Summary: Immunology And Disease

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• Mucosal immunity and diseases (Paul de Vos)

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• What is the role of adipocytokines?

  Adipocytokines are regulated by adipose tissue, important for regulation of energy and glucose homeostasis, PLUS it is also an immunoregulatory cytokine.

• What is the immuno-endo function of adiponectin?

  Adiponectin regulates insulin sensitivity
  
  High adiponectin --> extra calories are stored in adipose tissue
  
  Low adiponectin --> extra calories are stored in dangerous places such as liver, heart and muscles. Organs most sensitive for insulin resistance and diabetes. 
  
  Note: Obese mice with high adinopectin never develop diabetes.

• The gut is the largest immunological organ. How many of the lymphocytes does the gut contain and which immunoglobulines are produced here?

  The gut contains 3/4 of all lymphocytes (of which 90% are CD8+ T cells),
  and 90% of all immunoglobulines are produced here (5 gr IgA per day)

• The mucosal immune system consists of two distinct compartments, the epithelium and lamina propria. Which compartment contains which immune cells?

  Epithilium: CD8+ T cell, dendritic cells
  
  Lamina propria: CD4+ T cell, dendritic cells, B cells, macrophages, mast cells, plasma cells

• Describe the unique collaberation between epithelial cells and dendritic cells in Peyer's patches when encountered by an antigen.

  1) M cells take up antigen by endocytosis and phagocytosis.
  
  2) The antigen is then transported across the M cells in vesicles and released at the basal surface.  
  
  3) The antigen is then bound by dendritic cells, which activate T cells.

• Which cytokines released from the dendritic cell, makes the T cell express IFN-y and IL-17?

  IL-6 and TGF-B

• In what two ways can dendritic cells capture antigens from the lumen?

  - Dendritic cells can extend processes across the epithelial layer to capture antigen from the lumen of the gut
  - Antigens can cross the epithelial layer.

• Intraepithelial T-cells are always activated and ready to kill. Describe the process of how IELs get activated by a virus infecting a mucosal epithelium cell.

  1) The virus infects a mucosal epithelium cell.
  
  2) Infected cell displays viral peptide to CD8 IEL via MHC class 1
  
  3) Activated IEL kills the infected epithelial cell by perforin/granzyme and Fas-dependent pathways.     

• Intraepithelial T cells are always activated and ready to kill. Describe the process of how IELs get activated as a result of infection, damage, toxic peptides.

  1) Epithelial cells undergo stress as a result of infection, damage, or toxic peptides and as a result express MIC-A and MIC-B. 
  
  2) NKG2D on IELS bind to MIC-A,B and activate the IEL. CD8a:a homodimers bind to TL.
  
  3) Activated IEL kills the stressed cell via the perforin/granzyme pathway.

• What is the effect of disorders in intraepithelial T-cells?

  A disorder in IELs cause fast spread of pathogens in the epithelium (Listeria)