibody

screening and crossmatching as well as molecular-based human leukocyte antigen

(HLA) typing, followed by Chapter 20, which presents novel methods for monitoring

functional immunosuppression of alloreactivity in patients posttransplant.

This edition of the handbook provides a practical reference of the important

immunological parameters along with up-to-date descriptions of the methods

used for their assessment and applications in health and disease. The text is par￾ticularly relevant to practicing clinicians, clinical laboratory professionals, and stu￾dents interested in human immunology both from laboratory and applied clinical

perspectives.

CRC_1984_FM.indd x 1/16/2008 6:21:33 PM

xi

Editors

Maurice R.G. O’Gorman, PhD, is a professor of pediatrics and pathology at the

Feinberg School of Medicine of Northwestern University, Chicago, Illinois. He is

also the vice chair of the department of pathology and laboratory medicine and the

director of the diagnostic immunology and fl ow cytometry laboratories at Children’s

Memorial Hospital.

Dr. O’Gorman was born in Windsor, Ontario, Canada and graduated in 1981

from the University of Western Ontario, London, Ontario, with a BSc with honors in

microbiology and immunology. He then attended the University of British Columbia

and earned an MSc in pathology in 1985 and 3 years later, a PhD in academic pathol￾ogy from the same university. Following his doctorate, Dr. O’Gorman was awarded

a 1-year fellowship in the division of neurology at UBC to develop and implement

functional immune monitoring assays for clinical trials of new biological treatments

for multiple sclerosis (MS). The following year Dr. O’Gorman was awarded a 2-year

fellowship in clinical and diagnostic laboratory immunology in the department of

pathology at the University of North Carolina in Chapel Hill. His research as a post￾doctoral fellow evolved around the development, validation, and standardization of

new clinical assays, many of which were fl ow cytometry based.

In his present position at the Children’s Memorial Hospital in Chicago, Illinois,

Dr. O’Gorman has established the Diagnostic Immunology and Flow Cytometry

Laboratory at the Children’s Memorial Hospital as an internationally recognized

laboratory for the evaluation of primary immune defi ciency disorders, leukemia and

lymphoma immunophenotyping, and autoimmune disease. His clinical and develop￾mental research program encompasses broad areas in immunology, including the

establishment of normal reference ranges for the pediatric population, development

of surrogate markers for monitoring disease activity and response to therapy, and the

development of new diagnostic tests. He is also the codirector of the CPEP accred￾ited postdoctoral program in clinical and diagnostic laboratory immunology. His

main research interests are the investigation of immunopathogenetic mechanisms

and immune regulation in autoimmunity and primary immunodefi ciency diseases.

Dr. O’Gorman has over 100 scholarly publications, has been an invited lecturer at

numerous national and international venues, and has organized and chaired several

national and international conferences and training programs in immunology and

fl ow cytometry.

Dr. O’Gorman’s leadership positions have included among others, president of the

Association of Medical Laboratory Immunologists (AMLI, 2001–2003); president of

the Great Lakes International Image Analysis and Flow Cytometry Association (2004);

editor-in-chief of Clinical Immunology Newsletter (1994–2000); editor-in-chief of

Clinical and Applied Immunology Reviews (2000–2006); and reviews editor for the

Journal of Immunological Methods (2007). In 2005, Dr. O’Gorman earned an MBA

from the executive MBA program at the Kellogg School of Management. He is mar￾ried and has two sons, and enjoys a broad variety of sports and recreational activities.

CRC_1984_FM.indd xi 1/16/2008 6:21:33 PM

xii Editors

Albert D. Donnenberg was born in New York, in 1951. As an undergraduate student,

he studied philosophy at the University of Colorado, Boulder. He received his PhD in

infectious disease epidemiology at the Johns Hopkins University in 1980, studying

cellular immunity to herpes simplex virus. On graduation, he was elected to Delta

Omega, the honorary Public Health Society. After a postdoctoral fellowship under

the direction of bone marrow transplant pioneer Dr. George Santos at the Johns

Hopkins Oncology Center, Dr. Donnenberg was appointed instructor of oncology

in 1982, assistant professor in 1983, and associate professor in 1989. He worked on

adoptive transfer of donor immunity during allogeneic bone marrow transplantation,

and the development and clinical use of T-cell depletion of bone marrow to prevent

graft-versus-host disease, an early implementation of engineered cellular therapy.

He also performed early studies on cellular immunity in human immunodefi ciency

virus (HIV) infection, and codeveloped the concept of T-cell homeostasis.

In 1991, Dr. Donnenberg was recruited to the University of Pittsburgh to serve

as the director of laboratory research for the Bone Marrow Transplant Program. He

has also served as program codirector, and as interim director. He has directed the

UPMC Hematopoietic Stem Cell Laboratory and the University of Pittsburgh Can￾cer Institute’s Flow Cytometry Facility since 1998. He was promoted to professor of

medicine in 2001.

His current research interests are in stem cell therapy and graft engineering,

immunity after hematopoietic stem cell transplantation, and the role of stem cells

in neoplasia—a project he pursues with his wife Dr. Vera Donnenberg. He is inter￾nationally recognized for his work in somatic cell therapy and fl ow cytometry.

Dr. Donnenberg has authored more than 130 scholarly publications. He is the proud

father of four daughters and one son, and lives on Pittsburgh’s Southside with hob￾bies such as winemaking and art collecting.

CRC_1984_FM.indd xii 1/16/2008 6:21:34 PM

xiii

Ali Abdullah

Department of Pathology

University of Pittsburgh

Pittsburgh, Pennsylvania

Robert A. Bray

Department of Pathology and

Laboratory Medicine

Emory University

School of Medicine

Atlanta, Georgia

Nydia Chien

Department of Pathology

University of Pittsburgh

Pittsburgh, Pennsylvania

Barbara Detrick

Department of Pathology

Johns Hopkins

School of Medicine

Baltimore, Maryland

Albert D. Donnenberg

Department of Medicine

Division of Hematology and Oncology

University of Pittsburgh

Pittsburgh, Pennsylvania

Vera S. Donnenberg

University of Pittsburgh Schools of

Medicine and Pharmacy

UPMC Heart Lung and Esophageal

Surgery Institute

Pittsburgh, Pennsylvania

Marcelo A. Fernández-Viña

Department of Pathology and

Laboratory Medicine

MD Anderson Cancer Center

University of Texas

Houston, Texas

James D. Folds

Department of Pathology and

Laboratory Medicine

University of North Carolina at

Chapel Hill

Chapel Hill, North Carolina

Howard M. Gebel

Department of Pathology and

Laboratory Medicine

Emory University

School of Medicine

Atlanta, Georgia

Patricia C. Giclas

Department of Pediatric

Allergy and Immunology

National Jewish

Medical and Research

Center

Denver, Colorado

Jennifer S. Goodrich

University of North Carolina

Hospitals

Chapel Hill, North Carolina

Stefano Guandalini

Department of Pediatrics

Comer Children’s Hospital

University of Chicago

Chicago, Illinois

Robert G. Hamilton

Department of Medicine

Division of Allergy and

Clinical Immunology

Johns Hopkins

School of Medicine

Baltimore, Maryland

Contributors

CRC_1984_FM.indd xiii 1/16/2008 6:21:34 PM

xiv Contributors

Denise L. Heaney

Department of Pathology and

Laboratory Medicine

Emory University

School of Medicine

Atlanta, Georgia

John J. Hooks

Laboratory of Immunology

National Eye Institute

National Institutes of Health

Bethesda, Maryland

Bana Jabri

Department of Pathology

Comer Children’s Hospital

University of Chicago

Chicago, Illinois

Andrés Jaramillo

Department of Pathology

Rush University Medical Center

Chicago, Illinois

Chethan Ashok Kumar

Department of Pathology

University of Pittsburgh

School of Medicine

Pittsburgh, Pennsylvania

Alison Logar

Department of Pathology

University of Pittsburgh

School of Medicine

Pittsburgh, Pennsylvania

Holden T. Maecker

BD Biosciences

Becton, Dickinson and Company

San Jose, California

Susana G. Marino

Department of Pathology

University of Chicago

Chicago, Illinois

Melissa B. Miller

Department of Pathology and

Laboratory Medicine

University of North Carolina at

Chapel Hill

Chapel Hill, North Carolina

Chandrasekharam N. Nagineni

Laboratory of Immunology

National Eye Institute

National Institutes of Health

Bethesda, Maryland

Maurice R.G. O’Gorman

Department of Pathology

and Pediatrics

Feinberg School of Medicine

Northwestern University

Chicago, Illinois

Maria A. Proytcheva

Department of Pathology

Feinberg School of Medicine

Northwestern University

Chicago, Illinois

Noel R. Rose

Departments of Pathology and Molecular

Microbiology and Immunology

Johns Hopkins University

Baltimore, Maryland

Chee L. Saw

Department of Pathology and

Laboratory Medicine

Emory University

School of Medicine

Atlanta, Georgia

John L. Schmitz

Department of Pathology and

Laboratory Medicine

University of North Carolina at

Chapel Hill

Chapel Hill, North Carolina

CRC_1984_FM.indd xiv 1/16/2008 6:21:34 PM