Autoimmune Diseases Flashcards
Autoimmune diseases may be described as…
- Tissue specific
- Organ specific
Thyroid autoimmunity: Hyperthyroidism/thyrotoxicosis
- Characterised by high levels of T4/T3 and low levels of TSH
- Resultant of the production of TSI (thyroid stimulating immunoglobulin)
- TSI binds to TSH receptor, stimulating the production of thyroid hormone
- Active Grave’s disease in the third trimester of pregnancy may result in the transfer of autoreactive IgG across the placenta
- The baby will then experience symptoms, until the maternal antibodies are degraded (passive immunity)
Hyperthyroidism: Mechanism of exopthalmos
- Autoantibodies target the connective tissue of the eye
- Inflammation results. Inflammatory exudate infiltrates
- GAGs accumulate
- Osmotic movement seen.
- Causes ‘bulging’ of the eyes
Thyroid autoimmunity: Hypothyroidism
Resultant of an autoreaction to the thyroid gland, preventing the synthesis of thyroid hormone
Breakdown of thryoid tissue = atrophic thyroiditis
Enlargement of the thyroid gland is seen due to infiltration of immune cells
Levels of TSH are high but T4/T3 levels are low
Common autoreaction Igs: Anti-TPO, TGB or TSH receptor
- All DECREASE thyroid hormone synthesis
Pernicious anaemia: Outline the mechanism
- An autoimmune reaction against cells of the stomach
- Destruction of parietal cells cause loss of intrinsic factor secretion
- Through autoreactive T cells and autoantibodies which bind intrinsic factor (may prevent binding to receptor in ileum)
- This prevents intrinsic factor mediated B12 absorption in the ileum
- B12 is a co-factor for nucelotide synthesis
- Resultantly RBC production is decreased, leading to anaemia
Myasthenia gravis: Outline the mechanism of the disease
- Autoantibodies cross-link to the AChR seen on the surface of muscle cells
- This causes the internalisation and degradation of the receptor
- The Igs may also block binding of ACh to its receptor
- Muscle contraction is prevented, leading to paralysis
- Cholinesterase inhibitors may be used to relieve symptoms
Autoimmune haemolytic anaemia: Outline the mechanism
- A type II hypersensitivity
- Auto-antibodies bind to the surface of RBCs.
- This opsonises the RBC, leads to complement activation and destruction
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Allergic haemolytic anaemia:
- Medications may bind to the surface of the RBC
- Anitbodies may then bind these molecules
- Leads to lysis of the RBC
Goodpasture’s disease: Outline the mechanism of the disease
- Type II hypersensitivity
- Principally targets the kidneys
- May also occur within the alveoli. Smoking exposes the alveolar basement membrane.
- Autoantibodies bind the glomerular basement membrane
- Leads to complement activation and immune cell infiltration
Pemphigus Vulgaris: Outline the mechanism of the disease
- Autoantibodies bind epidermal cadherin (superficial layers of the skin)
- Leads to the formation of fragile blisters
Pemphigoid
- Mainly in the dermis
- Tough blisters form
SLE: Outline the mechanism of the condition
- Arises due to poor clearance of apoptotic cells, leading to secondary necrosis
- Cellular contents leak, allowing interaction with auto-antibodies and subsequent immune response
- Commonly Auto-Igs directed against nuclear material
- DNA-AntiIg complexes circulate and may become stuck in the glomeruli. This can trigger damage to the glomeruli. Leads to potential kidney failure - type III hypersensitivity mechanism
- Butterfly rash seen - photosensitive
- Vasculitis commonly seen
- May affect the CNS and joints
- Describe the role of TSHR-stimulating antibodies in Graves’ disease and why they induce hyperthyroidism.
- Describe the pathogenetic features of Graves’ ophthalmopathy and pre-tibial myxoedema.
- Describe the immunological basis of atrophic thyroiditis and Hashimoto’s thyroiditis, and explain why these conditions result in hypothyroidism.
- Outline the overlap in the occurrence of endocrine/organ-specific autoimmune diseases, and the subclinical occurrence of autoimmunity.
- Explain the autoimmune basis of pernicious anaemia and of type 1 diabetes mellitus.
- Describe the nature and role of autoantibodies in myasthenia gravis, autoimmune haemolytic anaemia, Goodpasture’s disease and pemphigus.
- Describe the nature of kidney, skin and blood vessel involvement in systemic lupus erythematosus.
- Outline the involvement of rheumatoid factors and lymphocytes in rheumatoid arthritis.
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Type I Diabetes Mellitus: Outline the mechanism of this disease
- Sees destruction of pancreatic beta cells
- Commonly mediated by CD8 T cells
- Epitope recognised
- Islet cell autoantibodies are used to detect the condition
- Insulin production becomes insufficient after around 80 % of cell have undergone destruction
How is autoimmunity distinguished from allergy?
Both cause harm to self
Autoimmunity is triggered by recognition of self-molecules
Allergy is triggered by recognition of foreign particles
Describe how such a wide repertoire of Igs are generated and how this can allow autoimmunity to arise
- VDJ recombination allows many Igs to be generated
- However, this process does not take into account the molecule that will be recognised following this process. Due to this reason auto-reactive antibodies result
Outline the mechansim of central tolerance
Occurs at primary lymphoid tissues: thymus and bone marrow
Involves the presentation of self-antigen to lympocytes. Those which react strongly undergo apoptosis/clonal deletion.
The thymus expresses genes which allow it to express a wide array of tissue specific proteins, e.g. insulin. Allows auto-reactive T cells to be identified.
- The importance of this process is seen in APS1
Central tolerance is not 100 % effective, some autoreactive T cells remain. Further tolerance mechanisms are seen throughout the body.
