Autoimmunity Flashcards
Autoimmunity
Adaptive immune response to self-antigens (loss of tolerance)
- Autoantibodies - antibodies directed at normal cellular components
- Autoreactive T-cells - not eliminated by thymus
Autoimmunity mechanisms
Breakdown of peripheral (T-cell) tolerance due to combined genetic predisposition and environmental factors
- Access to self-antigens
- Loss of anergy (presence of co-stimulation)
- MHC1/2 increase presentation of self-antigens
Tissue damage occurs through hypersensitivity reactions type II, III, IV
Autoimmunity genetic aetiology
Polymorphisms
e. g.
- HLA inheritance (poor self-antigen binding)
- Poor self-antigen expression
- Impaired DNA clearance
Autoimmunity environmental aetiology
- Infection
- Drugs
- UV exposure
- Gluten in diet
- Pregnancy
Autoimmunity Molecular Mimicry
Structural similarity between self-proteins and microbial antigens may trigger autoimmunity
e. g.
- Group A strep + cardiac muscle antigens similar (rheumatic fever)
Autoimmune disease
Tissue damage or disturbed function resulting from an autoimmune response
- Non-organ specific
- Organ-specific
Examples of autoimmune disease
- TSH receptor: hyper/hypothyroidism
- Insulin receptor: hyper/hypoglycaemia
- Acetylcholine receptor: myasthenia gravis
- Cell adhesion molecules: blistering
- Plasma proteins: haematological disorders
- RBCs: haemolytic anaemia
- Intracellular enzymes: related to function
Type 1 diabetes (organ-specific autoimmunity)
- Pancreatic islet antigens poorly presented in thymus (genetic)
- Autoreactive T cells escape thymus and enter pancreas
- Environmental factor presence may produce cytokines resulting in co-stimulation of T-cells in pancreas
SLE (non-organ specific autoimmunity)
Auto-antigen is DNA
- Infection -> cell destruction
- DNA leaks out and not contained by complement system
- Complexes form
Autoimmunity treatment
- Immunosuppressive drugs
- Anti-inflammatory drugs (corticosteroids)
- Replacement (hormones, insulin)
