Immuno 5: Autoinflammatory And Autoimmune Diseases 1

Question 1

What is the difference between auto-inflammatory and auto-immune disease ?

Answer 1

Auto-inflammatory: affects innate immune response

Auto-immune: affects adaptive immune response

Question 2

Give 1 example of a monogenic auto-inflammatory disease ?

Answer 2

Familial Mediterranean fever

Question 3

Which gene is mutated in Familial Mediterranean fever ?

How does this cause the disease ?

Answer 3

MEFV gene (autosomal recessive)

Causes defect in pyrin-marenostrin protein which causes activation of Neutrophils by cryopyrin to become deregulated.

Question 4

How is Familial Mediterranean fever associated with amyloidosis and Nephrotic syndrome ?

Answer 4

The inflammation causes the liver to produce acute phase protein: Amyloid

AMyloid deposits in the kidneys causing proteinuria and hence nephrotic syndrome

Question 5

Name 3 monogenic Auto-immune disease ?

Answer 5

APS1 (auto-immune polyendocrine syndrome type 1) (APECED)
IPEX 
ALPS (auto-immune lymphoproliferative syndrome)

Question 6

What is the main treatment for Familial Mediterranean Fever ?

Answer 6

Colchicine

Question 7

What causes APACED ?

Answer 7

Defect in AIRE transcription factor

(Promotes the apoptosis of auto-reactive T cells in the thymus)

Leads to a loss in central tolerance

Question 8

Name the 2 most common auto-immune conditions seen in APS1 (APECED)?

Answer 8

Hypoparathyroidism

Addison’s disease

Question 9

What causes IPEX ?

Answer 9

Mutation in Foxp3 gene

Foxp3 is required for development of Treg cells

Question 10

What are the 3 Ds of conditions seen in IPEX ?

Answer 10

Diarrhoea
Dermatitis
Diabetes

Question 11

What causes ALPS ?

Answer 11

Mutation in Fas pathway

causes defect in apoptosis of Lymphocytes

Question 12

A child is examined and found to have splenomegaly, lymphadenopathy. Her blood tests show a high Lymphocyte count . The professor tells you that this is a monogenic Auto-immune disease and children have an increased risk of Lymphoma. What is the likely diagnosis ?

Answer 12

ALPS

Question 13

Which genetic mutation has been found to be associated with Crohn’s disease ?

Answer 13

NOD2

Question 14

Give 5 examples of polygenic auto-inflammatory diseases ?

Answer 14

Crohn’s disease 
Ulcerative colitis 
Osteoarthritis 
Giant cell arteritis 
Takayasu’s arteritis

Question 15

List 4 drugs used to treat Crohn’s disease ?

Answer 15

Corticosteroids
Azathioprine (steroid sparing)
Anti-TNF alpha antibody
Anti- IL12/23 antibody

Question 16

Give 3 example of mixed pattern diseases (auto inflammatory and auto immune) ?

Answer 16

Ankylosis spondylitis
Psoriatic arthritis
Behcet’s syndrome

Question 17

Which HLA type is associated with Ankylosing spondylitis ?

Answer 17

HLA B27

Question 18

What are the main 2 treatments for Ankylosing spondylitis ?

Answer 18

NSAIDS

Anti-TNF alpha antibodies

Question 19

List 6 polygenic Auto-immune diseases ?

Answer 19

Rheumatoid arthritis
Myasthenia gravis
Pernicious anaemia 
Addison’s disease 
SLE
PBC (primary biliary cirrhosis)

Question 20

Which diseases are associated with HLA-DR3 polymorphisms ?

Answer 20

Graves’ disease
SLE
Type 1 diabetes Mellitus

Question 21

Which diseases are associated with HLA-DR4 polymorphisms ?

Answer 21

Type 1 diabetes Mellitus

Rheumatoid arthritis

Question 22

Which disease is associated with HLA-DR15 polymorphisms ?

Answer 22

Goodpasture’s disease

Question 23

List 3 areas of immune privilege in the body ?

Answer 23

Eyes
Testes
CNS

Question 24

Describe type 1 immune reaction ?

Answer 24

Immediate hypersensitivity which is IgE mediated

Question 25

Describe type 2 immune reaction ?

Answer 25

Antibody reacts to cellular antigen

Question 26

Describe type 3 immune reaction ?

Answer 26

Antibody reacts with soluble antigen to form an immune complex

Question 27

Describe type 4 Immune reaction ?

Answer 27

Delayed type hypersensitivity

T cell mediated response

Question 28

These auto-immune diseases are considered to involve Type 2 cytotoxic hypersensitivity.

Match the auto-immune disease with the antigens

Goodpasture disease:::::TSH receptor
Myasthenia Gravis:::::Epidermal Cadherin
Pemphigus Vulgaris:::::basement membrane collagen type IV
Grave’s disease:::::acetylcholine receptor

Answer 28

Goodpasture disease:::::basement membrane collagen type IV
Myasthenia Gravis:::::acetylcholine receptor
Pemphigus Vulgaris:::::epidermal Cadherin
Grave’s disease:::::TSH receptor

Question 29

Give examples of regions where Immune complexes deposit and the pathology they cause ?

Answer 29

Skin- Cutaneous vasculitis (purpuric rash)
Kidneys- glomerulonephritis/renal failure
Joints- Arthritis

Question 30

Which disease is considered to cause a type 3 hypersensitivity reaction ?

Answer 30

SLE

Question 31

Name 2 disease is considered to cause a type 4 hypersensitivity reaction ?

Answer 31

Type 1 diabetes mellitus

MS

Question 32

Afrocaribbean boy presents after recurrent chest infections with hypothyroidism, alopecia, gonadal failure and vitiligo. Blood tests show hypocalcaemia.

Most likely diagnosis ?
Which gene is mutated ?

Answer 32

APACED

AIRE gene

loss of central immune tolerance of T cells

Question 33

List 4 features of APACED ?

Answer 33

• Hypoparathyroidism
• Hypothyroidism
• Addisons
• DM type 1
• Vitiligo
• Alopecia
• Hypogonadism