Central & Peripheral tolerance Flashcards

1
Q

Define immune tolerance

A

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)

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2
Q

Describe the 2 forms of tolerance

A
  • 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
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3
Q

What are the types of immune tolerance?

A
  • Self tolerance (central)
  • Neonatal (central)
  • Adult (peripheral)
  • Oral (peripheral)
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4
Q

What is meant by positive/ negative T cell selection?

A
  • 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.
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5
Q

How are B cells educated in the bone marrow?

A
  • BCR+ cells thats interact with self antigens are deleted by apoptosis
  • Mature B lymphocytes then move onto secondary lymphoid organs
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6
Q

Are most antigens T or B cell dependant?

A

T cell

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

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7
Q

Why is peripheral tolerance important?

A
  • 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.
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8
Q

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

A
  • Anergy
  • Immunological ignorance
  • Antigen presenting cell failure
  • T regulatory cells (Tregs)
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9
Q

Explain the process of anergy

A
  • 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.
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10
Q

Describe regulatory T cells

A
  • 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)
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11
Q

What is the role of nTreg cells?

A
  • 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
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12
Q

What happens if immune tolerance fails?

A
  • Allergic (abnormal) IR to environmental antigens

- Autoimmunity develops

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13
Q

What is hyposensitisation/ immunotherapy?

A
  • Administration of selected allergens and low dose with alum adjuvant
  • Intradermnal injection
  • Sublingual administration
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14
Q

Describe adult peripheral tolerance during pregnancy

A
  • Local immunosuppresion- evidence for Tregs and split immunlogical tolerance
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