Lecture 33 - Immunopathology II

Question 1

Three things needed for autoimmunity

Answer 1

1) Genetic susceptibility
2) Environmental factors
3) Loss of self-tolerance

Question 2

Where are rates of autoimmune diseases the highest?

Answer 2

Western countries

Question 3

Why are circulating auto-reactive lymphocytes not always activated?
1)
2)
3)

Answer 3

1) Antigen not available
2) Lack of signal 2 (DCs don’t receive PAMP or DAMP activation)
3) Auto-reactive B cells don’t have auto-reactive T cells for activation

Question 4

Why mightn’t an auto-reactive T cell come into contact with cognate autoantigen?

Answer 4

Autoantigen might be in the periphery, while the auto-reactive antibody is in a lymph node

Question 5

Difference between autoimmune response and autoimmune disease

Answer 5

An autoimmune response is where an autoreactive lymphocyte attacks an autoantigen.
An autoimmune disease entails chronic autoimmune response with sustained tissue damage (lack of tissue repair, or regulation of autoreactive lymphocytes)

Question 6

B cell autoimmune disease types
1)
2)

Answer 6

1) Type II (including ligand-mediated interactions)

2) Type III (immune complex formation)

Question 7

T cell autoimmune disease types
1)
2)
3)

Answer 7

1) Delayed-type hypersensitivity (Th1 activates macrophages, cytokine production, pro-inflammatory mediator release)
2) CTL killing of stromal cells (EG: type I diabetes)
3) Th help of autoreactive B cells

Question 8

Two types of autoimmune disease

Answer 8

1) Systemic

2) Organ-specific

Question 9

Systemic autoimmune disease
1)
2)

Answer 9

1) Recognised antigens are more ubiquitous

2) Multiple organs affected

Question 10

Organ-specific autoimmune disease

Answer 10

Antigens recognised are organ-specific

Question 11

Examples of systemic autoimmune disease
1)
2)

Answer 11

Systemic lupus erythematosus

Rheumatoid arthritis

Question 12

Examples of B cell mediated autoimmunity
1)
2)
3)

Answer 12

1) Grave’s disease
2) Myasthenia gravis
3) Systemic lupus erythematosus

Question 13

Grave's disease
1)
2)
3)
4)

Answer 13

1) Pituitary gland releases thyroid stimulating hormone
2) Thyroid normally releases hormones to suppress pituitary gland (negative feedback)
3) In Grave’s disease, autoantibodies bind to TSH receptors in thyroid, stimulate release of thyroid hormones
4) Hyperthyroidism results. Pituitary gland releases no more TSH, but this has no effect on Ab production

Question 14

Type of autoimmune disease that is Grave’s disease

Answer 14

B cell mediated, organ-specific

Question 15

Myasthenia gravis
1)
2)
3)

Answer 15

1) B cells produce autoantibodies that bind to nicotinic ACh receptors in neuromuscular junction
2) Results in internalisation, degradation of ACh receptors
3) No Na+ influx, no muscle contraction

Question 16

How can Grave’s disease be transmitted?

Answer 16

Through placenta, from mother to child

Question 17

Systemic lupus erythematosus 
1)
2)
3)
4)
5)

Answer 17

1) Unknown aetiology
2) B cell hyper-reactivity observed
3) DNA autoantibodies produced
4) Immune complexes deposited in kidneys
5) Numerous autoantibodies produced, multiple organ systems affected

Question 18

Pathogenesis of systemic lupus erythematosus
1)
2)
3)

Answer 18

1) Immune complex deposition in basement membrane of kidney
2) This activates complement cascade
3) Tissue damage from leukocyte activation and inflammation

Question 19

Examples of T cell-mediated autoimmunity
1)
2)
3)

Answer 19

1) Type I diabetes mellitus
2) Multiple sclerosis
3) Coeliac disease

Question 20

Type I diabetes
1)
2)
3)

Answer 20

1) Organ-specific, T cell mediated (CD4+ and CD8+)
2) Autoimmune destruction of beta cells in pancreatic islets (alpha and delta cells are spared)
3) Characterised by lymphocyte infiltration, weak autoantibody response, T cell reactivity with islet proteins

Question 21

HLA type that type I diabetes is more common with
1)
2)

Answer 21

1) DR3-DQ2

2) DR4-DQ8

Question 22

How do Th1 cells contribute to type I diabetes?
1)
2)
3)
4)

Answer 22

1) Chemokines recruit macrophages to pancreas
2) IFNg causes macrophages to release inflammatory mediators
3) TNF causes tissue destruction, expression of adhesion molecules on blood vessels
4) IL-3, GM-CSF cause bone-marrow production of macrophages

Question 23

Multiple sclerosis
1)
2)
3)
4)
5)

Answer 23

1) Polygenic degenerative disorder of the CNS
2) Episodes of paralysis in early stages, chronic paralysis in later stages
3) CD4+ specific to myelin antigens degrade myelin
4) Th1, Th17 associated with inflammation.
5) Th2 associated with recovery

Question 24

HLA types associated with multiple sclerosis
1)
2)

Answer 24

1) DR15

2) DQ6

Question 25

Is coeliac disease an autoimmune disease?

Answer 25

No
It is a type IV hypersensitivity
Antigen is a food antigen, not a self antigen

Question 26

Coeliac disease incidence in Europe

Answer 26

1/300

Question 27

HLA associated with coeliac disease
1)
2)
3)

Answer 27

1) Over 95% of patients are DQ2 positive
2) Some DQ8 positive
3) Homozygous for DQ2 leads to higher risk of disease

Question 28

Coeliac disease

Answer 28

Type IV hypersensitivity to gliadins and gliadin-like molecules in wheat, barley and rye

Question 29

Effects of coeliac disease

Answer 29

Villous atrophy in jejunum

Question 30

What is gluten?

Answer 30

A complex mix of glutamine and proline rich polypeptides

Question 31

How might DQ2 and DQ8 interact with gluten?

Answer 31

1) Tissue transglutaminase converts glutamine in gluten to glutamic acid, which is negatively charged
2) HLA-DQ2 and DQ8 bind negatively charged residues (gliadins) more avidly
3) This results in T cell activation
4) Innate system can be triggered via unknown mechanisms. release of IL-15,

Question 32

What are gliadins?

Answer 32

A large portion of gluten proteins

Question 33

How can autoreactive antibodies be generated?
1)
2)
3)

Answer 33

1) Circulating B cell binds self antigens released by damaged cells
2) B cell presents antigen, cognate T cell activates B cell
3) B cell maturation, proliferation

Question 34

Good animal model for type I diabetes

Answer 34

Non-obese diabetic mouse

Question 35

Role of infection in autoimmunity

Answer 35

Infection can activate DCs presenting autoantigen, lead to activation of autoreactive T cells