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Block 4 > Tolerance and Autoimmunity > Flashcards

Tolerance and Autoimmunity Flashcards

1
Q

Define Immunological Tolerance

A

Unresponsiveness of the immune system to a particular antigen (self or non-self)

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2
Q

Define Autoimmunity

A

A failure of immunological tolerance resulting in an immune response to self-antigens (influenced by genetic and environmental factors)

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3
Q

Define Antigen

A

Any substance capable of inducing an immune response

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4
Q

Describe central tolerance

A

Immunological tolerance that develops in bone marrow and thymus, begins in foetal development and declines after birth.
Prevents immature foetal lymphocytes from initiating autoimmune response by clonal deletion (apoptosis) and clonal anergy (t lymphocyte regulation)

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5
Q

Describe peripheral tolerance

A

Immunological tolerance that develops in peripheral lymphoid tissues, prevents autoimmune responses of mature lymphocytes against foetus, gut flora, plant pollens.
Active throughout life.
Prevents autoimmune responses through clonal suppression by T lymphocytes.

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6
Q

What branch of specific immunity is most affected in loss of tolerance (autoimmunity)?

A

B-cells

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7
Q

Variations in what proteins are associated with autoimmune conditions?

A

Class I and II MHC proteins

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8
Q

Why does B-cell mediation make autoimmune conditions easier to diagnose?

A

Can be diagnosed through measurement of autoantibodies.

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9
Q

What is the negative aspect of B-cell mediation being responsible for autoimmune conditions?

A

Autoantibodies can cross the placenta causing babies to be born with autoimmune conditions (e.g. neonatal lupus)

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10
Q

What specific autoantibody is associated with RA?

A

Rheumatoid factor (RhF)

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11
Q

What specific antibody is associated with systemic lupus?

A

Anti Nuclear Antibody (ANA) (95% specificity)

double stranded DNA (dsDNA) (50% sens, 99% spec)

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12
Q

What specific antibody is associated with Hashimoto’s Thyroiditis?

A

Thyroid Peroxidase

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13
Q

What specific antibody is associated with Grave’s disease?

A

TSH receptor

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14
Q

Explain molecular mimicry

A

Immune system responds to antigens and produces immune response but also produces response against self-antigens similar to the initial insulting antigen.

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15
Q

Give examples of infectious molecular mimicry

A

Streptococcal infection- rheumatic fever
Campylobacter gastroenteritis- Guillan Barre syndrome
Urethritis/gastroenteritis- reactive arthritis

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16
Q

How does autoimmunity occur?

A

Through genetic recombination T and B cells are pre-programmed to recognise infinite number of antigens, including self antigens. Autoimmunity occurs when control of T and B cells that recognise self antigens fails- loss of immunological tolerance.

17
Q

How do steroids help treat autoimmune conditions?

A

Anti-inflammatory and immunosuppressive: Decrease cytokines and decrease the action of cell mediated and humoral immunity.

18
Q

Name 3 disease modifying drugs used in autoimmune conditions

A

Methotrexate
Azathioprine
Sulfasalozine

19
Q

Name 2 monoclonal antibody drugs used in autoimmune conditions

A

Infliximab

Rutiximab

20
Q

Which genes are most associated with autoimmunity?

A

Major Histocompatilibity Complex

human leukocyte antigen

21
Q

What diseases are the HLA-B27 gene associated with?

A

Ankylosing spondylitis

Reactive arthritis

22
Q

What disease is the HLA-DR2 gene associated with?

A

Systemic Lupus Erythematosus

23
Q

What diseases are the HLA-DR4 gene associated with?

A

Rheumatoid arthritis

T1DM

24
Q

How does the environment contribute to autoimmunity?

A

Infection
Chemicals
Neoplasms
Trauma

25
Q

What gene is associated with rheumatoid arthritis and T1DM?

A

HLA-DR4

26
Q

What gene is associated with Sjogren’s syndrome, T1DM, SLE and autoimmune hepatitis\

A

HLA-DR3

27
Q

What gene is associated with ankylosing spondylitis and reactive arthritis?

A

HLA-B27

28
Q

What gene is associated with systemic lupus erythematosus?

A

HLA-DR2

29
Q

What is the more specific autoantibody for rheumatoid arthritis?

A

anti-CCP

anti-cyclic citrullinated peptide

30
Q

What autoantibody is associated with Sjogren’s syndrome?

A

ANA

31
Q

What autoantibody is associated with coeliac disease?

A

Anti-gliadin and anti-endomysial

32
Q

How does central tolerance prevent immune responses to self antigens?

A

Controls immature T-lymphocytes that recognise self antigens by:

  • Clonal deletion (apoptosis)
  • Clonal anergy (regulatory T-lymphocytes)
33
Q

How does peripheral tolerance prevent immune responses to self-antigens?

A

Controls mature T-lymphocytes that recognise self or benign antigens by clonal suppression (regulatory T-lymphocytes)

34
Q

Give examples of some chemical molecular mimicry

A

Anticonvulsants/antibiotics -> Drug-induced lupus

Halothane -> liver necrosis

35
Q

Give examples of a neoplastic molecular mimicry

A

Teratoma -> autoimmune encephalitis

36
Q

How can trauma cause molecular mimicry?

A

Exposure of self-antigens in protected sites (e.g. eyes, testes)

37
Q

Explain the mechanism of Grave’s disease

What would you expect the blood results to be?

A

Autoantibodies towards TSH receptor result in persistent stimulation of the thyroid gland.
Increased thyroid hormones (T3 and T4) = Increased basal metabolic rate and sensitivity to catecholamines
Autoantibodies against ophthalmic muscles= exophthalmos.

Bloods: High T3 and T4, low TSH, presence of anti-TSH receptor antibodies.

Block 4 (20 decks)

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