First Aid, Chapter 8, Immunologic Disorders, Deficiency in Innate Immunity, NK cell deficiency

Question 1

What is the clinical presentation of IRAK4/MyD88 deficiency?

Answer 1

Severe/early-onset recurrent pyogenic bacterial infections (e.g., Pneumococcus, Staphylococcus).

Meningitis Septicemia Liver abscess

Low/absent fever/inflammatory responses

Question 2

What are the lab findings in IRAK4/MyD88 deficiency?

Answer 2

Normal Ig levels, impaired IgG response to polysaccharide antigens, normal B- and T-lymphocyte numbers (may have completely normal screen).

Diagnose with decreased PBMC cytokine production when stimulated by TLR agonists (except TLR 3 agonists)

Question 3

What is the gene defect in IRAK4/MyD88 deficiency? What are the genes involved in?

Answer 3

IRAK4 ( IRAK4, interleukin 1 receptor-associated kinase 4)
MyD88 ( myeloid differentiation primary factor 88- adaptor protein)

Involve in signaling of TLRs to the activation of NFκB and AP-1

Question 4

What is the therapy for IRAK4/MyD88 deficiency?

Answer 4

IVIG therapeutic and prophylactic antibiotics (TMPSMZ + PenV)

Question 5

What is the cycle in the IFN γ/IL-12/IL-23 Axis?

Answer 5

Interferon gamma (IFNγ) is produced by Th1 cells, dendritic cells, and NK cells; it is essential for both innate and adaptive immune responses to viral and intracellular infections. Th1-produced IFNγ induces IL-12 production by dendritic cells and macrophages; and, in turn, IL-12 induces further IFNγ production by NK and T lymphocytes. See Figure 8-3 for IFN γ/IL-12/IL-23 axis.

Question 6

What are the subunits of IL-12?

Answer 6

p35

p40

Question 7

What are the subunits of IL-23?

Answer 7

p19

p40

Question 8

What is the cytokine receptor of IL-12?

Answer 8

IL-12R

Question 9

What is the cytokine receptor of IL-23?

Answer 9

IL-23R

Question 10

What are the subunits of the IL-12R?

Answer 10

IL-12B1, IL-12B2

Question 11

What are the subunits of the IL-23R?

Answer 11

IL-12B1

IL-23R

Question 12

Patients with a mutation in the IFNγR (IFNγR1 and IFNγR2), p40 subunit, IL-12β1, NFκB essential modifier (NEMO), or signal transducers and activator of transcription (STAT) 1 are susceptible to infections with which organism(s)?

Answer 12

Atypical mycobacteria and Salmonella

Question 13

What disorders also have NK deficiency?

Answer 13

All causes of hemophagocytic lymphohistiocytosis (HLH):
o Primary HLH: XLP, familial, Chediak-Higashi syndrome, and WiskottAldrich syndrome (WAS)
o Secondary HLH (reactive hemophagocytic syndrome)

NEMO 
LAD-1 
Defect in IL-12/IFNγ axis 
HIV infection 
Malignancies

Question 14

What are the gene defects in classical NK cell deficiency?

Answer 14

GATA2, MCM4 mutation

Question 15

What are the lab findings in classical NK cell deficiency?

Answer 15

↓ CD16 by flow cytometry and

↓ NK function (cytotoxicity)

Question 16

What is the clinical presentation of classical NK deficiency?

Answer 16

Recurrent infections with herpes viruses, papillomavirus and mycobacteria

Question 17

What is the gene defect in functional NK deficiency?

Answer 17

FCRG3A (CD16) mutation CD16 = Low-affinity IgG receptor

Question 18

What are the lab findings in functional NK deficiency?

Answer 18

Normal CD16 by flow cytometry but ↓ NK function (cytotoxicity)

Question 19

What is the clinical presentation of functional NK deficiency?

Answer 19

Recurrent infections with herpes viruses