Clinical Autoimmunity

Question 1

Define autoimmunity.

Answer 1

Failure of self-tolerance.

Question 2

List the 2 types of autoimmunity.

Answer 2

1 - Tissue specific.

2 - Systemic.

Question 3

List 2 types of factors that underlie the pathogenesis of autoimmunity.

Answer 3

1 - Genetic predisposition.

2 - Environmental triggers.

Question 4

List 2 process that maintain central T cell tolerance.

Answer 4

1 - Thymic positive selection.

2- Thymic negative selection.

Question 5

List 2 processes that maintain central B cell tolerance.

Answer 5

1 - Early antigen encounter.

2 - Pre-lymphoid tissue deletion or anergy.

Question 6

List 4 processes that maintain peripheral T cell tolerance.

Answer 6

1 - Ignorance (privilege).

2 - Anergy (due to no (co)stimulation).

3 - Apoptosis (due to no (co)stimulation).

4 - Suppression (due to Treg cells).

Question 7

Give an example of an area in the body that develops peripheral T cell tolerance due to privilege (being separated from the immune system).

Answer 7

The eyes.

Question 8

How does loss of T cell tolerance in cells of the eye due to privilege work?

Answer 8

• The immune system is not exposed to the environment of the eye (as it must remain transparent).
• Nor does AIRE express antigens for proteins in the eye.
• Therefore the immune system will not recognise the environment of the eye as ‘self’.

Question 9

What is sympathetic ophthalmia?

Answer 9

Inflammation of the eye due to contact with immune tissue, in which granulomas form.

Question 10

What are the functions of CD28 and CTLA4?

Answer 10

• CD28 accelerates T cell activity by providing the cell with costimulatory signals.
• CTLA4 suppresses T cell activity.
• These are surface proteins on T cells.

Question 11

Describe the pathophysiology of rheumatoid arthritis.

Answer 11

• There is a loss of Treg function due to deficiencies in CTLA4, leaving the activity of CD28 un-antagonised.
• In some patients, autoantibodies are also implicated.

Question 12

List 5 mechanisms by which autoantibodies cause disease.

Answer 12

1 - Complement-dependent lysis.

2 - Opsonisation.

3 - Immune complexes.

4 - Receptor blockade.

5 - Receptor stimulation.

Question 13

Give an example of a disease that is due to autoantibodies causing disease by complement-dependent lysis.

Answer 13

Paroxysmal cold haematuria.

Question 14

Give an example of a disease that is due to autoantibodies causing disease by opsonisation.

Answer 14

Most haemolytic anaemias.

Question 15

List 2 diseases that are due to autoantibodies causing disease by forming immune complexes.

Answer 15

1 - Serum sickness.

2 - Systemic lupus erythematosus.

Question 16

List 2 diseases that are due to autoantibodies causing disease by blockade of receptors.

Answer 16

1 - Myasthenia gravis.

2 - Pernicious anaemia.

Question 17

Give an example of a disease that is due to autoantibodies causing disease by stimulation of receptors.

Answer 17

Graves disease.

Question 18

List 6 organs / tissues.

For each, give at least one example of an autoimmune disease that affects it.

Answer 18

1 - Thyroid - Graves’ and Hashimoto’s.

2 and 3 - Kidney and lungs - Goodpasture’s syndrome.

4 - Pancreas - Diabetes mellitus.

5 - Parietal cells - Pernicious anaemia.

6 - Adrenal gland - Addison’s disease.

Question 19

How specific are the autoantibodies involved in Graves’ disease?

Answer 19

Not very specific, as they also stimulate:

1 - Orbital fat cells.

2 - Muscle cells.

3 - Fibroblasts.

Question 20

To which cells are the autoantibodies of Goodpasture’s syndrome directed?

Answer 20

The capillary basement membrane of the glomerulus and lung alveoli.

Question 21

What is rheumatoid factor?

Answer 21

• An autoantibody that is sometimes (in 2/3 of cases) present in patients with rheumatoid arthritis.
• An antibody against the Fc region of IgG.

Question 22

List 2 other diseases with which rheumatoid factor is associated (other than rheumatoid arthritis).

Answer 22

1 - Systemic lupus erythematosus.

2 - Scleroderma (a group of autoimmune diseases).

Question 23

In which process is citrullination common?

Answer 23

Inflammation.

Question 24

Give an example of an autoantibody involved in rheumatoid arthritis (other than rheumatoid factor).

Answer 24

Anti-CCP, an antibody against citrullinated proteins (commonly found at sites of inflammation).

Question 25

How does using anti-CCP compare to rheumatoid factor as a diagnostic test for rheumatoid arthritis?

Answer 25

- The anti-CCP test has fewer false-positives. | - However, only 60% of patients with rheumatoid arthritis have anti-CCP, so the anti-CCP test has more false negatives.

Question 26

What is the APIPPRA trial?

Answer 26

A study whose aim is to determine whether rheumatoid arthritis can be prevented if therapy is given to individuals at high risk of developing the disease, as defined by the presence of autoantibodies in the blood, together with joint symptoms.