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2. Immunosuppression induced by ultraviolet irradiation and the role of urocanic acid

Author

Gilmour, Jill W.

Subjects
616.079
Abstract

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.

Published
1993

6. Oral Typhoid Vaccination With Live-Attenuated Salmonella Typhi Strain Ty21a Generates Ty21a-Responsive and Heterologous Influenza Virus–Responsive CD4+ and CD8+ T Cells at the Human Intestinal Mucosa

Author

Pennington, Shaun H., Thompson, Ameeka L., Wright, Adam K. A., Ferreira, Daniela M., Jambo, Kondwani C., Wright, Angela D., Faragher, Brian, Gilmour, Jill W., Gordon, Stephen B., and Gordon, Melita A.

Subjects
Pathogenesis and Host Response, Adult, CD4-Positive T-Lymphocytes, Male, T cells, immunoglobulins, Administration, Oral, Enzyme-Linked Immunosorbent Assay, cellular immunity, CD8-Positive T-Lymphocytes, Vaccines, Attenuated, Major Articles and Brief Reports, Ty21a, Young Adult, Immunogenicity, Vaccine, Salmonella, heterologous immunity, humoral immunity, Humans, Intestinal Mucosa, Immunity, Cellular, Polysaccharides, Bacterial, Typhoid-Paratyphoid Vaccines, Salmonella typhi, Orthomyxoviridae, Antibodies, Bacterial, cytokines, Immunity, Humoral, Female, typhoid
Abstract

Background. Oral vaccination with live-attenuated Salmonella Typhi strain Ty21a is modestly efficacious, but the mechanisms of protection are currently unknown. While humoral and cellular immune responses are well described in peripheral blood, the cellular response at the intestinal mucosa has never been directly assessed. Methods. We vaccinated healthy adults with Ty21a and assessed humoral and cellular immunity in vaccinated volunteers and controls after 18 days. Immunoglobulin levels were assessed in peripheral blood by an enzyme-linked immunosorbent assay. Cellular responses were assessed in peripheral blood and at the duodenal and colonic mucosa by flow cytometry. Results. We demonstrate the generation of Ty21a-responsive and heterologous influenza virus–responsive CD4+ and CD8+ T cells at the duodenal mucosa. All duodenal responses were consistently correlated, and no responses were observed at the colonic mucosa. Peripheral anti-lipopolysaccharide immunoglobulin G and immunoglobulin A responses were significantly correlated with duodenal responses. The assessment of integrin β7 expression intensity among peripheral and duodenal T-cell subsets revealed varied capacities for mucosal homing and residence. Conclusions. The breadth of duodenal cellular responses was not reflected peripherally. The direct evaluation of mucosal immune defense may yield functional correlates of protection and could provide insight into mechanisms that may be manipulated to enhance vaccine immunogenicity.

Published
2016

9. Oral Typhoid Vaccination With Live-AttenuatedSalmonellaTyphi Strain Ty21a Generates Ty21a-Responsive and Heterologous Influenza Virus–Responsive CD4+and CD8+T Cells at the Human Intestinal Mucosa

Author

Pennington, Shaun H., primary, Thompson, Ameeka L., additional, Wright, Adam K. A., additional, Ferreira, Daniela M., additional, Jambo, Kondwani C., additional, Wright, Angela D., additional, Faragher, Brian, additional, Gilmour, Jill W., additional, Gordon, Stephen B., additional, and Gordon, Melita A., additional

Published
2016
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