Textbook of Allergen Tolerance

317 Pages·2022·14.242 MB·English

by  Vladimir V. Klimov

Textbook
of Allergen
Tolerance
Vladimir V. Klimov
123
Textbook of Allergen Tolerance
Vladimir V. Klimov
Textbook of Allergen
Tolerance
Vladimir V. Klimov
Clinical Immunology and Allergy Department
Siberian State Medical University
Tomsk, Russia
ISBN 978-3-031-04308-6 ISBN 978-3-031-04309-3 (eBook)
https://doi.org/10.1007/978-3-031-04309-3
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2022
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Werd ich zum Augenblicke sagen:
“Verweile doch! Du bist so schon!”
Dann magst du mich in Fesseln schlagen,
dann will ich gern zugrunde gehn!
Johann Wolfgang von Goethe
Faust I, 1699–1702
When, to the Moment then, I say:
“Ah, stay a while! You are so lovely!”
Then you can grasp me: then you may,
Then, to my ruin, I'll go gladly!
Johann Wolfgang von Goethe
Faust I, 1699–1702
The author dedicates this textbook to the
memory of Dr. Leonard Noon (St. Mary’s
Hospital, Paddington/Imperial College
London, United Kingdom), who helped
millions of people with his revolutionary
invention, allergen-specific immunotherapy.
Preface
The immune system is engaged in many fields related to health and illness, includ-
ing allergy and nervous diseases, but can play both beneficial and harmful roles in
the body. In many ways, it depends on the expression of either “good” or “bad”
genes inherited from our ancestors. Such is the course of nature. Of course, our
knowledge is still insufficient, but must respond to almost everyday attacks of aller-
gens, microbes, tumor cells, and stress. These attacks continue to confront humans
and well-being globally; in particular, a deep understanding of the immunologic
mechanisms and processes will lead us to healthcare improvement.
This manual is written at the interface of allergy, basic immunology, and neuro-
science. It may be helpful for postgraduate medical students, clinical allergists, and
researchers in fundamental allergy and neuroscience fields. The textbook has been
set out in a logical order to allow the reader to understand the basic principles of the
subject.
Tomsk, Russia Vladimir V. Klimov
ix
Acknowledgments
The author wishes to express his gratitude to Professor Vladimir A. Kozlov, DSc,
Research Supervisor, Academician, Novosibirsk Research Institute of Fundamental
and Clinical Immunology (Russia) and Dr. Peter J. Mitchell, FCIL, CL, Founding
Head, Department of Translation and Language Communication National Research
Tomsk State University (United Kingdom, Russia).
Tomsk, Russia Vladimir V. Klimov
xi
Contents
1 Antigens and Allergens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Antigens and Immune Responses . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2.1 Sensitization to Allergens . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 Allergenicity of Allergens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.1 Allergen Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.4 Concept of Atopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
1.5 House Dust Mites (HDM), “Masters of Allergenicity” . . . . . . . . . . . 15
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2 Immune Tolerance at a Glance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.2 Tolerance at a Glance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.3 Antigen Tolerance Due to Primary Organs in the Fetal Life . . . . . . . 30
2.4 Peripheral Tolerance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3 Immune-Derived Maintenance of Allergen Tolerance . . . . . . . . . . . . . . 45
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
3.2 Tolerogenic Dendritic (tDCs) Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 48
3.3 Regulatory T (Tregs) Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
3.4 Other Pro-Tolerogenic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
3.4.1 Regulatory B (Breg) Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
3.4.2 Macrophages (M2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
3.4.3 Myeloid-Derived Suppressor (MDSC) Cells . . . . . . . . . . . . . 55
3.5 Immunosuppressive Cytokines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3.6 Coinhibitory Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
3.7 Blocking or Competing Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . 58
3.8 Tolerogenic Microbiota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
3.9 Pro-Inflammatory Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
3.9.1 Mast Cells and Basophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
3.9.2 Eosinophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.9.3 ILC2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
3.9.4 Neutrophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
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3.9.5 Monocytes and Macrophages (M1) . . . . . . . . . . . . . . . . . . . . 67
3.9.6 Inflammatory Dendritic Cells . . . . . . . . . . . . . . . . . . . . . . . . 67
3.9.7 Helper T Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
3.9.8 Inflammatory Chemokines . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
3.9.9 Molecular Patterns Promote Allergic Inflammation . . . . . . . 70
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
4 The Role of the Neuroimmune Network in Allergic
Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
4.2 Innervation of the Allergic Target Organs . . . . . . . . . . . . . . . . . . . . . 84
4.3 Functional Organization of the Neuroimmune Network . . . . . . . . . . 86
4.4 Types of Synaptic Transmission Neuro Molecules . . . . . . . . . . . . . . 88
4.4.1 Neurotransmitter Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . 89
4.4.2 Place of Neuro Molecules in Allergen Tolerance
Maintenance and Breakdown . . . . . . . . . . . . . . . . . . . . . . . . . 90
4.5 Prevalent Pro-Immunogenic Neuro Molecules . . . . . . . . . . . . . . . . . 93
4.6 Predominant Pro-Tolerogenic Neuro Molecules . . . . . . . . . . . . . . . . 99
4.7 Prevalent Neuro Molecules in the Target Organs. . . . . . . . . . . . . . . . 103
4.8 Polymorphisms and Mutations in Some Neuro Molecules
Genes, and Related Genes, Which May Concern Allergies . . . . . . . . 104
4.9 “Neurogenic Inflammation” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
5 Conventional Atopic Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
5.2 Allergologic Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
5.2.1 Patient’s Current and Past Medical History
and Physical Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
5.2.2 Component Resolved Diagnosis (CRD) . . . . . . . . . . . . . . . . 119
5.2.3 Debates in Allergic Skin Tests . . . . . . . . . . . . . . . . . . . . . . . . 120
5.3 Allergic Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
5.4 Allergic Rhinitis (Rhinoconjunctivitis) . . . . . . . . . . . . . . . . . . . . . . . 127
5.5 Atopic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
5.6 Urticaria and Anaphylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
5.7 Medication Therapy for Allergies . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
5.7.1 Antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
5.7.2 Membrane Stabilizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
5.7.3 Topical Corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
5.7.4 Calcineurin Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
5.7.5 Leukotriene Receptor Antagonists . . . . . . . . . . . . . . . . . . . . . 149
5.7.6 Biologics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
6 Local Atopic Disorders in the Unified Airway . . . . . . . . . . . . . . . . . . . . 165
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
6.2 Local Allergic Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167