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Title: Immunosuppression induced by ultraviolet irradiation and the role of urocanic acid
Author: Gilmour, Jill W.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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Ultraviolet radiation (UVR) results in a transient suppression of selected immune responses to antigens encountered following exposure. Urocanic acid (UCA), found in the stratum corneum of the epidermis as the trans-isomer, absorbs UV light whereupon it changes to the cis-isomer. Cis-UCA mimics many of the suppressive effects of UVR on immune responses. Previously cis-UCA has been shown to produce a dose dependent, antigen specific suppression of the delayed hypersensitivity (DH) response to herpes simplex virus (HSV) in a murine model of infection, in an identical manner to UVB-irradiation. A time course of DH revealed an initial response 1 hour after antigen challenge, followed by a second response at 24 hours, both of which were suppressed if the mouse had been UV irradiated or treated with cis-UCA prior to infection. Skin painting murine ears with cis-UCA resulted in a reduction in the number of ATPase positive cells (Langerhans cells) in epidermal sheets prepared 24 hours later, while trans-UCA had no effect. In an attempt to elucidate the mechanism of action of cis-UCA two histamine receptor antagonists were employed; cimetidine (H2) and terfenadine (H1). When cis-UCA was applied together with either of the antagonsists no significant reduction in the number of ATPase positive cells was observed. Similarly if cis-UCA was applied together either antagonists the suppression of the DH response to HSV was blocked. Thus cis-UCA may act through a histamine-like receptor. A number of structural analogues of UCA were tested for their ability to suppress the DH response to HSV to further elucidate the structures required to induce immunosuppression. Tumour necrosis factor-α (TNF-α) has been implicated to be of major importance in the induction of UV-induced immunosuppression. Mice pretreated with neutralizing antibodies to TNF-α were found to be resistant to the immunosuppressive effects of UV, but there was little effect on cis-UCA induced suppression of the DH response to HSV. These results extend the mechanism by which cis-UCA modulates suppression of immune responses.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available