Autoimmunity

Question 1

When does autoimmunity occur?

What is developed?

Answer 1

The immune system has self-tolerant mechanisms (recognise self from non-self). When these breakdown, autoimmunity occurs.

• autoreactive antibodies and autoreactive T cells develop, recognising normal parts of the body

Question 2

What are the two ends of the spectrum of autoimmunity?

Answer 2

• organ specific e.g. hashimotos thyroiditis
• thyroid, stomach, adrenal, pancreas
• involve many organs e.g. systemic lupus erythematosus (SLE)
• muscle, skin, joints, kidneys

Question 3

List some general points regarding autoimmune diseases

Answer 3

• an individual may have more than one autoimmune disease e.g. rheumatoid arthritis and SLE
• autoimmune diseases can occur in families, certain HLA haplotypes predispose to auto-immunity e.g. rheumatoid arthritis HLA-DR1 and DR4
• prevalence around 3.5% population
• overall, women are 2.7X more likely than men to develop autoimmune disease

Question 4

How can autoantibodies cause disease?

Answer 4

Human autoantibodies can be directly pathogenic e.g. graves disease

• autoantibodies produced to receptor for TSH
• act on receptor
• stimulate thyroid cell
• overproduction of thyroid hormones due to autoantibodies constantly being present

Question 5

Explain autoantibodies and pernicious anaemia

Answer 5

Autoantiibodies directed against intrinsic factor causes pernicious anaemia

• normally dietary vitamin B12 is absorbed as a complex with intrinsic factor
• in Pernicious anaemia, autoantibodies directed against intrinsic factor are produced
• binding of autoantibody to intrinsic factor prevents interaction with vitamin B12
• as a result, vitamin B12 is not absorbed

Question 6

Describe ways of immunopathological damage by:

a) autoantigen
b) immune complexes

Answer 6

AutoAg is localised to a particular organ

• Type II hypersensitivity and cell mediated reactions
• damange due to complement activation and phagocyte degranulation

Immune complexes appear to be pathogenic in systemic autoimmunity

e. g. in SLE deposits of IC containing autoAg and autoAb in kidney
- type III hypersensitivity reactions
- actue tissue damage

Question 7

Describe the pathology of rheumatoid arthritis:

Answer 7

• inflammatory infiltrate foind in synovial membrane
• erosion of synovial cartilage and bone
• IC and neutrophils present in joint space
• IC can arise through self association of rheumatoid factors = IgG molecules with unusual oligosaccharides attached

Question 8

List some autoimmune diseases affecting head and neck:

Answer 8

• hashimotos thyroiditis
• hashimotors persistent goiter
• graves disease
• non-goitrous hyperthyroidism
• cicatricial pemphigoid: chronic autoimmune disease of mucosal membranes and/or skin, lining of mouth a common site

Question 9

What is Sjogrens syndrome?

Answer 9

Chronic inflammatory autoimmune disorder

• can occur in isolation or with SLE, RA of other rheumatic AI diseases
• more common in females
• characterised by a lymphocytic infiltrate in salivary and lacrimal glands –> slow destruction and replacement of glandular tissue with fibrotic tissue
• lack of saliva and tear secretion –> dental caries and oral candidiasis
• confirmed by presence of autoantibodies in serum

Question 10

How can autoimmune diseases be treated?

Answer 10

• metabolic contol in some organ specific diseases
• anti-inflammatory drugs e.g. glucocorticosteriods, NSAIDs
• immunosuppresive drugs
• monoclonal antibodes to block specific cytokines or their receptors –> inhibots immune response and alleviates symptoms