Mario Capecchi
The Role of Microglia in Controlling Behaviour
Disruption of Hoxb8 causes chronic anxiety and pathological overgrooming. We have shown that optogenetic stimulation of Hoxb8 microglia in specific regions of the brain induces elevated anxiety and/or pathological grooming. Conversely behavioural stimulation of mice induces calcium transients within microglia within specific regions of the brain. Calcium signaling is responsible for the induction of behaviours. Similar processes occur in humans.
Immunology as a field of medical enquiry has drifted away often to turn purely academic, because the interest and appreciation of protective immunity in infectious disease medicine has been overtaken by ‘l’art pour l’art’ of so-called ‘basic immunology’. This development deprives much of immunological sciences of the biological basis and understanding that must be linked to co-evolution of infectious agents and hosts’ protective immunity. It is this co-evolutionary context that renders this field so different from studying yeast, bacteria, fibroblasts, lymphocytes, or neuronal cells in splendid isolation in in vitro model situations, where everything is possible (and permitted or mistakes forgiven without repercussions) because the co-evolutionary context is ignored by too many. The key role of protective antibody levels is their transferability from mother to immune incompetent offspring.
Dan Shechtman
Quasi-Periodic Materials – A Paradigm Shift in Crystallography
Crystallography has been one of the mature sciences. Over the years, the modern science of crystallography that started by experimenting with x-ray diffraction from crystals in 1912, has developed a major paradigm – that all crystals are ordered and periodic. Indeed, this was the basis for the definition of “crystal” in textbooks of crystallography and x-ray diffraction. Based upon a vast number of experimental data, constantly improving research tools, and deepening theoretical understanding of the structure of crystalline materials no revolution was anticipated in our understanding of the atomic order of solids.
However, such revolution did happen with the discovery of the Icosahedral phase, the first quasi-periodic crystal (QC) in 1982, and its announcement in 1984 [1, 2]. QCs are ordered materials, but their atomic order is quasiperiodic rather than periodic, enabling formation of crystal symmetries, such as icosahedral symmetry, which cannot exist in periodic materials. The discovery created deep cracks in this paradigm, but the acceptance by the crystallographers' community of the new class of ordered crystals did not happen in one day. In fact, it took almost a decade for QC order to be accepted by most crystallographers. The official stamp of approval came in a form of a new definition of “Crystal” by the International Union of Crystallographers. The paradigm that all crystals are periodic has thus been changed. It is clear now that although most crystals are ordered and periodic, a good number of them are ordered and quasi-periodic.
While believers and nonbelievers were debating, a large volume of experimental and theoretical studies was published, a result of a relentless effort of many groups around the world. Quasi-periodic materials have developed into an exciting interdisciplinary science.
This talk will outline the discovery of QCs and discuss their structure as well as the role of TEM in the discovery.
[1] D. Shechtman, I. Blech, Met. Trans. 16A (June 1985) 1005-1012.
[2] D. Shechtman, I. Blech, D. Gratias, J.W. Cahn, Phys. Rev. Letters, Vol 53, No. 20 (1984)
Rolf M. Zinkernagel
Immunological Memory Is an Idea, Antigen Re-Exposure the Mechanism
With the help of infectious viruses, I shall critically review the following parameters:
- Definition of specificity; by very small phenolic haptens or by protective antigenic sites against infections and e xplain efficient stereotypically defined vs. less efficient cross protective vaccines.
- The importance of antigen as the (major, only?) regulator of immunity versus the idea of regulatory T cells.
- Protective immunity by vaccines against the classical acute childhood infections (e.g. rabies or measles), by neutralizing antibodies, whereas vaccines are often not efficient against chronic persistent infections (e.g. TB, leprosy, HIV or malaria).
- Affinity maturation of antibodies against poor or cytolytic infections is too slow, and against noncytopathic agents so slow, that HIV or plasmodia escape by mutation.
- So called immunological memory is an experimental artefact. It is the pre-existent level of protective (neutralizing) antibodies (or the number of pre-activated T cells) that determine protection. Re-stimulation of so-called memory B cells to become antibody secreting plasma cells or T cells take about five days and therefore is generally too slow for rapid efficient protection.
In summary, I conclude that we cannot do better immunologically than co-evolution if we use the same tools as evolution has been using so far. However, we certainly can do better if we use new tools not used by evolution such as antibiotics, antivirals, autoantibodies, and, very important, education.
