Primary Immunodeficiency Affecting the Innate Immune System


Primary immunodeficiencies are a heterogeneous group of genetically inherited diseases quantitively or functionally affecting innate or adaptive immunity. The innate and adaptive arms of the immune system work synergistically to efficiently control and neutralise the wide range of pathogens that challenge vertebrates. Although at first glance innate immunity might appear primitive, innate immune cells can orchestrate discrete immune responses to different infections through the recognition of diverse pathogens by germline‐encoded pattern recognition receptors. Neutrophils, macrophages, dendritic cells, natural killer (NK) cells and NKT cells, in conjunction with natural antimicrobial agents, opsonins (as Complement) and cytokines, are critical innate components in neutralising infectious agents. Primary immunodeficiencies are understood as a state of primary lack of protective immunity. Different compartments of the innate immune system are analysed in this article to highlight their critical pathophysiological role in host defences and protective immunity.

Key Concepts:

  • The innate immune system includes epithelial and mucosal barriers, cells, natural antimicrobial product, pattern recognition receptors (PRR) and cytokines to protect the host from infections without the need of previous exposure to those microorganisms.

  • Neutrophil disorder should be suspected in patients with recurrent, severe, bacterial or fungal infections, especially those caused by unusual organisms.

  • The mononuclear phagocytes are crucial for antigen presentation and for protection against intracellular infections, especially mycobacteria.

  • Natural killer cell deficiency could involve quantitative and functional defects, in both cases showing increased susceptibility to viral infections.

  • Natural killer T (NKT) cells constitute a distinctive subpopulation of mature lymphocytes that coexpress NK (CD56) and T (CD3) cell antigens and play a central role in infectious (e.g. virus), allergic (e.g. asthma) and autoimmune diseases (e.g. hepatitis), as well as tumour control.

  • The complement system is a cascade system of more than 30 serum and membrane‐bound proteins that, when deficient, leads to impaired host defence and inappropriate inflammation.

Keywords: innate immunity; neutrophils; macrophages; NK cells; NKT cells; complement; primary immunodeficiency

Figure 1.

Schematic diagram of Complement activation.



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Further Reading

Ochs HD, Edvard Smith CI and Puck JM (2007) Primary Immunodeficiency Diseases: A molecular and Genetic Approach, 2nd edn. New York: Oxford University Press.

Stiehm RE, Ochs HD and Winkelstein JA (2004) Immunologic Disosrders in Children and Infants, 5th edn. Philadelphia: Elsevier Saunders.

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Rosenzweig, Sergio D(Feb 2011) Primary Immunodeficiency Affecting the Innate Immune System. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001240.pub2]