Advances in Immunology [Vol 12] - F. Dixon, H. Kunkel (AP, 1970) WW

431 Pages·1970·23.26 MB·English

ADVANCES I N

I m m u n o l o g y

V O L U M E 1 2

CONTRIBUTORS TO THIS
VOLUME

NABIH I. ABDOU

KEITH J. DORRINGTON

PETER DUKOR

H. HEMMINCSEN

B. D. KAHAN

RICHARD M. KRAUSE

HENRY METZCER

J. RADOVICH

R. A. REISFELD

MAXWELL RICHTER

D. W. TALMACE

CHARLES
TANFORD

GERALD WEISSMANN

ADVANCES IN
Immunology

E D I T E D B Y

F. J. DIXON, JR.
H E N R Y 6. KUNKEL

Division of Experimental Pathology
Scrippr Clinic and Research Foundation
l a lollo, California

The Rockefeller University
New York, New York

V O L U M E 1 2

1 9 7 0

ACADEMIC PRESS
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PRINTED IN THE UNITED STATES O F AMERICA

CONTENTS

LIST OF CONTRIBUTORS .
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PREFACE .
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CONTENTS
OF PREVIOUS
VOLUMES .
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xiii

The Search for Antibodies with Molecular Uniformity

RICHARD M. KRAUSE

I. htroduction
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11. Immunoglobulin Heterogeneity and Antibody Properties Indicative of
Limited Heterogeneity .
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111. Human Antibodies with Restricted Heterogeneity
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IV. Experimental Generation of Antibodies with Restricted Heterogeneity .
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V. Myeloma Protein and Paraproteins with Antibody Activity
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VI. Discussion and Summation .
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References
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Structure and Function of y M Macroglobulins

HENRY METZCER

I. Introduction
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11. Isolation and Storage of Macroglobulins
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111. Structure of Mammalian Macroglobulins .
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IV. Subunits, Polypeptide Chains, and Proteolytic Fragments .
VI. Functional Properties of Macroglobulins
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VII. Genetic Basis of Macroglobulin Structure .
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VIII. Biosynthesis and Metabolism of Macroglobulins
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IX. Macroglobulin-Like Proteins from Nonmammalian Species
X. Role of Macroglobulins in the Immune Response
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XI. Prospects
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References
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V. Low Molecular Weight hlacroglobulin-Like Proteins

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Transplantation Antigens

R. A. REISFELD
AND B. D. KAHAN

I. Introduction
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11. Extraction and Solubilization of Transplantation Antigens
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111. Physical and Chemical Nature of Transplantation Antigens .
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IV. Biological Activity of Extracted Transplantation Antigens
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V. Perspectives
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VI. Summary
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References
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V

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CONTENTS

The Role of Bone Marrow in the Immune Response

NABIH 1 . ABDOU AND MAXWELL
RICHTER

I . Introduction .
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I1 . A Brief Survey of the Techniques Used for the Detection of Immuno-
competent Cells
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I11 . Bone Marrow as a Source of Immunocompetent Cells
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IV . Cells Involved in the Humoral Immune Response .
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V . Cell Interactions Resulting in the Induction of the Immune Response .
Vl . Effects of Irradiation on the Immune Response .
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IX . Bone Marrow Transplantation-Application
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X . Conclusions
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References
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VII . Cells Involved in Cell-Mediated Immunity
VIII . Cells Affected in Immunological Tolerance

Cell Interaction in Antibody Synthesis

D . W . TALMACE.
J . RADOVICH.
AND H . HEMMINGSEN

I . Introduction
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I1 . Two Universes of Immunocompetent Cells

V . Enhancing Effect of Multiple Antigenic Determinants

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I11 . The Adherent Cell
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IV . Antigenic Competition .
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VI . Enhancing and Suppressive Effects of Passively Administered Antibody .
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References
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VII . Discussion and Speculations

The Role of Lysosomes in Immune Responses

GERALD WEISSMANN AND PETER DuKon

I . Introduction
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I1 . Processing of Antigen by the Vacuolar System
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IV . Lysosomes in Four Types of Immune Injury .
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References
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111 . Mediators of Tissue Injury Found in Lysosomes

Molecular Size and Conformation of Immunoglobulins

KEITH J . DORRINGTON AND CHARLES TANFORD
I . Introduction
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I1 . Molecular Size of Immunoglobulins and Subunits .
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I11 . Conformation of Immunoglobulins and Subunits
IV . Recovery of Native Conformation Following Chain Dissociation and
Unfolding
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V . Conclusions
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References
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AUTHOR INDEX .
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SUBJECT INDEX .
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202

203
207
213
237
244
246
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255
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271
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276
276
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277
279

283
285
304
306
322

333
334
341

366
375
376

383

409

LIST OF CONTRIBUTORS

Numbers in parentheses indicate the pages on which the authors’ contributions begin.

NABIH I. ABDOU,* The Harry Webster Thorp Laboratories, Division of
lmmunochemistry and Allergy, McGill University Clinic, Royal
Victoria Hospital, Montreal, Quebec, Canada ( 201)

KEITH J. DORRINGTON,
M . R. C. Molecular Pharmacology Unit, Medical
School, University of Cambridge, Cambridge, England ( 333)

PETER DUKOR,
Department of Medicine (Cell Biology and Genetics),
New York University School of Medicine, New York, New York (283)

H. HEMMINGSEN,
Department of Microbiology, University of Colorado
Medical Center, Denver, Colorado (271)

B. D. KAHAN, Department of Surgery, Massachusetts General Hospital,
Boston, Massachusetts ( 117)

RICHARD M. KRAUSE, Rockefeller University, New York, New York (1)

HENRY METZGER,
Arthritis and Rheumatism Branch, National Institute of
Arthritis and Metabolic Diseases, National lnstitute of Health,
Bethesdu, Maryland (57)

J. RAWVICH, Department of Microbiology, University of Colorado Medi-
cal Center, Denver, Colorado (271 )

R. A. REISFEW, Laboratory of Immunology, National Institute of Allergy
and Infectious Diseases, Bethesda, MaryIand (117)

MAXWELL RICHTER,~ The Harry Webster Thorp Laboratories, Division of
Immunochemistry and Allergy, McGill University Clinic, Royal
Victoria Hospital, Montreal, Quebec, Canada ( 201 )
D. W. TALMAGE,
Department of Microbiology, University of Colorado
Medical Center, Denver, Colorado (271)
CHARLES
TANFORD, Department of Biochemistry, Duke University Medi-
cal Center, Durham, North Carolina (333)

GERALD WEISSMANN, Department of Medicine (Cell Biology and Ge-
netics), New York University School of Medicine, New Yark, New
York (283)

Present address: Division of Immunology and Allergy, School of Medicine, Uni-
versity of Pennsylvania, Philadelphia, Pennsylvania.
+ Medical Research Associate, Medical Research Council, Canada.
vii

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PREFACE

The pace of immunologic research has quickened as the problems and
potentialities of immunology have appealed to investigators with widely
differing backgrounds. The important subjects reviewed in the twelfth
volume of this serial publication represent the contributions of chemists
and biologists as well as immunologists. With the increasing scope of
immunology, thoughtful, authoritative summations of knowledge in
rapidly developing areas have become essential if those working in this
field are to stay familiar with its overall progress. We are indebted to the
authors of this volume for making this possible by taking the time to
share with us their expertise.
The first article deals with the recently observed molecular uniformity
of antibodies to bacterial carbohydrate antigens. Dr. Krause, who has
initiated and carried out much of this research, discusses the practical
aspects of the production of uniform antibodies and points out their
potential usefulness. These molecules will play an important role in the
study of the amino acid composition and topography of the antibody
combining site, and by virtue of their allotypic homogeneity also should
aid in the definition of the location and character of the various molecular
determinants of allotypic specificity. Early sequence data from uniform
rabbit antibodies already indicate significant homology in the variable
regions of the human kappa and rabbit light chains, suggesting a common
ancestral relationship. Finally, because of their ready detectability by
physical means, uniform antibodies provide an additional means of
analysis of antibody responses and the cellular and/ or genetic events
involved.
In the second chapter Dr. Metzger discusses in depth the physical,
chemical, and biological aspects of yM antibodies, a subject to which he
has contributed much. The physical characteristics, chemical composition,
and subunit structure of the typical circular yM pentomers are presented,
and the relationship of these molecules to low molecular weight yM-like
proteins is considered, The characteristics of the interaction of yM anti-
bodies with antigens, i.e., the nature and number of antigen combining
sites, and the interaction of yM antibodies with the complement system
are compared to the corresponding properties of yG antibodies. Finally,
the biosynthesis and metabolism of yM antibodies and their peculiar
role in the immune response are considered.
Perhaps the major barrier to rapid achieverncnt in homotransplanta-
ix