Immunodeficiency, Primary: Affecting the Adaptive Immune System


Primary immunodeficiency (PID) is an intrinsic defect of the immune system. Patients with PID have increased susceptibility to recurrent and persistent infections, and they may also have autoimmune and cancer‐related symptoms. PIDs are mainly rare hereditary disorders of the immune system which often have serious consequences. Infections are the hallmarks of PIDs. Clinical descriptions have already been made for about 250 PIDs, for which approximately 200 genetic aetiologies have been described. There are several different mechanisms behind PIDs. Some PIDs affect T‐ or B‐cell functions, and when both cell types are affected, it leads to severe combined immunodeficiencies (SCIDs). Other PIDs affect major histocompatibility complex, antibody production, lymphocyte apoptosis, phagocytosis, complement cascade or the innate immune system. PIDs are a constantly growing group of mainly rare diseases that help to understand how the complex immune system is composed, acting and regulated.

Key Concepts

  • Adaptive immunity is a specific and long‐lasting response of lymphocytes to antigens.
  • Combined immunodeficiency affects both B and T cells.
  • Lymphocytes are white blood cells including B and T cells.
  • Signal transduction is a process by which a cell converts one kind of signal or stimulus into another. In a signalling cascade, an extracellular signal interacts with a cell surface receptor, which leads to a change in the level of a second messenger and ultimately a change in the cells functioning.

Keywords: adaptive immunity; immunodeficiency; immune system; B cell; T cell; signal transduction; immunoglobulin

Figure 1. Differentiation of B cells from stem cells. The cellular stages affected by PIDs are indicated by the placement of the factors. Antibody deficiency‐related genes/proteins are indicated.
Figure 2. Differentiation of T cells from stem cells. The cellular stages affected by PIDs are indicated by the placement of the factors.
Figure 3. Differentiation of B and T cells from stem cells. The cellular stages affected by combined PIDs are indicated by the placement of the factors.


Al‐Herz W, Bousfiha A, Casanova JL, et al. (2014) Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Frontiers in Immunology 5: 162.

Berglöf A, Turunen JJ, Gissberg O, et al. (2013) Agammaglobulinemia: causative mutations and their implications for novel therapies. Expert Review of Clinical Immunology 9: 1205–1221.

Conley ME and Casanova JL (2014) Discovery of single‐gene inborn errors of immunity by next generation sequencing. Current Opinion in Immunology 30: 17–23.

Durandy A, Kracker S and Fischer A (2013) Primary antibody deficiencies. Nature Reviews Immunology 13: 519–533.

Mohamed AJ, Yu L, Bäckesjö C‐M, et al. (2009) Bruton's tyrosine kinase (BTK): function, regulation, and transformation with special emphasis on the PH domain. Immunological Review 228: 58–73.

Notarangelo LD (2010) Primary immunodeficiencies. Journal of Allergy and Clinical Immunology 125 (suppl 2): S182–S194.

Piirilä H, Väliaho J and Vihinen M (2006) Immunodeficiency mutation databases (IDbases). Human Mutation 27: 1200–1208.

Qamar N and Fulehian RL (2014) The hyper IgM syndromes. Clinical Reviews in Allergy & Immunology 46: 120–130.

Samarghitean C, Ortutay C and Vihinen M (2009) Systematic classification of primary immunodeficiencies with clustering and network methods bases on clinical, pathological and laboratory parameters. Journal of Immunology 183: 7569–7575.

Väliaho J, Smith CIE and Vihinen M (2006) BTKbase: mutation database for X‐linked agammaglobulinemia. Human Mutation 27: 1209–1217.

van der Burg M, van Zelm MC, Driessen GJ and van Dongen JJ (2012) New frontiers of primary antibody deficiencies. Cellular and Molecular Life Sciences 69: 59–73.

Yong PF, Thaventhiran JE and Grimbacher B (2011) “lA rose is a rose is a rose,” but CVID is Not CVID common variable immune deficiency (CVID), what do we know in 2011? Advances in Immunology 111: 47–107.

Further Reading


Ochs HD, Smith CIE and Puck J (2013) Primary Immunodeficiency Diseases. A Molecular and Genetic Approach, 3rd edn. Oxford: Oxford University Press.

Samarghitean C, Väliaho J and Vihinen M (2007) IDR knowledge base for primary immunodeficiencies. Immunome Research 3: 6. Immunodeficiency Resource,

Sullivan KE and Stiehm ER (2014) Stiehm's Immune Deficiencies. Philadelphia, PA: Elsevier.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Vihinen, Mauno(Sep 2015) Immunodeficiency, Primary: Affecting the Adaptive Immune System. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001239.pub4]