Autoimmunity Flashcards
How common are autoimmune diseases?
5 - 8% in most western populations
What percentage of autoimmune diseases affect females?
75% (4th largest class of disease in females)
What are autoimmune diseases caused by?
Usually complex, interplay between multiple genes, and external factors (genetic predisposition and environmental modulators/triggers)
What autoimmune diseases are caused by a single gene?
- Autoimmune polyglandular syndrome type 1 (APS-1), AIRE
- Autoimmune lymphoproliferative syndrome (ALPS) FAS, FASL
What organ does autoimmune uveitis affect?
Eyes
What organ does sjogrens syndrome affect?
Mouth
What organ does pemphigus affect?
Skin and mucosa
What organ does Goodpasture’s affect?
Lung
What is tolerance?
The process that keeps the immune system from attacking ‘self’
What cels are deleted in the thymus?
T cells which bind to your own MHC and self peptides with too much high affinity - some may escape
What is peripheral tolerance?
Works on the ability of T cells which can react with self peptides and self MHC not becoming active and releasing pro inflammatory cytokines - but becoming a T regulatory cell - release cytokines that stop other autoreactive T cells from becoming activatied through suppresive cytokines (IL-10 TGFB) dapmen down immune responses
What are the mechanisms involved in the breakdown of tolerance?
- Failure to delete autoreactive lymphocytes (APS-1, ALPS)
- Central or peripheral tolerance failure
- Molecular mimicry
- Abnormal presentation of self antigens
- Aberrant expression of HLA class II molecules
- Release of sequestered self antigens
- Overproduction of self anitigens
- Cyptic T cell epitopes
- Epitope spreading
What is a classic example of molecular mimicry?
Rheumatic fever
WHat is Rheumatic fever?
- Group A Streptococcus infection, typically in throat
- Antibodies generated against Strep carbohydrate GlcNAc
- These antibodies cross react on cardiac myosin
- T cells also produced
- Heart valves damage, but also brain/neuronal damage possible
What are the signs/symptoms of Systemic Lupus Erythematous (SLE)?
- Butterfly rash
- Raised red patches on skin
- Light sensitivity
- Mouth ulcers
- Heart / Lung lining inflammation
- Seizures / nerves problems
- Proteinuria (lupus nephritis)
- Raynaud’s phenomenon (cold pale fingers)
- Arthritis
- ANA - antinuclear antibodies
What are the treatments for Systemic Lupus Erythmatous (SLE)?
- Systemic corticosteroids
- Steroid creams
- Antimalarials (hydroxychloroquine)
- Monoclonal antibodies (rituximab)
What are the signs/symptoms of Sjorgen’s syndrome?
- Typically presents with dry salivary glands
- Articular problems (38%)
- Glandular (palpable glands e.g parotid) (22%)
- Pulmonary (11%)
- Cutaneous (10%)
- Lymph nodes enlarged (9%)
- Constitutional symptoms (9%)
- Peripheral neuropathy (6%)
- Renal (5%)
- Muscular (2%)
- CNS (2%)
What is the treatment of Sjogren’s syndrome?
- Eye drops
- Antifungals
- NSAIDs
- Hydroxychloroquine
- Methotrexate
What cancer is at a 5x increased risk in Sjorgen’s syndrome?
Non-Hodgkin lymphoma (swollen glands, night sweats, unexplained weight loss)
What is a classic Autoimmune disease of the thyroid?
Grave’s disease
What happens in Grave’s disease?
- Overstimulation of thyroid
- Antibodies generated against TSH receptor which mimics TSH
- Causes typically buldging eyes
What is the treatment of Grave’s disease?
- Methimazole
- Thyroidectomy
- Radioactive iodine
What is hashimoto’s thyroiditis?
- Autoimmune hypothyroidism
- Antibodies to thyroglobulin and thyroid peroxidase
- Fatigue, feeling cold, TSH increase, weight gain, enlarged thyroid
What is an example of a condition which causes an underactive thyroid?
Hashimoto’s thyroiditis
What is the treatment for Hashimoto’s thyroiditis?
Replacement therapy - levothyroxine
What do antibodies attack in myasthenia gravis?
Ach receptors
What are the signs symptoms of myasthenia gravis?
- Long-term neuromucular problems
- Double vision (diplopia)
- Ptosis
- Affects other facial muscles
- Skeletal muscle weakness esp after exercise
What is the treatment for myasthenia gravis?
- Thymectomy
- Immunosuppressive drugs
- Plasmapherisis to remove circulating antibodies
What is autoimmune pernicious anemia?
- Autoimmune condition of the stomach
- Antibodies generated to parietal cells and intrinsic factor
- Deficiency in vitamin B12 results as no binding to intrinsic factor and absorption
What is the treatment of Autoimmune pernicious anemia?
B12 injections
What is autoimmune haemolytic anemia?
- Antibodies binding to RBC
- Lysis, clumping, clearence by spleen
- Induced by drug or agent modifying RBC surface, neo antigen created
What are the symptoms of autoimmune haemolytic anemia?
- Chills
- Jaundice
- Tachycardia
- Pale
- Fatigue
- Dark urine
What is the treatment for autoimmune hemolytic anemia?
- Avoid activating drug
- Plasmapherisis
- Splenectomy
What cells attack the myelin sheath in MS?
CD4 and CD8 T cells
What are possible treatments for MS?
- Steroids, muscle relaxant for spasm
- Stem cell transplant
How many people does rheumatoid arthritis affect in the UK?
350,000 people
What is rheumatoid arthritis characterised by?
Inflammation of the lining or synovium of the joints - maylead to long term joint damage, chronic pain, and disability
When does rheumatoid arthritis usually diagnosed occur?
Between ages of 30 and 50 but can also affect young children
What gender does rheumatoid arthritis affect
3 times more common in women than men
WHat are the typical joints affected by Rheumatoid arthritis?
- Foot ankle and knee
- Hip (usually later onset)
- Hands and wrists
- Elbow
- Shoulders
What other organs are affected by Rheumatoid arhtritis?
- Blood (hypochromatic-microcytic anemia with low serum ferritin and low or normal iron-binding capacity)
- Nerves (cervical spine instability)
- Heart (pericardial effusion)
- Lungs (interstitial lung disease)
- Eyes (keratoconjunctivitis sicca, episcleritis, scleritis)
- Skin (rheuamatoid nodules in 50% of patients, dermal vasculitic lesions)
What genes are associated with rheumatoid arthritis?
- Specific human leukocyte antigen (HLA)-DR genes
- HLA-DR4 (2/3s of whites with RA)
- Reside in the MHC and participate in antigen presentation
- Higher risk of severity of disease; increased by homozygosity
What are the potential roles of HLA-DR genes?
- Binds to arthritogenic peptides
- Serves as a target for autoreactive T cells
- Closely linked to other genes in the MHC
What lab test can be done to diagnose rheumatoid arthritis?
- Imaging studies - Erythrocyte Sedimation Rate
- Blood tests - C-reactive protein
- Rheumatoid factor - Antinuclear antibodies (ANA)
What are the focuses of rheumatoid arthritis treatment?
- Relieving pain
- Reducing inflammation
- Stopping or slowing joint damage
- Improving fnctioning and sense of well-being
What are the medications used for rheumatoid arthritis?
Symptomatic medications - NSAIDs - Analgesics - Corticosteroids Disease Modifying Drugs - Methotrexate - Sulfasalazine- Azathioprine - Cyclosporine - Hydroxychloroquine - Minocycline Biologic modifiers - Inflixamab (anti-TNF) - Rituximab (anti-CD20) - Combination DMARD therapy
What organ is attacked in Coeliac disease?
Small intestines (autoimmune reaction to gluten)
How common is coeliac disease?
1 in 100 (2 - 3 x higher in females)
What are the symptoms/signs of coeliac disease?
- Diarrhoea
- Abdo pain
- Bloating
- Complications (osteoperosis, iron, B12 deficiency, folate-deficiency anaemia, bowel cancer)
What genes can cause coealiac disease?
- HLA class II link - DQ 2.5 (most common)
- DQ8 and DQ2.2 (less common)
What is gluten?
Overall term for a series of proteins called gliadins
What protein attacks glutamine in coeliac disease?
Transglutamidase 2 (TG2) (changes into glutamic acid)
What does glutamic acid bind to a higher affinity for in coeliac disease - how does this affect the disease?
Class II molecules - stimulates autoreactive T cells - inflammatory response dmage gut lining (Th1 and Th17) - pro inflammatory cytokines can then damage gut wall
