4-
`
`(..14-7CA..1
`
`NIELS MYGIND MD
`Senior Lecturer in Otopathology
`Otopathological Laboratory
`University Ear Nose and Throat Clinic
`and Institute of Pathological Anatomy
`Rigshospitalet, Copenhagen, Denmark
`
`FOREWORD BY
`A.W.FRANKLAND
`MA, DM
`Guy's Hospital, London
`Formerly DireCtor, Allergy Department
`St Mary's Hospital, London
`President, European Academy of
`Allergology and Clinical Immunology
`
`SECOND EDITION
`
`BLACKWELL SCIENTIFIC PUBLICATIONS
`OXFORD LONDON EDINBURGH BOSTON MELBOURNE
`
`—2111111110°—'
`
`Aquestive Therapeutics, Inv. v. Neurelis, Inc. - IPR2019-00451
`Neurelis - EX. 2022
`
`

`

`Contents
`
`Foreword by A .W .Frankland
`Introduction
`Acknowledgements
`Abbreviations
`
`PART I: ULTRASTRUCTURE
`
`1 Structure and ultrastructure of the nose
`2 Applied physiology of the nose
`
`PART II: Il‘SUNOLOGY
`
`3 The immune system
`4 Allergens and allergen extracts
`5 Genetics and prevalence of atopic allergy
`6 Sensitization
`7 Mast cell degranulation
`8 Significance of IgG antibodies
`9 Non-immunological factors
`10 Inflammatory reactions
`11 Eosinophilleucocytes
`12 Allergy diagnosis
`13 Immunology of nasal secretion
`
`PART III: DISEASE
`
`14 Hay fever
`15 Perennial rhinitis
`16 Nasal polyps
`17 Secretory otitis media
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`239
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`

`•
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`Fig. 1.2 (cont.)
`(c) Partly ciliated peeudostratified epithelium. Some cells are covered by microvilli
`and others also by 50-100 cilia. lbe central cell is a filled goblet cell with central
`displacement of microvilli ( x 3,300). From Mygiod (1975). By courtesy of RhinolairY•
`
`being very complex (Fig. 1.4). Formerly it was believed that the central
`microtubules act as a 'skeleton ' and the peripheral microtubules as 'muscles'
`for the ciliary motion. This is not correct as the microtubulea are not
`contractile, but they are involved in the mechanism of ciliary motion
`(Seth' 1974).
`
`The energy for moving the cilium is supplied, as in other cellular work processes,
`by the breakdown of adenosin triphosphate (ATP). The enzyme that accomplishes
`this breakdown in cilia is an ATP-ase, named dynein. It is localized to a series of
`projections called dynein arms that protrude from one side of each of the nine outer
`doublets (Fig. 1.4). According to Satir (1974) energy production in the dynein arms
`causes peripheral microtubulee to slide past one another, and shear resistance in the
`
`St'
`
`DM
`1g CTM
`
`111
`IV
`II
`I
`Fig. 1.3. Transmissibtrelectron microscopic diagram of the four cell types in nasal
`respiratory epithelium.
`T: Non-ciliated columnar celrcovered by microvilli of uniform length. II: Goblet
`cell, packed with mucigest granules. Slight prominence of the cell at the luminal
`Basal cell. IV: Ciliated columnar
`surface, and disappearance of most microvilli.
`cell, covered by cilia and microvilli of uniform length. The cilia contain micro-
`tubules and are anchored to the cell surface by the basal bodies. Many mito-
`chondria in the luminal part of the cell.
`DM: Double-membrane, which constitutes the electron microscopic basement
`membrane. CTM: Connective tissue membrane, which together with the double-
`membrane constitute the light microscopic basement membrane.
`
`cilium changes sliding to bending. The hypothesis that this is the mechanism of
`ciliary motion is called the sliding-microtu bole hypothesis.
`In a few individuals a hereditary lack of dynein arms causes ciliary non.
`motility and result in severe chronic airways infection (Fig. 1.5) (Pedersen
`& Mygind 1976).
`The cilia in the human nose are 0.3 pm in diameter, 4 6µm long and there
`are about 100 per cell.
`There exists some doubt regarding the number of cilia per cell. Transmission
`electron microscopy of human trachea showed the number to be 250 (Rhodin 1974).
`Estimated by scanning electron microscopy the number is 50 100 in the anterior part
`of the human nose (Fig. 1.2c) (Mygind & Bretlsu 1974a), and 40-50 in the middle ear
`(Shimoda & Lim 1972). Differences in the methods used and the mucosa studied may
`account for the discrepancies.
`
`Aquestive Therapeutics, Inv. v. Neurelis, Inc. - IPR2019-00451
`Neurelis - EX. 2022
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