Immunodeficiencies - Kane

Question 1

Indicators of B-cell immunodeficiency

Answer 1

Absence of follicles and germinal centers and reduced serum Ig levels.

Question 2

Consequences of B-cell immunodeficiency

Answer 2

Pyogenic and enteric bacterial and viral infections.

Question 3

Indicators of T-cell immunodeficiency

Answer 3

Reduced T-cell zones, reduced T-cell proliferation in response to antigen

Question 4

Consequences of T-cell immunodeficiency

Answer 4

Bacterial and viral intracellular infections and pathogen-associated cancers.

Question 5

Phase I of Neutrophil response

Answer 5

Intracellular killing by ROS and NETs

Question 6

Phase II of Neutrophil response

Answer 6

Clearance of dying cells (efferocytosis) and suppression of inflammasomes

Question 7

Enzyme responsible for generating ROS in phagolysosomes

Answer 7

Phagocyte oxidase

Question 8

Chronic Granulomatous Disease

Answer 8

Characterized by impairment of neutrophil respiratory burst. Usually an X-linked mutation in CYBB gene which results in non-functional gp91phox.

Question 9

Common infections in CGD patients

Answer 9

Catalase positive bacteria (ex. staph aureus)

Question 10

Diagnosis of CGD

Answer 10

Reduction of ROS measured by flow cytometry.

Question 11

Severe Combined Immunodeficiency (SCID)

Answer 11

Loss of B or T-cell development or function by a multitude of impaired pathways.

Question 12

Common Gamma Chain Deficiency (X-linked SCID).

Answer 12

Major deficiency in common gamma chain (linked to many cytokine receptors). Most important is IL-7 which is involved in T-cell survival and maintenance as well as thymic development.

Question 13

Why would mutations that directly affect T-cell function also impair B-cell function?

Answer 13

Fully functional B-cell responses require CD4+ T-cell involvement to develop into plasma cells.

Question 14

Why would some these conditions not manifest until after the first several months of life?

Answer 14

1. Fc-mediated passive transfer of IgG via syncytiotrophoblasts prevent infection during first few weeks after birth.
2. After birth, PIgR-mediated IgA is transferred via breast milk.

Question 15

Clinical manifestations of X-linked SCID

Answer 15

Highly susceptible to all infections, sensitive to live attenuated vaccines, and susceptible to opportunistic pathogens (ex. CMV, HSV, and EBV).

Question 16

Treatments for SCID

Answer 16

Hematopoietic stem cell transplant, enzyme transplant, gene therapy

Question 17

Bruton’s X-linked Agammaglobulinemia

Answer 17

Absence of all immunoglobulins and few lymph nodes. No circulating B-cells due to defective BTK pro-B-cell heavy chain signaling.

Question 18

Clinical manifestations of Bruton’s X-linked disease

Answer 18

Highly susceptible to encapsulated bacteria, respiratory viruses and fungal infections are well tolerated.

Question 19

Common Variable Immunodeficiency (CVID) caused by what genes

Answer 19

Many mutations can lead to CVID but primarily: PI3K and LRBA

Question 20

Hyper-IgE Syndrome (Job Syndrome)

Answer 20

Deficiency in Th17 cell development via multiple pathways affecting IL-23, IL-17, and IL-23 signaling.

Question 21

What type of defect is caused by mutation in STAT3 gene

Answer 21

Dominant negative – Even one good copy = defective

Question 22

Acquired Immunodeficiency Syndrome

Answer 22

Caused by HIV infection of CD4+ T-cells. T-cells are depleted leading to increased susceptibility to opportunistic infections

Question 23

X4 (T-tropic) HIV infects which cells.

Answer 23

CD4+ T-cells expressing co-receptor CXCR4

Question 24

R5 (M-tropic) HIV infects which cells.

Answer 24

Macrophages expressing co-receptor CCR