Central & Peripheral tolerance

Question 1

Define immune tolerance

Answer 1

The failure of the adaptive immune system to respond to an antigen

(it is essential in the prevention of autoimmunity where the immune system attacks its own cells)

Question 2

Describe the 2 forms of tolerance

Answer 2

• Central: selection of T/B cells which only react to non-self antigens. Occurs in thymus and bone marrow.
• Peripheral: occurs in secondary lymphoid tissue. T/ B cells undergo further education/ regulation

Question 3

What are the types of immune tolerance?

Answer 3

• Self tolerance (central)
• Neonatal (central)
• Adult (peripheral)
• Oral (peripheral)

Question 4

What is meant by positive/ negative T cell selection?

Answer 4

• Occurs in thymus
• Positive: Selects T cells that bind to self MHC molecules
• Negative: deletes T cells that react STRONGLY with self peptide/ antigen or self MHC
• Means most of the T ells that survive only activate if a non-self peptide is presented by a self MHC molecule.

Question 5

How are B cells educated in the bone marrow?

Answer 5

• BCR+ cells thats interact with self antigens are deleted by apoptosis
• Mature B lymphocytes then move onto secondary lymphoid organs

Question 6

Are most antigens T or B cell dependant?

Answer 6

T cell

- induction of T cell tolerance will lead to B cell tolerance

Question 7

Why is peripheral tolerance important?

Answer 7

• Many antigens are not presented to T cells whilst in the thymus, these cells may activate and immune response to the novel antigens if not controlled.
• Some T cells that react to self peptide escape the thymus and so must be controlled during peripheral tolerance to prevent autoimmune responses.

Question 8

What are the mechanisms by which T cells become tolerant/ unresponsive in periphery?

Answer 8

• Anergy
• Immunological ignorance
• Antigen presenting cell failure
• T regulatory cells (Tregs)

Question 9

Explain the process of anergy

Answer 9

• The failure to react to specific antigens
• TCR engages MHC and antigen
• Cytokines that upregulated co-stimulatory molecules are absent
• T cell isn’t activated and cannot undergo clonal expansion so becomes apoptotic and dies.

Question 10

Describe regulatory T cells

Answer 10

• Inhibit Th1 and Th2 cell function via production of inhibitory cytokines (TGF-B and IL-10) or direct cell-cell contact
• 3 types:
  Natural Tregs
  T regulatory cells (Treg1)
  T helper 3 cells (Th3)

Question 11

What is the role of nTreg cells?

Answer 11

• Inhibit immune responses
• Their activation causes large concentration of IL-10 to be produced
• IL-10 is immunosuppressant on the activity of both Th1 and 2.
• Inhibition of Th2 leads to inhibition of B cell activity/ AB production

Question 12

What happens if immune tolerance fails?

Answer 12

• Allergic (abnormal) IR to environmental antigens

- Autoimmunity develops

Question 13

What is hyposensitisation/ immunotherapy?

Answer 13

• Administration of selected allergens and low dose with alum adjuvant
• Intradermnal injection
• Sublingual administration

Question 14

Describe adult peripheral tolerance during pregnancy

Answer 14

• Local immunosuppresion- evidence for Tregs and split immunlogical tolerance