nutr4320 midterm

• Microbiota


  All the bacteria in the environment
• Microbiome


  All the genetic material found in the microbiota
• What is lactose?

  galactose and glucose
• How does lactose pass through the apical border?

  by SGLT1
• What are the 4 phases of monosaccharide absorption?

  1. remove Na+ from the cell
  2. SGLT1 requires Na+ and glucose
  3. GLUT2 allows diffusion into blood
  4. SGLT1 needs continuous removal of Na+
• Primary lactase deficiency?

  inherited, irreversible
• Secondary lactase deficiency?

  acquired, reversible
• Lactase non-persistance?

  wildtype, low lactase activity due to low lactase gene expression
• Lactase persistance?

  mutant, individuals who retain intolerance into adulthood
• Global prevalence of lactose intolerance?

  70%
• SNP?


  single nucleotide polymorphisms, associated with lactase persistance (mutant), located on the MCM6 gene which influence the lactase promoter
• What do CDX2 and HNF-1a do?

  activate LCT transcription
• PDX1?

  Blocks CDX2 and HNF-1a, the ability to activate LCT transcription
• What does low PDX1 cause?

  LCT gene expression
• Osteoporosis?


  decrease in bone quality and quantity
• Organs relevant to calcium homeostasis?

  1. small intestine: absorption
  2. kidney: reabsorption
  3. bone: resorption
• Hormonal control maintaining calcium?

  1. PTH: 1st response to low blood calcium, increase calcium by stimulating bone to release calcium
  2. calcitriol: 2nd response to low blood calcium, increase blood calcium by bone resorption
  3. calcitonin: response to high blood calcium, inhibits resorption
• How do you stop the PTH?

  Calcium binds with CASR (calcium sensing receptor)
• Bone cells?

  • osteoblast: bone forming through ossification
  • osteoclast: bone resorption/ breakdown
  • osteocyte: stimulates osteoblast
• What is bone made of?

  organic matrix and bone salts (phosphorus, calcium, hydroxyapatite)
• Bone formation?

  deposition of proteins, osteocalcin binds calcium and hydroxyapatite, osteoectin binds hydroxyapatite to collagen to form a lattice
• Regulating osteoclast activation (bone breakdown)?

  • RANK-L binds to RANK, stimulating cell to mature osteoclasts, bone breakdown
  • stimulated by: calcitriol, PTH, inflammatory cytokines
  • Osteoprotegerin: RANK-L antagonist, binds to RANK-L forming a complex that blocks RANK, inhibits osteoclast maturation, stimulated by estrogen
• Bone remodelling?

  • osteoclast expression of RANK-L stimulated by M-CSF
  • no M-CSF= no RANK-L= no osteoclast expression
  • osteoclast sealed by integrin and vitronectin
• Bone turnover?

  • resorption stimulators: inflammatory cytokines (TNFa, IL-6), RANK-L bound to RANK, PTH
  • resorption inhibitors: cytokines (IFNY, IL-4), calcitonin
• dietary bioactives and bone resorption

  long chain n-6 PUFA: balance between osteoclast and osteoblast, increases RANK-L

  long chain n-3 PUFA: decreases NFKB, STAT3
• metabolic syndrome requirements?

  1 of: type 2 diabetes, impaired glucose intolerance, impaired fasting glucose, insulin resistance

  2 of: high blood pressure, dislipidemia, high waist circumference, microalbuminuria
• Antigen presenting cells?

  • at the entry sites: GI tract, skin, airway
  • presenting of antigens (gluten) to T cells by MHC2
  • MHC2 binds with T receptor on CD4+ cell
• absorption of proteins in small intestine (CD)

  • Antigen (gluten) associated with MHC molecule transported to cell surface
  • MHC molecule and antigen (gluten) recognized by T cell
  • T cell activates= T helper cells= T helper 1
  • T cell proliferation= T cell clones, release cytokines
• CD4+ T cell subsets?

  • Th0= naive T cells, have never seen gluten before
  • Th0 differentiation to T helper and T cell clones
  • T helper cells= CD4+ T cells
  • T reg= regulatory T cell, stop celiac immune response
  • T reg suppressed in celiac disease
• grain subfamily?

  pooidae
• Physiology of celiac disease?

  • high proline= resistant to digestion
  • high glutamine= deamination by transglutaminase (TTG/tTG)
  • Result it large peptide with high proline and glutamine
  • HLA encode for MHC2 receptors
  • HLA-DQ2 and HLA-DQ8 express celiac disease
  • HLA-DQ2: negative residues at 4, 6, 7
  • HLA-DQ8: negative residues at 9
• Explain celiac disease

  1. gluten incompletely digested, leaks across epithelial barrier, increase gluten peptides bind with HLA-DQ2, HLA-DQ8
  2. Naive CD4+ T cell encounter gluten for the first time, T cells to TH1, produce TFNY, tissue damage
  3. IFNY promotes apoptosis, activate APC to secrete TFNa, release MMP-1 and MMP-3, tissue damage
  4. mucosa damage, loss of micovilli and villi

  
• What do B cells in celiac disease do?

  make antibodies against the small intestine causing damage
• Anti-gluten antibodies?

  • anti-gluten and gluten bind with CD71
  • CD71 transports gluten across epithelial barrier to lamina propria and brings gluten to TTG
  • Signals a gluten immune response
• B cells and celiac

  • anti-TTG should neutralize TTG
  • when TTG bound to anti-TTG, can't function right and becomes leaky
  • associated with type 1 diabetes and herpetiformis
• Zonulin

  • increased zonulin with celiac disease= increase permeability of epithelial barrier
  • Zonulin binds with CXCR3
  • Zonulin-CXCR3 loosens tight junctions, increases permeability