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ADVANCES IN
Immunology
VOLUME 79
This Page Intentionally Left Blank
ADVANCES IN
Immunology
EDITED BY
FRANK J. DIXON
The Scripps Research Institute
La Jolla, California
ASSOCIATE EDITORS
Frederick Alt
K. Frank Austen
Tadamitsu Kishimoto
Fritz Melchers
Jonathan W. Uhr
VOLUME 79
San Diego San Francisco
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Copyright 
C 2001 by ACADEMIC PRESS
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International Standard Serial Number: 0065-2776
International Standard Book Number: 0-12-022479-8
PRINTED IN THE UNITED STATES OF AMERICA
01 02 03 04 05 06 SB 9 8 7 6 5 4 3 2 1
CONTENTS
CONTRIBUTORS ix
Neutralizing Antiviral Antibody Responses
ROLF M. ZINKERNAGEL, ALAIN LAMARRE, ADRIAN CIUREA,
LUKAS HUNZIKER, ADRIAN F. OCHSENBEIN, KATHY D. MCCOY,
THOMAS FEHR, MARTIN F. BACHMANN, ULRICH KALINKE,
AND HANS HENGARTNER
I. Introduction 1
II. Antiviral Antibody Responses 2
III. Mechanisms of Neutralization by Antibodies 6
IV. The Role of Complement, Natural Antibodies, and
Fc-Receptors in Antiviral Responses 9
V. The Role of Antigen Structure, Organization, and Dose on
B Cell Responses 12
VI. T-Cell Dependent Activation of B Cells in Viral Infections 16
VII. B Cell Unresponsiveness 17
VIII. Examples of Nonclassical Virus Neutralization 21
IX. Virus Escape from Neutralizing Antibody Responses 24
X. Immunological Memory 28
XI. Neutralizing Antibodies and Vaccine Strategies 31
XII. Conclusions 34
References 34
Regulation of Interleukin-12 Production in Antigen-Presenting Cells
XIAOJING MA AND GIORGIO TRINCHIERI
I. Introduction 55
II. The Discovery of IL-12 55
III. Molecular Structure of IL-12 56
IV. Biological Functions of IL-12 58
V. Receptors of IL-12 and Signaling 58
VI. Producer Cells of IL-12 59
VII. Pathways of IL-12 Induction 62
VIII. Molecular Regulation of the Expression of IL-12 Genes 66
v
vi CONTENTS
IX. Cytokine-Mediated Regulation of IL-12 Production 73
X. Role of Cell-Surface Receptors in the Regulation
of IL-12 Production 77
XI. Endotoxin-Tolerance-Mediated Inhibition of IL-12 80
XII. Inhibition of IL-12 Production by Anti-inflammatory
Hormones and Small Molecules 80
XIII. Looking to the Future 81
References 82
Mechanisms of Signaling by the Hematopoietic-Specific Adaptor Proteins,
SLP-76 and LAT and Their B Cell Counterpart, BLNK/SLP-65
DEBORAH YABLONSKI AND ARTHUR WEISS
I. The Role of Adaptors in Signaling by ITAM-Coupled Receptors:
An Overview 93
II. Genetic Models Reveal the Essential Roles of SLP-76, LAT,
and BLNK in ITAM-Coupled Signaling Pathways 100
III. Interactions Mediated by LAT, SLP-76, and BLNK and
Their Role in Antigen Receptor Signaling 110
IV. Mechanisms of Signaling by LAT and SLP-76 118
References 121
Xenotransplantation
DAVID H. SACHS, MEGAN SYKES, SIMON C. ROBSON,
AND DAVID K. C. COOPER
I. Introduction 129
II. The Need 129
III. History of Clinical Xenotransplantation 130
IV. Choice of Species 131
V. Mechanisms of Xenograft Rejection 133
VI. Therapeutic Approaches 155
VII. Nonimmunologic Barriers to Xenotransplantation 184
VIII. Future of Xenotransplantation 190
References 192
Regulation of Antibacterial and Antifungal Innate Immunity
in Fruitflies and Humans
MICHAEL J. WILLIAMS
I. Introduction 225
II. Recognition of Foreign Molecules 228
III. Serine Protease Cascades and Thioester-Containing Proteins 235
CONTENTS vii
IV. Induction and Regulation of the Antimicrobial Genes 238
V. Concluding Remarks 249
References 250
Functional Heavy-Chain Antibodies in Camelidae
VIET KHONG NGUYEN, ALINE DESMYTER,
AND SERGE MUYLDERMANS
I. Introduction 261
II. Natural Occurrence of Heavy-Chain Antibodies in Camelidae 261
III. Adaptations in the H Chain 265
IV. The L Chains 269
V. Heavy-Chain Antibody Generation 270
VI. Isolation of Antigen-Specific Heavy-Chain Antibodies, or VHHs 275
VII. VHH Structure and VHH–Antigen Interaction 285
VIII. Biotechnological Importance of VHHs 289
References 290
Uterine Natural Killer Cells in the Pregnant Uterus
CHAU-CHING LIU AND JOHN DING-E YOUNG
I. Immunobiology of Pregnancy: An Overview 297
II. Uterine Natural Killer Cells of Rodents: Granulated Metrial
Gland Cells 299
III. Uterine Natural Killer Cells of Human and Other
Mammalian Species 307
IV. Biological Functions of Uterine Natural Killer Cells
during Pregnancy 310
V. Concluding Remarks 321
References 321
INDEX 331
CONTENTS OF RECENT VOLUMES 341
This Page Intentionally Left Blank
CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors’ contributions begin.
Martin F. Bachmann (1), Institute of Experimental Immunology, Department
of Pathology, University Hospital, CH-8091 Zürich, Switzerland
Adrian Ciurea (1), Institute of Experimental Immunology, Department of
Pathology, University Hospital, CH-8091 Zürich, Switzerland
David K. C. Cooper (129), Transplantation Biology Research Center,
Massachusetts General Hospital/Harvard Medical School, and Department
of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School,
Boston, Massachusetts 02129
Aline Desmyter (261), Vlaams Interuniversitair Instituut voor Biotechnologie,
Vrije Universiteit Brussel, Sint Genesius Rode, 1050 Bruxelles, Belgium
Thomas Fehr (1), Institute of Experimental Immunology, Department of
Pathology, University Hospital, CH-8091 Zürich, Switzerland
Hans Hengartner (1), Institute of Experimental Immunology, Department of
Pathology, University Hospital, CH-8091 Zürich, Switzerland
Lukas Hunziker (1), Institute of Experimental Immunology, Department of
Pathology, University Hospital, CH-8091 Zürich, Switzerland
Ulrich Kalinke (1), Institute of Experimental Immunology, Department of
Pathology, University Hospital, CH-8091 Zürich, Switzerland
Alain Lamarre (1), Institute of Experimental Immunology, Department of
Pathology, University Hospital, CH-8091 Zürich, Switzerland
Chau-Ching Liu (297), Department of Medicine, University of Pittsburgh
School of Medicine, Pittsburgh, Pennsylvania 15213
Xiaojing Ma(55),DepartmentofMicrobiologyandImmunology,WeillMedical
College of Cornell University, New York, New York 10021
Kathy D. McCoy (1), Institute of Experimental Immunology, Department of
Pathology, University Hospital, CH-8091 Zürich, Switzerland
Serge Muyldermans (261), Vlaams Interuniversitair Instituut voor Biotech-
nologie, Vrije Universiteit Brussel, Sint Genesius Rode, 1050 Bruxelles,
Belgium
ix
x CONTRIBUTORS
Viet Khong Nguyen (261), Vlaams Interuniversitair Instituut voor Biotech-
nologie, Vrije Universiteit Brussel, Sint Genesius Rode, 1050 Bruxelles,
Belgium
Adrian F. Ochsenbein (1), Institute of Experimental Immunology, Depart-
ment of Pathology, University Hospital, CH-8091 Zürich, Switzerland
Simon C. Robson (129), Transplantation Biology Research Center, Massachu-
settsGeneralHospital/HarvardMedicalSchool,andDepartmentofMedicine,
Beth Israel Deaconess Medical Center/Harvard Medical School, Boston,
Massachusetts 02129
David H. Sachs(129),TransplantationBiologyResearchCenter,Massachusetts
General Hospital/Harvard Medical School, and Department of Medicine,
Beth Israel Deaconess Medical Center/Harvard Medical School, Boston,
Massachusetts 02129
Megan Sykes (129), Transplantation Biology Research Center, Massachusetts
General Hospital/Harvard Medical School, and Department of Medicine,
Beth Israel Deaconess Medical Center/Harvard Medical School, Boston,
Massachusetts 02129
Giorgio Trinchieri (55), Schering-Plough Laboratory of Immunological Re-
search, 69571 Dardilly, France
Arthur Weiss (93), Departments of Medicine and of Microbiology and
Immunology, and the Howard Hughes Medical Institute, University of
California, San Francisco, California 94143
Michael J. Williams (225), Umeå Centre for Molecular Pathogenesis, Umeå
University, S-901 87 Umeå, Sweden
Deborah Yablonski (93), Department of Pharmacology, Rappaport Faculty of
Medicine, Technion-Israel Institute of Technology, Bat Galim, Haifa 31096,
Israel
John Ding-E Young (297), Laboratory of Cellular Physiology and Immunology,
The Rockefeller University, New York, New York 10021
Rolf M. Zinkernagel (1), Institute of Experimental Immunology, Department
of Pathology, University Hospital, CH-8091 Zürich, Switzerland
ADVANCES IN IMMUNOLOGY, VOL. 79
Neutralizing Antiviral Antibody Responses
ROLF M. ZINKERNAGEL,1 ALAIN LaMARRE,1 ADRIAN CIUREA, LUKAS HUNZIKER,
ADRIAN F. OCHSENBEIN, KATHY D. McCOY, THOMAS FEHR, MARTIN F. BACHMANN,
ULRICH KALINKE, AND HANS HENGARTNER
Institute of Experimental Immunology, Department of Pathology,
University Hospital, CH-8091 Zürich, Switzerland
I. Introduction
Antibody responses have been studied in infectious diseases, particularly
against toxins isolated from pathogenic bacteria. Indeed, antibody quality re-
quirements for protection against diphtheria toxin were among the first to be
elucidated (Von Behring and Kitasao, 1890; Ehrlich, 1906; Jerne, 1951). How-
ever, the inability to purify these toxins and the complexity of the biological
material forced immunologists to use chemically pure substances in order to
quantitatively study antigens and their reactions with antibodies (Evans, 1943).
Therefore, immunochemists used haptens, usually small phenyl groups, that
were easily synthesized in various configurations and could be linked to large
proteins (Heidelberger, 1956; Eisen and Siskind, 1964). Because of their small
size they could pass through the then-available dialysis bags to measure physico-
chemical parameters of antibody/antigen interactions and define binding affini-
ties and specificities. Only recently has it become possible to express and pu-
rify biological substances sufficiently not only to repeat some of these analyses
in vitro but also to correlate such measurements with protection against disease
in vivo (Fazekas de St. Groth and Webster, 1961; Staudt and Gerhard, 1983;
Webster and Rott, 1987; Laver et al., 1990; Bachmann et al., 1997b).
Individuals with defective antibody responses, such as patients with Bruton’s
disease or other antibody defects, are more susceptible to infections (Wilfert
et al., 1977; Graham et al., 1983; Englund et al., 1998), as are mice devoid of
B cells, such as the μMT mouse (Good and Zak, 1956; Kitamura et al., 1991;
Bründler et al., 1996). Protective or neutralizing antibody responses, particularly
against acute cytopathic agents, are among the most critical defense mechanisms
(Sabin, 1981; Steinhoff et al., 1995; Zinkernagel et al., 1996). These responses
represent the result of a long co-evolution between the host and various infec-
tious agents. However, because of the shorter generation time and greater num-
bers, adaptation of infectious agents is considerably faster than that of the host.
This review attempts to summarize from an evolutionary point of view evidence
that neutralizing antibodies (nAbs) are key to protecting the species against many
viruses, particularly cytopathic ones. Such viruses have the potential to upset
1 These authors contributed equally to this work.
1
Copyright 
C 2001 by Academic Press.
All rights of reproduction in any form reserved.
0065-2776/01 $35.00
2 ROLF M. ZINKERNAGEL ET AL.
the balance between host and pathogen; therefore, an equilibrium must have
evolved to enable the survival of both. This balance is maintained by the ability
of the host to mount rapid neutralizing antibody responses which is achieved by
directly encoding virus-specific neutralizing antibodies in the germline. Thus, it
is mandatory to assess the protective capacity of antibodies by in vivo adoptive
transfer experiments or by in vitro neutralization assays, rather than measuring
antigen binding in an enzyme-linked immunosorbent assay (ELISA).
Interestingly, although not surprisingly, there is a certain geography of the
antibody response: local IgA in the mucosa, systemic short-lived IgM and long-
lived IgG in blood. In addition, antibodies not only neutralize viruses and thereby
prevent infection but also trap virus in the spleen and prevent it from reaching
the blood. They thereby enhance immune responses in general and B cell re-
sponses in particular. This review also presents evidence that, in general, B cells
are not negatively selected and are largely regulated by antigen structure and
availability of cognate T help. We also review evidence supporting the notion
that B cell memory, in the form of high neutralizing antibody serum levels, is
the main contributor to immunological memory. Finally, both general and spe-
cific examples of neutralizing antibody responses are used to illustrate rules that
govern B cell responses. These rules are also discussed with respect to their role
in autoimmunity and how they can be exploited for vaccines.
II. Antiviral Antibody Responses
During their development in the bone marrow, B cell precursors undergo
sequential recombination-activating gene (RAG)-mediated rearrangements of
D to J and V to DJ elements of the immunoglobulin (Ig) heavy-chain variable
region (VH) and V to J elements of the Ig light-chain variable region (VL) (Tone-
gawa, 1983). Expression of functional Ig heavy and light chains promotes the
transition of precursor B cells to small IgM/IgD-positive mature B cells. Au-
toreactive antibody specificities generated by random rearrangement are either
deleted(NemazeeandBuerki,1989;NemazeeandBuerki,1989;Nemazee etal.,
1991; Hartley et al., 1993) or edited by secondary VL and possibly VH replace-
ments (Gay et al., 1993; Radic et al., 1993; Tiegs et al., 1993; Chen et al., 1995,
1997; Lang et al., 1996; Pelanda et al., 1997; Fang et al., 1998; Nemazee, 2000).
B cells that emigrate from the bone marrow and populate secondary lymphoid
organs constitute the primary B cell repertoire. The restricted number of V, D,
and J gene segments that can be encoded in the genome limits the size of the po-
tential repertoire. However, diversity of the preimmune repertoire of mice and
humans can be further expanded by hypermutation, whereas other species, such
as rabbits, sheep, pigs, and cattle, use gene conversion (Diaz and Flajnik, 1998).
It has recently been suggested that, together with hypermutation, secondary
Ig gene rearrangements may also contribute to repertoire diversification (Han
NEUTRALIZING ANTIVIRAL ANTIBODY RESPONSES 3
et al., 1997; Papavasiliou et al., 1997; Pelanda et al., 1997; Hertz et al., 1998;
Meffre et al., 1998; Lopez-Macias et al., 1999; Wilson et al., 2000b). However,
whether this considerably slower process confers a survival advantage to the host
remains to be formally demonstrated.
A. V(D)J REARRANGEMENTS IN ANTIVIRAL ANTIBODIES
The primary repertoire of vesicular stomatitis virus (VSV)-specific antibodies
was analyzed by isolating hybridomas 4 and 5 days after infection (Kalinke et al.,
1996a). Surprisingly, 87% of clones analyzed used V genes belonging to the
VHQ52 and Vκ19–28 families. Despite their polyclonal origin, the majority of
these clones expressed identical VH and VL germline segments. Because all
these antibodies failed to bind and neutralize the 51.12 VSV variant (which was
selected in the presence of one particular VHQ52/Vκ19–28-positive antibody),
they all appear to bind to the same subsite within the major antigenic site of
the glycoprotein of VSV (VSV-G). Analysis of the primary response to influenza
virus also revealed a restricted Vκ usage, with the predominance of a segment
belonging to the Vκ8 gene family (Clarke et al., 1990b). In contrast, the heavy-
chain variable region genes displayed much greater diversity, with several VH
families being used.
In contrast to primary response antibodies, hybridomas isolated from sec-
ondary and hyperimmune anti-VSV responses expressed a more diverse set of
V genes belonging to the VHJ558, VH7183, and VHQ52 families (Kalinke et al.,
1996a). The majority of these antibodies were shown to bind a different sub-
site of the major antigenic site of VSV-G than the primary response antibodies.
Thus, fine specificity diversification of secondary and hyperimmune responses
was achieved by newly appearing V gene combinations. Similar findings were ob-
tained from analysis of the secondary response to influenza virus where V region
usage differed considerably from the primary response (Clarke et al., 1990a).
B. THE ROLE OF HYPERMUTATION IN THE GENERATION
OF VIRUS-NEUTRALIZING ANTIBODIES
Interestingly, all anti-VSV mAbs isolated up to day 6 post infection, irrespec-
tive of which genetic elements they express, were devoid of somatic hypermu-
tation (Kalinke et al., 1996a). This indicates the presence of VSV specificities
in the mouse germline antibody repertoire. This was confirmed by the isolation
of VSV-neutralizing antibody fragments from phage display libraries generated
from naive mice (A. Lamarre, unpublished results). These findings are remark-
able because VSV is a new-world virus of ruminants while Mus musculus is an
old-world rodent. Therefore, the presence of VSV-specific, high-affinity antibod-
ies in the germline cannot be a result of recent co-evolution; instead, this suggests
that, in general, cytopathic viruses have been selected to fit the available antibody
repertoire rather than vice versa (Roost et al., 1995; Bachmann et al., 1997b).
4 ROLF M. ZINKERNAGEL ET AL.
Similarly, anti-influenza primary response antibodies were largely devoid of
somatic mutations (Clarke et al., 1990b). In contrast to primary antibodies,
secondary and hyperimmune mAbs did display hypermutations (Clarke et al.,
1990b; Kalinke et al., 1996a). Nevertheless, as with the primary VHQ52/Vκ19–28-
positive antibodies, hypermutated anti-VSV antibodies were not able to neu-
tralize the virus variant 51.12. However, compared to the germline antibodies,
hypermutated antibodies had approximately a 50-fold increase in their ability
to neutralize wild-type VSV (Kalinke et al., 1996a). Therefore, hypermutation
did not alter antibody specificity, as far as can be judged by binding competition
assays, but it did improve binding quality and neutralizing capacity.
To verify these conclusions, another more heterogeneous group of VSV-
neutralizing antibodies typical of secondary and hyperimmune responses was
analyzed (Kalinke et al., 2000). Although these antibodies expressed numerous
different light chains, they all used the same VH germline segment belonging to
the VH7183 family in combination with the JH2 segment. Again, all hyperimmune
antibodies contained hypermutations. Despite most of the hypermutated anti-
bodies not being clonally related, some of them showed the same single somatic
amino acid substitutions in CDR1 and CDR2. Because no virus variant resistant
to neutralization by all VH7183/JH2-positive antibodies could be generated, they
apparently bound different subsites within the major antigenic site of VSV-G.
To analyze the impact of the common amino acid substitutions on virus bind-
ing and neutralization, the secondary response antibody VI24 of the VH7183/JH2
group was expressed as a monovalent, recombinant, single-chain antibody con-
sisting of the Vκ and VH regions linked to a Cκ domain (Kalinke et al., 2000). This
antibody fragment expressed four somatic amino acid exchanges in VH, whereas
VL was germline. The antibody fragment was mutated back to a germline con-
figuration and mutations were introduced in VH encoding for one or both of
the common amino acid substitutions in CDR1 and CDR2. The binding of the
hypermutated VI24 antibody fragment was about 50- to 100-fold better than
the germline antibody fragment. Expression of the CDR2 amino acid substitu-
tion alone improved binding by about 10-fold, whereas the CDR1 substitution
did not affect binding. Antibody fragments were dimerized using an anti-Cκ
antibody. Dimerization of the VI24 antibody fragment did not improve its bind-
ing, whereas binding of the dimerized germline antibody fragment improved by
more than 10-fold. Thus, avidity effects did not contribute to the binding of the
hypermutated antibody, whereas they seemed to have a major impact on the
binding of the germline antibody fragment.
Analysis of the second group of antibodies confirmed the previous observa-
tion that hypermutation was no prerequisite for virus neutralization. However,
hypermutation improved the binding and the neutralization of VSV in vitro up
to a level where avidity effects do not seem to further contribute to the quality
of antibody binding.
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Has had an immense sale.
THE MODEL SUNDAY-SCHOOL SPEAKER. Containing
selections in prose and verse, from the most popular
pieces and dialogues for Sunday-school exhibitions.
Illust. Cloth. 75 cents. Boards, 50 cents A book very
much needed.
LEE AND SHEPARD Publishers Boston
Baker's Dialect Series
MEDLEY DIALECT
RECITATIONS
COMPRISING A SERIES OF
THE MOST POPULAR SELECTIONS
In German, French, and Scotch
EDITED BY
GEORGE M. BAKER
COMPILER OF THE READING CLUB AND HANDY SPEAKER,
THE PREMIUM SPEAKER, THE POPULAR SPEAKER, THE
PRIZE SPEAKER, THE HANDY SPEAKER, ETC.
BOSTON
LEE AND SHEPARD, PUBLISHERS
NEW YORK
CHARLES T. DILLINGHAM
1888
Copyright, 1887,
By GEORGE M. BAKER.
Medley Dialect Recitations.
RAND AVERY COMPANY,
ELECTROTYPERS AND PRINTERS,
BOSTON.
CONTENTS
PAGE
Hans Breitmann's Party Charles G. Leland 5
The Deutsch Maud Muller Carl Pretzel 6
The Dutchman's Serenade 7
Dyin' Vords of Isaac Anon. 9
Lookout Mountain, 1863—
Beutelsbach, 1880
George L. Catlin 10
Der Shoemaker's Poy 12
Der Drummer Charles F. Adams 13
The Yankee and the Dutchman's
Dog
14
Setting a Hen 16
What's the Matter with that
Nose?
Our Fat Contributor 17
Keepin' the De'il oot Mrs. Findley Braden 19
The Puzzled Census-Taker John G. Saxe 22
Dutch Security 23
The Frenchman and the Rats 24
Heinz von Stein
Charles G. Leland, from the
German
26
The Solemn Book-Agent Detroit Free Press 27
The Mother-in-Law Charles Follen Adams 28
Schneider's Tomatoes Charles F. Adams 29
Dutch Humor 30
Squire Houston's Marriage
Ceremony
31
Dot Delephone 31
The United Order of Half-Shells 33
Why no Scotchmen go to Heaven 35
Yawcob Strauss C. F. Adams 36
Leedle Yawcob Strauss—what he
says
Arthur Dakin 37
Isaac Rosenthal on the Chinese
Question
Scribner's Monthly 38
Question
Der Dog und der Lobster Saul Sertrew 39
Der Wreck of der Hezberus 41
Signs and Omens 43
A Dutchman's Answer 44
The Vay Rube Hoffenstein sells 45
A Dutch Recruiting Officer 46
Dot Baby off Mine 47
Dot Leetle Tog under der Vagon 49
Schnitzerl's Velocipede Hans Breitmann 50
The Latest Barbarie Frietchie 51
Mr. Hoffenstein's Bugle 52
Fritz and his Betsy fall out George M. Warren 54
Cut, Cut Behind Charles Follen Adams 57
Tickled all Oafer 58
An Error o' Judgment 59
Sockery Kadahcut's Kat 61
I vash so Glad I vash Here! 63
Dot Shly Leedle Raskel 64
A Jew's Trouble Hurwood 65
Der Mule shtood on der
Steamboad Deck
Anon. 66
Teaching him the Business 67
Der Good-lookin Shnow 69
How Jake Schneider went Blind 71
The Dutchman and the Raven 72
The Dutchman who gave Mrs.
Scudder the Small-Pox
74
Ellen McJones Aberdeen W. S. Gilbert 76
A Dutch Sermon 78
Shacob's Lament 79
Mr. Schmidt's Mistake Charles F. Adams 81
John and Tibbie Davison's
Dispute
Robert Leighton 82
Fritz und I Charles F. Adams 84
A Tussle with Immigrants Philip Douglass 86
A Doketor's Drubbles George M. Warren 86
Charlie Machree William J. Hoppin 90
A Dutchman's Dolly Varden Anon. 91
The Frenchmen and the Flea-
Powder
92
The Frenchman and the Sheep's
Trotters
94
I vant to Fly 96
The Frenchman's Mistake 98
Two Tollar? Detroit Free Press 100
A Frenchman on Macbeth Anon. 101
Like Mother used to Make
James Whitcomb Riley, in
New-York Mercury
101
John Chinaman's Protest 102
The Whistler 104
Mother's Doughnuts Charles Follen Adams 105
Over the Left W. C. Dornin 106
A Jolly Fat Friar 107
The Enoch of Calaveras F. Bret Harte 107
Curly-Head B. S. Brooks 109
Warning to Woman 111
An Exciting Contest 112
A Laughing Philosopher 114
In der Shweed Long Ago Oofty Gooft 117
Dot Stupporn Pony Harry Woodson 118
Spoopendyke opening Oysters Stanley Huntley 119
To a Friend studying German Charles Godfrey Leland 122
Tammy's Prize 124
The Scotchman at the Play 128
An Irish Love-Letter Geo. M. Baker 133
MEDLEY DIALECT RECITATIONS.
HANS BREITMANN'S PARTY.
Hans Breitmann gife a party: dey had piano playin'.
I felled in lofe mit a Merican frau; her name vos Matilda Yane.
She had haar as prown as a pretzel bun; her eyes were himmel-
blue;
And ven she looket into mine she shplit mine heart into two.
Hans Breitmann gife a party: I vent dar, you'll be pound.
I valzt mit der Matilda Yane, and vent shpinnin' round and round,—
De pootiest fraulein in de house: she weighed two hoondert pound.
Hans Breitmann gife a party: I tells you it cost him dear.
Dey rollt in more as seven kegs of foost-rate lager-bier;
And fenefer dey knocks de shpickets in, de Deutschers gife a cheer;
I dinks so fine a party not come to a hend dis year.
Hans Breitmann gife a party: dere all vas Saus and Braus.
Ven de sooper coom in, de gompany did make demselfs to house;
Dey eat das Brod und Gansebrust, Bratwurst, und Broten fine,
And vash deir Abendessen down mit four barrels of Neckar wein.
Hans Breitmann gife a party: ve all cot trunk as pigs.
I put mine mout' to a parrel of bier, and schwallowed up mit a
schwigs.
And den I kissed Matilda Yane, and she schlog me on de kop;
And de gompany fight mit taple-legs till de conshtoble made us
shtop.
Hans Breitmann gife a party: vere is dat party now?
Vere is de lofely golten cloud dat float on de mountain's prow?
Vere is de Himmelstrahlende Stern, de star of de spirits' light?
All goned afay mit de lager-bier, afay in de Ewigkeit.
Charles G. Leland.
THE DEUTSCH MAUD MULLER.
Maud Muller, von summer afternoon,
Vas dending bar in her fadder's saloon.
She solt dot bier, und singed Shoo Fly,
Und vinked at der men mit her lefd eye.
But, ven she looked oud on der shdreed,
Und saw dem gals all dressed so shweed,
Her song gifed oud on a ubber note,
Cause she had such a horse in her troat;
Und she vished she had shdamps to shpend,
So she might git such a Grecian Bend.
Hans Brinker valked shlowly down der shdreed,
Shmilin at all der gals he'd meed.
Old Hans vas rich, as I've been dold,
Had houses und lots und a barrel of gold.
He shdopped py der door; und pooty soon
He valked righd indo dot bier saloon.
Und he vinked ad Maud, und said, My dear,
Gif me, if you pblease, a glass of bier.
She vend to the pblace vere der bier-keg shtood,
Und pringed him a glass dot vas fresh and goot.
Dot's goot, said Hans: dot's a better drink
As effer I had in mine life, I dink.
He dalked for a vhile, den said, Goot tay;
Und up der shdreed he took his vay.
Maud hofed a sigh, and said, Oh, how
I'd like to been dot old man's frow!
Such shplendid close I den vood vear,
Dot all the gals around vood shdare.
In dot Union Park I'd drive all tay,
Und efery efenin go to der pblay.
Hans Brinker, doo, felt almighty gweer
(But dot might been von trinkin bier);
Und he says to himself, as he valked along
Humming der dune of a olt lofe-song,
Dot's der finest gal I efer did see;
Und I vish dot my vife she cood be.
But here his solilligwy came to an end,
As he dinked of der gold dot she might shbend;
Und he maked up his mind dot, as for him,
He'd marry a gal mid lots of din.
So he vent right off dot fery day,
Und married a vooman olt und gray.
He vishes now, but all in vain,
Dot he was free to marry again,—
Free as he vas dat afdernoon,
When he met Maud Muller in dot bier-saloon.
Maud married a man mitoud some soap;
He vas lazy, too; bud she did hope
Dot he'd get bedder ven shildren came:
But ven they had, he vas yoost the same.
Und ofden now dem dears vill come
As she sits alone ven her day's work's done,
Und dinks of der day ven Hans called her My dear,
Und asked her for a glass of bier;
But she don'd complain nor efer has:
Und oney says, Dot coodn't vas.
Carl Pretzel.
THE DUTCHMAN'S SERENADE.
Vake up, my schveet! Vake up, my lofe!
Der moon dot can't been seen abofe.
Vake oud your eyes, und dough it's late,
I'll make you oud a serenate.
Der shtreet dot's kinder dampy vet,
Und dhere vas no goot blace to set;
My fiddle's getting oud of dune,
So blease get vakey wery soon.
O my lofe! my lofely lofe!
Am you avake ub dhere abofe,
Feeling sad und nice to hear
Schneider's fiddle schrabin near?
Vell, anyvay, obe loose your ear,
Und try to saw if you kin hear
From dem bedclose vat you'm among,
Der little song I'm going to sung:
* * * * *
O lady, vake! Get vake!
Und hear der tale I'll tell;
Oh, you vot's schleebin' sound ub dhere,
I like you pooty vell!
Your plack eyes dhem don't shine
Ven you'm ashleep—so vake!
(Yes, hurry up, und voke up quick,
For gootness cracious sake!)
My schveet imbatience, lofe,
I hobe you vill oxcuse:
I'm singing schveetly (dhere, py Jinks!
Dhere goes a shtring proke loose!)
O putiful, schveet maid!
Oh, vill she efer voke?
Der moon is mooning—(Jimminy! dhere
Anoder shtring vent proke!)
Oh, say, old schleeby head!
(Now I vas getting mad—
I'll holler now, und I don't care
Uf I vake up her dad!)
I say, you schleeby, vake!
Vake oud! Vake loose! Vake ub!
Fire! Murder! Police! Vatch!
Oh, cracious! do vake ub!
* * * * *
Dot girl she schleebed—dot rain it rained,
Und I looked shtoopid like a fool,
Vhen mit my fiddle I shneaked off
So vet und shlobby like a mool!
DYIN' VORDS OF ISAAC.
Vhen Shicago vas a leedle villages, dher lifed dherein py dot Clark
Sdhreet out, a shentlemans who got some names like Isaacs; he
geeb a cloting store, mit goots dot vit you yoost der same like dhey
vas made. Isaacs vas a goot fellers, und makes goot pishness on his
hause. Vell, thrade got besser as der time he vas come, und dose
leetle shtore vas not so pig enuff like anudder shtore, und pooty
gwick he locks out und leaves der pblace.
Now Yacob Schloffenheimer vas a shmard feller; und he dinks of he
dook der olt shtore, he got good pishness, und dose olt coostomers
von Isaac out. Von tay dhere comes a shentlemans on his store, und
Yacob quick say of der mans, How you vas, mein freund? you like to
look of mine goots, aind it?—Nein, der mans say. Vell, mein
freund, it makes me notting troubles to show dot goots.—Nein; I
don'd vood buy sometings to-tay.—Yoost come mit me vonce, mein
freund, und I show you sometings, und so hellup me gracious, I
don'd ask you to buy dot goots.—Vell, I told you vat it vas, I don'd
vood look at some tings yoost now; I keebs a livery shtable; und I
likes to see mein old freund Mister Isaacs, und I came von Kaintucky
out to see him vonce.—Mister Isaacs? Vell, dot ish pad; I vas sorry
von dot. I dells you, mein freund, Mister Isaacs he vas died. He vas
mein brudder, und he vas not mit us eny more. Yoost vhen he vas on
his deat-ped, und vas dyin', he says of me, 'Yacob, (dot ish mine
names), und I goes me ofer mit his petside, und he poods his hands
of mine, und he says of me, 'Yacob' ofer a man he shall come von
Kaintucky out, mit ret hair, und mit plue eyes, Yacob, sell him dings
cheab;' und he lay ofer und died his last.
Anonymous.
LOOKOUT MOUNTAIN, 1863—
BEUTELSBACH, 1880.
Yah, I shpeaks English a leetle: berhaps you shpeaks petter der
German.
No, not a word.—Vel den, meester, it hardt for to be
oonderstandt.
I vos drei yahr in your country, I fights in der army mit Sherman—
Twentiet Illinois Infantry—Fightin' Joe Hooker's commandt.
So you've seen service in Georgia—a veteran, eh?—Vell, I tell you
Shust how it vos. I vent ofer in sixty, und landt in Nei-York;
I sphends all mine money, gets sick, und near dies in der Hospiddal
Bellevue:
Ven I gets petter I tramps to Sheecago to look for some vork.
Pretty young then, I suppose?—Yah, svansig apout; und der
peobles
Vot I goes to for to ask for some vork, dey hafe none for to geef;
Efery von laughs; but I holds my head ope shust so high as der
steeples.
Only dot var comes along, or I should have die, I belief.
Ever get wounded? I notice you walk rather lame and unsteady.
Pshaw! got a wooden leg, eh? What battle? At Lookout! don't say!
I was there too—wait a minute—your beer-glass is empty already
Call for another. There! tell me how 'twas you got wounded that
day.
Vell, ve charge ope der side of her mountain—der sky vos all smoky
and hazy;
Ve fight all day long in der clouds, but I nefer get hit until night—
But—I don't care to say mooch apout it. Der poys called me foolish
and crazy.
Und der doctor vot cut ofe my leg, he say, 'Goot'—dot it serf me
shust right.
But I dinks I vood do dot thing over again, shust der same, and no
matter
Vot any man say.—Well, let's hear it—you needn't mind talking to
me,
For I was there, too, as I tell you—and Lor'! how the bullets did
patter
Around on that breastwork of boulders that sheltered our Tenth
Tennessee.
So? Dot vos a Tennessee regiment charged upon ours in de
efening,
Shust before dark; und dey yell as dey charge, und ve geef a hurrah,
Der roar of der guns, it vos orful.—Ah! yes, I remember, 'twas
deafening,
The hottest musketry firing that ever our regiment saw.
Und after ve drove dem back, und der night come on, I listen,
Und dinks dot I hear somepody a callin'—a voice dot cried,
'Pring me some vater for Gott's sake'—I saw his pelt-bate glisten,
Oonder der moonlight, on der parapet, shust outside.
I dhrow my canteen ofer to vere he lie, but he answer
Dot his left handt vos gone, und his right arm proke mit a fall;
Den I shump ofer, und gife him to drink, but shust as I ran, sir,
Bang! come a sharp-shooter's pullet; und dot's how it vos—dot is
all.
And they called you foolish and crazy, did they? Him you befriended
—
The 'reb,' I mean—what became of him? Did he ever come 'round?
Dey tell me he crawl to my side, und call till his strength vos all
ended,
Until dey come out mit der stretchers, und carry us off from der
ground.
But pefore ve go, he ask me my name, und says he, 'Yacob Keller,
You loses your leg for me, und some day, if both of us leefs,
I shows you I don't vorget'—but he most hafe died, de poor feller;
I nefer hear ofe him since. He don't get vell, I beliefs.
e e ea o e s ce e do t get e , be e s
Only I alvays got der saddisfachshun ofe knowin'—
Shtop! vots der matter? Here, take some peer, you're vite as a sheet
—
Shteady! your handt on my shoulder! my gootness! I dinks you vos
goin'
To lose your senses avay, und fall right off mit der seat.
Geef me your handts. Vot! der left one gone? Und you vos a soldier
In dot same battle?—a Tennessee regiment?—dot's mighty queer—
Berhaps after all you're— Yes, Yacob, God bless you old fellow, I
told you
I'd never—no, never forget you. I told you I'd come, and I'm here.
George L. Catlin.
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Advances in Immunology 79 1st Edition Frank J. Dixon

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    Practical Immunology 4thEdition Frank C. Hay https://ebookultra.com/download/practical-immunology-4th-edition- frank-c-hay/ Advances in Immunology 92 1st Edition Frederick W. Alt (Eds.) https://ebookultra.com/download/advances-in-immunology-92-1st-edition- frederick-w-alt-eds/ Textile Advances in the Automotive Industry Woodhead Publishing in Textiles Number 79 1st Edition Roshan Shishoo https://ebookultra.com/download/textile-advances-in-the-automotive- industry-woodhead-publishing-in-textiles-number-79-1st-edition-roshan- shishoo/ Advances in Immunology Volume 108 1st Edition Frederick W. Alt (Ed.) https://ebookultra.com/download/advances-in-immunology-volume-108-1st- edition-frederick-w-alt-ed/ Advances in Immunology Volume 121 1st Edition Frederick W. Alt (Eds.) https://ebookultra.com/download/advances-in-immunology-volume-121-1st- edition-frederick-w-alt-eds/
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    Advances in Immunology79 1st Edition Frank J. Dixon Digital Instant Download Author(s): Frank J. Dixon ISBN(s): 9780120224791, 0120224798 Edition: 1 File Details: PDF, 2.76 MB Year: 2001 Language: english
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    ADVANCES IN Immunology EDITED BY FRANKJ. DIXON The Scripps Research Institute La Jolla, California ASSOCIATE EDITORS Frederick Alt K. Frank Austen Tadamitsu Kishimoto Fritz Melchers Jonathan W. Uhr VOLUME 79 San Diego San Francisco New York Boston London Sydney Tokyo
  • 10.
    This book isprinted on acid-free paper. ∞ Copyright C 2001 by ACADEMIC PRESS All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the Publisher. The appearance of the code at the bottom of the first page of a chapter in this book indicates the Publisher’s consent that copies of the chapter may be made for personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc. (222 Rosewood Drive, Danvers, Massachusetts 01923), for copying beyond that permitted by Sections 107 or 108 of the U.S. Copyright Law. This consent does not extend to other kinds of copying, such as copying for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. Copy fees for pre-2001 chapters are as shown on the title pages. If no fee code appears on the title page, the copy fee is the same as for current chapters. 0065-2776/01 $35.00 Explicit permission from Academic Press is not required to reproduce a maximum of two figures or tables from an Academic Press chapter in another scientific or research publication provided that the material has not been credited to another source and that full credit to the Academic Press chapter is given. Academic Press A division of Harcourt Inc. 525 B Street, Suite 1900, San Diego, California 92101-4495, USA http://www.academicpress.com Academic Press Harcourt Place, 32 Jamestown Road, London NW1 7BY, UK http://www.academicpress.com International Standard Serial Number: 0065-2776 International Standard Book Number: 0-12-022479-8 PRINTED IN THE UNITED STATES OF AMERICA 01 02 03 04 05 06 SB 9 8 7 6 5 4 3 2 1
  • 11.
    CONTENTS CONTRIBUTORS ix Neutralizing AntiviralAntibody Responses ROLF M. ZINKERNAGEL, ALAIN LAMARRE, ADRIAN CIUREA, LUKAS HUNZIKER, ADRIAN F. OCHSENBEIN, KATHY D. MCCOY, THOMAS FEHR, MARTIN F. BACHMANN, ULRICH KALINKE, AND HANS HENGARTNER I. Introduction 1 II. Antiviral Antibody Responses 2 III. Mechanisms of Neutralization by Antibodies 6 IV. The Role of Complement, Natural Antibodies, and Fc-Receptors in Antiviral Responses 9 V. The Role of Antigen Structure, Organization, and Dose on B Cell Responses 12 VI. T-Cell Dependent Activation of B Cells in Viral Infections 16 VII. B Cell Unresponsiveness 17 VIII. Examples of Nonclassical Virus Neutralization 21 IX. Virus Escape from Neutralizing Antibody Responses 24 X. Immunological Memory 28 XI. Neutralizing Antibodies and Vaccine Strategies 31 XII. Conclusions 34 References 34 Regulation of Interleukin-12 Production in Antigen-Presenting Cells XIAOJING MA AND GIORGIO TRINCHIERI I. Introduction 55 II. The Discovery of IL-12 55 III. Molecular Structure of IL-12 56 IV. Biological Functions of IL-12 58 V. Receptors of IL-12 and Signaling 58 VI. Producer Cells of IL-12 59 VII. Pathways of IL-12 Induction 62 VIII. Molecular Regulation of the Expression of IL-12 Genes 66 v
  • 12.
    vi CONTENTS IX. Cytokine-MediatedRegulation of IL-12 Production 73 X. Role of Cell-Surface Receptors in the Regulation of IL-12 Production 77 XI. Endotoxin-Tolerance-Mediated Inhibition of IL-12 80 XII. Inhibition of IL-12 Production by Anti-inflammatory Hormones and Small Molecules 80 XIII. Looking to the Future 81 References 82 Mechanisms of Signaling by the Hematopoietic-Specific Adaptor Proteins, SLP-76 and LAT and Their B Cell Counterpart, BLNK/SLP-65 DEBORAH YABLONSKI AND ARTHUR WEISS I. The Role of Adaptors in Signaling by ITAM-Coupled Receptors: An Overview 93 II. Genetic Models Reveal the Essential Roles of SLP-76, LAT, and BLNK in ITAM-Coupled Signaling Pathways 100 III. Interactions Mediated by LAT, SLP-76, and BLNK and Their Role in Antigen Receptor Signaling 110 IV. Mechanisms of Signaling by LAT and SLP-76 118 References 121 Xenotransplantation DAVID H. SACHS, MEGAN SYKES, SIMON C. ROBSON, AND DAVID K. C. COOPER I. Introduction 129 II. The Need 129 III. History of Clinical Xenotransplantation 130 IV. Choice of Species 131 V. Mechanisms of Xenograft Rejection 133 VI. Therapeutic Approaches 155 VII. Nonimmunologic Barriers to Xenotransplantation 184 VIII. Future of Xenotransplantation 190 References 192 Regulation of Antibacterial and Antifungal Innate Immunity in Fruitflies and Humans MICHAEL J. WILLIAMS I. Introduction 225 II. Recognition of Foreign Molecules 228 III. Serine Protease Cascades and Thioester-Containing Proteins 235
  • 13.
    CONTENTS vii IV. Inductionand Regulation of the Antimicrobial Genes 238 V. Concluding Remarks 249 References 250 Functional Heavy-Chain Antibodies in Camelidae VIET KHONG NGUYEN, ALINE DESMYTER, AND SERGE MUYLDERMANS I. Introduction 261 II. Natural Occurrence of Heavy-Chain Antibodies in Camelidae 261 III. Adaptations in the H Chain 265 IV. The L Chains 269 V. Heavy-Chain Antibody Generation 270 VI. Isolation of Antigen-Specific Heavy-Chain Antibodies, or VHHs 275 VII. VHH Structure and VHH–Antigen Interaction 285 VIII. Biotechnological Importance of VHHs 289 References 290 Uterine Natural Killer Cells in the Pregnant Uterus CHAU-CHING LIU AND JOHN DING-E YOUNG I. Immunobiology of Pregnancy: An Overview 297 II. Uterine Natural Killer Cells of Rodents: Granulated Metrial Gland Cells 299 III. Uterine Natural Killer Cells of Human and Other Mammalian Species 307 IV. Biological Functions of Uterine Natural Killer Cells during Pregnancy 310 V. Concluding Remarks 321 References 321 INDEX 331 CONTENTS OF RECENT VOLUMES 341
  • 14.
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    CONTRIBUTORS Numbers in parenthesesindicate the pages on which the authors’ contributions begin. Martin F. Bachmann (1), Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland Adrian Ciurea (1), Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland David K. C. Cooper (129), Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, and Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02129 Aline Desmyter (261), Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Sint Genesius Rode, 1050 Bruxelles, Belgium Thomas Fehr (1), Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland Hans Hengartner (1), Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland Lukas Hunziker (1), Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland Ulrich Kalinke (1), Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland Alain Lamarre (1), Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland Chau-Ching Liu (297), Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213 Xiaojing Ma(55),DepartmentofMicrobiologyandImmunology,WeillMedical College of Cornell University, New York, New York 10021 Kathy D. McCoy (1), Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland Serge Muyldermans (261), Vlaams Interuniversitair Instituut voor Biotech- nologie, Vrije Universiteit Brussel, Sint Genesius Rode, 1050 Bruxelles, Belgium ix
  • 16.
    x CONTRIBUTORS Viet KhongNguyen (261), Vlaams Interuniversitair Instituut voor Biotech- nologie, Vrije Universiteit Brussel, Sint Genesius Rode, 1050 Bruxelles, Belgium Adrian F. Ochsenbein (1), Institute of Experimental Immunology, Depart- ment of Pathology, University Hospital, CH-8091 Zürich, Switzerland Simon C. Robson (129), Transplantation Biology Research Center, Massachu- settsGeneralHospital/HarvardMedicalSchool,andDepartmentofMedicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02129 David H. Sachs(129),TransplantationBiologyResearchCenter,Massachusetts General Hospital/Harvard Medical School, and Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02129 Megan Sykes (129), Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, and Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02129 Giorgio Trinchieri (55), Schering-Plough Laboratory of Immunological Re- search, 69571 Dardilly, France Arthur Weiss (93), Departments of Medicine and of Microbiology and Immunology, and the Howard Hughes Medical Institute, University of California, San Francisco, California 94143 Michael J. Williams (225), Umeå Centre for Molecular Pathogenesis, Umeå University, S-901 87 Umeå, Sweden Deborah Yablonski (93), Department of Pharmacology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bat Galim, Haifa 31096, Israel John Ding-E Young (297), Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021 Rolf M. Zinkernagel (1), Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland
  • 17.
    ADVANCES IN IMMUNOLOGY,VOL. 79 Neutralizing Antiviral Antibody Responses ROLF M. ZINKERNAGEL,1 ALAIN LaMARRE,1 ADRIAN CIUREA, LUKAS HUNZIKER, ADRIAN F. OCHSENBEIN, KATHY D. McCOY, THOMAS FEHR, MARTIN F. BACHMANN, ULRICH KALINKE, AND HANS HENGARTNER Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland I. Introduction Antibody responses have been studied in infectious diseases, particularly against toxins isolated from pathogenic bacteria. Indeed, antibody quality re- quirements for protection against diphtheria toxin were among the first to be elucidated (Von Behring and Kitasao, 1890; Ehrlich, 1906; Jerne, 1951). How- ever, the inability to purify these toxins and the complexity of the biological material forced immunologists to use chemically pure substances in order to quantitatively study antigens and their reactions with antibodies (Evans, 1943). Therefore, immunochemists used haptens, usually small phenyl groups, that were easily synthesized in various configurations and could be linked to large proteins (Heidelberger, 1956; Eisen and Siskind, 1964). Because of their small size they could pass through the then-available dialysis bags to measure physico- chemical parameters of antibody/antigen interactions and define binding affini- ties and specificities. Only recently has it become possible to express and pu- rify biological substances sufficiently not only to repeat some of these analyses in vitro but also to correlate such measurements with protection against disease in vivo (Fazekas de St. Groth and Webster, 1961; Staudt and Gerhard, 1983; Webster and Rott, 1987; Laver et al., 1990; Bachmann et al., 1997b). Individuals with defective antibody responses, such as patients with Bruton’s disease or other antibody defects, are more susceptible to infections (Wilfert et al., 1977; Graham et al., 1983; Englund et al., 1998), as are mice devoid of B cells, such as the μMT mouse (Good and Zak, 1956; Kitamura et al., 1991; Bründler et al., 1996). Protective or neutralizing antibody responses, particularly against acute cytopathic agents, are among the most critical defense mechanisms (Sabin, 1981; Steinhoff et al., 1995; Zinkernagel et al., 1996). These responses represent the result of a long co-evolution between the host and various infec- tious agents. However, because of the shorter generation time and greater num- bers, adaptation of infectious agents is considerably faster than that of the host. This review attempts to summarize from an evolutionary point of view evidence that neutralizing antibodies (nAbs) are key to protecting the species against many viruses, particularly cytopathic ones. Such viruses have the potential to upset 1 These authors contributed equally to this work. 1 Copyright C 2001 by Academic Press. All rights of reproduction in any form reserved. 0065-2776/01 $35.00
  • 18.
    2 ROLF M.ZINKERNAGEL ET AL. the balance between host and pathogen; therefore, an equilibrium must have evolved to enable the survival of both. This balance is maintained by the ability of the host to mount rapid neutralizing antibody responses which is achieved by directly encoding virus-specific neutralizing antibodies in the germline. Thus, it is mandatory to assess the protective capacity of antibodies by in vivo adoptive transfer experiments or by in vitro neutralization assays, rather than measuring antigen binding in an enzyme-linked immunosorbent assay (ELISA). Interestingly, although not surprisingly, there is a certain geography of the antibody response: local IgA in the mucosa, systemic short-lived IgM and long- lived IgG in blood. In addition, antibodies not only neutralize viruses and thereby prevent infection but also trap virus in the spleen and prevent it from reaching the blood. They thereby enhance immune responses in general and B cell re- sponses in particular. This review also presents evidence that, in general, B cells are not negatively selected and are largely regulated by antigen structure and availability of cognate T help. We also review evidence supporting the notion that B cell memory, in the form of high neutralizing antibody serum levels, is the main contributor to immunological memory. Finally, both general and spe- cific examples of neutralizing antibody responses are used to illustrate rules that govern B cell responses. These rules are also discussed with respect to their role in autoimmunity and how they can be exploited for vaccines. II. Antiviral Antibody Responses During their development in the bone marrow, B cell precursors undergo sequential recombination-activating gene (RAG)-mediated rearrangements of D to J and V to DJ elements of the immunoglobulin (Ig) heavy-chain variable region (VH) and V to J elements of the Ig light-chain variable region (VL) (Tone- gawa, 1983). Expression of functional Ig heavy and light chains promotes the transition of precursor B cells to small IgM/IgD-positive mature B cells. Au- toreactive antibody specificities generated by random rearrangement are either deleted(NemazeeandBuerki,1989;NemazeeandBuerki,1989;Nemazee etal., 1991; Hartley et al., 1993) or edited by secondary VL and possibly VH replace- ments (Gay et al., 1993; Radic et al., 1993; Tiegs et al., 1993; Chen et al., 1995, 1997; Lang et al., 1996; Pelanda et al., 1997; Fang et al., 1998; Nemazee, 2000). B cells that emigrate from the bone marrow and populate secondary lymphoid organs constitute the primary B cell repertoire. The restricted number of V, D, and J gene segments that can be encoded in the genome limits the size of the po- tential repertoire. However, diversity of the preimmune repertoire of mice and humans can be further expanded by hypermutation, whereas other species, such as rabbits, sheep, pigs, and cattle, use gene conversion (Diaz and Flajnik, 1998). It has recently been suggested that, together with hypermutation, secondary Ig gene rearrangements may also contribute to repertoire diversification (Han
  • 19.
    NEUTRALIZING ANTIVIRAL ANTIBODYRESPONSES 3 et al., 1997; Papavasiliou et al., 1997; Pelanda et al., 1997; Hertz et al., 1998; Meffre et al., 1998; Lopez-Macias et al., 1999; Wilson et al., 2000b). However, whether this considerably slower process confers a survival advantage to the host remains to be formally demonstrated. A. V(D)J REARRANGEMENTS IN ANTIVIRAL ANTIBODIES The primary repertoire of vesicular stomatitis virus (VSV)-specific antibodies was analyzed by isolating hybridomas 4 and 5 days after infection (Kalinke et al., 1996a). Surprisingly, 87% of clones analyzed used V genes belonging to the VHQ52 and Vκ19–28 families. Despite their polyclonal origin, the majority of these clones expressed identical VH and VL germline segments. Because all these antibodies failed to bind and neutralize the 51.12 VSV variant (which was selected in the presence of one particular VHQ52/Vκ19–28-positive antibody), they all appear to bind to the same subsite within the major antigenic site of the glycoprotein of VSV (VSV-G). Analysis of the primary response to influenza virus also revealed a restricted Vκ usage, with the predominance of a segment belonging to the Vκ8 gene family (Clarke et al., 1990b). In contrast, the heavy- chain variable region genes displayed much greater diversity, with several VH families being used. In contrast to primary response antibodies, hybridomas isolated from sec- ondary and hyperimmune anti-VSV responses expressed a more diverse set of V genes belonging to the VHJ558, VH7183, and VHQ52 families (Kalinke et al., 1996a). The majority of these antibodies were shown to bind a different sub- site of the major antigenic site of VSV-G than the primary response antibodies. Thus, fine specificity diversification of secondary and hyperimmune responses was achieved by newly appearing V gene combinations. Similar findings were ob- tained from analysis of the secondary response to influenza virus where V region usage differed considerably from the primary response (Clarke et al., 1990a). B. THE ROLE OF HYPERMUTATION IN THE GENERATION OF VIRUS-NEUTRALIZING ANTIBODIES Interestingly, all anti-VSV mAbs isolated up to day 6 post infection, irrespec- tive of which genetic elements they express, were devoid of somatic hypermu- tation (Kalinke et al., 1996a). This indicates the presence of VSV specificities in the mouse germline antibody repertoire. This was confirmed by the isolation of VSV-neutralizing antibody fragments from phage display libraries generated from naive mice (A. Lamarre, unpublished results). These findings are remark- able because VSV is a new-world virus of ruminants while Mus musculus is an old-world rodent. Therefore, the presence of VSV-specific, high-affinity antibod- ies in the germline cannot be a result of recent co-evolution; instead, this suggests that, in general, cytopathic viruses have been selected to fit the available antibody repertoire rather than vice versa (Roost et al., 1995; Bachmann et al., 1997b).
  • 20.
    4 ROLF M.ZINKERNAGEL ET AL. Similarly, anti-influenza primary response antibodies were largely devoid of somatic mutations (Clarke et al., 1990b). In contrast to primary antibodies, secondary and hyperimmune mAbs did display hypermutations (Clarke et al., 1990b; Kalinke et al., 1996a). Nevertheless, as with the primary VHQ52/Vκ19–28- positive antibodies, hypermutated anti-VSV antibodies were not able to neu- tralize the virus variant 51.12. However, compared to the germline antibodies, hypermutated antibodies had approximately a 50-fold increase in their ability to neutralize wild-type VSV (Kalinke et al., 1996a). Therefore, hypermutation did not alter antibody specificity, as far as can be judged by binding competition assays, but it did improve binding quality and neutralizing capacity. To verify these conclusions, another more heterogeneous group of VSV- neutralizing antibodies typical of secondary and hyperimmune responses was analyzed (Kalinke et al., 2000). Although these antibodies expressed numerous different light chains, they all used the same VH germline segment belonging to the VH7183 family in combination with the JH2 segment. Again, all hyperimmune antibodies contained hypermutations. Despite most of the hypermutated anti- bodies not being clonally related, some of them showed the same single somatic amino acid substitutions in CDR1 and CDR2. Because no virus variant resistant to neutralization by all VH7183/JH2-positive antibodies could be generated, they apparently bound different subsites within the major antigenic site of VSV-G. To analyze the impact of the common amino acid substitutions on virus bind- ing and neutralization, the secondary response antibody VI24 of the VH7183/JH2 group was expressed as a monovalent, recombinant, single-chain antibody con- sisting of the Vκ and VH regions linked to a Cκ domain (Kalinke et al., 2000). This antibody fragment expressed four somatic amino acid exchanges in VH, whereas VL was germline. The antibody fragment was mutated back to a germline con- figuration and mutations were introduced in VH encoding for one or both of the common amino acid substitutions in CDR1 and CDR2. The binding of the hypermutated VI24 antibody fragment was about 50- to 100-fold better than the germline antibody fragment. Expression of the CDR2 amino acid substitu- tion alone improved binding by about 10-fold, whereas the CDR1 substitution did not affect binding. Antibody fragments were dimerized using an anti-Cκ antibody. Dimerization of the VI24 antibody fragment did not improve its bind- ing, whereas binding of the dimerized germline antibody fragment improved by more than 10-fold. Thus, avidity effects did not contribute to the binding of the hypermutated antibody, whereas they seemed to have a major impact on the binding of the germline antibody fragment. Analysis of the second group of antibodies confirmed the previous observa- tion that hypermutation was no prerequisite for virus neutralization. However, hypermutation improved the binding and the neutralization of VSV in vitro up to a level where avidity effects do not seem to further contribute to the quality of antibody binding.
  • 21.
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    The Project GutenbergeBook of Medley Dialect Recitations, Comprising a Series of the Most Popular Selections in German, French, and Scotch
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    This ebook isfor the use of anyone anywhere in the United States and most other parts of the world at no cost and with almost no restrictions whatsoever. You may copy it, give it away or re-use it under the terms of the Project Gutenberg License included with this ebook or online at www.gutenberg.org. If you are not located in the United States, you will have to check the laws of the country where you are located before using this eBook. Title: Medley Dialect Recitations, Comprising a Series of the Most Popular Selections in German, French, and Scotch Editor: George M. Baker Release date: February 2, 2016 [eBook #51108] Most recently updated: October 22, 2024 Language: English Credits: Produced by Richard Tonsing, David Edwards and the Online Distributed Proofreading Team at http://www.pgdp.net (This file was produced from images generously made available by The Internet Archive) *** START OF THE PROJECT GUTENBERG EBOOK MEDLEY DIALECT RECITATIONS, COMPRISING A SERIES OF THE MOST POPULAR SELECTIONS IN GERMAN, FRENCH, AND SCOTCH ***
  • 27.
    STANDARD ELOCUTIONARY BOOKS FIVE-MINUTEREADINGS FOR YOUNG LADIES. Selected and adapted by Walter K. Fobes. Cloth. 50 cents. FIVE-MINUTE DECLAMATIONS. Selected and adapted by Walter K. Fobes, teacher of elocution and public reader; author of Elocution Simplified. Cloth. 50 cents. FIVE-MINUTE RECITATIONS. By Walter K. Fobes. Cloth. 50 cents. Pupils in public schools on declamation days are limited to five minutes each for the delivery of pieces. There is a great complaint of the scarcity of material for such a purpose, while the injudicious pruning of eloquent extracts has often marred the desired effects. To obviate these difficulties, new Five-Minute books have been prepared by a competent teacher. ELOCUTION SIMPLIFIED. With an appendix on Lisping, Stammering, and other Impediments of Speech. By Walter K. Fobes, graduate of the Boston School of Oratory. 16mo. Cloth. 50 cents. Paper, 30 cents. The whole art of elocution is succinctly set forth in this small volume, which might be judiciously included among the text-books of schools.—New Orleans Picayune. ADVANCED READINGS AND RECITATIONS. By Austin B. Fletcher, A.M., LL.B., Professor of Oratory, Brown University, and Boston University School of Law. This book has been already adopted in a large number of Universities, Colleges, Post-graduate Schools of Law and Theology, Seminaries, etc. 12mo. Cloth. $1.50. Professor Fletcher's noteworthy compilation has been made with rare rhetorical judgment, and evinces a sympathy for the best forms
  • 28.
    of literature, adaptedto attract readers and speakers, and mould their literary taste.—Prof. J. W. Churchill, Andover Theological Seminary. THE COLUMBIAN SPEAKER. Consisting of choice and animated pieces for declamation and reading. By Loomis J. Campbell, and Orin Root, Jun. 16mo. Cloth. 75 cents. Mr. Campbell, as one of the editors of Worcester's Dictionaries, the popular Franklin Readers, and author of the successful little work, Pronouncing Hand-Book of 3,000 Words, is well known as a thorough scholar. Mr. Root is an accomplished speaker and instructor in the West, and both, through experience knowing the need of such a work, are well qualified to prepare it. It is a genuine success. VOCAL AND ACTION-LANGUAGE, CULTURE AND EXPRESSION. By E. N. Kirby, teacher of elocution in the Lynn High Schools. 12mo. English cloth binding. Price, $1.25. Teachers and students of the art of public speaking, in any of its forms, will be benefited by a liberal use of this practical hand- book.—Prof. Churchill. KEENE'S SELECTIONS. Selection for reading and elocution. A hand-book for teachers and students. By J. W. Keene, A.M., M.D. Cloth. $1. An admirable selection of practical pieces. LITTLE PIECES FOR LITTLE SPEAKERS. The primary school teacher's assistant. By a practical teacher. 16mo. Illustrated. 75 cents. Also in boards, 50 cents. Has had an immense sale. THE MODEL SUNDAY-SCHOOL SPEAKER. Containing selections in prose and verse, from the most popular pieces and dialogues for Sunday-school exhibitions.
  • 29.
    Illust. Cloth. 75cents. Boards, 50 cents A book very much needed. LEE AND SHEPARD Publishers Boston
  • 30.
    Baker's Dialect Series MEDLEYDIALECT RECITATIONS COMPRISING A SERIES OF THE MOST POPULAR SELECTIONS In German, French, and Scotch EDITED BY GEORGE M. BAKER COMPILER OF THE READING CLUB AND HANDY SPEAKER, THE PREMIUM SPEAKER, THE POPULAR SPEAKER, THE PRIZE SPEAKER, THE HANDY SPEAKER, ETC.
  • 31.
    BOSTON LEE AND SHEPARD,PUBLISHERS NEW YORK CHARLES T. DILLINGHAM 1888
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    Copyright, 1887, By GEORGEM. BAKER. Medley Dialect Recitations. RAND AVERY COMPANY, ELECTROTYPERS AND PRINTERS, BOSTON.
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  • 35.
    PAGE Hans Breitmann's PartyCharles G. Leland 5 The Deutsch Maud Muller Carl Pretzel 6 The Dutchman's Serenade 7 Dyin' Vords of Isaac Anon. 9 Lookout Mountain, 1863— Beutelsbach, 1880 George L. Catlin 10 Der Shoemaker's Poy 12 Der Drummer Charles F. Adams 13 The Yankee and the Dutchman's Dog 14 Setting a Hen 16 What's the Matter with that Nose? Our Fat Contributor 17 Keepin' the De'il oot Mrs. Findley Braden 19 The Puzzled Census-Taker John G. Saxe 22 Dutch Security 23 The Frenchman and the Rats 24 Heinz von Stein Charles G. Leland, from the German 26 The Solemn Book-Agent Detroit Free Press 27 The Mother-in-Law Charles Follen Adams 28 Schneider's Tomatoes Charles F. Adams 29 Dutch Humor 30 Squire Houston's Marriage Ceremony 31 Dot Delephone 31 The United Order of Half-Shells 33 Why no Scotchmen go to Heaven 35 Yawcob Strauss C. F. Adams 36 Leedle Yawcob Strauss—what he says Arthur Dakin 37 Isaac Rosenthal on the Chinese Question Scribner's Monthly 38
  • 36.
    Question Der Dog undder Lobster Saul Sertrew 39 Der Wreck of der Hezberus 41 Signs and Omens 43 A Dutchman's Answer 44 The Vay Rube Hoffenstein sells 45 A Dutch Recruiting Officer 46 Dot Baby off Mine 47 Dot Leetle Tog under der Vagon 49 Schnitzerl's Velocipede Hans Breitmann 50 The Latest Barbarie Frietchie 51 Mr. Hoffenstein's Bugle 52 Fritz and his Betsy fall out George M. Warren 54 Cut, Cut Behind Charles Follen Adams 57 Tickled all Oafer 58 An Error o' Judgment 59 Sockery Kadahcut's Kat 61 I vash so Glad I vash Here! 63 Dot Shly Leedle Raskel 64 A Jew's Trouble Hurwood 65 Der Mule shtood on der Steamboad Deck Anon. 66 Teaching him the Business 67 Der Good-lookin Shnow 69 How Jake Schneider went Blind 71 The Dutchman and the Raven 72 The Dutchman who gave Mrs. Scudder the Small-Pox 74 Ellen McJones Aberdeen W. S. Gilbert 76 A Dutch Sermon 78 Shacob's Lament 79 Mr. Schmidt's Mistake Charles F. Adams 81 John and Tibbie Davison's Dispute Robert Leighton 82
  • 37.
    Fritz und ICharles F. Adams 84 A Tussle with Immigrants Philip Douglass 86 A Doketor's Drubbles George M. Warren 86 Charlie Machree William J. Hoppin 90 A Dutchman's Dolly Varden Anon. 91 The Frenchmen and the Flea- Powder 92 The Frenchman and the Sheep's Trotters 94 I vant to Fly 96 The Frenchman's Mistake 98 Two Tollar? Detroit Free Press 100 A Frenchman on Macbeth Anon. 101 Like Mother used to Make James Whitcomb Riley, in New-York Mercury 101 John Chinaman's Protest 102 The Whistler 104 Mother's Doughnuts Charles Follen Adams 105 Over the Left W. C. Dornin 106 A Jolly Fat Friar 107 The Enoch of Calaveras F. Bret Harte 107 Curly-Head B. S. Brooks 109 Warning to Woman 111 An Exciting Contest 112 A Laughing Philosopher 114 In der Shweed Long Ago Oofty Gooft 117 Dot Stupporn Pony Harry Woodson 118 Spoopendyke opening Oysters Stanley Huntley 119 To a Friend studying German Charles Godfrey Leland 122 Tammy's Prize 124 The Scotchman at the Play 128 An Irish Love-Letter Geo. M. Baker 133 MEDLEY DIALECT RECITATIONS.
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    Hans Breitmann gifea party: dey had piano playin'. I felled in lofe mit a Merican frau; her name vos Matilda Yane. She had haar as prown as a pretzel bun; her eyes were himmel- blue; And ven she looket into mine she shplit mine heart into two. Hans Breitmann gife a party: I vent dar, you'll be pound. I valzt mit der Matilda Yane, and vent shpinnin' round and round,— De pootiest fraulein in de house: she weighed two hoondert pound. Hans Breitmann gife a party: I tells you it cost him dear. Dey rollt in more as seven kegs of foost-rate lager-bier; And fenefer dey knocks de shpickets in, de Deutschers gife a cheer; I dinks so fine a party not come to a hend dis year. Hans Breitmann gife a party: dere all vas Saus and Braus. Ven de sooper coom in, de gompany did make demselfs to house; Dey eat das Brod und Gansebrust, Bratwurst, und Broten fine, And vash deir Abendessen down mit four barrels of Neckar wein. Hans Breitmann gife a party: ve all cot trunk as pigs. I put mine mout' to a parrel of bier, and schwallowed up mit a schwigs. And den I kissed Matilda Yane, and she schlog me on de kop; And de gompany fight mit taple-legs till de conshtoble made us shtop. Hans Breitmann gife a party: vere is dat party now? Vere is de lofely golten cloud dat float on de mountain's prow? Vere is de Himmelstrahlende Stern, de star of de spirits' light? All goned afay mit de lager-bier, afay in de Ewigkeit. Charles G. Leland.
  • 42.
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    Maud Muller, vonsummer afternoon, Vas dending bar in her fadder's saloon. She solt dot bier, und singed Shoo Fly, Und vinked at der men mit her lefd eye. But, ven she looked oud on der shdreed, Und saw dem gals all dressed so shweed, Her song gifed oud on a ubber note, Cause she had such a horse in her troat; Und she vished she had shdamps to shpend, So she might git such a Grecian Bend. Hans Brinker valked shlowly down der shdreed, Shmilin at all der gals he'd meed. Old Hans vas rich, as I've been dold, Had houses und lots und a barrel of gold. He shdopped py der door; und pooty soon He valked righd indo dot bier saloon. Und he vinked ad Maud, und said, My dear, Gif me, if you pblease, a glass of bier. She vend to the pblace vere der bier-keg shtood, Und pringed him a glass dot vas fresh and goot. Dot's goot, said Hans: dot's a better drink As effer I had in mine life, I dink. He dalked for a vhile, den said, Goot tay; Und up der shdreed he took his vay. Maud hofed a sigh, and said, Oh, how I'd like to been dot old man's frow! Such shplendid close I den vood vear, Dot all the gals around vood shdare. In dot Union Park I'd drive all tay, Und efery efenin go to der pblay. Hans Brinker, doo, felt almighty gweer (But dot might been von trinkin bier); Und he says to himself, as he valked along Humming der dune of a olt lofe-song, Dot's der finest gal I efer did see;
  • 44.
    Und I vishdot my vife she cood be. But here his solilligwy came to an end, As he dinked of der gold dot she might shbend; Und he maked up his mind dot, as for him, He'd marry a gal mid lots of din. So he vent right off dot fery day, Und married a vooman olt und gray. He vishes now, but all in vain, Dot he was free to marry again,— Free as he vas dat afdernoon, When he met Maud Muller in dot bier-saloon. Maud married a man mitoud some soap; He vas lazy, too; bud she did hope Dot he'd get bedder ven shildren came: But ven they had, he vas yoost the same. Und ofden now dem dears vill come As she sits alone ven her day's work's done, Und dinks of der day ven Hans called her My dear, Und asked her for a glass of bier; But she don'd complain nor efer has: Und oney says, Dot coodn't vas. Carl Pretzel.
  • 46.
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    Vake up, myschveet! Vake up, my lofe! Der moon dot can't been seen abofe. Vake oud your eyes, und dough it's late, I'll make you oud a serenate. Der shtreet dot's kinder dampy vet, Und dhere vas no goot blace to set; My fiddle's getting oud of dune, So blease get vakey wery soon. O my lofe! my lofely lofe! Am you avake ub dhere abofe, Feeling sad und nice to hear Schneider's fiddle schrabin near? Vell, anyvay, obe loose your ear, Und try to saw if you kin hear From dem bedclose vat you'm among, Der little song I'm going to sung: * * * * * O lady, vake! Get vake! Und hear der tale I'll tell; Oh, you vot's schleebin' sound ub dhere, I like you pooty vell! Your plack eyes dhem don't shine Ven you'm ashleep—so vake! (Yes, hurry up, und voke up quick, For gootness cracious sake!) My schveet imbatience, lofe, I hobe you vill oxcuse: I'm singing schveetly (dhere, py Jinks! Dhere goes a shtring proke loose!)
  • 48.
    O putiful, schveetmaid! Oh, vill she efer voke? Der moon is mooning—(Jimminy! dhere Anoder shtring vent proke!) Oh, say, old schleeby head! (Now I vas getting mad— I'll holler now, und I don't care Uf I vake up her dad!) I say, you schleeby, vake! Vake oud! Vake loose! Vake ub! Fire! Murder! Police! Vatch! Oh, cracious! do vake ub! * * * * * Dot girl she schleebed—dot rain it rained, Und I looked shtoopid like a fool, Vhen mit my fiddle I shneaked off So vet und shlobby like a mool!
  • 50.
    DYIN' VORDS OFISAAC. Vhen Shicago vas a leedle villages, dher lifed dherein py dot Clark Sdhreet out, a shentlemans who got some names like Isaacs; he geeb a cloting store, mit goots dot vit you yoost der same like dhey vas made. Isaacs vas a goot fellers, und makes goot pishness on his hause. Vell, thrade got besser as der time he vas come, und dose leetle shtore vas not so pig enuff like anudder shtore, und pooty gwick he locks out und leaves der pblace. Now Yacob Schloffenheimer vas a shmard feller; und he dinks of he dook der olt shtore, he got good pishness, und dose olt coostomers von Isaac out. Von tay dhere comes a shentlemans on his store, und Yacob quick say of der mans, How you vas, mein freund? you like to look of mine goots, aind it?—Nein, der mans say. Vell, mein freund, it makes me notting troubles to show dot goots.—Nein; I don'd vood buy sometings to-tay.—Yoost come mit me vonce, mein freund, und I show you sometings, und so hellup me gracious, I don'd ask you to buy dot goots.—Vell, I told you vat it vas, I don'd vood look at some tings yoost now; I keebs a livery shtable; und I likes to see mein old freund Mister Isaacs, und I came von Kaintucky out to see him vonce.—Mister Isaacs? Vell, dot ish pad; I vas sorry von dot. I dells you, mein freund, Mister Isaacs he vas died. He vas mein brudder, und he vas not mit us eny more. Yoost vhen he vas on his deat-ped, und vas dyin', he says of me, 'Yacob, (dot ish mine names), und I goes me ofer mit his petside, und he poods his hands of mine, und he says of me, 'Yacob' ofer a man he shall come von Kaintucky out, mit ret hair, und mit plue eyes, Yacob, sell him dings cheab;' und he lay ofer und died his last. Anonymous.
  • 52.
  • 53.
    Yah, I shpeaksEnglish a leetle: berhaps you shpeaks petter der German. No, not a word.—Vel den, meester, it hardt for to be oonderstandt. I vos drei yahr in your country, I fights in der army mit Sherman— Twentiet Illinois Infantry—Fightin' Joe Hooker's commandt. So you've seen service in Georgia—a veteran, eh?—Vell, I tell you Shust how it vos. I vent ofer in sixty, und landt in Nei-York; I sphends all mine money, gets sick, und near dies in der Hospiddal Bellevue: Ven I gets petter I tramps to Sheecago to look for some vork. Pretty young then, I suppose?—Yah, svansig apout; und der peobles Vot I goes to for to ask for some vork, dey hafe none for to geef; Efery von laughs; but I holds my head ope shust so high as der steeples. Only dot var comes along, or I should have die, I belief. Ever get wounded? I notice you walk rather lame and unsteady. Pshaw! got a wooden leg, eh? What battle? At Lookout! don't say! I was there too—wait a minute—your beer-glass is empty already Call for another. There! tell me how 'twas you got wounded that day. Vell, ve charge ope der side of her mountain—der sky vos all smoky and hazy; Ve fight all day long in der clouds, but I nefer get hit until night— But—I don't care to say mooch apout it. Der poys called me foolish and crazy. Und der doctor vot cut ofe my leg, he say, 'Goot'—dot it serf me shust right. But I dinks I vood do dot thing over again, shust der same, and no matter
  • 54.
    Vot any mansay.—Well, let's hear it—you needn't mind talking to me, For I was there, too, as I tell you—and Lor'! how the bullets did patter Around on that breastwork of boulders that sheltered our Tenth Tennessee. So? Dot vos a Tennessee regiment charged upon ours in de efening, Shust before dark; und dey yell as dey charge, und ve geef a hurrah, Der roar of der guns, it vos orful.—Ah! yes, I remember, 'twas deafening, The hottest musketry firing that ever our regiment saw. Und after ve drove dem back, und der night come on, I listen, Und dinks dot I hear somepody a callin'—a voice dot cried, 'Pring me some vater for Gott's sake'—I saw his pelt-bate glisten, Oonder der moonlight, on der parapet, shust outside. I dhrow my canteen ofer to vere he lie, but he answer Dot his left handt vos gone, und his right arm proke mit a fall; Den I shump ofer, und gife him to drink, but shust as I ran, sir, Bang! come a sharp-shooter's pullet; und dot's how it vos—dot is all. And they called you foolish and crazy, did they? Him you befriended — The 'reb,' I mean—what became of him? Did he ever come 'round? Dey tell me he crawl to my side, und call till his strength vos all ended, Until dey come out mit der stretchers, und carry us off from der ground. But pefore ve go, he ask me my name, und says he, 'Yacob Keller, You loses your leg for me, und some day, if both of us leefs, I shows you I don't vorget'—but he most hafe died, de poor feller; I nefer hear ofe him since. He don't get vell, I beliefs.
  • 55.
    e e eao e s ce e do t get e , be e s Only I alvays got der saddisfachshun ofe knowin'— Shtop! vots der matter? Here, take some peer, you're vite as a sheet — Shteady! your handt on my shoulder! my gootness! I dinks you vos goin' To lose your senses avay, und fall right off mit der seat. Geef me your handts. Vot! der left one gone? Und you vos a soldier In dot same battle?—a Tennessee regiment?—dot's mighty queer— Berhaps after all you're— Yes, Yacob, God bless you old fellow, I told you I'd never—no, never forget you. I told you I'd come, and I'm here. George L. Catlin.
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