CSIM 1.58: Autoimmune Disease 2 Flashcards
Describe how autoimmunity mediated through type II hypersensitivity reactions causes tissue damage
Which diseases are caused by type II hypersensitivity autoimmunity?
Antibody-dependent (may have a direct effect by blocking or stimulating receptors). Complement may be involved in tissue destruction
- Haemolytic anaemia
- Autoimmune thyroid disease (Grave’s disease)
- Myasthenia gravis
- Goodpasture’s syndrome
Describe how autoimmune thyroid disease such as Grave’s disease comes about
Antibodies to thyrocytes TSH (thyroid stimulating hormone) receptor are produced, or antibodies that stimulate growth are produced: (IMG 135)
• Thyroid growth stimulating antibodies - this causes the thyroid gland to grow causing goitre
• Thyroid stimulating immunoglobulins - these stimulate the production of excessive thyroid hormone
Other antibodies stimulate the fat cells in the orbit to cause exophthalmos (bulging eyes)
Describe Goodpasture’s syndrome
Antibodies recognise type IV collagen in the basement membrane of the lung and kidney glomeruli
This causes renal failure and haemoptysis (coughing up blood)
What are the clinical features of Grave’s disease?
Thyroid features:
• Enlarged thyroid
• Lymphocytic infiltrate
• Excess expression of MHC II on thyrocytes
• Raised T4 (thyroxine) and T3 (triiodothyronine)
• Suppressed TSH
Systemic effects: • Tachycardia • Weight loss • Diarrhoea • Tremor • Exophthalmos (IMG 136)
How is Grave’s disease diagnosed?
- Raised T4, T3
- Suppressed TSH
- Presence of anti-thyroid antibodies
- Increased iodine uptake on scan
What MHC allele is Grave’s disease strongly associated with?
HLA-DR3
People with which antibodies present are more likely to develop thyroiditis in their lifetime?
Does thyroiditis increase or decrease thyroid function?
Antibodies against thyroid peroxidase
Can go either way
What can cause hypothyroidism?
What are the serological markers of this?
- Antibodies to thyroid peroxidase
- TSH-blocking antibodies
Low T4 and T3, raised TSH
What clinical features are present in hypothyroidism?
(Opposite to Grave's disease symptoms) • Weight gain • Bradycardia • Lethargic • Constipated
Which autoimmune diseases are associated with autoimmune thyroid disease and are more likely to occur with those with this disease?
1) Type 1 diabetes
2) Addison’s disease
3) Pernicious anaemia
How would you diagnose the following diseases?
1) Type 1 diabetes
2) Addison’s disease
3) Pernicious anaemia
4) Ovarian failure
1) Glucose tolerance test, raised blood sugar
2) Low cortisol, short synacthen test
3) Low B12, macrocytosis
4) Amenorrhoea, low oestrogen
What are the potential autoimmune causes of the following diseases?
1) Type 1 diabetes
2) Addison’s disease
3) Pernicious anaemia
4) Ovarian failure
1) Antibody to islet cells
2) Antibodies to adrenal cortex
3) Antibodies to gastric parietal cells and intrinsic factor
4) Antibodies to steroid-producing cells of the ovary
Describe the pathogenesis of myasthenia gravis
Autoimmune antibodies produced against acetylcholine receptors, causing them to be internalised and degraded
This prevents Na+ influx and thus prevents muscle contraction
(IMG 137)
What are the clinical features of Addison’s disease?
- Pigmentation of the gums
- Pigmentation of the creases in their hands
- Weight loss
- Low BP
What eye-related symptoms are seen in myesthenia gravis?
- Weak eyelids and eye muscles
* Double vision
How is myesthenia gravis diagnosed?
Tensilon test
How is myesthenia gravis treated
Acetylcholinesterase inhibitors
How is haemolytic anaemia tested for an autoimmune cause?
Coombs test (IMG 139) • Anti-human immunoglobulin antibody is added to red cells • If agglutination occurs, then haemolytic anaemia has autoimmune cause, agglutination will occur because the anti-human immunoglobulin will bind to the antibodies bound to the RBCs
Describe the pathogenesis of autoimmune haemolytic anaemia
Autoantibody against red cell membrane antigen (Rhesus)
• If IgM, the antibody binds complement and causes lysis of the red cell
• Ig IgG, the antibody signals for the RBC’s phagocytosis in the spleen
IMG 138
How does type III differ from type II autoimmunity/hypersensitivity?
Type III involves the formation of immune complexes and so produces more non-tissue specific autoimmunity, and more generalised autoimmunity
Describe an immune complex
Antibodies bound to soluble antigen
IMG 140
What can cause failure to clear immune complexes, and thus deposition?
- Large amounts of antigen
- Chronic infections (Hep C, bacterial endocarditis, etc.)
- Systemic Lupus Erythematosus pathogenesis also causes failure to clear immune complexes
Describe how immune complexes are normally cleared
RBCs bind to them with complement receptors to the liver or spleen where they are phagocytosed (IMG 141)
What happens when immune complexes are not properly cleared?
They are deposited
What is serum sickness? What type of reaction is this and why
What conditions does this relate to closely which use the same hypersensitivity reaction?
14 days after a high antigen exposure (e.g. from serum/injection) due to an acute immune complex reaction
• Arthralgia
• Rash
• Fever
• Renal impairment
This is a type III autoimmune hypersensitivity reaction because immune complexes are involved
IMGS 142 & I43
• Mixed essential cryoglobulinaemia
• Rheumatoid arthritis (also type IV)
NB: the only difference is that with these conditions there is a constant supply of the (self) antigen, and so the symptoms never subside
What is SLE?
A genetically-predisposed condition with unknown environmental triggers which causes widespread autoimmune complexes to antigens released by apoptosing cells, mediated by auto-reactive lymphocytes.
These complexes are deposited throughout the body causing further tissue damage causing masses of symptoms
Describe farmer’s lung
Inhaled allergens provoke the wrong response (IgG rather than IgE) stimulating the immune system (IgE usually causes typical asthma etc, whereas IgG actually causes immune complexes, etc.)
This causes immune complexes to form and deposit in the lung, followed by fluid, protein and cells (inflammation)
This slows blood gas interchange
How can SLE be identified with diagnostic tests?
- Low complement (it’s all being used up)
- Antinuclear antibodies present
- Raised IgG
- Raised ESR (erythrocyte sedimentation rate)
Which autoimmune-caused conditions have a type IV hypersensitivity reaction cause?
- Type 1 diabetes
- Rheumatoid arthritis
- MS
- Crohn’s
- Psoriasis
What causes glomerulonephritis in SLE?
Immune complex deposition (IMG 144)
Describe the pathogenesis of rheumatoid arthritis
- Unknown trigger initiates a focus of inflammation in a synovial membrane
- This attracts autoreactive leukocytes, which activate macrophages
- Bone-resorping osteoclasts are activated, while immune attack against synovial membranes begins
What is rheumatoid factor?
Anti-IgG IgG immunoglobulins
How is rheumatoid arthritis diagnosed?
- Symptoms of painful inflammatory joints
- Raised CRP
- Raised ESR
- Presence of rheumatoid factor
What extra-articular disease is rheumatoid arthritis often co-morbid with?
Sjogren’s syndrome
What are the early features of rheumatoid arthritis?
• Swelling and erosion of MCP and PIP joints
What hypersensitivity types characterise rheumatoid arthritis pathogenesis?
Type II (IMG 146) Type IV (IMG 145)
