Search

Exposure to UV radiation can cause suppression of specific immune responses. The pathways leading to the down-regulation are complex, starting from the absorption of UV photons by chromophores in the skin and ending with local and systemic changes in immune mediators, the generation of T and B regulatory cells and inhibition of effector and memory T cell activation. The consequences for human health are thought to be both beneficial and adverse. The former are illustrated by protection against polymorphic light eruption, and possible protection against T cell-mediated autoimmune diseases and asthma. The latter are illustrated by skin cancer, cutaneous lupus erythematosus and infectious diseases including vaccination. Many outstanding questions remain in this rapidly developing and controversial area, not least what advice to give the general public regarding their sun exposure. While considerable advances have been made in the development of strategies that preserve the health benefits of sunlight exposure and decrease its detrimental effects, further research is required before optimal levels of protection are achieved., (© 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.)

The appearance of lines CBA and C57Bl/6 in the urine of mice irradiation volatile excretions with immunosupression property was associated with the violation at mice of ability to immunogenesis. It was established, that immunosupression activity of excretions irradiated mice CBA and C57Bl/6 did not depend on genotip of mice. However, by irradiated mice C57Bl/6 immunosupression components, depressing antibody formation at intact mice, appeared earlier, than at CBA. Immunosypression, limited postradiation volatile secretion in view of depression humoral immune response at intact mice kept for not a long time and mostly expressed on the course 2-3 days after exposition with postradiation secretion.

Ultraviolet radiation is the most common environmental carcinogen humans are exposed to. It is now known that in order for skin cancers to develop, both genetic damage and immunosuppression is required. Ultraviolet-induced immunosuppression is therefore a key contributor to the development of skin cancer. Little is known about the relative contributions of the different ultraviolet spectra (A and B), however. Therefore detailed ultraviolet dose-response curves for systemic suppression of contact hypersensitivity in two mouse strains were determined to examine the relative contributions of each of these spectral components of sunlight to primary and secondary immunity. Whereas ultraviolet B caused a linear dose-related immunosuppression in both C57BL/6 and Balb/c mice, only C57BL/6 mice were immunosuppressed by medium doses of ultraviolet A. At higher ultraviolet A doses, C57BL/6 mice were protected from immunosuppression, suggesting a genetic predisposition to ultraviolet-A-induced immunomodulation. Surprisingly, we found that, in contrast to primary immunosuppression, low dose ultraviolet A enhanced the secondary immune response, whereas ultraviolet B caused antigen-specific tolerance. When ultraviolet A and ultraviolet B were combined to mimic sunlight (solar-simulated ultraviolet), immunosuppression and tolerance were only observed over a narrow dose range as the memory-enhancing effect of low dose ultraviolet A and the immunoprotective effect of higher dose ultraviolet A prevented the suppressive effects of ultraviolet B. These studies suggest that complex relationships between ultraviolet dose, immunomodulation, spectra, and genetic background are likely to be important for skin cancer induction. We also describe for the first time that low doses of ultraviolet A are able to enhance secondary immunity, which has important implications for vaccination strategies.

Ultraviolet B radiation (290-320 nm) initiates a dose and wavelength dependent down-regulation of cell-mediated immunity which is critical in experimental ultraviolet radiation (UV) carcinogenesis, preventing immune attack on highly antigenic UV-induced tumors. UV-induced immunosuppression has been demonstrated in humans and may be a risk factor for skin cancer. In this study, we have investigated genetic linkage of the autosomal loci controlling this trait. Previously, we had derived a model describing control of susceptibility to UV-induced immunosuppression in inbred mice by unlinked interacting autosomal and X-linked loci. A genome-wide scan using MIT microsatellite markers was carried out on 100 backcross (BALB/c x (BALB/c x C57BL/6) F1) mice derived from the inbred strains BALB/c (low susceptibility) and C57BL/6 (high susceptibility) and tested for systemic UV-induced immunosuppression of a contact hypersensitivity response. The values for % suppression for each animal and the genotype data were used to investigate genetic linkage by multiple regression analysis. Significance was assessed using the permutation test. Both main effects and interactive effects were investigated, first with each genotype marker singly, and secondly, in a novel approach using markers pairwise. A joint model was derived in which all loci and pairs of loci identified were included simultaneously in a multiple regression model. This model indicates four quantitative trait loci (QTLs) with significant main effects, one on chromosome 10 which decreased susceptibility to UV-induced immunosuppression and QTLs on chromosomes 6, 17 and 1 which increased susceptibility. Additionally, loci on chromosomes 14 and 19 showed significant interaction with the locus on chromosome 1. Further investigation indicated a potential three-way interaction involving the loci on chromosomes 1, 14 and 19.

An attempt was made to examine the regulatory effect of bifidumbacterin on the recovery of immunological and hemopoietic homeostasis in mice. Bifidumbacterin feeding to healthy animals had no effect, except for the below-normal values reaching the statistically mean characteristic of mice of this strain. Bifidumbacterin stimulated lymphoiesis in animals immunocompromized by the administration of antilymphocytic antibodies or radiation, but the values being no higher than the normal ones. The same action was seen with erythropoiesis during postradiation loss of red blood cells. The activation or suppression of erythro- or myelopoiesis, which was not caused by direct damage to these cellular populations, but which occurred with the activation of nonspecific T helpers or T suppressors in impairments or recovery of the count of circulating mature lymphocytes under the action of bifidumbacterin, was blocked.

Acute, low-dose ultraviolet B (UVB) radiation alters the local skin site such that epicutaneous application of hapten fails to induce contact hypersensitivity (CH), but induces tolerance in UVB-susceptible mice. Although the inability of irradiated skin to support CH induction may be a strictly local effect, there may also be systemic immune consequences of UVB radiation delivered in this manner. To examine this matter, abdominal skin of C57BL/6 mice was exposed to acute, low-dose UVB radiation. Dinitrofluorobenzene was immediately painted directly on the irradiated site, or at a distant (unirradiated) site. In separate experiments, epicutaneous application of the hapten on a distant site was delayed for 1-3 days. The mice were tested for acquisition of CH, and for tolerance, i.e. the capacity to become sensitized when exposed subsequently to hapten via normal body wall skin. It was found that, immediately after completion of the UVB regimen, CH was inducible via unirradiated, but not via irradiated, skin. At 3 days post-UVB exposure, CH was no longer inducible even through unirradiated skin. Mice that first encountered hapten via UVB-exposed skin developed tolerance, as did mice that first encountered hapten via unirradiated skin of UVB-treated mice. Neutralizing anti-tumor necrosis factor-alpha TNF-alpha antibodies failed (a) to restore the ability of unirradiated skin to support induction of CH, and (b) to interfere with tolerance induction, whether hapten was first painted on irradiated or unirradiates skin. The data indicate that the acute, low-dose regimen of UVB radiation produces effects on the immune system that are manifest locally as well as systemically. By demonstrating that the disruption of CH induction following UVB radiation is TNF-alpha dependent, whereas locally and systemically induced tolerance is not, our findings encourage further search for other UVB-related modulators of systemic immunity and tolerance.

Increasing UVB radiation at the earth's surface might have adverse effects on in vivo immunologic responses in humans. We prospectively randomized subjects to test whether epicutaneous immunization is altered by prior administration of biologically equalized doses of UV radiation. Multiple doses of antigens on upper inner arm skin (UV protected) were used to elicit contact sensitivity responses, which were quantitated by measuring increases in skin thickness. If a dose of UVB sufficient to induce redness (erythemagenic) was administered to the immunization site prior to sensitization with dinitrochlorobenzene (DNCB), we noted a marked reduction in the degree of sensitization (P less than 0.0006) that was highly dose responsive (r = 0.98). Even suberythemagenic UV (less than a visible sunburn) resulted in a decreased frequency of strongly positive responses (32%) as compared to controls (73%) (P = 0.019). The rate of immunologic tolerance to DNCB (active suppression of a subsequent repeat immunization) in the groups that were initially sensitized on skin receiving erythemagenic doses of UV was 31% (P = 0.0003). In addition, a localized moderate sunburn appeared to modulate immunization with diphenylcyclopropenone through a distant, unirradiated site (41% weak responses) as compared to the control group (9%) (P = 0.05). Monitoring antigen presenting cell content in the epidermis revealed that erythemagenic regimens induced CD1a-DR+ macrophages and depleted Langerhans cells. In conclusion, relevant and even subclinical levels of UV exposure have significant down modulatory effects on the ability of humans to generate a T-cell-mediated response to antigens introduced through irradiated skin.

The primary immune response elicited by host antigens in a grafted population of immunologically competent cells has been compared in conditions where the same dose of parental cells were grafted simultaneously to F(1) hybrid embryos of 13 or 17 days of age. The enlarged chimeric spleens harvested 4 days later were analyzed for donor cell proliferation by using the sex chromosomes as karyological markers, and for proliferation of immunological activity by means of transfer to secondary hosts of the same genotype. Whereas the total number of dividing donor cells were on the average 16 times higher in 17-day than in 13-day hosts, the recovery of immunological reactivity showed a 6- to 7-fold difference in the opposite direction. The experiments cast doubt on the proposition that cellular proliferation is necessary for development of a primary immune response. They suggest that there exists an alternative way in which a primary immune response may unfold from involving a few to involving a much larger number of cells.