L8 - immunology of gut mucosa 1

• what does the mucosal immune system do?

  protects internal epithelial surfaces from pathogens and microbes

  include the gut, respiratory tract, urinogenital tract and exocrine secretory glands linked to these organs eg salivary, lachrymal, pancreas and mammary glands
• mucosal surface - surface that secretes mucus
• challenges to mucosal surfaces?

  respiratory tract

  • particulates
  • pollutants
  • allergens
  • airborne pathogens

  gastrointestinal tract

  • food
  • commensals
  • ingested pathogens

  urogenital tract

  • introduced pathogens
  • sperm
• small quantities of food and proteins absorbed intact

  Not just aa absorbed into body, also absorb whole proteins (small amount) - important to understand

  • Important to view of food allergies - immune B cell response is mounted more towards the whole antigens than peptides
  • Immune response towards whole antigens are where most antibody responses are directed to
  • Conformational epitopes
• infection of oral tolerance (mucosally-induced systemic tolerance) - classic mucosal immunology protocol

  feed ovalbumin to 1 group of mice, then 14 days challenge mouse or inject OVA into mouse to look for antibody or cellular immune response

  2nd group, feed mouse with control - PBS - just saline, then challenge with OVA and look for antibody or cellular immune response
• why is ovalbumin used?

  is a model protein from chickens - very good antigen for stimulating tolerance in animals
• tolerance induction by prior feeding in mice


  /????
• innate immune defences

  the tissues of the mucosal immune system are the lymphoid organs and cells associated with the gastrointestinal, respiratory, and urogenital tracts, as well as the oral cavity, pharynx, middle ear, and the glands associated with these tissues, such as the salivary glands and lacrimal glands. The lactating breast is also considered part of the mucosal immune system
• innate immune defences

  barriers - mucus, cilia, pH, tight-cell junctions

  cells - epithelial cells, neutrophils, tissue macrophages, DC

  receptors - TLRs, mannose, scavenger

  mediators - lysozyme, defensins, cathelicidins
• adaptive immune defences

  tissues

  • mucosa associated lymphoid tissue
  • regional lymph nodes

  cells

  • T-cells
  • B-cells
• mucosa associated lymphoid tissue

  • Nasal associated lymphoid tissue, NALT, e.g. tonsils
  • Bronchial associated lymphoid tissue, BALT
  • Gastrointestinal associated lymphoid tissue, GALT, e.g. Peyers patches
• regional lymph nodes

  • Retropharyngeal, submaxillary and parotid LN
  • Mediastinal LN
  • Mesenteric LN
• T-cells

  • Th1, Th2, Th17, Treg
• B-cells

  • Lots of IgA plasma cells, some IgM, and some IgG secreting cells
• mucosal associated lymphoid tissues

  large aggregates of lymphoid tissue in the intestine
• Mucosal Associated Lymphoid Tissues


  ???
• Mucosal Associated Lymphoid Tissues

  Peyer's patches

  isolated lymphoid follicles

  cryptopatches
• Peyer's patches

  multi-follicular
• isolated lymphoid follicles


  exist in a range of sizes, with larger displaying germinal center characteristics
• cryptopatches


  considered to develop into single B-cell follicles

  contain mainly innate lymphoid cells (ILCs)