Chapter 26 - Testing the innate immune system

Abstract

The innate immune system compromises many different components that provide the initial response to foreign antigens. Neutrophil disorders, natural killer (NK) cell defects, complement disorders, and defects in the interferon-gamma (IFN-γ/interleukin (IL)-23 axis are the major groups of disorders that compromise immune defects. The clinical presentation of an innate immune defect is variable and specific to each defect but in general, patients are susceptible to specific infections and a dysregulated inflammatory response. Patients with neutrophil disorders are susceptible to invasive bacterial and fungal infections, those with NK cell, Toll-like receptor (TLR), and nuclear factor kappa light-chain enhancer of activated B-cells (NF-κB) defects are most susceptible to invasive viral infections, while patients with IFN-γ/IL-23 defects are susceptible to nontuberculous mycobacterial disease. While there is significant intersection between the cells and cellular products of the innate immune system, testing this branch of the immune system requires ordering specific evaluations based on the component of concern due to infectious or inflammatory history. When a neutrophil disorder is suspected, neutrophil quantity and morphology should be assessed with an absolute neutrophil count and peripheral smear, respectively. When chronic granulomatous disease is suspected, a dihydrorhodamine assay is the most appropriate test to evaluate for neutrophil oxidative burst. NK cell defects are assessed by measuring NK cell quantities and evaluation of NK cell cytotoxicity. Recurrent or invasive bacterial infections are hallmark for complement disorders and so evaluating a CH50 and AH50 in patients with recurrent bacterial infections is warranted. TLR and NF-κB defects can be evaluated by assessment of TLR activity, but genetic testing is usually necessary to establish a diagnosis. IFN-γ quantity and stimulation through the IFN-γ/IL-23 axis should be assessed in patients with invasive nontuberculous mycobacterial disease. The most commonly used techniques of laboratory evaluation and methods for testing the innate immune system will be described.