Autoimmunity

Question 1

What are the exceptions where a single gene mutation leads to an autoimmune disease

Answer 1

• Autoimmune polyglandular syndrome type 1 - Low expression of self antigens in thymus so allows for autoreactive T cells into periphery.
• ALPS (Autoimmune lymphoproliferative syndrome) - Failure of apoptosis of some self reactive T and B cells.

Question 2

What is tolerance in relation to the immune system? How does it occur?

Answer 2

The process that keeps the immune system from attacking ‘self’. This occurs either by cytokines inhibiting self-reactive T cells or the self-reactive T cells are deleted in the thymus (however sometimes they may escape deletion, travel into periphery and cause tissue damage)

Question 3

What are some mechanisms that are thought to be involved in the breakdown of tolerance?

Answer 3

• Failure to delete autoreactive lymphocytes,
• 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 antigens,
• Cyptic T cell epitopes,
• Epitope spreading

Question 4

Describe features of rheumatic fever

Answer 4

• Group A streptococcus infection (normally in throat),
• Antibodies generate against strep can cross react on cardiac myosin causing heart valve damage but can also brain/neuronal damage.

Question 5

Describe the signs and treatments of systemic lupus erythematosus

Answer 5

Common signs - Butterfly rash, raised red patches, light sensitivity, mouth ulcers, heart/lung lining inflammation, seziures/nerve problems and ANA (Antinuclear antibodies)
Treatments - Systemic corticosteroids, steroid creams, antimalarials (hydroxychloroquine) or monoclonal antibodies (rituximab)

Question 6

Describe the signs and treatments of Sjogren’s syndrome

Answer 6

Symptoms - dry eyes, dry mouth, fever, involuntary weight loss, Night sweats, Arthralgia with morning stiffness, also increases risk of non-Hodgkin’s lymphoma
Treatment - eye drops, antifungals, NSAIDS, hydroxychloroquine or methotrexate.

Question 7

Describe features of Grave’s disease

Answer 7

• Overstimulation of the thyroid due to antibodies generated against TSH receptors which mimic action of TSH.
• Treat with methimazole (prevents thyroid producing hormones), thyroidectomy, radioactive iodine

Question 8

Describe features of Hashimoto’s thyroiditis

Answer 8

• Autoimmune hypothyroidism what occurs when there are antibodies to thyroglobulin and thyroid peroxidase.
• Symptoms are fatigue, feeling cold, TSH increase, weight gain and enlarged thyroid.
  Treatment - Replacement therapy (levothyroxine)

Question 9

Describe features of myasthenia gravis

Answer 9

• Antibodies to acetylcholine receptors causing diplopia, ptosis and skeletal muscle weakness especially after exercise.
• Treatment - thymectomy, immunosuppressive drugs or plasmapheresis to remove circulating antibodies.

Question 10

Describe features of autoimmune pernicious anaemia

Answer 10

• Autoimmune condition affecting the stomach as antibodies attack intrinsic factor and parietal cells resulting in vitamin B12 deficiency. Therefore treated with vitamin B12 injections

Question 11

Describe features of autoimmune haemolytic anaemia

Answer 11

• Antibodies bind to RBC causing lysis, clumping, and clearance to spleen. Commonly drug induced.
• Symptoms are chills, tachycardia, pale, fatigue, dark urine and jaundice.
• Treatment - avoid activating drug, plasmapheresis and in severe cases splenectomy

Question 12

Describe features of multiple sclerosis

Answer 12

• CD4 and CD8 T cells recognise and attack the CNS causing damage to myelin sheath surrounding nerves.
• Treatment is steroids and muscle relaxant for spasms.
• Stem cell transplants are more commonly used too

Question 13

Describe features of rheumatoid arthritis

Answer 13

• Characterized by inflammation of lining or synovium of the joints,
• More common in women,
• Associated with human leukocyte antigen-DR genes.

Question 14

What are some of the joints affected by rheumatoid arthritis?

Answer 14

• Foot and ankle and knee,
• Hip (early manifestations are not apparent),
• Hands and wrists (affected in virtually all people with RA),
• Elbow,
• Shoulders (neck stiffness and loss of motor function.

Question 15

What are some of the organs affected by RA?

Answer 15

Blood - hypochromatic-microcytic anaemia with low serum ferritin,
Nerves - mononeuritis multiplex.
Heart - pericardial effusion,
Lungs - Interstitial lung disease,
Eyes - Keratoconjunctivitis sicca or episcleritis scleritis.
Skin - Rheumatoid nodules

Question 16

How do you diagnose RA?

Answer 16

Medical History, Physical examination and lab tests such as imaging studies (erythrocyte sedimation rate), blood tests (CRP) or rheumatoid factor (antinuclear antibodies)

Question 17

What are the medications for RA?

Answer 17

Symptomatic medications - Nonsteroidal anti-inflammatory drugs, Analgesics, Corticosteroids.

Disease Modifying Drugs - Methorexate, azathioprine, hydroxychloroquine.

Biological modifiers such as infliximab (anti-TNF), and rituximab (anti-CD20) combinded with DMARD therapy.

Question 18

Describe features of coeliac disease

Answer 18

\It is driven by an autoimmune reaction to gluten causing inflammation of the small intestines. Results in diarrhoea, abdominal pain, bloating, osteoporosis, iron/vitamin B12/folate deficiency anaemia and increased risk of bowel cancer. 
HLA class 2 link (DQ2.5)