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PATH2220 > 12 - Autoimmunity > Flashcards

12 - Autoimmunity Flashcards

1
Q

Autoimmunity

A
  • The presence of auto-antibodies and/or self reactive T cell responses
  • Only when these responses cause clinical abnormality is an autoimmune disease present
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2
Q

How does the body control self reactivity

A

Immunological tolerance

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3
Q

Immunological tolerance

A
  • Lack of response of T or B cells to self-antigen exposure
  • Central and peripheral tolerance
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4
Q

Principal mechanisms of immunological tolerance

A
  • Clonal deletion of self-reactive lymphocytes
  • Tolerance due to clonal anergy
  • Suppression of self-responses by regulatory T cells
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5
Q

Autoimmune disease

A
  • When the mechanisms controlling and maintaining tolerance function poorly or breakdown, autoimmunity and autoimmune disease can develop
  • Most associated with autoantibody production, some due to self-reactive cell mediated immune responses
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6
Q

Autoimmune disease is cell-mediated and/or antibody mediated

A

T cells specific for self antigens can cause direct tissue injury and play a role in sustaining autoantibody responses

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7
Q

Mechanisms of autoimmune disease

A

Multifactorial, Drugs, viral illness

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8
Q

Aetiology of autoimmune disease

A
  • Genetic susceptibility
  • External triggers (sunlight, diet, stress, pathogens)
  • Females (sex hormones and chromosomes)
  • Random variables (immunoglobulin and TCR collections)
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9
Q

Organ and non organ specific autoimmune disease

A
  • Organ-specific such as Hashimoto’s thyroiditis with organ-specific autoantibodies or lesions are localised to a single organ but the autoantibodies are not organ specific (eg Primary Biliary Cirrhosis)
  • Non-organ specific diseases, where lesions and auto-antibodies are not confined to any one organ e.g. Systemic Lupus Erythematosus (SLE)
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10
Q

Systemic lupus erythematosus

A
  • Non organ-specific, antibody-mediated (immune complex)
  • Chronic multi-system inflammatory disease
  • Occurs predominantly in females
  • Strong genetic links
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11
Q

hallmark of SLE

A

Production of anti-nuclear antibodies (ANAs; IgG)

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12
Q

What is SLE associated with

A
  • Uncontrolled interaction between T and B cells
  • Polyclonal B-cell activation
  • Anti-nuclear antibodies (ANA)
  • Probable defects in regulation of B cells +/- T cells
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13
Q

Detection of ANA in patient serum

A
  • Hep-2 cells
  • Add patients serum
  • Antinuclear IgG (ANA) in patients serum binds to nucleus
  • Add fluorescein labelled anti IgG
  • Fluorescein labelled anti IgG detects ANA
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14
Q

Is a positive ANA test specific for SLE

A

No

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15
Q

How do autoantibodies mediate pathology of SLE

A
  • Binding to cell surface antigens
  • Forming immune complexes that are then deposited in tissues and interfere with function
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16
Q

Autoantibodies binding to cell surface antigens in SLE

A
  • Red blood cells: Haemolytic anaemia
  • Platelets - Autoimmune thrombocytopenia
  • Neutrophils and lymphocytes – Leukopenia
  • Neuronal cells - Diffuse CNS disease
17
Q

Two categories of thyroid autoimmune disease

A
  • Hyperthyroidism (Graves’ disease)
  • Hypothyroidism (Hashimoto’s thyroiditis)
18
Q

Graves’ disease

A
  • Most common cause of hyperthyroidism
  • Overproduction of thyroid hormones
19
Q

Predisposing factors of graves’ disease

A
  • High iodine consumption
  • Female sex
20
Q

Symptoms of Graves’ disease

A
  • anxiety, fatigue, weight loss,
  • goitre
  • Grave’s ophthalmopathy = bulging eyes
21
Q

two types of pathogenesis of Graves’ disease

A
  • Thyroid Stimulating Hormone (TSH) Receptor Antibodies
  • Dense lymphocytic infiltrate
22
Q

Thyroid Stimulating Hormone (TSH) Receptor Antibodies

A
  • IgG
  • Compete with TSH for receptor binding
  • Stimulate glandular function → hyperthyroidism
  • Titre of antibodies correlates well with severity
23
Q

Dense lymphocytic infiltrate in graves’ disease

A
  • Autoreactive CD4+ T cells
  • Help B-cells to produce autoantibodies
24
Q

Hashimoto’s thyroiditis

A
  • Chronic inflammatory disease of thyroid, autoimmune factors important
  • Underproduction of thyroid hormones
25
Q

Predisposing factors of hashimoto’s thyroiditis

A
  • Peaks in middle age
  • Female (20:1)
26
Q

2 types of pathogenesis of hasimotos disease

A
  • Dense lymphocytic infiltrate
  • High titres of anti-thyroid peroxidase and antithyroglobulin antibodies
27
Q

Dense lymphocytic infiltrate in hashimotos disease

A

CD4+ T-cells may help B cells to produce anti-thyroid autoantibodies

28
Q

High titres of anti-thyroid peroxidase and antithyroglobulin antibodies

A
  • Almost always present
  • Not 100% specific for Hashimoto’s thyroiditis
  • Valuable exclusionary test in patients with thyroid disease
29
Q

Anti-thyroid peroxidase(TPO)

A
  • Two possible roles:
  • Kill thyroid cells in presence of complement
  • Bind to and interfere with function of peroxidase
30
Q

Anti-thyroglobulin (TG)

A
  • Unlikely to have pathogenic role
  • Usually low in titre
  • Does not appear to fix complement

PATH2220 (33 decks)

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