Narrowly focused susceptibility to infections is more likely
to result from defects in the innate immune response (Table
187-1).3 A predilection toward infections
with neisserial species with deficiency of terminal complement components and,
to a lesser extent, in components of the alternate pathway of complement
activation. Phagocytic cell defects typically present with recurrent
pyogenic and fungal infections. A particular form of phagocytic
cell defect, chronic granulomatous disease, predisposes the individual
to infections with catalase-positive organisms. Mutations in the
IL-12/IL-12/IL-23 receptor interferon gamma receptor/STAT1
axis give rise to undue susceptibility to mycobacterial infections.
Deficiency of the adaptor protein MYD88 and the downstream kinase interleukin-1
receptor-associated kinase 4, both coupled to several Toll-like
receptors, results in invasive infections with pyogenic and encapsulated
organisms. Deficiency of the MYD88-independent Toll-like receptor
(TLR) 3 and of the endoplasmic reticulum resident membrane protein
UNC93, which is involved in intracellular trafficking of TLR3 and
the nucleotide-sensing receptors TLR7-9, results in peculiar susceptibility
to herpes simplex encephalitis, which is caused by an infection
with an individual pathogen (herpes simplex).4,5 Although
this infection may occur only once in a lifetime and was previously
thought to be due to a random event, it is now understood that this
infection represents a specific host susceptibility. Undue susceptibility
to papilloma viruses have been uncovered in two syndromes: WHIM
(warts, hypogammaglobulinemia, infections, and myelokathexis), resulting
from mutations in the chemokine receptor CXCR4 syndrome, and epidermodysplasia
verruciformis, resulting from mutations in the keratinocyte proteins EVER1/2.