Autoimmune Diseases L6-7

Question 1

Define an autoimmune response.

Answer 1

An immune response specific for “self”.

Question 2

Define an autoimmune disease.

Answer 2

An autoimmune response central to pathogenesis.

Question 3

What are the 2 types of autoimmune disease?

Answer 3

• Organ-specific

- Non-organ-specific (systemic)

Question 4

Name some organ-specific autoimmune diseases.

Answer 4

• Type 1 diabetes mellitus
• Goodpasture’s syndrome
• MS
• Grave’s disease
• Myasthenia gravis
• Hashimoto’s thyroiditis
• Autoimmune pernicious anemia
• Autoimmune Addison’s disease
• Vitiligo

Question 5

Name some non-organ-specific autoimmune diseases.

Answer 5

• Rheumatoid arthritis
• Scleroderma
• Systemic lupus erythematosus
• Polymyositis
• Primary Sjogren’s syndrome

Question 6

Describe autoantibodies.

4

Answer 6

• Often >1 autoantibody
• May be primary or secondary
• Overlap between organ-specific diseases
• Also between non-organ-specific diseases

Question 7

Autoimmune disease may be antibody or ___ ___ -mediated.

Answer 7

T cell

Question 8

Describe the role of autoantibodies in Pernicious anemia.

Answer 8

Ab to intrinsic factor in pernicious anaemia, preventing absorption of vitamin B12.

Question 9

Describe the role of autoantibodies in Myasthenia gravis.

Answer 9

Ab to acetyl choline receptor in myasthaenia gravis that binds to receptor causing its removal from the muscle surface.

Question 10

Describe the role of autoantibodies in Grave’s disease.

Answer 10

Ab to TSH receptor in Graves’ disease which mimics the effect of TSH causing excessive secretion of thyroid hormones.

Question 11

Describe the role of autoantibodies in autoimmune haemolytic anemia.

Answer 11

Autoantibodies mediate the destruction of red blood cells.

Question 12

Describe the role of autoantibodies in immune thrombocytopenic purpura.

Answer 12

Autoantibodies mediate the destruction of platelets.

Question 13

Name the 3 pathogenic effects of autoantibodies.

Answer 13

• Interference with molecular function
• Mediation of cell desctruction (Type 2 hypersensitivity)
• Immune complex mediated reactions (Type 3 hypersensitivity)

Question 14

Describe the role of autoantibodies in systemic lupus erythematosus.

Answer 14

Autoantibodies to DNA form complexes which are deposited at susceptible sites leading to symptoms of disease (skin, kidneys, joints).

Question 15

Which type of hypersensitivity causes T-cell-mediated pathogenesis.

Answer 15

Type 4.

Question 16

The best evidence of T-cell-mediated pathogenesis comes from where?

Answer 16

Animal models.

Question 17

Which disease is the animal model for MS?

Answer 17

EAE (Experimental allergic encephalitis).

Question 18

Describe Rheumatoid arthritis and the role of synovial fibroblasts.

Answer 18

Joints are infiltrated by CD4 T cells that activate macrophages to secrete inflammatory cytokines.

Role of synovial fibroblasts

• Secrete matrix metalloproteases: damage tissue
• Express RANK ligand: activate osteoclasts to break down bone

Question 19

True or false? Single gene defects causing autoimmune disease are common.

Answer 19

False. They are rare.

Question 20

In mice which genes can be knocked out to give rise to an autoimmune disease?

Answer 20

• CTLA4
• IL-2
• IL-10

Question 21

Name the 4 genetic factors in diabetes.

Answer 21

• HLA
• Insulin gene
• CTLA-4
• PTPN22

Question 22

Autoreactive T-helper cells are normally unresponsive due to what 4 mechanisms?

How does a full autoimmune response occur?

Answer 22

1. Clonal deletion
2. Clonal anergy
3. Suppression (by Treg)
4. Inadequate autoantigen presentation

A full autoimmune response requires these mechanisms to be bypassed or subverted

Question 23

Name the 5 ways in which autoimmune disease could arise.

Answer 23

1. Molecular mimicry
2. Microbes provide ‘danger signals’
3. Autoantigens act as ligands for TLRs, so interpreted as foreign by immune system
4. Release of “sequestered” antigen
5. Abnormal expression of autoantigens to which there is no tolerance

Question 24

Describe molecular mimicry in the development of an autoimmune disease.

Answer 24

Microbial antigen is similar to an autoantigen and induces a cross-reactive immune response.

Question 25

What do microbe released ‘danger signals’ do in the development of an autoimmune disease?

Answer 25

• Upreguate costimulator molecules

- Induce inflammatory cytokines

Question 26

Give an example of how the release of “sequestered” antigen could play a role in the development of an autoimmune disease.

Answer 26

Traumatic damage to one eye can lead to an autoimmune response affecting the other eye.

Question 27

Describe Narcolepsy.

Answer 27

• Narcolepsy is a sleep disorder causing daytime sleepiness
• Associated with deficiencies in the wakefulness hormone hypocretin
• Neurones that produce hypocretin are deficient in narcoleptic brains
• Thought to be an autoimmune disease because of very strong HLA-association (HLA-DQB1*0602)

Question 28

Gut microbes have been shown to influence the development of type 1 diabetes in a mouse model.
The incidence is higher in females, why is this?

Answer 28

Due to protective effect of microbes in males since male mice in germ-free conditions show a similar incidence of disease to females.
Microbes in male mice induced increased production of testosterone and protected against the development of diabetes.

Question 29

List the treatments of autoimmune diseases.

Give examples.

Answer 29

• Metabolic control
  e. g. insulin in diabetes
• Anti-inflammatory drugs
  e. g. steroids in SLE
• Immunosuppressive drugs
  e. g. cyclosporin A, anti-mitotics