Immun

• Cells of GIT

  • Epithelial cells
  • Parenchymal cells
  • Goblet cells
  • M cells
  • Paneth cells
• Epithelial cells


  • Layer the GIT
  • Secrete cytokines
  • Absorptive (nutrients)
• Goblet cells


  • Secrete mucus
  • Reside at top of intestinal vili
• M cells


  • Antigen sampling cells
  • On top of lymphoid tissue (dome)
• Paneth cells


  • Secrete anti-bacterial peptides
  • At bottom of crypts
• Innate Immunity of GIT

  • Non-specific physical barrier
  • Non-specific chemical barrier
  • Defensins (Anti-microbial peptides)
• Tight junction


  Between adjacent epithelial cells to prevent entry of pathogens
• Mucus


  Secreted by goblet cells to form thick layer on epithelial cells to prevent pathogen entry
• Defensins


  Anti-microbial peptides produced by epithelial cells and Paneth cells to prevent bacterial invasion
• Toll-like Receptors (TLR)


  Express by epithelial cells to recognize PAMP
• PAMP

  Pathogen associated Molecular Patterns
• PAMP also express by commensal and pathogenic bacteria
• Activation of TLR which facing lumen cause tightening of cells gap
• Activation of TLR at intracellular or bottom induce immunity, only pathogenic bacteria are able to invade epithelial cells
• Adaptive Immunity of GIT

  • Humoral immunity by dimeric IgA
  • Cell mediated immunity by Th17 cells and Regulatory T cells
• Dimeric IgA

  Prevent colonization and invasion of lumen commensal & pathogenic bacteria
• Th17 cells

  Produce IL-17 to induce expression of proteins important for barrier function
• Th2 cells

  Produce IL-4 & IL-13 to enhance mucous secretion and mucosal barrier
• Regulatory T cells (Treg)


  Inhibitory T cells that prevent inflammation against commensal
• GALT - Gut Associated Lymphoid Tissues


  Peyer's Patch - Consist of germinal center (B cells), T cells, DC & macrophages, Dome region between follicles & under the epithelial layer, Not encapsulated, Antigen is not delivered by lymphatic system
• M cells

  Microfold cells located adjacent to dome region of GALT, Transcellular transport of various substance from gut lumen across epithelial barrier to underlying APC
• Some bacteria take advantage on M cells to invade and infect, e.g. Salmonella typhimurium
• Antigen uptake and presentation

  1. DC at lamina propria can extend cytoplasmic tail between the junction to sample the antigen

  2. Once naïve lymphocytes stimulated by DC in Peyer's patch or mesenteric lymph, transform into effector cells

  3. Effector cells released into circulation but homing to GIT
• Humoral Immunity

  Mainly by IgA, but small quantities of IgM & IgG, Neutralize toxins & microbes by inhibiting binding with receptors on host, Produced at lamina propria by plasma cells in dimer forms, bond by J chain, IgA transported to lumen of gut by poly-Ig-receptor via transcytosis
• Total surface area of GIT is 200 m2
• Ileum & Colon have vili & microvili to accommodate large amount of bacteria
• GIT contains 500 different species of bacteria, 10 times > than total cell numbers of human cells
• Defective secretion of defensins cause Crohn's disease
• Colostrums contain high levels of IgA
• Regulatory T cells secrete anti-Inflammatory cytokines IL-10 and TGF-beta
• The aging population is an important health issue
• By 2050: world's population > 60 years = 2 billion
• People are living longer, not necessarily healthier than before
• Lecture Outline

  • Aging of the immune system
  • Cardiovascular disease and inflammation
  • Nutrient deficiencies in the elderly and their link to immunity

  
• Aging


  Gradual changes in structure and function that begins upon maturation and ends in death, that are not due to disease or accident
• Cardiovascular diseases (CVD) such as myocardial infarct and stroke are the leading cause of death worldwide
• Relevant blood tests for CVD

  • Lipid profile
  • hs-CRP
• hs-CRP

  A high-sensitivity C-reactive protein test that is more sensitive than a standard C-reactive protein test, used to check for cardiovascular disease
• Aspirin


  A nonsteroidal anti-inflammatory drug (NSAID) used to minimise the effects of inflammation, pain and fever

  
• Low-dose aspirin


  • Can be prescribed by a physician to help prevent heart attacks and strokes in people who are at high risk of them
  • Common side effects include indigestion, stomach ulcers (if above is untreated), and bleeding