Autoimmune diseases Flashcards
What 3 factors contribute to the development of autoimmune disease?
1) Genes
2) Immune regulation
3) Environment
What is the most common gene implicated in autoimmune disease?
MHC/HLA
What role do MHC/HLA genes play in autoimmune disease?
MHC/HLA genes have different subtypes DR1, DR2 etc. each of them has a different shape which are better at presenting particular Ags, eg. the Ab found in rheumatoid arthritis directly fits into the type of MHC gene associated with rheumatoid arthritis
What are the 2 types of MHC/HLA?
Class 1 - all cells have it, important in viral infection and malignancy
Class 2 - found in APCs, pick up Ag from elsewhere in the body and take them to T cells
What MHC/HLA gene is found commonly in Type 1 DM? 2
DR3,DR4
What MHC/HLA gene is found in MS? 1
DR2
What MHC/HLA gene is found in Graves Disease?
DR3
What 2 MHC/HLA genes are commonly found in systemic lupus erythematosus?
DR2, DR3
What 2 MHC/HLA genes are commonly found in rheumatoid arthritis?
DR1, DR4
How is the FOXP3 gene implicated in autoimmune diseases?
Mutation of FOXP3 causes failure to develop regulatory T cells - severe autoimmunity from birth
How is the PTPN22 gene implicated in autoimmune diseases?
Mutations in PTPN22 cause T cells to be activated more easily - get a stronger immune response in general
Where does the process of developing central tolerance take place?
1) B cells in bone marrow
2) T cells in the thymus
Other than genetics what other factors show a causative association with autoimmune diseases?
1) Sex - more common women
2) Age - more common in the elderly
3) Sequestered Ag - may be recognised as foreign by the immune system eg. cell nucleus, eye, testis
4) Environmental triggers
Name 3 environmental for autoimmune disease development?
1) Infection
2) Trauma-tissue damage
3) Smoking
Which environmental trigger is most important in rheumatoid arthritis?
smoking
In what 3 ways does autoimmunity cause disease? 3
1) Autoreactive B cells and auto-Ab - directly cytotoxic, activation of complement, interfere with normal physiological function
2) Autoreactive T cells - directly cytotoxic, inflammatory cytokine production
3) General inflammation and end-organ damage
What are the 2 main differences between organ specific and systemic autoimmune diseases?
1) Organ specific = 1 organ
Systemic = affects several organs simultaneously
2) Organ specific = autoimmunity restricted to autoantigens of that organ
Systemic = Autoimmunity associated with autoantigens found in most cells of body
Organ specific autoimmune diseases often overlap with other organ specific diseases, which is typical?
Autoimmune thyroid disease
Systemic autoimmune diseases often overlap with other non-organ specific autoimmune diseases, which are typical?
Connective tissue disease
What is the basic disease process of Hashimotos thyroiditis?
1) Destruction of thyroid follicles by autoimmune process
2) Leads to hypothyroidism
What are the 2 types of auto-Ab associated with Hashimotos thyroiditis?
1) Auto-Ab to thyroglobulin
2) Auto-Ab to thyroid peroxidase
What is the disease process of Grave’s disease?
1) Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
2) Leads to hyperthyroidism
What is the auto-Ab associated with Grave’s disease?
anti-TSH-autoantibody
What is the disease process of Myasthenia Gravis?
Auto-Ab which bind to the Ach receptor at the neuromuscular junction, they don’t stimulate they just block it - get muscle weakness as reduced signalling
What is the classic symptom of myasthenia gravis?
Fatigable muscle weakness (gets worse with repeated movement) - eyes commonly affected
Why is pernicious anaemia a macrocytic anaemia?
Have enough Hb but cant produce enough red blood cells so have reduced number of cells all stuffed full
What is the role of auto-Ab in pernicious anaemia?
Auto-Ab to intrinsic factor block it preventing it to form a complex with B12 required for B12 to be absorbed
Name 4 connective tissue disorders?
1) Systemic lupus erythematosus
2) Scleroderma
3) Polymyositis
4) Sjogrens syndrome
What are the 6 common symptoms of SLE?
1) Photosensitive rash on the face which spares the naso-labial fold (photosensitivity in general)
2) Multiple mouth ulcers
3) Alopecia
4) Arthralgia (painful joints)
5) Arthritis
6) Fatigue
What kind of Ab are present in SLE?
Anti-nuclear Ab - Ab against proteins and DNA in the nuclei of cells
What is meant by the statement ‘nuclei of cells are usually a sequestered antigen?
Substances within the nucleus are antigens
B cells and T cells float around the body and don’t normally contact with nuclei and this is a form of protection
Why does the formation of anti-nuclear Ab is SLE explain the symptoms?
Anti-nuclear Ab bind to antigens from apoptotic cells causing 1) direct attack of tissue (eg. skin rash) or 2) immune complex deposits mediated inflammation (eg. kidney)v
Other than the 6 main symptoms of SLE, what other 3 organs can commonly become involved, does this involvement occur in all patients?
1) Lungs - pleural effusion
2) Brain - cerebral lupus, seizures, strokes
3) Kidneys - lupus nephritis
What is the disease process in lupus nephritis?
1) Immune complex deposition
2) Inflammation
3) Leaky glomerulus
4) Loss of renal functioning
5) Scarring
6) Irreversible renal failure
How do you test for SLE?
Anti-nuclear Ab
What is the treatment for SLE? 3
Immunosuppression
Glucocorticoids
B cell depletion
What is vasculitis?
Inflammation of small blood vessels
What are the 3 forms of ANCA Vasculitis?
1) Microscopic polyangitis (MPA)
2) Granulomatosis with polyangitis (GPA)
3) Eosinophilic granulomatosus with polyangitis (EGPA)
What are the 2 components of Granulomatosus with polynangitis?
1) Granulomas (mass of inflammed tissue)
2) Polyangitis (inflammation of many vessels)
What are the common sights of destructive lesions in granulomatosus and polynangitis? 5
1) Nose
2) Sinuses
3) Trachea
4) Lung
5) Orbits
Inflammation of small vessels in what 4 organs occurs in granulomaotsus with polyangitis?
1) Skin
2) Kidney
3) Lung
4) Gut
What was granulomatosus with polyangitis previously known as?
Wegener’s Granulomatosus
How do you test for ANCA vasculitis?
Anti-neutrophil-cytoplasmic-Abs
What is the treatment for ANCA vasculitis? 3
Immunosuppression
Glucocorticoids
B cell depletion
Are patients ANA (anti nuclear Ab) positive or negative in primary raynauds?
ANA negative
Are patients ANA positive or negative in secondary Raynaud’s?
ANA positive
What conditions may secondary Raynaud’s be associated with?
Scleroderma (also SLE and other diseases)
In which group is primary Raynaud’s common?
Young women
What are the main features of Scleroderma? 3
1) Autoimmunity leads to ischaemia and fibrosis
2) Raynaud’s phenomenon
3) Skin thickening and tightening in fingers and face
Fibrosis in scleroderma may affect which 3 organs?
1) Lungs
2) Gut
3) Kidneys
How would you test for scleroderma?
Anti nuclear Ab (looking for anti-centromere or anti-Scl-70 Ab)
What is the treatment for Scleroderma? 4
Immunosuppression - but often poor response
Vasodilating drugs
Cyclophosphamide
Autologous stem cell transplant
What is meant by connective tissue diseases?
Not really diseases of connective tissue
Immunity against ubiquitous self antigens causes inflammation or fibrosis in any tissue
What is the treatment for Hashimoto’s thyroiditis?
Replace thyroxine
What is the treatment for Grave’s disease?
Block thyroid function
What is the treatment for myasthenia gravis? 3
1) Acetyl cholinesterase inhibitors
2) Plasmapharesis
3) Thymectomy
