D2 Oral tolerance

Question 1

Describe how anaphylatic reactions could be inhibited

Answer 1

Feeding prior to immunisation

Question 2

Define oral tolerance

Answer 2

State of unresponsiveness that exists for non-pathogenic antigens present w/in the gut lumen
(specifically down-regulated to maintain homeostasis)

Question 3

How to prevent DTH response of antigen

Answer 3

Feed antigen > immunise footpad with antigen > challenge footpad > no DTH + no IFNy/Ab production

Question 4

Is cell mediated or humoral immune reposes easier to tolerise

Answer 4

Cell mediated: requires less antigen & lasts longer

• Th1 easier to tolerise than Th2
• IgE responses extremely sensitive to OT

Question 5

What effect does OT have on lymphocyte migration

Answer 5

OT induces defective lymphocyte migration

Question 6

How can OT be broken

Answer 6

Tolerance of Ab production can be broken if the defective Th cells are bypassed with an unrelated carrier or LPS

Question 7

Name the major mechanisms of OT (3)

Answer 7

1. clonal deletion
   - high dose
   - Tc responding to oral antigens are deleted in same way as selection in thymus
   - (Programmed cell death)
2. clonal anergy
   - low dose
   - Tc exposed to antigen in absence of costimulatory molecules do not respond
   - (Tc do not respond (APC presents antigen to Tc but co-stim & danger signals not present))
3. Regulatory Tc
   - Tc exposed to antigen in presence of TGF-b and/or IL-10 are polarised to be come Treg
   - TGF-b found in high levels in epithelial cells in gut

Question 8

What type of processing generates tolerogenic protein

• which cells play a role
• what does intestinal filtration result in
• give example of something that doesn’t transfer tolerance

Answer 8

Intestinal processing
(serum taken 1hr after feeding can can transfer OT/ inhibit DTH via adoptive transfer)
Intestinal filtration results in deaggregated monomers that are tolerogenic in other systems
- Serum taken following antigen administration doesnt transfer tolerance
- Tc play role

Question 9

What dose of antigen is clonal

1. deletion
2. anergy - what reverses

Answer 9

1. High dose of antigen in absence of co-stim molecules

2. Low dose of antigen in absence of co-stim & is being ignored
lacks inflammatory signals
addition of IL-2 reverses

Question 10

OT is prevented if

1. what functions are activated
2. if what cells depleted
3. blocking with type of T cell
4. If what enzymes are inhibited

Answer 10

APC functions
CD4 cells depleted: Tolerance can be transferred by CD4 cells
Treg
inhibition of pancreatic enzymes

Question 11

What is required for maintenance of OT

Answer 11

Antigen persistence

Question 12

coeliac disease is linked closely to which locus

Answer 12

HLA-DQw2 locus