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Chapter 79 : Evaluation of Natural Killer (NK) Cell Defects

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Evaluation of Natural Killer (NK) Cell Defects, Page 1 of 2

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Abstract:

Genetic defects in natural killer (NK) cell and cytotoxic T lymphocyte (CTL) function generally lead to one of two outcomes: (i) life-threatening and/or severe chronic infections with viruses, particularly from the family member viruses Epstein-Barr virus, cytomegalovirus, herpes simplex viruses, and varicella-zoster virus but also other viruses such as human papillomaviruses; or (ii) a life-threatening hyperinflammatory disorder called hemophagocytic lymphohistiocytosis (HLH).

Citation: Risma K, Marsh R. 2016. Evaluation of Natural Killer (NK) Cell Defects, p 775-780. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch79
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Figures

Image of FIGURE 1
FIGURE 1

Transient NK lymphopenia. A two-and-a-half-year-old child with life-threatening RSV infection was evaluated for low lymphocyte counts on hospital days (HD) 3 and 5. No detectable NK cells in the peripheral blood were seen in the first sample, and a reduced number was noted (<1%) 2 days later. In contrast, CD8 and CD4 T cells were in the normal range. NK cell numbers were normal at follow-up (age-appropriate normal ranges are shown in parentheses).

Citation: Risma K, Marsh R. 2016. Evaluation of Natural Killer (NK) Cell Defects, p 775-780. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch79
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Image of FIGURE 2
FIGURE 2

Example of assessment of perforin staining and NK cell functional testing by Cr release assay. (A) Intracellular perforin staining on NK cells is performed by flow cytometry using whole-blood samples. Gating on CD56 lymphocytes, histograms from a healthy control, a patient with biallelic mutations, and a representative, heterozygous carrier (family member) of mutations are shown. The patient's perforin is not detectable, whereas the sibling has one-half the normal perforin detection. (B) NK function against K562 target cells as measured by Cr release is measured by preparing peripheral blood mononuclear cells (PBMC) from the patient and family members as described for panel A. PBMC were diluted at ratios of 50:1 down to 6.25:1 target cells. K562 target cells release Cr to the supernatant upon death in a 4-h assay. Family members with one-half the normal perforin protein have reduced function compared to healthy controls but are not at risk for developing HLH. E/T, effector/target cell ratio.

Citation: Risma K, Marsh R. 2016. Evaluation of Natural Killer (NK) Cell Defects, p 775-780. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch79
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Image of FIGURE 3
FIGURE 3

Examples of assessment of NK cell degranulation in a representative control and in patients with genetic forms of HLH. Peripheral blood mononuclear cells from a representative control and patients with UNC13D, STXBP2, STX11, and RAB27A mutations were incubated with target cells in medium containing a fluorochrome-labeled antibody directed against CD107a in the presence of monensin. Following that, cells were surface stained for CD3 and CD56. NK cells were identified as CD3-negative, CD56-positive lymphocytes. CD107a detection following incubation (Stimulated) was quantified in the NK cells by flow cytometric analysis in comparison to baseline CD107a expression (Spontaneous) and isotype control staining (not shown). Examples courtesy of the Diagnostic Immunology Laboratory, Cincinnati Children's Hospital.

Citation: Risma K, Marsh R. 2016. Evaluation of Natural Killer (NK) Cell Defects, p 775-780. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch79
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References

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Tables

Generic image for table
TABLE 1

Primary immunodeficiencies presenting with severe herpesvirus and/or human papillomavirus infections due to exclusive NK defects

Citation: Risma K, Marsh R. 2016. Evaluation of Natural Killer (NK) Cell Defects, p 775-780. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch79
Generic image for table
TABLE 2

Primary immunodeficiency presenting with development of HLH

Citation: Risma K, Marsh R. 2016. Evaluation of Natural Killer (NK) Cell Defects, p 775-780. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch79

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