Disorders in which part of the body's immune system is missing or does not function normally

Aetiology

• PIDs are due to genetic causes - may result from a single genetic defect, but most are multifactorial

Pathophysiology

PIDs of the innate immune system

Severe congenital neutropenia

• Low neutrophils
• SCN Type I is the commonest form - autosomal dominant in the gene which codes for neutrophil elastase, causing a defect in neutrophil development

Leukocyte adhesion deficiency

• Caused by defect in the CD18 integrin gene - neutrophils cannot recognise markers expressed on endothelial cells, which results in failure of neutrophil adhesions and migration

Chronic granulomatous disease

• Inability of macrophages to generate oxygen/nitrogen free radicals (ROS/RNS) → impaired killing of intracellular microorganisms → excessive inflammation → granuloma

PIDs of the adaptive immune system

Severe combined immunodeficiency

• Failure of production of lymphocytes

X-linked SCID

• Mutation of IL-2 receptor → inability to respond to cytokines → failure of T and NK cell development, production of immature B cells

Bruton’s X-linked hypogammaglobulinaemia

• Mutations in BTK gene - essential for B cell development

Defects in the IL-12: IFN𝛾 network