01 - September 10, 2013 - notes.docx

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University of Toronto St. George
Laboratory Medicine and Pathobiology

LMP402 September 10, 2013 Mortality curves Sharp drop and straight line – 150 years ago – equal likelihood of dying in twenties and sixties Sixty percent of deaths due to infectious diseases 5 to ten thousand years ago – mortality curves identical to 150 years ago – suggests lack of medical access or poor medical care Infectious diseases have been with us a long time – large impact on survival Immune system effective at population level – good enough so can allow for population to reach reproductive years How bacterial toxins cause disease, if they do – and how the immune system detects bacteria/pathogen and how it responds Tests – answer based Host-microbe interactions 90% of cells are bacterial in body Commensals in the gut Difficult to grow in culture – majority of commensal bacterial When fighting pathogens, initiate inflammatory response – if too dramatic, can damage host – energy intensive response Do not want to be mounting response against commensal bacteria Avoiding inflammation by commensals Mucus layer – acting as physical barrier so no interaction between microbes and epithelial cells and initate inflammation In small intestine – absorbing nutrients – in small intestine, one of the mechanisms to reduce inflammation is to release anti-microbial peptides into lumen of the gut – insert themselves in the membrane of the microbes and disrupt the membrane and kills them – close to the intestine and keep them segregated away PAPER Vaishnava, S. et al Lectin = carbohydrate binding protein Raising the question Only bacteria cells have 16S rRNA probe; this probe can interact with all the microbes – “UNIVERSAL” Looked at mice lacking Myd88 – what is the role of innate immune system in forming spatial segregation? Physical separation – dependent on myd88? Why knockout myd88 but not say TLR4? MyD88 is almost universal – so can make only one knockout species Suggesting Epithelial cells are sensing the microbe, and doing something to create the segregation zone Results – right side Figure 1 Quantitating the wild-type mice in solid circles – knockout in white circles Looking at amount of fluorescence with increasing distance from villus The graph in panel B – show that there is a zone of segregation, where in the wild-type, low
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