Immunological and Clinical Aspects of Allergy

439 Pages·1980·19.498 MB·English

by  T. A. E. Platts-Mills (auth.), M. H. Lessof (eds.)

Immunological and
Clinical Aspects
of Allergy
Immunological and
Clinical Aspects
of Allergy
EDITED BY
M. H. Lessor
Proj'essor oj'Medicine
Guy's Hospital Medical School
London
FISONS LTD., PHARMACEUTICAL DIVISION
LIBRARY
~
MTP~LIMITED
International Medical Publishers
Copyright © 1981 MTP Press Limited
Softcover reprint of the hardcover I st edition 1981
All rights reserved. No part of this publication
may be reproduced. stored in a retrieval system,
or transmitted in any form or by any means,
electronic, mechanical, photocopying, recording
or otherwise, without prior permission from the
publishers.
British Library Cataloguing in Publication Data
Immunological and clinical aspects of allergy.
1. Allergy - Immunological aspects
1. Lessof, Maurice Hart
616.9'7'079 RC584
ISBN-13: 978-94-011-6219-7 e-lSBN-13: 978-94-011-6217-3
001: 10.1007/978-94-011-6217-3
Contents
List of contributors Vll
Preface
IX
1 The biological role of allergy
T. A. E. Platts-Mills
2 Pharmacological mediators of allergy
L. J. F. Youlten 39
3 Diagnostic tests
Prick, Scratch and intradermal tests
M. H. Lessof 53
II Patch tests
M. G. C. Dahl 61
III Challenge tests - oral, nasal and bronchial
R. J. Davies 67
IV Laboratory techniques in immediate hypersensitivity
T. A. E. Platts-Mills 85
4 Allergy in infancy and childhood
I Genetic aspects
M. W Turner 101
II Other aspects
J. F. Price 115
5 Gastrointestinal reactions
M. H. Lessof and P. D. Buisseret 141
v
CONTENTS
6 Allergy and the skin
M. G. C. Dahl 179
7 Respiratory allergy
R. J. Davies 217
8 Hyposensitization therapy
J. F. Price 297
9 Allergy and other organs
I Allergic disorders of the eye
D. L. Easty 311
II Allergic disorders of the ear
N. Mygind and J. Thomsen 357
III Allergy and the kidney
D. Gwyn Williams 365
10 Allergy, insects and arachnids
A. W. Frankland and M. H. Lessof 373
11 Drug allergies
H. E. Amos 389
12 The effect of antibacterial antibiotics on immune reactions and
host resistance to infection
J. M. Dewdney 407
Index 429
vi
List of Contributors
H. E. Amos N. Mygind
Medical Department. Otopathological Laboratory,
ICI Pharmaceuticals Ltd, Rigshospitalet,
Mereside, Copenhagen, Denmark
Alderley Park,
Macclesfield. Cheshire SK 10 4TG T. A. E. Platts-Mills
Division of Immunological Medicine
P. D. Buisseret MRC Clinical Research Centre,
Department of Medicine, Harrow, Middlesex HAl 3UJ
Louisiana State University Medical Center,
New Orleans, Louisiana, USA J.F.Price
Department of Child Health,
M. G. C. Dahl King's College Hospital,
University Department of Dermatology, London SE5 9RS
Royal Victoria Infirmary,
Newcastle upon Tync NEI 4LP J. Thomsen
University ENT Department,
R. J. Davies Rigshospitalet,
Academic Unit of Respiratory Medicine, Copenhagen, Denmark
St Bartholomew's Hospital,
London ECIA 7BE M. W. Turner
Department of Immunology,
J. M. Dewdney Institute of Child Health,
Beecham Pharmaceuticals Research Division, London WCIN IEH
Biosciences Research Centre,
Great Burgh, Epsom, D. Gwyn Williams
Surrey KTl8 5XQ Renal Unit, Department of Medicine,
Guy's Hospital Medical School,
D. L. Easty London SEl 9RT
Department of Ophtl' Ilmology,
University of Bristol L. J. F. YouIten
Bristol Department of Medicine,
Guy's Hospital Medical School,
A. W. Frankland London SEI 9RT
139 Harley Street,
London WIN lDJ
M. H. Lessof
Department of Medicine,
Guy's Hospital Medical School,
London SEI 9RT
Vll
Preface
In the scientific aspects of immunology, the pace of advance has been almost
overwhelming, but with some notable exceptions, clinical benefits have been
slow. For those who are interested in allergy, the situation has been somewhat
different. Here, the scientific aspects have lagged sadly behind other branches
of immunology. There has, however, been a recent explosion of knowledge,
which began with the discovery of immunoglobulin E, and a curious situation
has come to light. The speculations of the older allergists, which had often
been derided as mere inventions, now appear to be largely true. A number of
'preposterous' hypotheses have acquired the respectability that comes with
scientific proof and the entire field is now full of excitement and challenge. It is
no longer doubted that 'reaginic' antibody can sensitize cells that reside
beneath the surface of the skin or mucous membranes. Skin prick tests with
'hair of the tail of the dog' have been legitimized by correlating them with the
carefully validated results of radioallergosorbent tests. It has furthermore
been shown beyond doubt that immunotherapy with increasing amounts of
bee venom really can 'hyposensitize' patients who have previously suffered
anaphylactic reactions to bee stings.
This book has been published in the hope that, in the field of allergy, it will
bridge the gap between basic science and the clinical application. Like many
another volume it has depended on the collaboration of a team of scientists
and clinicians, on the help of an excellent secretary (Miss Sally Wood) and on
the forbearance of the editor's wife and family. To all of these I extend my
thanks.
MAURICE H. LESSOF
ix
1
The Biological Role
of Allergy
T. A. E. PLATTS-MILLS
INTRODUCTION
Allergy as known to lay persons ranges from mild rhinitis in dusty conditions
to severe and even fatal anaphylactic reactions to bee stings or penicillin
injections. However, in all its forms, allergy is known only as a disadvantage.
It is therefore reasonable to ask why the tendency to allergy has persisted, or
put another way, what the biological role of these reactions is. Before making
any assessment of this kind it is essential to understand the underlying
immunological events. Firstly, it is necessary to limit and define the groups of
allergic conditions we are considering. Allergy or 'a state of altered reactivity'
covers a wide range of clinical conditions. In many cases the underlying events
are very poorly understood and the present discussion will be restricted to .
three groups of conditions. Firstly, those conditions characterized by
'immediate' symptoms, positive weal and flare reactions to prick tests and in
most cases evidence for specific IgE antibodies. Secondly, conditions charac
terized by reactions within a few hours and the presence of serum precipitins;
farmer's lung is typical of this group. The third group is characterized by
delayed responses, in particular the wide range of contact sensitivities of which
nickel sensitivity is typical. In each of these groups there is good evidence that
the patients have made an immune response to a protein or chemical
compound. Other individuals who are not allergic either fail to make an
immune response or make a response that does not lead to symptoms.
However, the important feature in all these cases is that the substance that
elicits the reaction does not appear to be harmful in the absence of the allergic
responses. For example, pollen grains, hay dust and nickel are not considered
2 IMMUNOLOGICAL ASPECTS OF ALLERGY
to be toxic materials. It is only in the presence of a particular type of immune
response that they become so.
Although these allergies can be very troublesome to many people and
dangerous to a few, it is not clear that they represent a biological
disadvantage. There appear to be two possible explanations for the persist
ence of allergy. These responses might be an accidental result of an immune
response to certain types of antigen or antigen exposure, which persists
because it is biologically irrelevant. Alternatively, under different circum
stances, these types of response may represent an important part of the
immune reaction to harmful substances or organisms. This chapter will first
summarize what is known about immune responses to allergens and then
speculate about the importance of these reactions.
Allergens and purified allergens
The study of allergy is based on an understanding of the substances that cause
the reactions. Before Blackleyl and Wyman2 demonstrated that grass pollen
was responsible for summer hay fever the nature of the disease was obscure.
Similarly the study of dust allergy has become much more interesting since
Voorhorst et al,3 established that many of the patients were allergic to
the mites growing in the dust. For many years it was thought that allergens
must be inherently toxic. Noon first justified injections of pollen extract as a
method of raising immunity to pollen toxin4• More recently Berrens has
again related allergenicity to non-specific irritant activity5. He also postu
lated that this was due to activation of complement by sugars linked through
N-glycosides to protein5. Studies on purified allergens have generally led to
different conclusions.
Table 1.1 Some purified allergens used as models in studying the antibody responses in allergic
persons
Allergy Source of allergen * Purified allergen Status Molecular
weight
Grass hay fever rye grass pollen group I protein; Rye It major! 27000
Ragweed hay fever short ragweed antigen E; AgEt major 37800
pollen antigen 3 Ra3 mmor 11000
antigen 5 Ra5 mmor 5000
House dust allergy Dermatophagoides Dermatophagoides
pteronyssinus antigen P, P,t major 26000
culture
Bee sting allergy honey bee venom phospholipase A; PLA major 19500
Penicillin allergy benzylpenicilloyl-
polY-L-lysine; BPO major
* Source from which allergen has been purified
t These purified antigens have been shown to account for a large proportion of the IgE antibody to the crude allergen, and
a significant proportion of the total serum IgE
t Purified allergens have been judged 'major' because a high proportion (~90%) of patients with this allergy have IgE antibody
to the allergen
THE BIOLOGICAL ROLE OF ALLERGY 3
A major object of studies on allergen purification has been to understand
what properties lead these substances to give rise to allergy. In most cases the
major allergens have turned out to be freely soluble proteins which are neither
toxic nor irritant to non-allergic persons (Table l.1). Although the function
(e.g. in the pollen grain or dust mite) of most of the purified allergens is not
known, they do not appear to have special biochemical properties. Thus
amino acid analysis and even sequencing have not revealed any distinctive
features of the allergens (reviewed by T. P. King6 and D. G. Marsh7).
Although the chemical properties of allergens do not appear to be related to
their 'allergenicity' the physical properties are distinctive. In addition to being
water soluble they are generally stable and very similar in size. Thus all the
major allergens (e.g. AgE, Rye I, Timothy B, PLA, Dermatophagoides
pteronyssinus P horse dander allergen b cod allergen M, etc.) are between
lo 2,
10 000 and 40000 daltons. The size appears to be limited because molecules
larger than this will not pass freely through mucosal surfaces8. The lower limit
is certainly not absolute, the minor ragweed antigen 5 is only 5000 daltons,
however it is assumed that in general smaller molecules are less immunogenic.
The reason for this might be a lack of repeating structures or simply too few
determinants making it less likely that the molecule would be recognized by
lymphocytes or macrophages. In addition to physical size it is probable that
the rate at which proteins can elute from a pollen grain or dust particle is
important. It has been estimated that under normal conditions a pollen grain
which lands in the nose will be swallowed within 30 minutes7. Belin
systematically studied the time course of elution of allergens from birch
pollen Similar studies on ragweed pollen suggest that AgE elutes slowly
9.
( < 50% in 100 minutes) while other allergens including Ra5 elute rapidly (95%
in 5 minutesf. Thus in assessing an allergen it is necessary to know its size,
solubility, rate of elution and quantity. It is worth sounding a note of caution
because 'major' allergens are the substances to which immune responses have
already occurred. In vivo these allergens are inhaled in pollen grains or dust
which contains other substances. The observations about non-specific irritant
activity have been predominantly made on unpurified extracts, and it is
possible that other substances playa critical role in stimulating the initial
response to an allergenS. Thus the 'irritant materials' might have an adjuvant
effect for an antibody response to the non-irritant 'major' allergens. The
critical experiment would be to show that allergic people can be sensitized by
inhaling small quantities of a purified allergen (see page 13).
Most 'major' allergens represent only a small proportion of the crude
material ( < 1% by weight)? However, much of the material in pollen grains is
not soluble and would not pass through the mucous membrane. Indeed when
aqueous extracts are studied it appears that 'major' allergens often represent a
reasonable or even large proportion of the total protein. Certainly aqueous
extract of rye grass pollen contains good quantities of Rye I (possibly as high
as 15%). Our recent studies on D. pteronyssinus culture illustrate a similar