Chemical and biological properties of food allergens edited by lucjan jędrychowski, harry j wichers

Chemical and
Biological
Properties of
Food Allergens


Chemical and Functional Properties of Food Components Series
SERIES EDITOR

Zdzisław E. Sikorski

Chemical and Biological Properties of Food Allergens
Edited by Lucjan Jędrychowski and Harry J. Wichers

Food Colorants: Chemical and Functional Properties
Edited by Carmen Socaciu

Mineral Components in Foods
Edited by Piotr Szefer and Jerome O. Nriagu

Chemical and Functional Properties of Food Components, Third Edition
Edited by Zdzisław E. Sikorski

Carcinogenic and Anticarcinogenic Food Components
Edited by Wanda Baer-Dubowska, Agnieszka Bartoszek and Danuta Malejka-Giganti

Methods of Analysis of Food Components and Additives
Edited by Semih Ötleş

Toxins in Food

Edited by Waldemar M. Dąbrowski and Zdzisław E. Sikorski

Chemical and Functional Properties of Food Saccharides
Edited by Piotr Tomasik

Chemical and Functional Properties of Food Lipids
Edited by Zdzisław E. Sikorski and Anna Kolakowska

Chemical and Functional Properties of Food Proteins
Edited by Zdzisław E. Sikorski


Chemical and
Biological
Properties of
Food Allergens
EDITED BY

Lucjan Jedrychowski
Institute of Animal Reproduction & Food Research
Olsztyn, Poland

Harry J. Wichers
Wageningen University and Research Centre
Netherlands

Boca Raton London New York

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Library of Congress Cataloging-in-Publication Data
Chemical and biological properties of food allergens / editors, Lucjan Jedrychowski,

Harry J. Wichers.
p. ; cm. -- (Chemical and functional properties of food components series)
Includes bibliographical references and index.
ISBN 978-1-4200-5855-0 (hardcover : alk. paper)
1. Food allergy. 2. Allergens. I. Jedrychowski, Lucjan. II. Wichers, Harry. III. Title. IV.
Series: Chemical and functional properties of food components series.
[DNLM: 1. Allergens--chemistry. 2. Food Hypersensitivity--immunology. WD 310
C517 2010]
QR188.C47 2010
616.97’5--dc22
Visit the Taylor & Francis Web site at

and the CRC Press Web site at


2009028070


Contents
Preface......................................................................................................................vii
Acknowledgments .....................................................................................................ix
Editors .......................................................................................................................xi
Contributors ........................................................................................................... xiii
Abbreviations .........................................................................................................xvii
Chapter 1

Molecular, Cellular, and Physiological Mechanisms of
Immunological Hyporesponsiveness/Sensitization to Food ................. 1
Elz˙ bieta Kucharska, Joanna Bober, and Tadeusz Ogon´ski

Chapter 2

Immunomodulating Properties of Food Components ........................ 43
Lucjan Je˛drychowski, Anna Halász, Edina Németh,
and András Nagy

Chapter 3

Methods for Detection of Food Allergens.......................................... 83
Lucjan Je˛drychowski, André H. Penninks, Maciej Kaczmarski,
Beata Cudowska, Elz.bieta Korotkiewicz-Kaczmarska,
Andrea Harrer, Anja Maria Erler, Gabriele Gadermaier,
Michael Faltlhansl, Fátima Ferreira, and Martin Himly

Chapter 4

Recombinant Food Allergens and Their Role in
Immunoassay and Immunotherapy .................................................. 169
Karin Hoffmann-Sommergruber, Christina Oberhuber,
and Merima Bublin

Chapter 5

General Characteristics of Food Allergens ...................................... 185
Lucjan Je˛drychowski

Chapter 6

Milk Allergens ................................................................................. 193
Barbara Wróblewska and Lucjan Je˛drychowski

Chapter 7

Egg Allergens ................................................................................... 213
Sabine Baumgartner and Patricia Schubert-Ullrich

v


vi

Chapter 8

Contents

Fish Allergens................................................................................... 223
Patrick Weber and Angelika Paschke

Chapter 9

Seafood Allergen Overview: Focus on Crustacea............................ 233
Andreas Lopata and Samuel Lehrer

Chapter 10 Nut Allergens ................................................................................... 259
Agata Szymkiewicz
Chapter 11 Peanut (Arachis hypogea) Allergens ................................................ 267
Agata Szymkiewicz
Chapter 12 Soy (Glycine max) Allergens............................................................ 281
Sabine Baumgartner and Patricia Schubert-Ullrich
Chapter 13 Wheat (Triticum aestivum) Allergens .............................................. 293

Joanna Leszczynska
Chapter 14 Brief Characteristics of Other Important Food Allergens ............... 319
Lucjan Je˛drychowski, Matthias Egger, Michael Hauser,
Georg Schmidt, Nicole Wopfner, Fátima Ferreira,
Michael Wallner, and Andreas Lopata
Chapter 15 Risk Analysis of Food Allergens ..................................................... 387
Marielle Spanjersberg, Niels Lucas Luijckx, and Geert Houben
Glossary ................................................................................................................ 399
Appendix ...............................................................................................................405
Index ...................................................................................................................... 415


Preface
Hypersensitivity, including a hypersensitive response to foodstuffs, is one of the
major health problems nowadays. Symptoms of food hypersensitivity cause acute
discomfort for patients and are becoming an increasing social and economic problem, although much progress has been made in recent years in many areas related
to food allergies. Many food allergens have been characterized at a molecular
level, their spatial structure has been determined, and allergen fragments (epitopes)
responsible for reactions with IgE antibodies have also been characterized. A
deeper understanding of the mechanism of the immunopathogenesis of food allergies has been reached, and this may soon lead to novel diagnostic and therapeutic
approaches. Many informative books have been published on this subject. However,
we need to constantly update ourselves to keep abreast of the latest developments in
the many sciences related to food hypersensitivity. On the other hand, the advances
in research on food hypersensitivity open a wide range of potential new solutions
and possibilities. International teams of scientists committed to research in fields
such as medicine, molecular biology, food biotechnology, and foodstuff assays have
achieved remarkable results.
This book should help in understanding the problems related to the occurrence of
allergies, particularly food allergies. It contains up-to-date information on the mechanisms involved in hypersensitive responses and threats caused by ingesting foodstuffs and their components that are often associated with modern food-processing
technologies. It provides in-depth knowledge on allergens and related disciplines.

It also responds to the need for popular social education, which aims to instruct
potential patients on methods of avoiding harmful allergens. This objective is aided
by the presentation of the problems, which consists of a detailed characterization of
the major groups of allergens, a description of their behavior during various technological and biotechnological processes, as well as an indication of potential reactions
with other allergens. Due to its educational value, this book may also be of interest
to general consumers, allergic consumers, representatives of the agro-food industry
(including primary producers, manufacturers, and retailers), and health professionals and regulators. It should also be a dependable reference for researchers (clinicians, food scientists, dieticians, and nutritionists) and students of molecular biology
(particularly the up-to-date characterizations of mechanisms causing allergies and
genetic modifications aimed at decreasing allergenic activity of food products), food
technology (mainly health risks related to particular food components and the effect
of technological processes on allergenic activity of food products as well as foodstuff
assays), biotechnology (primarily allergenic threats caused by microorganisms and
microbial metabolites), and food safety, as well as medical studies connected with
diagnostic methods (elimination diets and food challenges) and allergy therapies.

vii


viii

Preface

This book draws its material from existing databases on allergens and from Web
pages devoted to this issue. Hence, it encourages the readers to expand their knowledge on their own—it can be especially beneficial for college students. It should
be present on the shelves of libraries at all universities, especially universities
and scientific institutes that specialize in biological research.
Lucjan Je˛drychowski


Acknowledgments

I would like to thank my wife and children for being so understanding and patient
while I was absent from home writing this book. I am also grateful to all the
co-authors and my co-workers for their assistance and kindness.
Lucjan Je˛drychowski

ix



Editors
Lucjan Je˛ drychowski is a researcher in biotechnology, food sciences, and food allergies, and is
the head of the Department of Food Enzymes and
Allergens at The Polish Academy of Sciences’
Institute of Animal Reproduction and Food
Research in Olsztyn. His research interests include
the investigation and determination of radionuclide contamination of food, exploring possibilities for the decontamination and application of
radionuclides S-35 and P-32 by incorporation into
chlorella for inducing mutations, the evaluation of
properties of enzymes and applications of enzyme
preparation in the food industry and in food analysis, food allergens, the application of immunological methods (ELISA, ELISPOT) for investigating
biologically active compounds in food (mainly allergens), and the investigation of
biologically active compounds in food for both their positive and negative effects in
an organism. He is a coauthor of 365 publications, 5 books, and 2 patents.
Harry J. Wichers is a biochemist by training. He
received his PhD on the topic “Biotechnological
production of pharmaceuticals with plant cell
cultures” from the University of Groningen.
After working for five years at the TNO-Zeist,
Department of Biotechnology, he joined the
Wageningen University and Research Centre in the

early 1990s, where he worked on the biochemical
characterization of food quality parameters.
Wichers has been program leader of research on
the relationship between food and health. In this
research, data on the physiological effects of food
constituents are integrated with data of their characteristics in the raw materials and their behavior
during processing in order to develop foods that are
attractive to the senses and have a positive impact on human health.
Wichers is one of the founders of the Allergy Consortium Wageningen; in this
expertise center, research teams from each science group of Wageningen-UR
cooperate to develop strategies for allergy management.
He has held a chair entitled “immune modulation by food” since April 2005.
Through this chair, the interactions between food (constituents) and the (human or
animal) immune system are studied in order to contribute to the development of
xi


xii

Editors

foods, feed, or ingredients that can aid in balancing, fortifying, or sustaining an
appropriate immune response. In this research, structure–activity relationships of
immune-modulating natural compounds are studied. The immunological readout
systems include receptor-binding studies, and gene expression through expression
array–based analyses.


Contributors
Sabine Baumgartner

Department for Agrobiotechnology,
IFA-Tulln
University of Natural Resources and
Applied Life Sciences
Vienna, Austria

Michael Faltlhansl
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria

Joanna Bober
Department of Medical Chemistry
Pomeranian Medical University
of Szczecin
Szczecin, Poland

Fátima Ferreira
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria

Merima Bublin
Department of Pathophysiology
Medical University of Vienna
Vienna, Austria

Beata Cudowska
IIIrd Department of Pediatrics
Medical University of Bialystok
Bialystok, Poland
Matthias Egger
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria
Anja Maria Erler
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria

Gabriele Gadermaier
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria
Anna Halász
Department of Biology
Central Food Research Institute
Budapest, Hungary
Andrea Harrer
Department of Molecular Biology
Christian Doppler Laboratory for

Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria
Michael Hauser
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria

xiii


xiv

Martin Himly
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria
Karin Hoffmann-Sommergruber
Department of Pathophysiology
Medical University of Vienna
Vienna, Austria
Geert Houben
Department of Food and Chemical
Risk Analysis
TNO Quality of Life
Utrecht, Netherlands

Lucjan Je˛drychowski
Department of Food Enzymes
and Allergens
Institute of Animal Reproduction
and Food Research
Polish Academy of Sciences
Olsztyn, Poland
Maciej Kaczmarski
IIIrd Department of Pediatrics
Medical University of Bialystok
Bialystok, Poland
.
Elzbieta Korotkiewicz-Kaczmarska
University Children’s Hospital
Bialystok, Poland
.
Elzbieta Kucharska
Department of Human Nutrition
Faculty of Food Sciences
and Fisheries
West Pomeranian University of
Technology
Szczecin, Poland

Contributors

Samuel Lehrer
Section of Allergy, Rheumatology, &
Clinical Immunology
Health Science Center

Department of Medicine
Tulane University Medical School
New Orleans, Louisiana
Joanna Leszczynska
Faculty of Biotechnology and Food
Sciences
Technical University of Lodz
Lodz, Poland
Andreas Lopata
College of Science, Engineering and
Health
School of Applied Sciences
Royal Melbourne Institute of
Technology
Melbourne, Victoria, Australia
Niels Lucas Luijckx
Department of Food and Chemical
Risk Analysis
TNO Quality of Life
Utrecht, Netherlands
András Nagy
Department of Biology
Central Food Research Institute
Budapest, Hungary
Edina Németh
Faculty of Veterinary Science
Department of Pharmacology and
Toxicology
Szent Istvána University
Budapest, Hungary

Christina Oberhuber
Biomay AG
Vienna, Austria


Contributors

Tadeusz Ogon´ski
Faculty of Biotechnology and Animal
Breeding
Department of Physiological Chemistry
West Pomeranian University of
Technology
Szczecin, Poland
Angelika Paschke
Department of Chemistry, Food
Chemistry
University of Hamburg
Hamburg, Germany
André H. Penninks
Department of Toxicology and Applied
Pharmacology
Experimental Immunology
TNO Quality of Life
Zeist, the Netherlands
Georg Schmidt
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg

Salzburg, Austria
Patricia Schubert-Ullrich
Department for Agrobiotechnology,
IFA-Tulln
University of Natural Resources and
Applied Life Sciences
Vienna, Austria
Marielle Spanjersberg
Department of Food and Chemical
Risk Analysis
TNO Quality of Life
Utrecht, Netherlands

xv

Agata Szymkiewicz
Department of Food Enzymes
and Allergens
Institute of Animal Reproduction
and Food Research
Polish Academy of Sciences
Olsztyn, Poland
Michael Wallner
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria
Patrick Weber
Department of Food Chemistry

Institute of Biochemistry and
Food Chemistry
University of Hamburg
Hamburg, Germany
Nicole Wopfner
Department of Molecular Biology
Christian Doppler Laboratory for
Allergy Diagnosis and Therapy
University of Salzburg
Salzburg, Austria

Barbara Wróblewska
Department of Food Enzymes
and Allergens
Institute of Animal Reproduction
and Food Research
Polish Academy of Sciences
Olsztyn, Poland



Abbreviations
ADCC—antibody-dependent cytotoxicity
AEDS—atopic eczema/dermatitis syndrome
AFM—atomic force microscopy
AOAC INTERNATIONAL—Association of Analytical Communities
AP 1—activating protein 1
APC—antigen-presenting cells
ATP—atopy patch test
ATR—attenuated total reflection

AUC—analytical ultracentrifugation
B10A—strain of the mouse
Balb/c—albino strain of laboratory mouse
BALT—bronchus-associated lymphoid tissue
BHA—butylated hydroxyanisole (antioxidant)
BHR—bronchial hyperreactivity
BHT—butylated hydroxytoluene (antioxidant)
BN rats—Brown Norway (BN) rats
BRs—brassinosteroids
BSA—bovine serum albumin
C3H/hej—strain of the mouse
CCD—cross-reactive carbohydrate determinants
CCDs—cross-reactive carbohydrates
CD—circular dichroism
CD—cluster of differentiation
Cd—parameter introduced by authors expressing the product of temperature and
time
CLA—cutaneous lymphocyte antigen
CM—cow’s milk
CMA—cow’s milk allergy
CmM—camel milk
CMPA—cow milk protein allergy
CMPI—cow milk protein intolerance
cns—central nervous system
CRIE—crossed radioimmunoelectrophoresis
CTACK—cutaneous T-cell-attracting chemokine
CTLA4—cytotoxic T lymphocyte associated antigen 4
DAG—diacylglycerol
DAO—diaminooxidase
DBA/2—strain of the mouse

DBPCFC—double-blind placebo-controlled food challenge method—the golden
standard in food allergy determination
DC—dendritic cell
xvii


xviii

Abbreviations

DDBJ—see EMBL
DLS—dynamic light scattering
DM—donkey’s milk
DNA—deoxyribonucleic acid
DNCB—2,4-dinitrochlorobenzene
DSC—differential scanning calorimetry
DTH—delayed cellular hypersensitivity
DXMS—deuterium exchange mass spectrometry
EAACI—European Academy of Allergology and Clinical Immunology
EAR—early anaphylactic phase
ECFA—eosinophil chemotactic factors of anaphylaxis
ECP—eosinophil cationic protein
EDN—eosinophil-derived neurotoxin
eHF—extensively hydrolyzed formula
ELISA—enzyme-linked immunosorbent assay
EMBL—European Molecular Biology Laboratory (Heidelberg) Nucleotide
Sequence Database (also known as EMBL-Bank). The database is produced in an international collaboration with GenBank (USA) and the DNA
Database of Japan (DDBJ). The EMBL nucleotide sequence database is
part of the Protein and Nucleotide Database Group (PANDA)
EPO—eosinophil peroxidase

ESI—electrospray ionization
EU—European Union
FA—food allergy
FACS—Facial Action Coding System
FAO—Food and Agriculture Organization
FEV1—forced expiratory volume in 1 s
FLAG–tag—polypeptide protein tag that is added to a recombinant expressed
protein
FTIR spectroscopy—Fourier transform infrared spectroscopy
GALT—gut-associated lymphoid tissue
GI—gastrointestinal
GITR—glucocorticoid-induced tumor necrosis factor receptor
GITR—glucocorticoid-induced tumor necrosis factor receptor of TNF
GITR-L—glucocorticoid-induced tumor necrosis factor receptor ligand
GM—goat’s milk
GMCSF—granulocyte-macrophage colony stimulating factor
GMP—Good Manufacturing Practice
GRAS—generally regarded as safe
HLA—human leukocyte antigen
HP—hypersensitivity pneumonitis
HPLC—high-performance liquid chromatography
Hsp70—the 70 kDa heat-shock proteins
HT-29—designations of the cell line—synonym ATCC® Number HTB-38™
i.p.—intraperitoneal
ICAM-1—intracellular adhesion molecules-1


Abbreviations

xix

IDO—indoleamine 2,3-dioxygenase
IFNγ—interferon-gamma
IgA—immunoglobulin A
IgE—immunoglobulin E
IgG—immunoglobulin G
IL—interleukin
IP3—inositol 1,4,5-triphosphate
ISP—ice structuring protein
IT—informatic technology
ITAM—immunoreceptor tyrosine-based activation motif
IUIS—International Union of Immunological Societies
JAK—Janus kinases
JNK—Jun N-terminal kinases
kDa—kiloDalton
LAB—lactic acid bacteria
LAR—late anaphylactic phase
LIC technology—The strategy for ligation independent cloning (LIC) is a special
technique used to amplify the gene of interest employing gene-specific
primers that include complementary linearized vectors. This method can
also be easily adapted for high-throughput cloning. The main advantage of
the LIC protocol is that it completely avoids restriction digestion and ligation of the inserted DNA that is particularly significant for large genes.
LOAEL—lowest observed adverse effect level
LOD—limit of detection—defined as the analyte concentration interpolated from
a standard curve at a response level equivalent to zero concentration plus
three standard deviations
LOQ—limit of quantitation—the lowest and highest standard used in the analysis
LPS—lipopolysaccharide
LTB4 —leukotriene B (4)
LTP—lipid-transfer protein

MALDI—matrix-assisted laser desorption ionization
MALT—mucosa-associated lymphoid tissue
MAO—monoaminooxidase
MAPK—mitogen-activated protein kinases
MBP—major basic protein
MC—mucosal cell
MCP 1—monocyte chemoattractant protein 1
MDC—macrophage-derived chemokine
MED—minimal eliciting dose
MHC—major histocompatibility complex
MIF—macrophage inhibitory factor
MIP 1—macrophage inflammatory protein 1
MIP 2—macrophage inflammatory protein 2
MM—mare’s milk
MMC—mucosal mast cells
MoM—mother’s milk


xx

Abbreviations

MS—mass spectrometry
MW—molecular weight synonym of the molecular mass (abbreviated M)—is the
mass of one molecule
NALT—nose-associated lymphoid tissue
nanoLC-MSMS—nanoliquid chromatography–tandem MS
NCF—neutrophil chemotactic factors
NFA—nuclear factor of activated T-lymphocytes
NF-kappaB—nuclear factor kappa B

NK—cells natural killer cells
NMR—nuclear magnetic resonance
NOAEL—the highest tested dose without adverse effects (no-observed-adverseeffect level)
NOE—nuclear Overhauser enhancement
nsLTPs—nonspecific lipid-transfer protein
OAS—oral allergy syndrome
OFC—oral food challenge
OVA—ovalbumin
PAF—platelet activating factor
PAMP—pathogen-associated molecular patterns
PANDA—see EMBL
PBMCs—primary blood mononuclear cells
PCR—polymerase chain reaction
PDB codes—Protein Data Bank codes (see also wwPDB)
PDDF—pair distance distribution function
PFS—pollen-food syndrome
pHF—partially/moderately hydrolyzed formulae
PKC—protein kinase C
PPV—positive predictive value
PR—pathogenesis-related proteins
PST—prick skin tests
RANTES—factor regulated on activation normal T cells expressed and secreted
RAST—radioallergosorbent test
RBL—functional rat-basophil assay
RIVM—public health and environment
s.c.—subcutaneous
SALT—skin-associated lymphoid tissue
SAXS—small-angle x-ray scattering
SCF—stem cell factor
SCS—spent culture supernatant

SDS-PAGE—sodium dodecyl sulfate polyacrylamide gel electrophoresis
SEC—size exclusion chromatography
SF—soy formulae
SIT—specific immunotherapy
SLIT—sublingual immunotherapy
SM—sheep’s milk
SNP—single nucleotide polymorphism


Abbreviations

xxi

SPT—skin prick test
STAT—signal transducer and activator transcription
STI—soybean trypsin inhibitor
TARC—thymus activation-regulated chemokine
TCC—T-cell clones
TCL—T-cell line
TCR—T-cell antigen receptor
TGF-b—transforming growth factor-β
TLPs—thaumatin-like proteins
TLR—toll-like receptors
TMV—tobacco mosaic virus
TNF—tumor necrosis factor
TNF-a—tumor necrosis factor-α
TNO—Netherlands Organisation for Applied Scientific Research
TROSY—transverse relaxation-optimized spectroscopy
UHT—ultrahigh temperature—food prepared during partial sterilization by heating
it for a short time, around 1–2 s, at a temperature exceeding 135°C

VC—Netherlands Nutrition Centre
VCAM-1—vascular cell adhesion molecule-1
VEGF—vascular endothelial growth factor
VIP—vasoactive intestinal peptide
VPAC1 and VPAC2 —vasoactive intestinal peptide (VIP) receptors
WDEIA—wheat-dependent exercise-induced anaphylaxis
WHO—World Health Organization
wwPDB—Worldwide Protein Data Bank (group which joined the wwPDB in 2006)
consists of organizations that act as deposition, data processing, and distribution centers for PDB data. The founding members are RCSB PDB
(USA), PDBe (Europe) PDBj (Japan), and BMRB (USA). The mission of
the wwPDB is to maintain a single protein data bank archive of macromolecular structural data that is freely and publicly available to the global
community
a-la—α-lactalbumin (alfa-lactalbumin)
b-lg—β-lactoglobulin (beta-lactoglobulin)



Cellular,
1 Molecular,
and Physiological
Mechanisms of
Immunological
Hyporesponsiveness/
Sensitization to Food
Elz˙bieta Kucharska, Joanna Bober,
and Tadeusz Ogon´ski
CONTENTS
1.1

1.2

Putative Mechanism Suggested for Intestinal Induction of Oral
Tolerance according to Luminal Antigen Dose ................................................2
1.1.1 Molecular and Cellular Mechanisms of Food Allergy..........................4
1.1.1.1 Allergens ................................................................................4
1.1.1.2 Anaphylaxis ...........................................................................4
1.1.1.3 Type II Allergy .......................................................................8
1.1.1.4 Type III Allergy......................................................................8
1.1.2 Mechanisms of Cell-Mediated Delayed Hypersensitivity
Reactions (Th1) ....................................................................................9
1.1.2.1 Gluten-Sensitive Enteropathy (Celiac Disease) ................... 12
1.1.2.2 Enteropathy Induced by Cow Milk Proteins and Other
Allergens .............................................................................. 13
1.1.3 Role of the Deletion, Energy Suppression, “Ignorance,” and
Apoptosis Mechanisms in Food Antigen Tolerance ........................... 15
1.1.4 Mechanism and Symptoms of Individualistic Adverse Reactions
to Foods...............................................................................................20
Influence of Several Factors: Genetic Background; Age Dependence
in Food Allergy, First Exposure; Food Allergy in Children and Allergy
March; Nature, Dose, and Balance between Tolerance (Suppression)
and Sensitization (Priming) ............................................................................ 21
1


2

Chemical and Biological Properties of Food Allergens

1.2.1 Genetic Background ........................................................................... 21
1.2.2 Age Dependence in Food Allergy, First Exposure .............................. 23

1.2.3 Allergy March .....................................................................................26
1.2.4 Balance between Tolerance (Suppression) and Sensitization
(Priming) ............................................................................................. 27
1.3 Application of Functional Genomics and Proteomics in Allergy and
Clinical Immunology ......................................................................................28
1.3.1 Functional Proteomics and Genomics ................................................28
1.3.2 Functional Genomics in Clinical Immunology and Allergology ........ 29
1.3.3 Functional Proteomics in Allergology and Clinical Immunology ...... 31
References ................................................................................................................34

1.1

PUTATIVE MECHANISM SUGGESTED FOR INTESTINAL
INDUCTION OF ORAL TOLERANCE ACCORDING
TO LUMINAL ANTIGEN DOSE

It is a fascinating quality of the gastrointestinal tract to generate an immunological
response to bacteria and food components taken in. In a healthy state, the immune
response is adequate to the degree of hazard. Inflammatory reaction is not triggered
by the case of food components and microorganisms which are constantly present
in the gastrointestinal tract flora. They are treated as self. This is possible due to the
anatomy and histology of their structure and to the functional diversification of the
gastrointestinal tract cells. It also results from the capacity to develop a food tolerance phenomenon. This phenomenon is necessary in protecting a macroorganism
against overstimulation of the immune system.
The estimated area of the gastrointestinal tract is approximately 300 m2 and the
estimated amount of food taken in is many tons. Reduced food tolerance could result
in developing chronic and then autoimmunological inflammations.
The balance between induction and inhibition processes is maintained, thanks to
specific and nonspecific immunity. One of the basic factors is the normal structure
of the gastrointestinal tract.

From the intestinal lumen, the esophagus, stomach, and intestines are covered
with two layers of mucus—mobile and static. Mucus creates gel containing mucopolysaccharides and glycoproteins which isolate a cylindrical-epithelium-covered
surfaces. The nondissolving mucus layer is covered by the mobile dissolving layer.
They don’t demonstrate any chemical difference from each other (Mowat, 2003).
Humans are protected against physiological and pathogenic flora invasion by
means of nonspecific humoral response factors. These include low pH of gastric
juice, proteolytic enzymes, lactoferrin, lysozyme, and defensins. Another crucial element is physiological bacterial flora, whose content changes throughout the human
life cycle, and that hinders the development of pathogenic flora; moreover, it also has
immunoregulative functions.
Specific humoral response depends mainly on secretory IgA that are found in
mucus on the surface of intestinal epithelium. They are responsible for blocking
adhesive receptors against pathogenic bacterial flora and hindering protein molecule