Autoimmunity

Question 1

What is Autoimmunity?

Answer 1

The immune system has self-tolerant mechanisms. When these breakdown, autoimmunity occurs.

Autoreactive antibodies and autoreactive T cells develop. These recognise self antigens. i.e. normal componenets of the body

Question 2

What is the spectrum of autoimmunity?

Answer 2

Can be organ-specific

• E.g. Hashimoto’s thyroiditis - thyroid-specific

Or involve many organs

• E.g. SLE (systemic lupus erythematosus)
• Non-organ specific, one of the dominant antibodies is directed against cell nucleus

Question 3

What happens in Hashimoto’s thyroiditis?

Answer 3

Enlarged thyroid in Hashimoto’s thyroiditis

Antibodies are directed against thyroglobulin

• Antibodies in serum of Hashimoto’s disease patient bind to residual thyroglobulin in colloid and acinar epithelial cells

Question 4

What are 2 different ways u can have the disease and who is more likely to get it, men or woman?

Answer 4

1. An individual may have more than one autoimmune disease
   e. g. Rheumatoid Arthritis often associated with SLE
2. Autoimmune diseases can occur in families Certain HLA haplotypes predispose to auto-immunity

E.g. Hashimoto’s thyroiditis - HLA-DR5

Rheumatoid Arthritis - HLA-DR1 and -DR4

3. Prevalence: ~3.5% population have autoimmune disease
4. Overall, women are 2.7x more likely than men to develop autoimmune disease

Question 5

What is an example of Human autoantibodies being directly pathogenic?

Answer 5

Thyrotoxicosis (Graves’ disease)

1. AutoAb (autoantibody) produced to receptor for Thyroid Stimulating Hormone (TSH)
2. Act on receptor
3. Stimulate thyroid cell
4. Overproduction of thyroid hormones

AutoAb is autoantibodies that are made against substances formed by a person’s own body

Question 6

What happens in Pernicious Anaemia?

Answer 6

1. Normally dietary vitamin B12 is absorbed as a complex with intrinsic factor (IF)
2. In pernicious anaemia autoantibodies directed against IF are produced
3. Binding of autoantibody to IF prevents interaction with Vit B12
4. As a result, Vit B12 is not absorbed

Question 7

What is Sjögren’s syndrome?

Answer 7

1. Chronic inflammatory autoimmune disorder
2. Can occur in isolation or with SLE, RA or other rheumatic autoimmune disorders
3. Majority of patients are women symptoms develop in 4th-5th decade actual onset probably in 1st-2nd decade
4. May affect 1-2% of population
5. Characterised by a lymphocytic infiltrate in salivary and lacrimal glands
6. Slow destruction and replacement of glandular tissue with fibrotic tissue
7. Lack of saliva and tear secretion - dental caries, oral Candida
8. Condition confirmed by presence in serum of autoantibodies

Question 8

How can Autoimmune Disorders be treated?

Answer 8

1.In some organ-specific diseases, metabolic control is sufficient e.g.:

• anti-thyroid drugs in Graves’ disease
• injection of Vit B12 in pernicious anaemia

2. Anti-inflammatory drugs - e.g. corticosteriods or non-steroidal anti-inflammatory drugs (NSAIDs)
3. Immunosuppressive drugs - e.g. cyclosporin
4. Monoclonal antibodies to blockade certain cytokines or their receptors

Question 9

Answer 9