CSIM 1.57 58 Autoimmune Disease 1 And 2

Question 1

What is the principle cause of autoimmune disease?

Answer 1

Breakdown of self-tolerance.

Question 2

Explain central tolerance

Answer 2

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)

Question 3

What 4 characteristics does peripheral tolerance depend on?

Answer 3

Immunologically privileged sites
Anergy
Regulatory tolerance
Apoptosis

Question 4

Describe how an immunologically privilege site can trigger an immune response

Answer 4

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

Question 5

What is anergy? And how does it lead to peripheral tolerance

Answer 5

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.

Question 6

What is regulatory tolerance and how does it help in peripheral tolerance?

Answer 6

Mediated by TRegs, regulatory T cells that can suppress autoreactive lymphocytes.

Question 7

Explain APECED

Answer 7

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.

Question 8

What is IPEX syndrome?

Answer 8

X linked autosomal defect leading to defective Treg cells.

Question 9

Describe how an infection can cause an autoimmune disease

Answer 9

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.

Question 10

Difference between organ specific and non-organ specific autoimmune disease?

Answer 10

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.

Question 11

Describe Goodpasture’s disease

Answer 11

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.

Question 12

Describe autoimmune thyroid disease

Answer 12

Antibodies form against TSH receptor in thyroid

Antibodies mimic structure of TSH, activate receptor

Gland make excess hormones.

Associated with HLA DR3

Question 13

Describe Grave’s disease

Answer 13

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.

Question 14

Treatment for Grave’s disease

Answer 14

Removal of thyroid gland, partial or complete through surgery or radioactive iodine ablation.

Give replacement therapy.

Question 15

Describe autoimmune haemolytic anaemia

Answer 15

Autoantibodies formed against RBC membrane antigen. Destroys RBC.

Question 16

Two ways of haemolysis in AIHA

Answer 16

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

Question 17

Investigation of AIHA

Answer 17

Anaemia

Unconjugated bilirubin

Reduced haptoglobin

Increased lactate dehydrogenase

Reticulocytosis with left shift

Question 18

Reason for reduced haptoglobin in AIHA?

Answer 18

Haptoglobin is a metabolic enzyme used in the degradation of haemglobin.

Increased haemylosis will deplete haptoglobin

Question 19

Treatment for AIHA?`

Answer 19

Steroids, immunosuppresive drugs like asathiprine, cychlophosphamide, rituximab

Question 20

How does haemolytic disease occur from newborns

Answer 20

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.

Question 21

Consequences of haemolytic disease of new born

Answer 21

Hydrops fetalis, anaemia, increased bilirubin, hepatsplenomegaly

Increased bilirubin lead to neurotoxicity -> kernicterus.

Question 22

How to prevent haemolytic disease of newborn?

Answer 22

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.

Question 23

Describe a type 3 HS reaction like farmer’s lung

Answer 23

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.

Question 24

Clinical features of farmers lungs

Answer 24

Fevers, chills, non-productive cough and SoB

Question 25

Describe pathogenesis of SLE

Answer 25

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.

Question 26

Clinical features of SLE

Answer 26

Varied and wide ranging, can affect any organ, depends on site

E.g. Arthritis, pleurisy, glomerulonephritis, Raynauds, etc

Question 27

How to investigate SLE?

Answer 27

Look for antinuclear antibodies to dsDNA. Low complement C4 and C3, raised IgG and raised ESR.

Question 28

Drugs for graves disease

Answer 28

antithyroid drugs like carbimazole and propylthiouracil