Immunosenescence - the role in the immunotherapy of older population.

With ageing of their populations, many societies are challenged with serious systemic diseases. One of the causes of these diseases could be the age-related defects in immune system termed immunosenescence. Immunosenescence is characterized by accumulation of memory and non-functional immune cells, impaired signalling due to restricted repertoire of receptors, overall pro-inflammatory environment and complete dysregulation of the immune system. Consequences of immunosenescence are serious, older people are not able to respond to new stimuli, including infections and vaccinations and are more prone to oncologic, neurodegenerative and autoimmune diseases (Ref. 49).

Prion protein prevents heavy metals overloading of cells and thus protects them against their toxicity.

Physiological function of a prion protein (PrP) is not known yet. Regarding the relation of PrP to heavy metals it is known that PrP is able to bind divalent ions of copper, zinc, manganese and nickel through its octarepeat region. It has been hypothesized but not yet confirmed that PrP could play a role in copper metabolism. In this study, cells expressing human full-length PrP (HuPrP1) and PrP-knockout (PrP0/0/1) cells were incubated with various concentrations of copper, zinc, manganese and nickel for 4 days and then were assayed for intracellular content of these metals and cell viability. The results showed that HuPrP1 cells accumulated less heavy metals than PrP0/0/1 cells when concentrations of heavy metals exceeded physiological level. In conclusion, HuPrP1 cells are more resistant to chronic overload with copper, manganese, zinc or nickel than PrP0/0/1 cells. The resistance to metals overload is caused solely by the presence of PrP, since HuPrP1 and PrP0/0/1 cells differ only in the expression of PrP. These results indicate that one of the functions of PrP can be the modulation of trace heavy metal concentrations in cells and protection of cells against heavy metals overload and subsequent oxidative stress.

Establishment of the cell line expressing human prion protein on PrP0/0 background.

In this work we described preparation of the novel cell lines expressing human prion protein on PrP0/0-background. Prepared cell lines originated from the Nagasaki mice (PrP0/0) and showed a fibroblast phenotype. The expression level of human prion protein in the developed cell lines was comparable to the physiological expression measured in GT1-7 cells. A great advantage of the prepared cell lines was their short doubling time that allowed obtaining of a large amount of cells for the proteomic experiments. Newly established cell lines open a broad spectrum of applications in the prion research. Besides the study of physiological function of the prion protein or its interactome, the new cell lines could be successfully employed as a unique tool for the better understanding of key events in the pathogenesis of prion diseases.

Chronic wasting disease.

Chronic wasting disease (CWD) is the only known prion disease affecting free-ranging animals and has become a serious epidemic in North America. Although any case was reported from Europe, the spread of the disease to other continents and regions cannot be excluded, because the transmission of CWD is the most efficient among prion diseases. This article reviews the host range of CWD including experimentally infected animals, models for potential transmissibility to humans, clinical signs of the disease, pathogenesis, and methods for CWD detection.