Week 6

Question 1

What is primary immunodeficiency?

Answer 1

• Congenital/inherited
• results from genetic defects
• deficiency causes disease

Question 2

What is secondary immunodeficiency?

Answer 2

• acquired

- result of other disease or conditions e.g. HIV, malnutrition, immunosuppression

Question 3

List some categories of primary immunodeficiencies.

Answer 3

• combined IDs
• combined with syndromic features
• antibody deficiencies
• phagocyte defects
• defects in innate immunity
• autoinflammatory disorders

Question 4

Give examples of combined IDs

Answer 4

• SCID (x-linked)
• ADA-SCID
• hyper IgM syndrome

Question 5

Discuss X-linked SCID

Answer 5

• mutation in cytokine receptors, IL-2Ry/common y chain
• T cells and NK cells fail
• B cells normal but no help from T cells so immune response affected

Question 6

Discuss ADA-SCID

Answer 6

• adenoside deaminase deficiency
• depletes T, B and NK cells
• cells will have basal expression of ADA but needs to be enhanced in thymocytes
• mostly recessive

Question 7

How can ADA-SCID now be treated?

Answer 7

1. Take patients bone marrow cells
2. Virus is altered ex vivo so it can’t reproduce
3. A gene is inserted into the virus
4. Altered virus is added to cells ex vivo
5. Cells genetically altered ex vivo
6. Patient conditions with chemo/radiotherapy
7. Altered cells transplanted back into patient
8. Altered cells expand and exert biological effect in vivo.

Question 8

Discuss hyper IgM syndrome

Answer 8

• high levels of IgM and low levels of other Igs so unable to class switch
• deficient in CD40L on T cells
• so B cells cannot switch from IgM to other class

Question 9

Give examples of combined IDs with syndromic features.

Answer 9

• FoxN1 deficiency

Question 10

Discuss FoxN1 deficiency.

Answer 10

• FoxN1 molecule important in immune response but also in epithelial cells
• athymic = no thymus > no T cells, alopecia
• B cells are normal but lack of T cells still affects immune system

Question 11

Give examples of antibody deficiencies.

Answer 11

• Bruton’s tyrosine kinase deficiency
• CD40L deficiency (hyper IgM)
• IgA deficiency

Question 12

What happens if you have a humoral or B cell defect?

Answer 12

• recurrent sepsis
• bacterial infections (often in airways)
• chronic gastroenteritis
• failure to thrive as an infant

Question 13

Discuss Bruton’s tyrosine kinase deficiency.

Answer 13

• mutation in Bruton’s tyrosine kinase gene
• prevents B cell development
• few follicles in lymph nodes
• results in low serum antibody levels
• X linked

Question 14

Discuss IgA deficiency

Answer 14

• very common
• possibly due to interleukin deficiency
• many people asymptomatic
• IgG can help e.g. protect mucosal immune system

Question 15

Give examples of phagocyte defects.

Answer 15

• defects of neutrophil function
• defects of respiratory burst
• Mendelian susceptibility to mycobacterial disease (MSMD)

Question 16

Discuss chronic granulomatous disease (defects of respiratory burst)

Answer 16

• no superoxide burst
• multiple granulomas form as a result of defective elimination of bacteria
• defects in the NADPH enzymes that generate the superoxide radicals involved in bacterial killing

Question 17

Give examples of autoinflammatory disorders.

Answer 17

• familial Mediterranean fever

- IL-10/10R deficiency

Question 18

Discuss familial Mediterranean fever

Answer 18

• an inflammasome converts pro-IL-1 to IL-1
• In FMF inflammasome regulators are mutated
• inflammasome activate so increased IL-1
• inflammation can respond to anti-IL-1 antibody for treatment