Gut Immunology. goes Africa October 2015
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1 Gut Immunology Michael J. Lentze Children s Hospital Medical Center University Hospitals Bonn/Germany and Givi Zhvania Academic Clinic of Pediatry Tbilisi/ Georgia goes Africa October 2015
2 History A 16 year old boy was refered to us because of vomiting of fresh blood A gastroscopy done in an external hospital revealed esophageal varices Besides the bleeding the boy was malnurished and had loose bloody stools per day The symptoms started several month ago goes Africa 2015
3 Case 1: 16 year old Adolescent
4 Clinical Examination Weight 37 kg, height 160 cm, BMI 14 Severe malnutrition Prominent abdomen Liver 5 cm below costal margin, hard, spleen 5 cm below costal margin Heart, lungs unremarkable What would you do next? goes Africa 2015
5 Macropathology of Bowel
6 Macropathology of the Liver
7 Epitheloid Cell Granulomas in M.Crohn
8 Primary Sclerosing Cholangitis
9 Topics to be covered: Gut Immunology Development of adaptive Immunity Host Bacterial interactions Innate Immunity factors Immunonutrition goes Africa 2015
10 Adaptive Immunity: MALT Dome-Areal with Dendritic Cells and T-cells Lamina propria with lymphocytes Postcapillary venoles Interfollicular region with lymphozytes Corona with B-cells Follicles with B-cells
11 The Intestinal Cell Barrier Peterson LW et al Nature Rev Immunol 14: , 2014
12 Intestinal IgA-Production Gutzeit C et al. Immunol Rev 260: 76-85, 2014
13 Intestinal Features in Germ free Animals Canani RB et al. J Clin Gastroenterol 42: S , 2008
14 Bacteriota in the Human Gut Body cells Bacteriota in Human Gut 10 14
15 Changes of Gut Microbiota during Life The old Paradigma Bacteria / g stool in log Birth Solid Food Adults Mitsuoka 1982
16 Microbiota in 32 Adults from USA over 5 Years Faith JJ et al. Science 341: , 2013
17 Microbiota in 32 Adults, 4 under a Hunger-Diet Faith JJ et al. Science 341: , 2013
18 Human Microbiom has 3 Enterotypes Europa Afrika Arumugam M et al. Nature 473: , 2011
19 Change of Microbiom by Nutrition within 24 Hours Wu GD et al. Science 334: , 2011
20 Adhesion, Colonisation and Crosstalk
21 Triggering of MALT by Bacterial Adherence Where do Lymphocytes come from?
22 Role of CCR9 and CCL25 in T-cell recruitment Homing to Intestine? Agace WW, Trends in Immunol 29: , 2008
23 Dendric Cells are responsible for Homing of T-Cells Agace WW, Trends in Immunol 29: , 2008
24 Homing of T-cells into PP Mechanism? Iwata M Immunity 21: , 2004
25 Homing of Gut T-cells in Vitamin A Deficient mice Vitamin A (+) Vitamin A (-) Iwata M Immunity 21: , 2004
26 Vitamin A helps the Gut T Cells find their way in the Dark Johansson-Lindborn B Nature Medicine 10: , 2004
27 Vitamine-regulated Immune Responese Lamichane et al. J Gastroenterol Hepatol. 28 (Suppl 4): 18-24, 2013
28 Response of Intestinal DCs to Infection Coombes JL, Nature Reviews Imunol. 8: , 2008
29 Role of extracellular ATP Lamichane et al. J Gastroenterol Hepatol. 28 (Suppl 4): 18-24, 2013
30 Sphingosin-1-Phosphate and Allergic Response Lamichane et al. J Gastroenterol Hepatol. 28 (Suppl 4): 18-24, 2013
31 Role of Eosinophils in the Gut Fulkerson PC, Best Pract Clin Gastroenterol 22, , 2008
32 Functions of Gut Eosinophils Fulkerson PC, Best Pract Clin Gastroenterol 22, , 2008
33 Role of Eosinophils in the Gut Woodruff SA et al. JPGN 52: , 2011
34 Clinical Entities Eosinophilic Esophagitis Allergic eosinophilic Gastroenteritis Food protein-induced enteropathy - Cow s milk allergy - DD: Coeliac disease Dietary protein-induced colitis Infantile colics and constipation Inflammatory bowel disease (IBD) goes Africa 2015
35 IEC regulate adaptive and innate Immunity Peterson LW et al Nature Rev Immunol 14: , 2014
36 Innate Immunity Factors: TLRs Cario E. Gut 54: , 2005
37 Microbial Recognition promotes Health and Function Peterson LW et al Nature Rev Immunol 14: , 2014
38 TRLx / NOD2 Pathway Cario E. Gut 54: , 2005
39 TLRx / NOD2 Physiology and Pathology Cario E. Gut 54: , 2005
40 TLRx / NOD2 and Crohn s Disease Cario E. Gut 54: , 2005
41 Inhibition of NOD2-RIPK2 Pathway Canning P et al. Chem Biol 22:1-11, 2015
42 Monogenic Disorders and IBD Uhlig HH Gut 62: ,2013
43 Very Early Onset IBD Uhlig HH et al. Gastroenterology 147: , 2014
44 Function of X-linked Inhibitor of Apoptosis (XIAP) Latour S et al. Semin Cell Develop Biol 39: , 2015
45 XIAP Deficiency Latour S et al. Semin Cell Develop Biol 39: , 2015
46 Antigenicity of MAB s depending of their Origin
47 Anti-Adhesion Antibodies
48 T-Cell Receptor Blockade
49 Blockade of IL-12/IL-23 Pathway
50 Model of Immunonutrion by Food Transfer of Immunomodulation Signals? Cellular? Humoral? Immumodulation of GALT? Food SCFA Food Antigens Fermentation Immumodulation?, Induction of Immune Tolerance?
51 Microflora triggers Development of Tolerance Food Antigens Canini et al. Nutrients 5:651-62, 2013
52 Protection on Infant Gut by Human Milk Glycans Newburh DS et al. Ped Research 61:2-8,2007
53 Effect of enteral Nutrition versus Steroids in Crohn s Disease in Children (n = 19) = Steroids = Enteral Nutrition Ruuska T et al., J Pediatr Gastroenterol Nutr 19: , 1994
54 Nutritional Protection against IBD Vladimiu M et al J Nutr Biochem 24: , 2013
55 Thank you very much for your Attention
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