Immunoglobulin E (IgE) occurs exclusively in mammals and is one of five immunoglobulin (Ig) classes found in man. Unlike other isotypes, IgE is best known for its pathological effects, whereas its physiological role remains somewhat elusive.To trace the emergence of IgE and other post-switch isotypes we have studied Ig expression in two monotreme species, the duck-billed platypus (Ornithorhynchus anatinus) and the short-beaked echidna (Tachyglossus aculeatus), leading to the cloning of IgE, two IgG isotypes in platypus and echidna IgE. The presence of IgE and the conservation of the overall structure in all extant mammalian lineages indicates an early appearance in mammalian evolution and a selective advantage of structural maintenance. Furthermore, both of the two highly divergent platypus γ-chains have three constant domains. Hence, the major evolutionary changes that gave rise to the IgE and IgG isotypes of present day mammals occurred before the separation of monotremes from the marsupial and placental lineages, estimated to have occurred 150-170 million years ago.As the central mediator in atopic allergy, IgE is a prime target in the development of preventive treatments. This thesis describes an active immunization strategy that has the potential to reduce IgE to a clinically significant extent…
Contents
Introduction.
Immunoglobulins
Immunoglobulin features
Immunoglobulins in evolution
What about Mammals
The rise of IgE
IgE features
Switching to IgE
The IgE Network
FcεRI
FcεRII/CD23
Regulation of and by IgE
Why do we have IgE?
IgE and parasitic defense
Other functions?
IgE deficiency
Atopic allergy
The allergic response
Why are allergies increasing?
Current therapeutic strategies
Hyposensitization
Allergen independent treatments
Passive immunization against IgE
Active Immunization against IgE
Present study
Aim
Results and discussion
Cloning and phylogenetic analysis of monotreme ε- and γ chains (I and II)
Comparative analysis of mammalian ε chains (Paper II)
Cloning, structural analysis and expression of Pig IgE (Paper III)
Active immunization against IgE (paper IV)
Loose Ends
Concluding remarks
Acknowledgements
References
Author: Vernersson, Molly
Source: Uppsala University Library
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