Natural cellular cytoxicity in tumour surveillance and immunity to infections

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White blood cells sense and attack microbes and tumours, eventually destroying them. Immunity to infections and cancer is regulated two main branches, which are known as natural, or innate, and acquired, or adaptive. Innate immunity protects us when we encounter a microbe, but it cannot store immunological memory and does not clear the infection. The adaptive immune system can do both, but it is slow to set in motion, taking at least 4-5 days for the first specific antibodies to be made. Conveniently, the innate immune system is geared up to keep the invasion under control during this time lag. So the two systems really depend on each other and cross talk to achieve the most effective response to microbes and tumours. We want to understand how these two systems talk to each other and, in particular, we want to know how natural killer (NK) cells - a special type of white blood cells that spontaneously kill infected and tumour cells participate in clearing microbes and delaying tumour growth. NK cells are part of the innate immune system. Their killing machinery is very similar to that of other white blood cells, which instead belong to the adaptive immune system and are called Cytotoxic T-Lymphocytes (CTL). The genes and proteins that regulate the killing process in the two cells are so similar that it has been very difficult, until today, to know what does what. Mouse models are important to help understanding of how physiological and pathological processes work in real life, in the whole animal. We have discovered a line of genetically modified laboratory mice that have normal killer cells in the adaptive immune system. But the killer cells of the innate immune system are totally faulty in these mice. The reason for that is the absence of a single gene (phospholipase C-gamma2) that regulate key steps in the organisation of the killing machinery of innate but not adaptive immunity. So we have the unique opportunity to learn more about the immune system in health and disease. We will learn how this gene can influence the clearance of viruses and bacteria, and whether it has an impact on the development of cancer. Knowing more about how innate and adaptive immune system work, we will be able to think of more effective cures against infections and cancer.

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