European Congress of Immunology – Part 5

One could think this post is late as the conference ended nearly a week ago but no it’s not. The post is well aged – just like the final session of ECI: a symposium on the ageing immune system.

The three speaker (Viktor Appay, Martina Prelog and Rafael Solana) gave an excellent overview over the field of immune ageing, which describes alterations of the immune system over time. It is a well-known fact that older people are more prone to get ill, as their immune response gets weaker. But why exactly is this happening?

One reason is exhausted haematopoiesis, the lack of new cells being generated. The frequency of CD34+ progenitor cells in the human blood, for example, decreases with age. In parallel the number of naïve T cells also decrease with age. This is due to the involution of the T cell forming organ, the thymus. Thereby the cells in the organ are gradually replaced by fat. In contrast, an increase of highly differentiated memory T cells can be seen in older people. But while highly specific T cells sound helpful, slow proliferating memory T cells cannot help against never-seen before pathogens, leaving older people more susceptible to disease.

Not just the number of cells differs between older and younger people, the cells are also functionally different. CD34+ progenitor cells, for example, differentiate less efficiently with age and become more likely to form lymphocytes than innate immune cells. NK cells, which also decrease in number with age, proliferate less and gain inhibitory functions in older people further impairing the immune response towards pathogens.

T cells also differ in their functionality in older people; especially CD8+ T cells show decreased activation. This led Viktor Appay to hypothesise that the higher incidence rate of cancer in older people is not just due to higher DNA mutation rates but also decreased immunosurveillance, the mechanism by which the immune system detects and fights cancer. Indeed, he was able to correlate CD8+ T cell activity with tumour prognosis. In order to test the anti-cancer abilities of CD8+ T cells in younger and older people, Appay measured the frequency of in vitro (= in culture) expanded melanoma (Melanin-A)- specific CD8+ T cells in healthy donors. We all carry these tumour-specific cytotoxic T cells in our blood, but do old people have the same number of cells compared to young people? No, they don’t, older people showed significantly less tumour-specific cells in their blood and the cells were also less active. This data strongly suggest a major role of immune cells in cancer development.

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