3.1 Autoimmunity

Question 1

What are some key points about autoimmune diseases?

Answer 1

• Autoimmune diseases are increasing
• 80% are women
• Increased morbidity and mortality
• Manifests during adolescence and adulthood mainly
• Incurable but managable

Question 2

What parts of the body are affected by autoimmune conditions?

Answer 2

Any organ

Question 3

What is autoimmunity?

Answer 3

Immune response against host due to loss of immunological tolerance of self-antigens

Question 4

What is autoimmune disease?

Answer 4

Conditions caused by tissue damage or disturbed physiological responses due to an immune response against self-antigens

Question 5

What is immunological tolerance?

Answer 5

Host processes that prevent potentially harmful immune responses against host or self antigens

Question 6

What mechanisms lead to the breakdown of immunological tolerance?

Answer 6

• Breakdown of central tolerance-failure to delete autoreactive T or B cells
• Breakdown of peripheral tolerance-regulatory T cell defects, impaired immunomodulation, altered self-antigens
• Activation of autoreactive B cells-T cell-independent activation of B cells, carrier effect (complex foreigen-self antigens)

Question 7

What is the difference between organ specific and non-organ specific autoimmune disease?

Answer 7

Organ specific
- One of multiple self-antigens within one single organ or tissue

Non-organ specific
- Widely distributed self-antigens throughout the body

Question 8

Outline hashimoto’s thyroiditis

Answer 8

Organ specific
- Thyroid peroxidase
- Thyroglobulin

TPO antibodies and thyroglobulin antibodies

Causes hypothyroidism

Type IV HSR

Graves’ disease is Type II HSR

Question 9

Outline T1DM

Answer 9

Organ specific
- Proteins in the pancreatic islet cells

Causes hyperglycaemia

Type IV HSR

Question 10

Outline multiple sclerosis

Answer 10

Organ specific
- Myelin sheath destruction
- Damaged oligodendrocytes

Type IV HSR

Question 11

Outline goodpasture’s disease

Answer 11

Organ specific
- Glomerular/alveolar basement membrane
- Type IV collagen affected

Causes glomerulonephritis

Type II HSR

Question 12

Outline addison’s disease

Answer 12

Organ specific
- Steroid-21 hydroxylase (adrenal cortex)

Causes adrenal insufficiency

Type II-IV HSR

Question 13

Outline myasthenia gravis

Answer 13

Organ specific
- AChR destruction in the NMJ

Skeletal muscle weakness

Type II HSR

Question 14

Outline pernicious anaemia

Answer 14

Organ specific
- Autoimmune destruction of parietal cells
- Decreased intrinsic factor, reduced B12 absorption

B12 Deficiency

Type II HSR

Question 15

Outline autoimmune haemolytic anaemia

Answer 15

Non-organ specific
- RBC antigens

Anaemia

Type II HSR

Question 16

Outline rheumatoid arthritis

Answer 16

Non-organ specific
- Rheumatoid factor (Fc portion of the IgG)

Inflammatory arthritis

Test via serum sample

Type III-IV HSR

Question 17

Outline systemic lupus erythematosus (SLE)

Answer 17

Non-organ specific
- Double stranded DNA and other nuclear proteins (histones)

Multisystemic

Test via serum sample

Type III HSR

Question 18

Outline sjorgen’s syndrome

Answer 18

Non-organ specific
- Nuclear antigens Ro and La

Dry eyes, mouth and arthritis

Type IV HSR

Question 19

How can tissue damage/physiological change occur due to autoimmune disease?

Answer 19

Autoantibody driven:
- Complement activation
- Antibody-mediated cell cytotoxicity
- Neutrophil activation

Autoreactive T cell driven:
- Cytotoxic T cells
- Macrophages

All either type II, III or IV HSRs

Question 20

What is the set of criteria for diagnosis of autoimmune disease?

Answer 20

1. Presence of autoantibodies/autoreactive T cells
2. Level of 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 healthy host induces autoimmune disease (eg vertical transmission)
5. Clinical benefit from immunomodulatory therapy
6. Family history

Question 21

What is the difference between primary and secondary autoantibodies ?

Answer 21

Primary drives disease, plasmapharesis improves condition

Secondary play potential role but do not drive disease

Question 22

Give 4 examples of primary autoantibodies

Answer 22

• Anti-TSHR-Graves’ disease
• Anti-acetylcholine receptor-Myasthenia gravis
• Anti-voltage-gated Ca2+ channel antibodies-Lambert-Eaton myasthenia syndrome
• Anti-glomerular basement membrane antibodies-Goodpasture’s syndrome

Question 23

Give 4 examples of secondary autoantibodies

Answer 23

• Anti-nuclear antibodies-SLE
• Anti-gastric parietal cell antibodies-pernicious anaemia
• Anti-thyroid peroxydase antibodies-Hashimoto thyroiditis
• Anti-Rheumatoid Factor antibodies-Rheumatoid arthritis

Question 24

What test do we use to detect antibodies?

Answer 24

Coomb’s Test

Auto-antibodies not always detected, cannot rule out if negative

Table for interest

Question 25

How are autoantidobies detected at site of tissue damage?

Answer 25

* Indirect immunofluoresence * Immunofluoresence * Radioimmunoassay * Coomb's test * Agglutination Take biopsy then test^

Question 26

What histological feature is present on hashimoto's thyroiditis?

Answer 26

Lymphocytic inflitration

Question 27

Complete the table

Answer 27

Question 28

What does it mean that myasthenia gravis is transient in neonates?

Answer 28

Mother's autoantibodies are replaced by own body's antibodies when the immune system matures

Question 29

How do you treat neonatal myasthenia gravis?

Answer 29

Neostigmine ACh Esterase inhibitor

Question 30

What triggers autoimmunity?

Answer 30

**Genetic factors** - Increased risk with affected sibling or identical twin - AIRE mutations that affect central tolerance (gene codes for T cells to not attack self antigens) - MHC variants (HLADR3/4) **Environmental factors** - Hormones - Infections - Drugs

Question 31

What is the significance of hormonal factor involvement in autoimmune disease?

Answer 31

Females affected much more In pregnancy hormones released by placenta can improve some autoimmune conditions

Question 32

What is another reason that females are affected by autoimmune conditions more than men?

Answer 32

Females are XX 1 X should be inactive, but in some cases 25% of genes are active on the second X chromosome Can cause problems with immune regulation

Question 33

Complete the table

Answer 33