First Aid, Chapter 8, Immunologic Disorders, Deficiency in Innate Immunity, NK cell deficiency Flashcards
What is the clinical presentation of IRAK4/MyD88 deficiency?
Severe/early-onset recurrent pyogenic bacterial infections (e.g., Pneumococcus, Staphylococcus).
Meningitis Septicemia Liver abscess
Low/absent fever/inflammatory responses
What are the lab findings in IRAK4/MyD88 deficiency?
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)
What is the gene defect in IRAK4/MyD88 deficiency? What are the genes involved in?
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
What is the therapy for IRAK4/MyD88 deficiency?
IVIG therapeutic and prophylactic antibiotics (TMPSMZ + PenV)
What is the cycle in the IFN γ/IL-12/IL-23 Axis?
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.
What are the subunits of IL-12?
p35
p40
What are the subunits of IL-23?
p19
p40
What is the cytokine receptor of IL-12?
IL-12R
What is the cytokine receptor of IL-23?
IL-23R
What are the subunits of the IL-12R?
IL-12B1, IL-12B2
What are the subunits of the IL-23R?
IL-12B1
IL-23R
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)?
Atypical mycobacteria and Salmonella
What disorders also have NK deficiency?
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
What are the gene defects in classical NK cell deficiency?
GATA2, MCM4 mutation
What are the lab findings in classical NK cell deficiency?
↓ CD16 by flow cytometry and
↓ NK function (cytotoxicity)
What is the clinical presentation of classical NK deficiency?
Recurrent infections with herpes viruses, papillomavirus and mycobacteria
What is the gene defect in functional NK deficiency?
FCRG3A (CD16) mutation CD16 = Low-affinity IgG receptor
What are the lab findings in functional NK deficiency?
Normal CD16 by flow cytometry but ↓ NK function (cytotoxicity)
What is the clinical presentation of functional NK deficiency?
Recurrent infections with herpes viruses
