2.3 Primary Immunodeficiency

Question 1

DiGeorge syndrome

• mech
• clinical findings

Answer 1

• failure to form 3rd and 4th pharyngeal pouches
• 22p11 microdeletion
• T-cell deficiency (thymic aplasia)
• Hypocalcemia (parathyroid aplasia)
• abnormalities of heart, great vessels, distinctive face where ears are lower

Question 2

Loss of T-Cells means trouble fighting what kind of infections

Answer 2

• Viruses

- Fungal

Question 3

SCID–Severe combined immunodeficiency:

3 major etiologies

Answer 3

• Both cell and humoral immunity
  1. Cytokine receptor defects (B and T cells cannot mature!)
  2. Adenosine deaminase deficiency (buildup of metabolites in nucleotide metabolism is toxic to lymphocytes)
  3. MHC II deficiency (lack of CD4 function leads to B and T cell problems)

Question 4

XLA–X Linked Agammaglobulinemia

• mech
• clinical findings, common infections and why

Answer 4

• Complete lack of Ab
• B cell cannot mature into plasma cells
• Bruton tyrosine kinase mutation, X-linked
• presents 6 months after birth, with 3 major recurrent infections:
  1. bacterial (lack of Ab opsonization)
  2. enterovirus (lack of IgA in mucosa)
  3. Giardia (lack of IgA in mucosa)
• avoid live vaccines

Question 5

CVID–Common variable immunodeficiency

• mech
• clinical findings: when does it present, and increased risk of what

Answer 5

• Low Ab due to B Cell or T cell defects
• presents in adulthood
• increased risk for:
  1. Bacteria
  2. Enterovirus
  3. Giardia
• increased risk for autoimmune disease and lymphoma

Question 6

IgA deficiency

• increased risk of what
• what specific disease is it associated with

Answer 6

• Most common Ig deficiency
• loss of mucosal immunity
• increased risk of mucosal infection, esp viral
• Associated with Celiac disease

Question 7

Most common immunoglobulin deficiency?

Answer 7

IgA deficiency

Question 8

Hyper-IgM syndrome

• mech
• clinical findings, why

Answer 8

• cannot class switch to A,G,E
• defect in CD40/CD40L signaling
• recurrent pyogenic infections because poor opsonization (lack of IgG)

Question 9

Wiskott-Aldrich syndrome

Answer 9

• mutation in WASP gene, x-linked
• defective humoral+cellular immunity
• thrombocytopenia
• eczema
• recurrent infections

-lower yield; memorize

Question 10

Complement deficiencies

• mech
• clinical findings

Answer 10

1. C5-9 deficiency
   - lack of MAC
   - increase risk of Neisseria
2. C1 esterase inhibitor deficiency
   - causes hereditary angioedema. overactive complement means excess inflammation, esp periorbital
3. Paroxysmal Noctural Hemoglobinuria
   - lack of DAF (decay-accelerating factor) on blood cell surface means complement will lyse blood cells.
   - Brown urine, typically at night when low O2 during sleep increases susceptibility of red cells to lyse

Question 11

List B-Cell primary deficiency diseases (2)

Answer 11

• XLA

- CVID

Question 12

List T-Cell primary deficiency diseases (2)

Answer 12

• DiGeorge syndrome (thymic aplasia)

- Hyper-IgM syndrome

Question 13

List combined B and T cell primary deficiency diseases (1)

Answer 13

-SCID

Question 14

List complement primary deficiency diseases (3)

Answer 14

• C5-9 deficiency
• Hereditary angioedema (C1 inhibitor)
• Paroxysmal Nocturnal Hemoglobinuria (lack of DAF)

Question 15

List Phagocyte deficiency diseases (4)

Answer 15

• Chediak Higashi syndrome (japanese railroad tracks)
• CGD
• Leukocyte adhesion deficiency syndrome
• MPO deficiency

Question 16

CATCH22 criteria

Answer 16

-digeorge

cardiac defects
abnormal facies
thymic hypoplasia
cleft palate
hypocalcemia
22 chromosome

Question 17

JONES criteria

Answer 17

-rheumatic fever

joints
heart
nodules
erythema marginatum
syndenham's chorea

Question 18

SCID screening:

Answer 18

TREC level low

-‘skids left by truck wreck’

Question 19

presence of Neisseria in child

Answer 19

-suspect C5-9 deficiency