Autoimmunity

Question 1

Autoimmunity vs autoimmune disease

Answer 1

Autoimmunity - immune response against host due to loss of immunological tolerance of self antigen(s)

Autoimmune disease - disease caused by tissue damage or disturbed physiological responses due to auto immune response (organ/ non organ specific, may affect multiple systems)

Question 2

Common organ specific autoimmune diseases and their self antigens

Answer 2

Hashimoto’s thyroiditis - thyroid peroxidase & thyroglobulin

Type 1 diabetes mellitus - pancreatic islet cells

Multiple sclerosis - myelin sheath

Goodpasture’s disease (glomerulonephritis) - glomerular/ alveolar BM

Addison’s disease - steroid-21 hydroxylase (adrenal cortex)

Graves’ disease - thyroid stimulating hormone receptor

Myasthenia gravis - acetylcholine receptor

Pernicious anaemia - intrinsic factor (terminal ileum)

Question 3

Common non-organ specific automimmune diseases and their self antigens

Answer 3

Automimmune haemolytic anaemia - RBCs antigens

Rheumatoid arthritis - rheumatoid factor (Fc portion of IgG)

Systemic lupus erythematous - double stranded DNA + other nuclear proteins

Sjögren’s syndrome (dry eyes, dry mouth and arthritis) - nuclear antigens (Ro & La)

Question 4

Organ specific automimmune diseases and their hypersensitivity reactions

Answer 4

Hashimoto’s thyroiditis - type 4

Type 1 DM - 4

Multiple sclerosis - 4

Goodpasture’s - 2

Addisons - 2-4

Graves - 2

Myasthenia gravis - 2

Pernicious anaemia - 2

Question 5

Non organ specific automimmune diseases and their hypersensitivity reactions

Answer 5

Automimmune haemolytic anaemia - 2

Rheumatoid arthritis - 3-4

SLE - 3

Sjögren’s syndrome - 4

Question 6

Difference between type 2 and 4 hypersensitivity reactions

Answer 6

Type 2 - membrane bound antigens, tends to be organ specific. Autoantibody driven - complement activation, antibody mediated cell cytotoxicity, neutrophil activation

Type 4 - cell mediated, delayed, autoreactive T cell driven - cytotoxic T cells, macrophages

Question 7

Criteria for diagnosis of autoimmune disease

Answer 7

1. Presence of autoantibodies/ autoreactive T cells
2. Levels autoantibodies correlate with disease severity
3. Autoantibodies/ autoreactive T cells found at site of tissue damage
4. Transfer of autoantibody or autoreactive T cells to a healthy host induces automimmune disease
5. Clinical benefit provided by immunomodulatory therapy
6. Family history

Question 8

List some primary autoantibodies and the diseases they cause (pathogenic, rare)

Answer 8

Anti- TSHR (Graves’)

Anti- acetylcholine receptor (myasthenia gravis)

Anti- voltage- gated Ca2+ channel (lambert- Eaton myasthenia syndrome)

Anti- glomerular BM (Goodpasture’s syndrome)

Question 9

List some secondary autoantibodies and the diseases they cause

Answer 9

Anti- nuclear (SLE)

Anti- gastric parietal cell (pernicious anaemia)

Anti- thyroid peroxydase (Hashimoto thyroiditis)

Anti- rheumatoid factor (RA)

Question 10

Difference between sensitivity and specificity

Answer 10

Sensitivity - how good is the test at identifying those with the condition (% individuals with condition that test identifies)

Specificity - how good is the test at telling who does not have the condition (% individuals without condition that test excludes)

Question 11

How do neonatal autoimmune diseases get caused? Give some examples

Answer 11

Mother’s IgG antibodies can cross placenta and cause neonatal autoimmune disease, usually lasts for 6 months (until maternal IgG antibodies disappear)

If it’s IgM driven won’t affect baby as chat cross placenta (too big)

E.g. autoantibody to platelets = thrombocytopenia, RBCs = haemolytic anaemia, TSH receptor = neonatal graves’, acetylcholine R = neonatal MG, nuclear antigen SSA/ Ro = neonatal SLE

Question 12

Triggers of autoimmunity

Answer 12

Genetic:
AIRE mutations (APECED syndrome) affect central tolerance 

Associated with MhC variants (HLADR3/ DR4)

80% automimmune disease are in females

Environmental:
Hormones - females
Infections - streptococcus pyogenes M protein (rheumatic fever), campylobacter jejuni glycoproteins (Guillain- barre syndrome), coxsakieviruse B4 nuclear protein (diabetes type 1)
Drugs

Question 13

What can D-penicillamine be used to treat?

Answer 13

Rheumatoid arthritis
Myasthenia gravis
Pemphigus
SLE
Glomerulonephritis

Question 14

What’s a therapeutic treatment for haemolytic anaemia?

Answer 14

Methyl-dopa (antihypertensive)

Question 15

What therapeutic agents can be used to treat systemic lupus erythematous?

Answer 15

D- penicillamine

Hydralazine (antihypertensive)

Procainamide (Antiarrhythmic)

Isoniazid (antituberculosis)

Minocycline (antibiotic) - can also cause symptoms

Question 16

Current therpeautic strategies for automimmune disease

Answer 16

Plasma exchange - Mg, Goodpasture’s syndrome, Graves’ disease

Immunosuppressive drugs - anti-T cell e.g. ciclosporin, anti-proliferation drugs e.g. azathioprine, cytotoxic drugs e.g. cyclophosphamide, anti-metabolite drugs e.g. methotrexate

Anti-inflammatory drugs

Replacement therapy surgery

Question 17

Examples of biological therapy in autoimmune disease

Answer 17

Rituximab - tumour regulator, targets CD20 antigen on normal and malignant B cells

Belimumab - monoclonal antibodies

Epratuzumab - monoclonal antibody

Question 18

Organ specific autoimmune diseases and their therapy

Answer 18

Hashimoto’s thyroiditis - replacement therapy

Type 1 DM - replacement therapy

MS - anti-inflammatory/ monoclonal antibodies

Goodpasture’s disease - plasmapheresis/ cytotoxic drugs/ renal dialysis

Addisons - replacement therapy

Graves - anti- thyroid drugs, plasmapheresis/ surgery

Myasthenia gravis - anticholinesterase drugs/ immunosuppressive drugs

Pernicious anaemia - replacement therapy

Question 19

Non-organ specific autoimmune diseases therapy

Answer 19

AI haemolytic anaemia- anti-inflammatory drugs/ splenectomy

Rheumatoid arthritis - immunosuppressive drugs/ monoclonal antibodies

SLE - immunosuppressive drugs/ monoclonal antibodies