Week 1: Mucosal Immunity

Question 1

Organization of GALT (gut associated lymphoid tissue)

Answer 1

1. Peyer’s patches: lymphoid structure where antigens interact with gut immune system and prime naive lymphocytes
2. Effector lymphocytes: scattered in intraepithelial and lamina propria
   - intraepithelium: CD8 with CCR9+ and integrin aEb7 homing T cells
   - lamina propria: CD4, CD8, with CCR9 and integrin a4b7 homing. Also have plasma cells, Macs, DCs, eos, mast cells
   - Peyer’s patches: naive T cells with CCR7 and L selection homing

Question 2

How does antigen get to Peyer’s patch? What happens to the T cells (migration)?

Answer 2

• M cells: specialized epithelial cells that transport luminal antigens into Peyer’s patches to prime T and B cells
• antigens taken up by M cells activate immature DCs. Matured DCs activate naive T cells
• activated T cells drain via mesenteric lymph node to thoracic duct. Return to gut via blood stream via homing molecules

Question 3

B cell function in the gut

Answer 3

• primed B cells home to gut. Induced by T cells to switch to IgA
• Secreted IgA on gut surface can bind and neutralize toxins
• IgA can bind and neutralize toxins internalized in endosomes
• IgA can export toxins and pathogens from lamina propr. back to lumen while being secreted

Question 4

Homeostasis of GALT: regulatory T cells

Answer 4

• 2 types of Treg
• Tregs suppress immune response against commensals
  1. Thymic: during development, requires recognition of self antigen. In peripheral tissues to prevent harmful reactions to self
  2. Peripheral Treg cells
• from mature naive CD4 T cells that are exposed to antigen in periphery
• in presence of commensal bacterial, production of TGFb and other cytokines inhibit DC maturation. immature DCs induce T cells to Treg cells

Question 5

Contributing factors to pathogenesis of inflammatory bowel disease.

Answer 5

1. mucosal immune homeostasis is broken
   - Treg is defective or effector T cells are overactive
2. interacting factors
   - genetic susceptible patients (NOD2 mutations-loss of function may induce increased immune response due to loss of modulation of Nf-kB activation–>hyper activation of NFkB->increased inflammatory cytokines )
   - excessive immune responses to normal gut flora or other foods

Question 6

Mechanisms for different therapeutic options for IBD.

Answer 6

1. steroids and immunosuppressants
2. antibiotics
3. anti-TNFa
   - may increase susceptibility to opportunistic infections: TB, fungal.
4. anti-cytokines
5. Inhibition of NFkB
6. T Cell homing blocker
7. Augment the T reg responses:
8. Probiotics