Abstract Malignant transformation of melanocytes and further neoplastic progression may be associated with qualitative and/or quantitative changes in expression of HLA class I and class II antigens. Since previous immunohistochemical studies of surgically removed melanoma lesions have suggested a relationship in the expression of HLA class I and class II antigens, we have investigated the expression of these antigens at the single cell level. Double immunofluorescence staining of frozen sections of melanoma metastases and immunoelectron microscopic double labelling of melanoma cell suspensions prepared from three of these lesions has detected three HLA phenotypes on the large majority of melanoma cells: either both HLA class I and class II antigens, neither HLA antigen or only HLA class I antigens. In four out of the 11 lesions a few melanoma cells were found to express HLA class II antigens and to lack HLA class I antigens. A relationship was also found in the level of expression of HLA class I and class II antigens, as estimated by the intensity of staining with monoclonal antibodies. The level of expression of HLA class II antigens appeared to be similar to or lower than that of HLA class I antigens on the large majority of melanoma cells. This coordinated heterogeneity in the expression of HLA class I and class II antigens by melanoma cells may have implications in the interactions of tumour cells with the host's immune system.
The main objective of this
thesis is to improve the understanding of the role of helminth infections in
the development of insulin resistance, hence type 2 diabetes, and to gain
insight into the immunological mechanisms underlying this possible interaction.
To this end, we initiated a large scale cluster randomized controlled trial,
assessing the effect of anthelmintic treatment on insulin resistance and other
metabolic, as well as immunological parameters, in a rural area of Indonesia.
Deworming significantly reduced the prevalence of helminths, as well as
infection intensity. Although treatment did not lead to an increase of
whole-body insulin resistance at the community level, a significant increase in
insulin resistance was observed among helminth-infected subjects. Furthermore,
by comparing immune cells of helminth-infected Indonesians before and after
treatment, we gained insight into the specific cell populations that
participate in the type 2 and regulatory networks, and show that treatment
affects specific cell subsets in these networks. Altogether, the studies
described in this thesis show that helminth infections in humans, as well as
the administration of helminth molecules in obese mice, have a beneficial effect
on the insulin sensitivity, and have shed light on the immunomodulatory effects
of helminths.
