Biomedical subjects

Gregory M Woods

Publications and source records attributed to Gregory M Woods.

5 recordsLinked to original sources

PubMed2006

Neonatal exposure to UV-B radiation leads to a large reduction in Langerhans cell density, but by maturity, there is an enhanced ability of dendritic cells to stimulate T cells.

Australia has the highest incidence of skin cancer in the world and ultraviolet (UV)-B radiation has been implicated as its major aetiological agent. Despite the link between melanoma and exposure to UV-B radiation in childhood, little work has been carried out to determine the effects of UV-B on neonatal skin. In this study, we investigated the response of adult and neonatal Langerhans cells (LC) to UV-B radiation to determine whether exposure in the neonatal period impairs the development of the skin immune system, thus having implications for the immune response later in life. Neonatal and adult mice were irradiated with a single dose of UV-B radiation and epidermal sheets prepared to determine the number of LC present. In addition, antigen carriage and T-cell proliferation assays were carried out to assess the immune response when the mice reached maturity. Results showed that neonatal LC were more susceptible than adult LC to depletion at 2 kJ/m(2) UV-B exposure; however, there was similar susceptibility at lower doses. When mice that were irradiated as neonates were analysed at maturity, there was an increased ability to respond to cutaneously applied antigen as more antigen was transported to the lymph node and the lymph node dendritic cells had an enhanced ability to stimulate T-cell proliferation. In addition, this response was skewed towards a Th2 type response. Thus, single high-dose UV-B exposure alters the development of neonatal LC, resulting in a short-term reduction in the number of LC but an enhanced immune response when assessed at maturity.

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PubMed2003

Antibody response to sheep red blood cells in platypus and echidna.

There is limited information regarding the kinetics of antibody responses exhibited by the platypus and the echidna in response to a T cell dependent antigen. In this preliminary study a platypus, an echidna and a rabbit were inoculated with sheep red blood cells to compare their antibody responses and kinetics. The antibody titres, produced by the platypus and echidna, were less than those elicited in the rabbit. Furthermore, the echidna and platypus exhibited a weak secondary response. This was most likely due to a failure of the platypus and echidna to undergo the characteristic IgM to IgG isotype switch following second antigen exposure. The conformational structure of these antibodies may differ from eutherian antibodies. This was further supported by a heat sensitivity experiment that indicated that these antibodies are more labile than rabbit immunoglobulins and therefore structurally less stable.

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PubMed2003

DEC-205lo Langerinlo neonatal Langerhans' cells preferentially utilize a wortmannin-sensitive, fluid-phase pathway to internalize exogenous antigen.

Antigen treatment of neonatal epidermis results in antigen-specific immune suppression. Compared with adult counterparts, neonatal Langerhans' cells (LC) demonstrate an impaired ability to transport antigen to the lymph node (LN). As it is possible that neonatal LC have a reduced ability to endocytose antigen, we evaluated the acquisition of endocytic function, the expression of uptake receptors and the internalization of soluble and small particulate antigens in neonatal, juvenile and adult mice. Although LC from 4-day-old mice were weakly positive for the mannose-type receptor, Langerin, they were capable of internalizing fluorescein isothiocyanate (FITC)-dextran, but to a lesser extent than LC from 6-week-old mice. However, when ratio data were calculated to account for variations in fluorescence intensity at 4 degrees, it was demonstrated that neonatal LC continued to internalize antigen over a longer period of time than adult mice and, as the ratios were much higher, that neonatal cells were also relatively more efficient in antigen uptake. When receptors for mannan and mannose were competitively blocked, LC from neonatal mice, but not adult mice, could still efficiently internalize FITC-dextran. Consequently, the uptake of FITC-dextran, in part, occurred via alternative receptors or a receptor-independent fluid-phase pathway. A feasible pathway is macropinocytosis, as LC from 4-day-old mice demonstrated a reduction in FITC-dextran internalization by the macropinocytosis inhibitor, wortmannin. Evidence of a functional macropinocytosis pathway in neonatal LC was further supported by internalization of the soluble tracer Lucifer Yellow (LY). We conclude that neonatal LC preferentially utilize a wortmannin-sensitive, fluid-phase pathway, rather than receptor-mediated endocytosis, to internalize antigen. As neonatal LC are capable of sampling their environment without inducing immunity, this may serve to avoid inappropriate immune responses during the neonatal period.

Androstadienes↗

PubMedDate not supplied

Decrease in langerhans cells and increase in lymph node dendritic cells following chronic exposure of mice to suberythemal doses of solar simulated radiation.

Exposure of certain strains of mice to ultraviolet radiation (UVR) causes suppression of some innate and adaptive immune responses. One such consequence of acute UVB exposure is a reduction in the number of Langerhans cells (LC) in the epidermis and an increase in dendritic cells (DC) in lymph nodes draining the irradiated skin sites. Exposure to chronic UVB irradiation also has effects on the immune system, but it is unknown what effects are caused by repeated doses of solar simulated radiation (SSR). Consequently, the main aims of the present study were to determine whether repeated exposure to low doses of SSR would lead to similar changes in these cell populations and whether chronic doses of SSR activate a protective photoadaptation mechanism. Groups of C3H/HeN mice were irradiated daily with 3.7 J/cm(2) SSR from Cleo Natural lamps for 2, 10, 20, 30 or 60 days. Further groups of mice received an additional dose of 7.4 J/cm(2) SSR on days 2, 10, 30 or 60 to test for photoadaptation. The numbers of LC in the epidermis and DC in the lymph nodes draining irradiated skin sites were counted 24 h after the final irradiation. With the exception of mice irradiated for only 2 days, LC were significantly reduced throughout the chronic irradiation protocol, and no recovery occurred. DC numbers were significantly increased in the draining lymph nodes of mice irradiated for 20 days and 60 days.

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PubMedDate not supplied

The skin immune system and the challenge of tumour immunosurveillance.

The Skin Immune System (SIS) is a relatively new concept central to the issue of cutaneous tumour surveillance. The Langerhans cell (LC) is a key component of SIS. Skin cancer causing agents such as ultraviolet B (UV-B) irradiation and chemical carcinogens like dimethylbenz(a)anthracene (DMBA) alter LC function, resulting in immunosuppression and the promotional phase of tumour development. Once tumours, such as melanoma, are established they may show evidence of tumour regression due to immune reaction but frequently escape immune attack and metastasise. This article explores our knowledge of LC and SIS in these responses. For tumour immunosurveillance to be an effective reality at the clinical level, experiments are required to provide a more precise base for immunotherapy.

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