Table VI.

Defects in Innate Immunity

Disease	Affected Cell	Functional Defect	Associated Features	Inheritance	Gene Defect/Presumed pathogenesis
Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID)	Lymphocytes + Monocytes	NFκB signalling pathway	anhidrotic ectodermal dysplasia + specific antibody deficiency (lack of Ab response to polysaccharides) various infections (mycobacteria and pyogens)	XR	Mutations of NEMO (IKBKG), a modulator of NF-κB activation
Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID)	Lymphocytes + Monocytes	NFκB signalling pathway	anhidrotic ectodermal dysplasia + T cell defect + various infections	AD	Gain-of-function mutation of IKBA, resulting in impaired activation of NF-κB
Interleukin-1 Receptor Associated kinase 4 (IRAK4) deficiency	Lymphocytes + Monocytes	TIR-IRAK signalling patwhay	Bacterial infections (pyogens)	AR	Mutation of IRAK4, a component of TLR-signaling pathway
WHIM (Warts, Hypogammaglobulinemia infections,Myelokathexis) syndrome	Granulocytes + Lymphocytes	Increased response of the CXCR4 chemokine receptor to its ligand CXCL12 (SDF-1)	Hypogammaglobulinemia, reduced B cell number, severe reduction of neutrophil count, warts/HPV infection	AD	Gain-of-function mutations of CXCR4, the receptor for CXCL12
Epidermodysplasia verruciformis	Keratinocytes and leukocytes	?	Human Papilloma virus (group B1) infections and cancer of the skin	AR	Mutations of EVER1, EVER2
Herpes simplex encephalitis (HSE)	Central nervous system resident cells, epithelial cells and leukocytes	UNC-93B-dependent IFN-α, -β, and –γ induction	Herpes simplex virus 1 encephalitis and meningitis	AR	Mutations of UNC93B1
Herpes simplex encephalitis (HSE)	Central nervous system resident cells, epithelial cells, dendritic cells, cytotoxic lymphocytes	TLR3-dependent IFN-α, -β, and –γ induction	Herpes simplex virus 1 encephalitis and meningitis	AD	Mutations of TLR3

NF-κB: nuclear factor Kappa B; TIR: Toll and Interleukin 1 Receptor; HPV: human papilloma virus; TLR: Toll-like receptor