Katwa: Immune Function

Question 1

M cells

Answer 1

• specialized epithelial cells on top of peyer’s patches
• sample the contents of the small intestine
  
  • provide info about the GI lumen to the immune cells and GALT
  • constantly transport gut bacteria and antgiens to lyphoid tissue
• present antigens to macrophages and lymphcytes
  
  • immune cells secrete cytokines
  • cytokines trigger inflammatory response
  • increase in Cl-, fluid, and mucus secretion

Question 2

Gut Epithelium: Immune Function

Answer 2

• M Cells
  
  • found in epithelium over GALT
  • transport gut bacteria and antigens from gut lumen to lumphoid tissue
• Dendritic cells
  
  • lamina propria
  • sample gut bacteria
• Epithelium also filled with:
  
  • CD8b T cells
• Lamina Propria also filled with:
  
  • CD4 T cells, macrophages, Plasma Cells (IgA producing)

Question 3

Secretory Diarrhea

Answer 3

• Enterotoxin-induced chloride secretion
  
  • from E. Coli

Question 4

Colonic Microflora

Answer 4

• Mix of microbes
  
  • diversity and composition
  • healthy & Sick
  • plays a role in:
    
    • obesity
    • malnutrition
    • Crohn’s disease
• Microorganisms instead of Flora
  
  • 700-1000species
• account for 60% of feces dry weight
• Symbiotic relationship:
  
  • Produce vitamin K and B (Biotin, B7)
  • ferment starches into fatty acids
    
    • SCFA absorption
  • Stimulate deverlopment of immune system
  • Probiotics, prebiotics, and synbiotics

Question 5

Colonic Microflora: Probiotics, Prebiotics, Synbiotics

Answer 5

• Probiotics
  
  • for life
  • bacteria resistant to gastric acid and proteolysis
  • prevent or treat a variety of digestive disorders
• Prebiotics:
  
  • special form of diet fiber
  • nourishes the good bacteria already present in the colon
  • limit the growth and invasion of pathogenic microorganisms
• Synbiotics:
  
  • contain both prebiotic and probiotic activity

Question 6

Colonic Microflora: Metabolic effects

Answer 6

Question 7

Serotonin produciton

Answer 7

• produce Metabolites that stimulate ECL cells to produce 5HT
  
  • SCFA
  • Metabollic Products
  • Secondary Bile Acids
    
    • deoxycholate
• Stimulate ECL: Tph1 and Chga Genes
  
  • `Tph1=rate-limiting enzyme in serotonin pathway
  • Chga-released with serotonin
  • releases 5HTStimulates:
    
    • Smooth Muscle
    • Blood Vessel
    • Platelet mediated transportDistal effects:
      
      • Bone development
      • Cardiac Function
• Microbiota release 5HT directly to M cells
  
  • release serotonin
  • stimulate
    
    • Enteric Nervous system (2nd brain)
    • Immune system

Question 8

Intestinal Gas

Answer 8

• ~1L odorless gas/day
• Produced by intestinal bacteria
  
  • digestion/fermentation of nutrients in colon
  • polysaccharides (beans, lentils)
    
    • not digested in small intestine

Question 9

Composition of Intestinal Gas

Answer 9

• Nitrogen
• Co2
• Methane
• Hydrogen
• Butyric acid, hydrogen sulfide, carbonyl sulfide

Question 10

Hydrogen Sulfide

Answer 10

• smells like rotten eggs
• colon cancer metabolism

Question 11

Gut Micronbiota: Developement and disease

Answer 11

• continuously influences human health from birth to old age
• Early enviromental factors (Method of delivary), nutritional factors (Beast or bottle-feeding) and epigenetic factors
  
  • influence development of gut and microbial symbionts
• Altered gut microbiota composition in early life increase developing disease
  
  • IBS/IBD/Cancer
  • Ulcers
  • Asthma, HTN
  • Mood & Behavior
    
    • GLP1 signaling

Question 12

Gut microbiota is made up of what microorangisms

Answer 12

• 2 bacterial phyla
  
  • gram negative-Bacteroidetes
  • Gram positive-Firmicutes

Question 13

Xenobiotic Metbolism

Answer 13

• aka Drug Metabolism
• Xenobiotics/drugs
  
  • inhibits microbial growth
  • cause cell death
• Microbiota interacts:
  
  • directly
    
    • catalyze various biotransformations
  • indirectly
    
    • effect expression and activity

Question 14

Swallowing a Drug

Answer 14

• Tilt the gut-brain axis
  
  • alleviates the symptoms of neurodegenerative diseases (Parkinsons)
• Can resist tilt
  
  • Gut Microbe metabolize and lessen the efficacy of levodopa
  • TyrDC from E. faecalis and Dodh from E. lenta A2
    
    • metabolize Levadopa into metatyramine

Question 15

Infant Gut Microbiome

Answer 15

• Beast fed
  
  • contain
    
    • mainly Bifidobacterium infantis
    • some other microbes
• Formula fed
  
  • mixed
    
    • less B. infantis
• Digestion of Human milk oligosaccharides (HMOs) by Milk oriented microbiomes (MOM) Bifdiobacterium result in production of into gut lumen:
  
  • lactate
  • short chain fatty acid acetate
• These lower the pH in the intestine, and improves their transport into the epithelium for use by the host
  
  • creates a undesirable enviroment for pathogens (E. coli)

Question 16

Bifidobacterium: Benefits

Answer 16

• B. Bifidum Eat only subsets of HMOs (human milk oligosaccharides)
  
  • Glycosyl hydrolases
    
    • breakdown HMOs into mono and disaccharides in extracellular space
    • transported and cross-feeding
      
      • instestinal microbes eat
    • Mono and disaccharides further metabolized into acetate and lactate
  • B. Bifidum is less eficient consumer of HMOs
    
    • produces less acetate and lactate
• B. infantis consumes all HMO over any other carbohydrate source
  
  • binding proteins GLOM on to HMOs and bring carbs to transporters that bring them into bacterial cell
  • Intracellular glychosyl hydrolases break glycosidic linkage of all HMO structures
    
    • produce monosaccharides
  • Monosacchardies are metqabolized into acetate and lactate and secreted from cell