Autoimmune disease Flashcards

1
Q

What are the features of MHC I?

A
  • Encoded by genes in HLA-A, HLA-B, HLA-C
  • On all nucleated cells
  • Presents antigen to CD8+ T cells
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2
Q

What are the features of MHC II

A
  • Encoded by genes in HLA-DP, HLA-DQ, HLA-DR
  • On dedicated APCs
  • Presents antigen to CD4+ T cells
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3
Q

Where does central tolerance take place?

A

Thymus for T cells

Bone marrow for B cells

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4
Q

What are the features of peripheral tolerance?

A

Regulatory T cells (express FOXP3)

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5
Q

What are the common risk factors for autoimmune disease?

A
  • Sex (hormonal influence)
    • women&raquo_space; men
  • Age
    • autoimmunity more common in elderly
  • Sequestered Antigents
    • May be recognised as foreign by the immune system (e.g. cell nucleus, eye, testis)
  • Environmental triggers
    • Infection
    • Trauma-tissue damage
    • smoking
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6
Q

What is the relevance of molecular mimicry in autoimmune disease?

A

In rheumatic fever antibodies against M protein of Streptococcus also react against the glycoproteins of the heart

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7
Q

How might changes in amount or nature or autoantigens cause autoimmunity?

A
  • Citrullination of proteins make them more immunogenic (rheumatoid arthritis)
  • Tissue transglutamase alters gluten to help it bind to HLA-DQ (coeliac disease)
  • Failure to clear apoptotic debris increases availability of sequestered antigens inside the cell (systemic lupus erythamatosus)
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8
Q

What is the potential pathophysiology of autoimmune disease?

A
  • Autorective B cells and autoantibodies
    • Directly cytotoxic
    • Activation of complement
    • Interfere with normal physiological function
  • Autoreactive T cells
    • Directly cytotoxic
    • Inflammatory cytokine production
  • General inflammation and end-organ damage
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9
Q

What is thought to be the aetiology of SLE?

A

Defects in apoptosis?

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10
Q

What causes the malar rash?

A

Sunlight - Anti-nuclear antibodies bind to skin cells that have been damaged by UV light and form immune complexes with their antigen.

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11
Q

How does lupus become systemic?

A

Immune complex deposition in other organs.

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12
Q

How might T cells contribute to autoimmunity?

A

Cause inflammation by inflammatory cytokines or by helping B cells make autoantibodies

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13
Q

What is the pathophysiology of Hashimoto’s Thyroiditis?

A
  • Destruction of thyroid follicles by autoimmune process
  • Associated with autoantibodies to thyroglobulin and to thyroid peroxidase
  • Leads to hypothyrodism
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14
Q

What is the pathophysiology of Grave’s disease?

A
  • Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
  • Leads to hyperthyrodism
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15
Q

What is the pathphysiology of myasthenia gravis

A

Autoantibodies block the muscarinic ACh receptor and target it for destruction.

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16
Q

What is the pathophysiology of pernicious anaemia?

A

anti-IF or anti-IF receptor autoantibodies block the uptake of B12 from the gut.

17
Q

What kind of autoantibodies are formed in SLE?

A

anti-nuclear

18
Q

Which part of the immune system is involved in autoinflammation?

A

Innate

19
Q

Which part of the immune system is involved in autoimmunity?

A

Adaptive

20
Q

Are autoantibodies usually present during autoinflammation?

A

No

21
Q

What are the clinical features of autoinflammation?

A

Recurrent and unpredictable attacks

22
Q

What are the clinical features of autoimmunity?

A

Continuous progression

23
Q

What is the conceptual understanding of autoinflammation?

A

Tissue-specific factors/danger signals

24
Q

What is the conceptual understanding of autoimmunity?

A

Breaking of self-tolerance

25
Q

Where is the main genetic susceptibility for autoinflammation?

A

Cytokine and bacterial sensing pathways

26
Q

Where is the main genetic susceptibility for autoimmunity?

A

MHC II, adaptive response genes, anti B and T cell

27
Q

Give examples of autoinflammation.

A

Monogenic hereditery periodic fevers, polygenic Crohn’s disease, spondylarthropathies

28
Q

Give examples of autoimmunity.

A

RA, SLE, IPEX

29
Q

Give and example of an autoimmune disease that leads to ischaemia and fibrosis.

A

Scleroderma