immune tolerance

Question 1

what is immune tolerance

Answer 1

state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune respone

Question 2

what are the 3 types of immune tolerance

Answer 2

1. self tolerance
   - prevents damage to self by autoreactive T and B cells (central tolerance and peripheral tolerance)
2. neonatal (reproductive) tolerance
   - necessary for the survival of foetus and placental within pregnant animal (peripheral tolerance)
3. oral tolerance
   - essential that food is tolerated. failure leads to dietary hypersensitivity or IBD (peripheral tolerance in GALT)

Question 3

what are the mechanisms of central tolerance

Answer 3

• potisive selection (survival of functional lymphocytes)
• negative selection ( deletion of self-reactive lymphocytes)

Question 3

what are the mechanisms of peripheral tolerance

Answer 3

• apoptosis (B and T cells)
• anergy (B and T cells)
• inactivation by regulatory T cells, macrophages and dendritic cells (B and T cells)
• receptor revision (B cells)

Question 4

outline the events that occur during the development of tolerance

Answer 4

1. central tolerance starts in thymus and is supported by thymic epithelial cells, fibroblasts and dendritic cells
2. positive selection of T cells = CD4+ and CD8+ double positive T cells maintain contacts with TEC, T cells interact with class 1 and 2 MHC on surrounding cells and those T cekks are retained (MHC1 binding leads to CD8+ cells and MHC2 = CD4+) this ensures T cells are functional
3. negative selection = T cells undergo neg selection against self antigens. T cells which ignore self peptides are retained and those that dont are deleted and recycled. leads to self tolerance
4. B cells basically do the same but with more receptor editing and are made in bone marrow (or bursa of fabricius in birds but who cares about birds)
5. peripheral tolerance detects faulty T and B cells in secondary lymphoid tissues and delete them or make them anergic. (failure = hypersensitivity)

Question 5

what 2 signals are required for the activation of naive T cells

Answer 5

1. interaction of antigen in association with MHC molecules on the surface of antigen presenting cells
2. interactions of co-stimulatory activating molecules such as CD28 on T cells with CD86

Question 6

how does apoptosis occur

Answer 6

• lack of co-stimulatory signal 2 from antigen presenting cell
• downregulation of survivial factors such as IL-2 in the tissue
• binding of the death receptor

irreversible

Question 7

how does anergy occur

Answer 7

• lack of co-stimulatory signal 2 from antigen presenting cell
• functional inactivation of lymphocytes that encounter antigen. the inhibitory receptor on antigen presenting cells

reversible

Question 8

how is peripheral tolerance enforced

Answer 8

• anergy
• apoptosis
• receptor revision

Question 9

what is oral tolerance

Answer 9

• occurs in the intestinal tract, therefore peripheral (GALT)
• can be antigen specific or inhibit lymphocytes of any specificity in the vicinity
• failure results in hypersensitivity disease

goal: shoudlnt respond to dietary antigens or commensals, but can respond to pathogens

Question 10

how is oral tolerance developed

Answer 10

• microbiota plays key role in development through promotion of tolerogenic macrophages, dendritic cells and tregs secreting anti-inflammatory molecules like IL-10
• absence of microbiota is associated with a susceptibility to food allergy
• tolerogenic dendritic cells deliver antigen to the draining lymph node and induce od tregs and promote their homing to GALT
• tregs which home to the lamina propria where they interact with macrophages produce IL-10 and expand treg population in situ
• T and B cell anergy and apoptosis also contribute to oral tolerance
• the role of antibodies in iummune tolerance is poorly understood

Question 11

failure of oral tolerance leads to

Answer 11

immune response to food items leading to food allergies which manifest as:
- atopic dermatitis
- otitis externa
- inflammatory bowel disease
- gluten sensitive eneropathy in irish setters
- protein loosing enteropathy and protein loosing nephropathy in the soft coated wheaten terrier