Introduction to Immunodeficiency

Question 1

What are the three defects in innate immunity?

Answer 1

Chronic granulomatous disease, Leukocyte adhesion deficiency and Complement deficiencies

Question 2

What is the genetic deficiency of CGD?

Answer 2

Mutations in the genes encoding components of the phagocyte oxidase enzyme

Question 3

What is the functional deficiency of CGD?

Answer 3

Defective production of ROS (reactive oxygen species) by phagocytes; phagocytic cells can’t kill phagocytosed microbes

Question 4

What occurs with CGD?

Answer 4

Accumulation of phagocytes around sites of infection forming granulomas

Question 5

What is the genetic defect in LAD?

Answer 5

Mutations in beta chain of beta 2-integrins (LAD-1) or in protein required for E- and P-selectin ligands (LAD-2)

Question 6

What are the functional deficiencies in LAD?

Answer 6

Defective binding of leukocytes to vascular endothelium, so leukocytes are unable to migrate across vascular endothelium into sites of infection in tissues

Question 7

What are the types of complement deficiencies?

Answer 7

C3 deficiency and C3/C4 (mutation in both)

Question 8

What are the functional deficiencies associated with C3 deficiency?

Answer 8

All pathways of complement activation disabled; usually fatal

Question 9

What are the functional deficiencies associated with C2/C4 deficiency?

Answer 9

Classical pathway and lectin pathway of complement activation disabled; increased susceptibility to infections

Question 10

What is the genetic defect in x-linked hyper-IgM syndrome?

Answer 10

Mutations in CD40L (CD154), the ligand for CD40

Question 11

What is the functional deficiency of x-linked hyper-IgM syndrome?

Answer 11

Absence of CD40L leading to defective T cell help for Bcells, lack of isotype switching (IgM abnormally high and IgG/IgA essential non existent, defective TH1 cell dependent macrophage activation

Question 12

What is CVID?

Answer 12

Common Variable Immunodeficiency; heterogeneous group of disorders in both men and women often diagnosed in early adult life due to recurrent infections

Question 13

What characterizes CVID?

Answer 13

Low serum IgG and IgA; often low IgM

Question 14

What characterizes Bare lymphocyte syndrome?

Answer 14

Class II MHC deficiency caused by mutations in genes encoding transcription factors necessary for expression of class II MHC genes

Question 15

What does Bare lymphocyte syndrome disrupt?

Answer 15

Antigen presentation and activation of CD4+ T cells

Question 16

General approach to diagnosing SCID cases

Answer 16

Patients develop recurrent infections early in life (weeks
Typically present with failure to thrive, diarrhea, unusual rashes
Sometimes family history of neonatal death or consanguinity
Abnormally low total lymphocyte count

Question 17

General approach to diagnosing antibody deficiency cases

Answer 17

Present later in life (several months) due to presence of maternal IgG
Some forms present as late adulthood CVID
Most common indication is chronic or recurrent bacterial respiratory infections

Question 18

How would you generally test for immunodeficiencies?

Answer 18

Immune system work-up (serum Igs, cell pop, functional studies)
Genetic testing follows preliminary diagnosis of immunodeficiency with known genetic defect

Question 19

How would you treat mild immunodeficiencies?

Answer 19

Prophylactic Igs

Question 20

How would you treat severe antibody deficiencies?

Answer 20

Ig replacement therapy

Question 21

How would you treat SCID?

Answer 21

Bone marrow transplant (stem cell) is required

Until transplant can be done, efforts made to protect patient from infection (prophylactic Igs, no live vaccines)

Question 22

What characterizes AIDS?

Answer 22

Depletion of CD4+ T cells