Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.796106
Title: Langerhans' cells and local cellular immunity in the cervix uteri
Author: Hawthorn, Robert James Seton
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1988
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Abstract:
Dermatological research has shown there is a likely role for Langerhans' cells in initiating the local immune response. They are known to act as antigen presenting cells. Antigen presentation is essential for the generation of the T-cell response. The process involves helper T-cell interaction in the afferent limb of the immune response, with cytotoxic T-cells involved in efferent response. The resultant immune response has been shown to be dependent on the numbers of Langerhans' cells in the epithelium. T-cell mechanisms are primarily involved in immunity to tumours and to viral infections. The study was designed to investigate the possible role of the Langerhans' cell and local immune system in the cervix in relation to neoplastic changes especially since a virus - human papillomavirus (HPV) - is currently thought to be implicated in the aetiology of cervical neoplasia. The investigation of the local immune system with special regard to tumour immunosurveillance is relevant and well suited to studies in the cervix, although access to tissue is limited without specialised techniques such as colposcopy and biopsy. The well documented and easily identifiable preinvasive phase associated with carcinoma of cervix makes it possible to study the whole spectrum of neoplastic change in the cervix. The study therefore involved examination of normal patients, those with cervical carcinoma, patients with cervical intraepithelial neoplasia (CIN), patients at high risk of such changes and other groups of patients in whom T-cell function is known to be compromised. Several methods of identifying Langerhans' cells in the cervix were evaluated. However, the indirect immunoperoxidase technique on frozen sections proved optimal since with the range of specific monoclonal available, Langerhans' cells and T-cell subsets could be easily identified in-situ. The simplest method of quantification used a standard length of basement membrane as the denominator (100 basal cells) but counts with computerised image analyser techniques were also used. Good correlation was shown between the Langerhans' cell count per 100 basal cells and the other methods of enumeration investigated. Studies in normal patients showed that Langerhans' cells were a consistent finding in the cervical epithelium of the transformation zone and ectocervix, being present in both areas in similar numbers. Examination showed the majority of the cellular infiltrate in the epithelium and stroma was of T-cell origin. Helper T-cells were shown to predominate in the stroma and cytotoxic T-cells in the epithelium. The image analyser was most useful in quantifying this lymphocytic infiltrate. The T-cell infiltrate was shown to be similar in the ectocervix and transformation zone. A series of 142 patients with CIN were investigated using the same techniques. Internal control biopsies of ectocervix were available for comparison in most instances. Analysis of results showed that two groups were distinguishable, one with concomitant histological features of human papillomavirus infection and the other without. The Langerhans' cells were significantly reduced in the first group and significantly increased in the second compared with the numbers in internal control biopsies. In the lesions showing histological evidence of HPV infection the lymphocytic infiltrate appeared to be influenced by the presence of class II Major Histocompatibility (MHC) antigens on the epithelial cells. The number of helper and cytotoxic T-cells were significantly greater in the epithelium and stroma of MHC class II positive lesions. The percentage composition of the infiltrate was not different comparing the MHC class II positive with the class II negative lesions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.796106  DOI: Not available
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