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Pathology - Y5 > Autoimmune and Autoinflammatory Disease 2 > Flashcards

Autoimmune and Autoinflammatory Disease 2 Flashcards

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1
Q

What is the pathophysiology of polygenic auto-immune diseases?

A

Mutations in genes encoding proteins involved in pathways associated with adaptive immune cell function.

HLA associations are common.

Aberrant B cell and T cell responses in primary and secondary lymphoid organs lead to breaking of tolerance with development of immune reactivity towards self-antigens.

Auto-antibodies are found.

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2
Q

What are the genetic polymorphisms of polygenic auto-immune disease?

A

PTPN 22

  • Protein tyrosine phosphatase non-receptor 22.
  • Lymphocyte specific tyrosine phosphatase which suppresses T cell activation.
  • Allelic variants found in SLE, T1DM, RhA.

CTLA4

  • Cytotoxic T lymphocyte associated protein 4. Expressed by T cells and transmits inhibitory signal to control T cell activation.
  • Allelic variants found in SLE, T1DM, RhA, Auto-immune thyroid disease.
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3
Q

What is the association between polygenic auto-immune diseases and HLA presentations?

A

HLA presentation of antigen is required for development of T cell and T cell-dependent B cell responses.

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4
Q

What is the susceptibility allelle and relative risk (fold) increase of Goodpasture Disease?

A

HLA -DR15

10

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5
Q

What is the susceptibility allelle and relative risk (fold) increase of Grave’s Disease?

A

HLA-DR3

4

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6
Q

What is the susceptibility allelle and relative risk (fold) increase of SLE?

A

HLA-DR3

6

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7
Q

What is the susceptibility allelle and relative risk (fold) increase of T1DM?

A

HLA -DR3/DR4

25

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8
Q

What is the susceptibility allelle and relative risk (fold) increase of RhA?

A

HLA-DR4

4

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9
Q

What is the Gel and Coobs classification for hypersensitivities?

A

Type I: Anaphylactic hypersensitivity.
Immediate hypersensitivity which is IgE mediated – rarely self antigen.

Type II: Cytotoxic hypersensitivity.
Antibody reacts with cellular antigen.

Type III: Immune complex hypersensitivity.
Antibody reacts with soluble antigen to form an immune complex.

Type IV: Delayed type hypersensitivity.
T-cell mediated response.

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10
Q

What are Type II antibody driven auto-immune diseases?

A

Goodpasture Disease

Pemphigus vulgaris

Graves Disease

Myaesthenia Gravis

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11
Q

Which auto-antigen and symptoms are associated with Goodpasture Disease?

A

Noncollagenous domain of basement membrane collagen type IV.

Glomerulonephritis, pulmonary hemorrhage.

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12
Q

Which auto-antigen and symptoms are associated with Grave’s Disease?

A

Thyroid stimulating hormone (TSH) receptor

Hyperthyroidism

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13
Q

Which auto-antigen and symptoms are associated with pemphigus vulgaris?

A

Epidermal cadherin

Blistering of skin

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14
Q

Which auto-antigen and symptoms are associated with myaesthenia gravis?

A

Acetylcholine receptor

Muscle weakness

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15
Q

What is a Type III immune complex driven autoimmune disease?

A

SLE

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16
Q

Which auto-antigen and symptoms are associated with SLE?

A

DNA, Histones, RNP

Rash, glomerulonephritis, arthritis

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17
Q

What is a Type IV T-cell mediated disease?

18
Q

Which auto-antigen and symptoms are associated with T1DM?

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A

Pancreatic b-cell antigen

b-cell destruction: CD8+ T-cells

19
Q

What are some organ specific diseases mediated by organ specific antibodies?

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A

Graves disease

Hashimotos thyroiditis

Type I diabetes

Pernicious anaemia

Myaesthenia gravis

Goodpasture disease

20
Q

Which antibodies are specific for RhA?

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A

Rheumatoid factor

Anti-CCP antibody

21
Q

What are some multisystem diseases mediated by anti-nuclear antibodies?

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A

SLE

Sjogren’s syndrome

Systemic sclerosis

Dermato/Polymyostis

22
Q

What antibodies are specific for ANCA-associated vasculitis?

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A

Anti-neutrophil cytoplasmic antibody

23
Q

What is the pathophysiology of Graves Disease?

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A

Excessive production of thyroid hormones.

Mediated by IgG antibodies which stimulate the TSH receptor.

  • Stimulating autoantibodies against TSH-receptor bind to receptor.
  • Act as TSH agonists.
  • Induce uncontrolled overproduction of thyroid hormones.
  • Negative feedback cannot override antibody stimulation.
24
Q

What is the evidence that Graves Disease is mediated by IgG antibodies?

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A

Evidence:

  • Antibodies stimulate thyrocytes in vitro.
  • Passive transfer of IgG from patients to rats often produces similar symptoms.
  • Babies born to mothers with Graves’ may show transient hyperthyroidism.
25
What is the pathophysiology of Hashimoto's Disease?
Commonest cause of hypothyroidism in iodine-replete areas. **Goitre:** Enlarged thyroid infiltrated by T and B cells. Associated with anti-thyroid peroxidase antibodies: * Presence correlates with thyroid damage and lymphocyte inflammation. * Some shown to induce damage to thyrocytes. Associated with presence of anti-thyroglobulin antibodies.
26
What is the pathophysiology of T1DM?
Antibodies pre-date development of disease. * Anti-islet cell antibodies * Anti-insulin antibodies * Anti-GAD antibodies * Anti-IA-2 antibodies Individuals with 3-4 of the above are highly likely to develop type I diabetes. Detection of antibodies does not currently play a role in diagnosis.
27
Which diseases are the following autoantibodies associated with? **a)** Anti-TSH R antibody (Anti-thyroid stimulating hormone receptor antibody) **b)** Anti-thyroglobulin antibodies **c)** Anti-thyroid peroxidase antibodies
**a)** Graves disease (hyperthyroidism) **b)** Hashimoto disease **c)** Hashimoto disease
28
What is the pathophysiology of pernicious anaemia?
Failure of vitamin B12 absorption. Vitamin B12 deficiency. Macrocytic anaemia. Neurological features with subacute combined degeneration of cord (posterior and lateral columns), peripheral neuropathy, optic neuropathy. Antibodies to gastric parietal cells or intrinsic factor - are useful in diagnosis.
29
Which diseases are the following autoantibodies associated with? **a)** Anti-intrinsic factor antibody **b)** Anti-gastric parietal cell antibody **c)** Anti-TTG (anti-tissue transglutaminase antibody) **d)** Anti-endomyosial antibody **e)** P-ANCA (anti-neutrophil cytoplasmic antibody, perinuclear staining)
**a)** Pernicious anaemia **b)** Pernicious anaemia **c)** Coeliac **d)** Coeliac **e)** Ulcerative colitis\>Crohns
30
Which diseases are the following auto-antibodies associated with? **a)** ANA (anti-nuclear antibodies) **b)** SMA (smooth muscle antibodies) **c)** Anti-LKM (antibodies vs liver kidney microsomal proteins) **d)** AMA (anti-mitochondrial antibody **e)** P-ANCA (anti-neutrophil cytoplasmic antibody, perinuclear staining)
**a)** Autoimmune hepatitis, Primary biliary cholangitis **b)** Autoimmune hepatitis **c)** Autoimmune hepatitis **d)** Primary biliary cholangitis **e)** Autoimmune hepatitis, Primary biliary cholangitis
31
What is the pathophysiology of myaesthenia gravis?
Anti-acetylcholine receptor antibodies present in ~75% patients and are useful in diagnosis. Offspring of affected mothers may experience transient neonatal myaesthenia.
32
Which diseases are the following auto-antibodies associated with? **a)** Anti-acetylcholine receptor antibody **b)** Anti-striational antibody **c)** Anti-AQP4 (aquaporin) **d)** Anti-MOG (myelin oligodendrocyte glycoprotein) **e)** Anti-NMDA receptor (Anti-N-methyl D-aspartate (NMDA) receptor) **f)** Anti-GABA receptor (gamma aminobutyric acid receptor)
**a)** Myaesthenia Gravis **b)** Myaesthenia Gravis with myositis **c)** Neuromyelitis optica spectrum disorder (NMOS) **d)** Optic neuritis, encephalomyelitis **e)** Encephalitis (may be malignancy associated) **f)** Seizures (may be malignancy associated)
33
What diseases are the following auto-antibodies associated with? a**)** Anti-glomerular basement membrane (GBM) antibody **b)** P-ANCA (anti neutrophil cytoplasmic antibody, perinuclear staining, anti-myeloperoxidase) **c)** C-ANCA (anti-neutrophil cytoplasmic antibody, cytoplasmic staining, anti-proteinase 3)
**a)** Goodpasture disease. **b)** ANCA associated vasculitis - Microscopic polyangiitis / Eosinophilic granulomatosis with polyangiitis. **c)** ANCA associated vasculitis - Granulomatosis with polyangiitis
34
Which autoantibodies are associated with RhA?
HLA DR4 (DRB1 0401, 0404, 0405) and HLA DR1 (DRB1 0101) alleles Peptidyl arginine deiminase (PAD)2 and PAD4 polymorphisms PTPN22 polymorphism.
35
What is the pathophysiology of rheumatoid arthritis?
Peptidylarginine deiminases PAD type 2 and 4. Enzymes involved in deimination of arginine to create citrulline. Polymorphisms are associated with increased citrullination. This creates a high load of citrullinated proteins.
36
What environmental factors increase citrullination in rheumatoid arthritis?
Smoking associated with development of erosive disease and increased citrullination. Gum infection with Porphyromonas gingivalis associated with rheumatoid arthritis. P. gingivalis is only bacterium known to express PAD enzyme and thus promote citrullination.
37
Which antibodies are in RhA?
Antibodies to cyclic citrullinated peptide: * Bind to peptides in which arginine has been converted to citrulline by peptidylarginine deiminase (PAD). * Around 95% specificity for diagnosis of rheumatoid arthritis. * Around 60-70% sensitivity for diagnosis of rheumatoid arthritis. * Best blood test for diagnosis of rheumatoid arthritis.
38
What is rheumatoid factor?
A rheumatoid factor is an antibody directed against the common (Fc) region of human IgG. IgM anti-IgG antibody is most commonly tested although IgA and IgG rheumatoid factors may also be present in some individuals. Around 60-70% specificity and sensitivity for diagnosis of rheumatoid arthritis.
39
Which of the following is an example of Gel and Coombs type III hypersensitivity? * Goodpasture disease * Eczema * SLE * Multiple sclerosis * Graves disease
SLE
40
Which of the following antibodies are characteristically found in Myaesthenia Gravis? * Anti-GAD antibody * Anti-thyroglobulin antibody * Anti-basement membrane antibody * Anti-intrinsic factor antibody * Anti-acetylcholine receptor antibody * Anti-cyclic citrullinated peptide antibody * Anti-TSH receptor antibody
Anti-acetylcholine receptor antibody
41
Which of the following antibodies are characteristically found in Pernicious Anaemia? * Anti-GAD antibody * Anti-thyroglobulin antibody * Anti-basement membrane antibody * Anti-intrinsic factor antibody * Anti-acetylcholine receptor antibody * Anti-cyclic citrullinated peptide antibody * Anti-TSH receptor antibody
Anti-intrinsic factor antibody

Pathology - Y5 (59 decks)

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