CSIM 1.57 58 Autoimmune Disease 1 And 2 Flashcards
What is the principle cause of autoimmune disease?
Breakdown of self-tolerance.
Explain central tolerance
Thymocytes maturing in the thymus go through a process where cells that recognise self antigen are apoptosed. The protein responsible for presenting self antigen is the AIRE protein (autoimmune regulator protein)
What 4 characteristics does peripheral tolerance depend on?
Immunologically privileged sites
Anergy
Regulatory tolerance
Apoptosis
Describe how an immunologically privilege site can trigger an immune response
Tissue in such sites do not usually have immune cells circulating in them, this means that immune cells have never encountered them before and will react to them if encountered.
This might happen because of an injury, causing immunologicaly privileged cells to activate immune cells, triggering an immune response against that particular type of tissue.
E.g. Sympathetic opthalmia, multiple sclerosis
What is anergy? And how does it lead to peripheral tolerance
Anergy happens when a T cell encounters its antigen, but without a co-stimulatory signal. This means that activation has failed and the cell goes into anergy, preventing further activation.
This ensures that no immune response occurs without inflammatory signals.
What is regulatory tolerance and how does it help in peripheral tolerance?
Mediated by TRegs, regulatory T cells that can suppress autoreactive lymphocytes.
Explain APECED
APECED occurs when there is a defect in the AIRE protein, this leads to autoreactive T cells to be released into the system.
This leads to destruction of host tissue and can lead to diseases like Addison’s disease, hypoparathyroidism.
What is IPEX syndrome?
X linked autosomal defect leading to defective Treg cells.
Describe how an infection can cause an autoimmune disease
By releasing sequestered self-antigen from immunoprivileged sites (sympathatic opthalmia)
Or in cases like rheumatic fever where pathogenic antigen mimics self-antigen, causing auto reaction against self tissue.
Difference between organ specific and non-organ specific autoimmune disease?
The former results in immune response against a particular type of tissue (usually type 2 HS reaction e.g. T1DM, goodpastures, AIHA)
The latter results in multiple areas of the body affect regardless of tissue type e.g. RA, SLE, sjogrens.
Describe Goodpasture’s disease
Anti-glomerular basement membrane disease - type 2 HS
Antibodies formed againest collagen which affects glomerular basement membrane and alveoli.
Clinical ft- malaise, fever, weight loss, fatigue, joint ache and pain. Localised symptoms to lung haemoptysis, cough, chest pain sob.
Kidney symptoms - haematuria, proteinuria, peripheral edema, uraemia and hypertension.
Describe autoimmune thyroid disease
Antibodies form against TSH receptor in thyroid
Antibodies mimic structure of TSH, activate receptor
Gland make excess hormones.
Associated with HLA DR3
Describe Grave’s disease
Example of autoimmune thyroid disease
Causes hyperthyroidism.
Clinical ft- tachycardia, weight loss, diarrhea, exopthalmos, lid lag, pretibial myxodema, enlarged thyroid gland.
Suppresed TSH, raised T4 and T3.
Anti-thyroid antibody present.
Treatment for Grave’s disease
Removal of thyroid gland, partial or complete through surgery or radioactive iodine ablation.
Give replacement therapy.
Describe autoimmune haemolytic anaemia
Autoantibodies formed against RBC membrane antigen. Destroys RBC.
Two ways of haemolysis in AIHA
Extravascular haemolysis = IgG opsonisation of RBC, phagocytosed and transported to spleen for break down
Intravascular haemolysis = IgM made, forms immune complex, triggers complement activation and MAC
Investigation of AIHA
Anaemia
Unconjugated bilirubin
Reduced haptoglobin
Increased lactate dehydrogenase
Reticulocytosis with left shift
Reason for reduced haptoglobin in AIHA?
Haptoglobin is a metabolic enzyme used in the degradation of haemglobin.
Increased haemylosis will deplete haptoglobin
Treatment for AIHA?`
Steroids, immunosuppresive drugs like asathiprine, cychlophosphamide, rituximab
How does haemolytic disease occur from newborns
Mother pregnant with baby with different blood group (ABO or Rh)
First pregnancy, mother becomes sensitised to the antigen
Second pregnancy, hyper acute immune reaction occurs and destroys fetal blood cells.
Consequences of haemolytic disease of new born
Hydrops fetalis, anaemia, increased bilirubin, hepatsplenomegaly
Increased bilirubin lead to neurotoxicity -> kernicterus.
How to prevent haemolytic disease of newborn?
During first pregnancy, mother should be given Anti-Rh D (or whatever antigen), this prevents circulating antigen in the mother and prevents sensitisation of her immune system.
Describe a type 3 HS reaction like farmer’s lung
Antigen enters system, reacts with IgG to form immune complexes, these get deposited in tissue all over including the lungs.
Farmers come into contact with allergens like hay and compost.
These immune complexes build up in the lungs causing inflammatory response, fluid, protein build up.
Clinical features of farmers lungs
Fevers, chills, non-productive cough and SoB
Describe pathogenesis of SLE
Antibodies made against cell nuclei, cytoplasm and self tissues. Results in immune complexes formed depositing in various tissue.
Starts with loss of self-tolerance, apoptotic break down to expose nuclear antigen to immune system.
Antigens engulfed by APCs and presented to T cells whcih get activateds.
Results in B cell production of antibodies against that antigen, forming immune-complexes.
Clinical features of SLE
Varied and wide ranging, can affect any organ, depends on site
E.g. Arthritis, pleurisy, glomerulonephritis, Raynauds, etc
How to investigate SLE?
Look for antinuclear antibodies to dsDNA. Low complement C4 and C3, raised IgG and raised ESR.
Drugs for graves disease
antithyroid drugs like carbimazole and propylthiouracil
