Intestinal Immunity

1
Intestinal Immunity

• The intestinal mucosa must defend itself against
  many toxic agents yet ignore commensal organisms
  and dietary antigens which are not threats.
• There is constant antigenic exposure and self non
  self recognition of key importance.

2
GALTGut Associated lymphoid tissue

• Peyers patches contain specialised
  microfold(M)cells which transport antigens to the
  underlying lymphoid tissue.
• The remaining cells have tight junctions which
  allow transport of water and ions but not
  macromolecules(Digestive products?)
• Rich mucosal surface containing glycocalix mucus
  and IGA(40mg/kg body weight a day)
• Closely packed microvilli also prevent pathogen
  entry

3
M Cells

• Large particles such as bacteria enter by
  phagocytosis
• Viruses by endocytosis
• Direct delivery of pathogens to the immune
  system.
• Also shown to signal via interleukins to the
  immune system.
• Some pathogens (polio salmonella )use as route of
  entry to the body.

4
Immune response Th1VS Th2
Th1
Th2
5
Th2
Th1
Childhood development and antigenic exposure
influences adult Th responses.
6

• Th 1 increase in bacteria and virus infection
• Th2 in response to parasites and initiate mast
  cell deregulation and promote eosinophil
  production.
• Is IBD an inappropriate T cell response?
• Maybe if M cells loose their tight regulation of
  substance transport.

7
Genetic Advances

• Chromosomes Genes DNA Protein
• Chromosome 6 interleukin antagonist and close to
  MHC marker site also linked to site for TNFalpha
  gene.
• Chromosome1(CD)
• Chromosme3(CD)
• Chromosome5(cd)
• Chromosome12(UC)
• Chromosome 14(CD)

8
Chromosome16 NOD2 (CD)

• Nucleotide oligomerisation domain or CARD caspase
  activating recruitment domain
• Variants in 43 CD patients
• Early onset and ileal disease
• What does it do? Protein which regulates
  inflammatory response to bacterial infection
  recognises a protein in bacterial cell wall.

9
Other theories

• Under production and abnormnal mucus production.
• Microvasculature involvement
• Endothelin vasoconstrictor slows down leukocytes
  and allows them to adhere to endothelium
  potentiates inflammation
• Metabolic cellular changes