12 - Autoimmunity Flashcards
Autoimmunity
- The presence of auto-antibodies and/or self reactive T cell responses
- Only when these responses cause clinical abnormality is an autoimmune disease present
How does the body control self reactivity
Immunological tolerance
Immunological tolerance
- Lack of response of T or B cells to self-antigen exposure
- Central and peripheral tolerance
Principal mechanisms of immunological tolerance
- Clonal deletion of self-reactive lymphocytes
- Tolerance due to clonal anergy
- Suppression of self-responses by regulatory T cells
Autoimmune disease
- 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
Autoimmune disease is cell-mediated and/or antibody mediated
T cells specific for self antigens can cause direct tissue injury and play a role in sustaining autoantibody responses
Mechanisms of autoimmune disease
Multifactorial, Drugs, viral illness
Aetiology of autoimmune disease
- Genetic susceptibility
- External triggers (sunlight, diet, stress, pathogens)
- Females (sex hormones and chromosomes)
- Random variables (immunoglobulin and TCR collections)
Organ and non organ specific autoimmune disease
- 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)
Systemic lupus erythematosus
- Non organ-specific, antibody-mediated (immune complex)
- Chronic multi-system inflammatory disease
- Occurs predominantly in females
- Strong genetic links
hallmark of SLE
Production of anti-nuclear antibodies (ANAs; IgG)
What is SLE associated with
- Uncontrolled interaction between T and B cells
- Polyclonal B-cell activation
- Anti-nuclear antibodies (ANA)
- Probable defects in regulation of B cells +/- T cells
Detection of ANA in patient serum
- 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
Is a positive ANA test specific for SLE
No
How do autoantibodies mediate pathology of SLE
- Binding to cell surface antigens
- Forming immune complexes that are then deposited in tissues and interfere with function
Autoantibodies binding to cell surface antigens in SLE
- Red blood cells: Haemolytic anaemia
- Platelets - Autoimmune thrombocytopenia
- Neutrophils and lymphocytes – Leukopenia
- Neuronal cells - Diffuse CNS disease
Two categories of thyroid autoimmune disease
- Hyperthyroidism (Graves’ disease)
- Hypothyroidism (Hashimoto’s thyroiditis)
Graves’ disease
- Most common cause of hyperthyroidism
- Overproduction of thyroid hormones
Predisposing factors of graves’ disease
- High iodine consumption
- Female sex
Symptoms of Graves’ disease
- anxiety, fatigue, weight loss,
- goitre
- Grave’s ophthalmopathy = bulging eyes
two types of pathogenesis of Graves’ disease
- Thyroid Stimulating Hormone (TSH) Receptor Antibodies
- Dense lymphocytic infiltrate
Thyroid Stimulating Hormone (TSH) Receptor Antibodies
- IgG
- Compete with TSH for receptor binding
- Stimulate glandular function → hyperthyroidism
- Titre of antibodies correlates well with severity
Dense lymphocytic infiltrate in graves’ disease
- Autoreactive CD4+ T cells
- Help B-cells to produce autoantibodies
Hashimoto’s thyroiditis
- Chronic inflammatory disease of thyroid, autoimmune factors important
- Underproduction of thyroid hormones
Predisposing factors of hashimoto’s thyroiditis
- Peaks in middle age
- Female (20:1)
2 types of pathogenesis of hasimotos disease
- Dense lymphocytic infiltrate
- High titres of anti-thyroid peroxidase and antithyroglobulin antibodies
Dense lymphocytic infiltrate in hashimotos disease
CD4+ T-cells may help B cells to produce anti-thyroid autoantibodies
High titres of anti-thyroid peroxidase and antithyroglobulin antibodies
- Almost always present
- Not 100% specific for Hashimoto’s thyroiditis
- Valuable exclusionary test in patients with thyroid disease
Anti-thyroid peroxidase(TPO)
- Two possible roles:
- Kill thyroid cells in presence of complement
- Bind to and interfere with function of peroxidase
Anti-thyroglobulin (TG)
- Unlikely to have pathogenic role
- Usually low in titre
- Does not appear to fix complement
