Introduction to Immunodeficiencies

Question 1

What are congenital immunodeficiencies?

Answer 1

(primary immunodeficiency)

• results from genetic effects that affect
  
  • innate immunity – defects of phagocytic cells; deficiencies of complement or its regulation
  • lymphocyte maturation, activation, and function: defects in antibody-mediated immunity, defects affecting B or T lymphocytes, severe combined immunodeficiencies

Question 2

What are acquired immunodeficiencies?

Answer 2

(secondary immunodeficiencies)

• result from:
  
  • infections (HIV –> AIDS)
  • medical treatments or procedures: immunosuppressive therapy, chemotherapy, splenectomy
  • poor nutrition

Question 3

What is Chronic Granulomatous Disease?

Answer 3

• mutations in genes encoding phagocyte NADPH oxidase enzyme (produces O2- radical)
• X-linked or autosomal recessive
• defective production of ROS by phagocytes during respiratory burst
  
  • unable to kill phagocytized microbes
  • excessive phagocytes are recuited to site – forming granulomas

Question 4

What is leukocyte adhesion deficiency?

Answer 4

• mutations in integrin or protein required for synthesis of E and P selectin ligands
• defective binding of leukocytes to vascular endothelium
• increased susceptibility to fungal and bacterial infections
• autosomal recessive

Question 5

Complement Deficiencies

Answer 5

-lead to repeat (encapsulated) bacterial infections
C3 Deficiency
-mutation in C3 gene
-all pathways of complement pathway shut down
C2 & C4 Deficiencies
-mutatioons in C2 and C4, respectively
-classical and lectin pathway completely disabled

Question 6

What is X-linked hyper-IgM Syndrome?

Answer 6

• mutations in CD40L
• defective T cell help for B cells –> lack of isotype switching, serum IgM high, serum IgG & IgA deficient
• defective Th1 cell-dependent macrophage activation – inability to kill intracelullar bacteria and fungi

Question 7

What is Common Variable Immunodeficiency (CVID)?

Answer 7

• variable clinical presentaion
• diagnosed as an adult
• recurrent bacterial infections
• low serum IgG, IgA, and/or IgM
• T cell-B cell interactions or B cells maturation defect
• associated with autoimmunity and lymphoma

Question 8

What is selective IgA deficiency?

Answer 8

(most common)

• underlying defect unknown
• most patients have no clinical problems
• some have increased respiratory and intestinal infections

Question 9

What is Class II MHC Deficiency/Bare Lymphocyte Syndrome?

Answer 9

• mutations in genes encoding transcription factors for expression of Class II MHC genes
• both humoral and cellular immunity are deficient

Question 10

How do you diagnose and treat SCID?

Answer 10

Diagnose:
-diagnosed early in life
-present with failure to thrive, diarrhea, unusual rashes
-family history of neonatal death or consanguity
-abnormally low total lymphocyte count
Treatment:
-bone marrow transplant or hematopoeitic stem cell transplant
-prophylactic antibiotics before transplant
-no live vaccines

Question 11

Treatment for severe antibody deficiencies

Answer 11

Ig replacement therapy

intravenous passive immunity

Question 12

Treatment for mild immunodeficiency

Answer 12

prophylactic antibiotics

Question 13

Diagnosis of antibody deficiencies

Answer 13

• present later in life due to presence of IgGs from mom at birth
• chronic or recurrent bacterial respiratory infections

Question 14

How do you test for immunodeficiencies?

Answer 14

immune system work-up

genetic testing