Pharmacology of Immunodeficiency

Question 1

Mutations in what genes cause chronic granulomatous disease?

Answer 1

Caused by mutations in genes encoding subunits of the enzyme phagocyte NADPH oxidases, which catalases the production of microbicidal ROS in lysosomes

Question 2

Name an alterative source of free radicals that CGD leukocytes could use to kill bacteria.

Answer 2

Hydrogen peroxide

Question 3

WhName the 3 deficiencies in leukocyte adhesion deficiency.

Answer 3

1. Beta2 integrin (LADi)
2. Fucosylated selectin ligands (LADII)
3. Impaired ability to activate leukocyte integrin after chemokine stimulation (LADIII)

Question 4

Which complement proteins deficiency causes increased incidence of SLE?

Answer 4

C2 and C4

Question 5

What mutation causes Chédiak-Higashi syndrome?

Answer 5

Mutations in genes encoding LYST (protein involved in fusion of vesicles, lysosomes)

Question 6

What mutation causes X-linked SCID?

Answer 6

Mutations in the common y (yc) chain signalling subunit of the receptors for several cytokines

Question 7

What immunodeficiency causes a significant reduction in the numbers of mature T cells?

Answer 7

X-linked SCID
(Non-functional yc chain therefore they cannot proliferate in response to IL-7 therefore immature lymphocytes)
(Deficient NK cells too because the yc chain is also part of the receptor for IL-15)
DiGeorge syndrome
Deficiency in ADA (adenosine deaminase)

Question 8

X-linked SCID only affects males or females?

Answer 8

Males

Question 9

Which mutation causes TCR and Ig to be unable to recombine their genes?

Answer 9

RAG1 or RAG2 gene mutations

Question 10

DiGeorge syndrome causes….

Answer 10

defect in T cell maturation (disrupts development of the thymus)

Question 11

Which SCID causes a block in B-cell maturation?

Answer 11

X-linked agammaglobulinemia

Question 12

Mutations in which enzyme account for 50% of cases of autosomal recessive SCID?

Answer 12

Adenosine deaminase (ADA) enzyme

Question 13

Which metabolite accumulates as a result of ADA deficiency?

Answer 13

toxic purine metabolites (dATP)

Question 14

ADA deficiency results in a…..

Answer 14

block in T cell maturation

Question 15

Name two conditions which are classified as defective activation of T-lymphocytes.

Answer 15

Bare lymphocyte syndrome (decrease in CD4+ T cells)
Hemophagocytic lymphohistiocytosis (CD8+ T cells and NK cells are unable to kill virus-infected target cells)

Question 16

Name two conditions which are classified as defects in activation of B lymphocytes.

Answer 16

Common variable immunodeficiency (CVID) (Generation of plasma cells is significantly reduced) - treatment with Ig replacement therapy and antibiotics
X-linked hyper-IgM syndrome - failure to express functional CD40L leads to defective germinal centre reactions in T-cell dependant B cell responses. Treatment - Ig replacement therapy and antibiotics

Question 17

What’s Gamifant?

Answer 17

Monoclonal antibody that binds to and neutralizes IFN-y which is thought to contribute to hemophagocytic lymphohistocytosis

Question 18

What’s Revcovi?

Answer 18

Recombinant adenosine deaminase enzyme replacement therapy used in the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in paediatric and adult patients

Question 19

Name some micronutrient deficiencies.

Answer 19

Zinc, selenium, vitamin D