Hiding Lipid Presentation: Viral Interference with CD1d-Restricted Invariant Natural Killer T (iNKT) Cell Activation

The immune system plays a major role in protecting the host against viral infection. Rapid initial protection is conveyed by innate immune cells, while adaptive immunity (including T lymphocytes) requires several days to develop, yet provides high specificity and long-lasting memory. Invariant natural killer T (iNKT) cells are an unusual subset of T lymphocytes, expressing a semi-invariant T cell receptor together with markers of the innate NK cell lineage. Activated iNKT cells can exert direct cytolysis and can rapidly release a variety of immune-polarizing cytokines, thereby regulating the ensuing adaptive immune response. iNKT cells recognize lipids in the context of the antigen-presenting molecule CD1d. Intriguingly, CD1d-restricted iNKT cells appear to play a critical role in anti-viral defense: increased susceptibility to disseminated viral infections is observed both in patients with iNKT cell deficiency as well as in CD1d- and iNKT cell-deficient mice. Moreover, viruses have recently been found to use sophisticated strategies to withstand iNKT cell-mediated elimination. This review focuses on CD1d-restricted lipid presentation and the strategies viruses deploy to subvert this pathway.     

Tele and the social atom

Tele and the social atom are two of the most central concepts in the sociometric theory of Moreno and in the practice of classical psychodrama. Consequently, an abundance of literature has been devoted to these concepts, mainly from a clinical- theoretical point of view. However, progress in understanding the cognitive and neural processes involved in inter-individual behavior can be used to address these issues from a different perspective, inspiring a holistic outlook.The advances made by investigating perception and action in a social context show the implicit formation of an interactive ‘we’ identity during a joint action, thus supporting Moreno’s concept of a reciprocal interactive social process that cannot be broken down to separate subjective elements. Moreover, behavioral interactional synchrony correlates with the emergence of an inter-brain synchronization, accurately supporting Moreno’s “social physiology” hypothesis of corresponding organs in different individuals.Moreno’s sociometric thesis of tele being closely linked with the organization of social atoms is captured by other studies showing that social network size is determined by social cognitive competences and that these in turn are underpinned by the amount of neural matter devoted to the computational demands involved.The remarkable association between Moreno’s early hypotheses and recent scientific evidence suggests that he had a positive tele with science, and encourages methodical thinking about some of his hitherto meta-psychological ideas. By promoting this approach, one follows Moreno’s integrative legacy that combines “the concretely, actively magic-poetic, with the objectively, methodically scientific” (Moreno, Who shall survive? Foundations of sociometry, group psychotherapy and sociodrama, p. xxi, 1953).     

Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (<Emphasis Type="Italic">ELANE</Emphasis>) mutation

We have analysed a family with nine congenital neutropenia patients in four generations, several of which we have studied in a long-term follow-up of over 25 years. The patients were mild to severe neutropenic and suffered from various recurrent bacterial infections. Mutations in the genes ELANE, CSF3R and GFI1 have been reported in patients with autosomal dominant congenital neutropenias. Using a small-scale linkage analysis with markers around the ELANE, CSF3R, CSF3 and GFI1 genes, we were able to determine that the disease segregated with markers around the ELANE gene. We identified a novel mutation in the ELANE gene in all of the affected family members that was not present in any of the healthy family members. The mutation leads to an A28S missense mutation in the mature protein. None of these patients developed leukaemia. This is the first truly multigenerational family with mutations in ELANE as unambiguous cause of severe congenital neutropenia SCN.