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Immunomodulation of Langerhans cells by chemical carcinogens : implications for tumour development

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Qu, Miaomiao 1995 , 'Immunomodulation of Langerhans cells by chemical carcinogens : implications for tumour development', Unspecified thesis, University of Tasmania.

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Abstract

Application of the chemical carcinogen 7 ,12-dimethylbenz(a)anthracene
(DMBA) to murine skin causes tumour development as well as damaging the skin
immune system (SIS). Langerhans cells (LC), the major component of the SIS are
depleted from DMBA treated skin. The overall aim of this thesis was to analyse the
interaction of chemical carcinogens with the LC and to determine the significance of
this carcinogen-caused LC depletion in tumour development.

Analysis of the immune response to DMBA revealed similarities to a
normal antigen. Although BALB/c (H-2d) mice responded poorly to DMBA, this
carcinogen induced a contact hypersensitivity response (CHS) in C3H/HeN(H-2k)
mice, was trapped by the LC in the skin and cells bearing DMBA were detected in the
draining lymph nodes. The tumour promoter 12-0-tetradecanoylphorbol-13-acetate
(TPA) was also found to be antigenic as it induced a strong CHS response in BALB/c
mice as did the contact sensitisers (antigens). A significant decrease in LC number was
caused by the chemical carcinogens DMBA and TPA as well as by the antigens. This
LC depletion was found to be dose dependent and immune tolerance was induced
following application of a second antigen through skin depleted of LC. Consequently
carcinogen and antigen induced depletion both lead to tolerance. This suppression was
cell mediated, because it was adoptively transferred by spleen cells to naive syngeneic
mice.

The effect of LC depletion on the pathogenesis of skin cancer was
evaluated. A low dose (initiating dose) of DMBA that did not cause LC depletion also
failed to cause tumour development. This initiating dose of DMBA followed by
multiple applications of LC depleting doses of the antigen TNCB or the promoter TP A
induced tumour growth. Consequently the LC depleting dose of antigen functioned as
a tumour promoter. An application of the depleting dose of TNCB, when followed by
a large dose of DMBA (a complete carcinogen) accelerated tumour development.
Thus LC depletion, irrelevant to the causes, may impair immunosurveillance.

Item Type: Thesis - Unspecified
Authors/Creators:Qu, Miaomiao
Keywords: Langerhans cells, Cancer cells
Copyright Holders: The Author
Copyright Information:

Copyright 1995 the author - The University is continuing to endeavour to trace the copyright
owner(s) and in the meantime this item has been reproduced here in good faith. We
would be pleased to hear from the copyright owner(s).

Additional Information:

Includes bibliographical references. Thesis (M.Med.Sc.)--University of Tasmania, 1995

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