Vol 10, Issue 6, 2017 Online 2455 3891 Print 0974 2441 The role of The ClINICAl AND MoleCUlAr ASSAYS IN ProSTATe CANCer DeTeCTIoN fATeMeh MANSoUrI1,2* 1Department of Medical Immunology and Genetics, f[.]
THE JOHN CURTIN SCHOOL OF MEDICAL RESEARCH Division of Immunology and Genetics On the Role of Cell Mediated Cytotoxicity in a Mouse Model of Flavivirus Encephalitis Rosa Maria Licön Luna A thesis subm[.]
Our entire medical framework is based on the concept of disease, understood as a qualitative departure from normality (health) with a structural substrate (lesion), and usually an identifiable cause (aetiology). This paradigm is loaded with problems, some of which are discussed in the text. Nevertheless, we study, diagnose and treat diseases, and while often painfully conscious of the dysfunctionalities of this scheme, we can hardly imagine how we could practice medicine otherwise. However, most of the recent developments in basic sciences, and most notably in Immunology, Genetics and -omics, are inconsistent with this “health/disease” paradigm. The emerging scenario is that of complex networks, more in the spirit of Systems Biology. In these settings the qualitative difference between health and disease loses its mean- ing, and the whole discourse becomes progressively irreducible to our conventional clinical categories. As clinical re- search stagnates while basic sciences thrive, this gap is widening, and a change in the prevailing paradigm seems un- avoidable. However, all our clinical judgments (including Bayesian reasoning and Evidence Based Medicine) are rooted in the disease/health dichotomy, and one can hardly conceive how they could work without it. The shift in paradigm will not be easy, and certain turmoil is to be expected.
Mathematics has a long tradition in biology and medicine, going back at least to Gregor Mendel’s work in genetics and Theodor Boveri’s work on the nature of the chromosomes . However, as the various subfields have become more specialized, and understanding of biological systems more detailed, modelling has often been dismissed or ‘regarded with suspicion, partly because much modelling seems an empty intellectual exercise that fails to deliver biological insight’ . In immunology, the situation is not much different . Some com- monly cited reasons for the separation between experimental immunology and mathematical modelling are (i) the pace of discovery of new agents and new phenomena in the immune system, accompanied by new jargon, (ii) the rapid advance of technology, producing ever more data, and (iii) the contrast in aca- demic environments, culture and terminology. In our view, these issues (at least the first two) are in fact reasons why mathematical modelling will become increasingly important in immunology (and other fields of biology) . It is pre- cisely because intuition is insufficient beyond a certain level of complexity that analysis of the immune system must become more quantitative [5– 7].
ver the past 50 years, a few burning questions have been at the forefront of biological science. In textbook sketches, the lymphatic system stopped at the head. All along it felt wrong and there was a feeling that blushes were inevitable. We said things such as, ‘Don’t sneeze too hard – you’re losing brain cells!’ – almost taking every last sip from the cup of our predestined human potential. We were taught that nerves could never regenerate and that you should never bump your head. We had just mastered machines and begun to peer over the edge. We became fascinated with numbers. First it was, ‘How many genes does each one of us possess?’ After discovering that it was half that of the rice plant, we panicked a little, but had to find something to do with all those counting machines. So we counted something else and turned our attention to the microbes in our gut. To our horror, we realised that they made identical neurotransmitters to our own and used the same receptors to listen in on the cross-talk as we do. Genetics, epigenetics and artificial intelligence – the pebble was now skimming across the water. Yet did we ever ask, ‘How do immune cells get into and out of the brain?’
Molecular genetics approaches now offer one of the most exciting means of delivering a "subunit" vaccine which would be cost effective. The problem with subunit vaccines has been the inability to maintain sufficiently high levels of antigen in the gut to stimulate antibody production in a cost-effective manner. Recently, candidate antigen genes have been introduced into "harmless" enteric bacteria. These bacteria proliferate for some time and exhibit considerable greater staying power in the gut than simple gelatin capsules filled with antigen. This method of immunization is currently under investigation. But think about it, no microbe which can colonize a human should be considered totally"harmless." Also, some of the plasmid vectors used are marked with genes encoding antibiotic resistance 15 .
Over the past decade, there have been numerous advances in our current understanding of the immune system and how it functions to protect the body from infection. Given the complex nature of this subject, it is beyond the scope of this article to provide an in-depth review of all aspects of immunology. Rather, the purpose of this article is to provide medical students, medical residents, primary-care practitioners and other health- care professionals with a basic introduction to the main components and function of the immune system and its role in both health and disease. This article will also serve as a backgrounder to the immunopathological dis- orders discussed in the remainder of this supplement. The topics covered in this introductory article include: innate and acquired immunity, passive and active immu- nization and immunopathologies, such as hypersensitiv- ity reactions, autoimmunity and immunodeficiency.