Mixed T‐ and B‐Lymphocyte Deficiency Disorders


Mixed immunodeficiency diseases are intrinsic defects of the immune system affecting both B and T cells and thus the adaptive immune system. Mixed or combined immune deficiencies may also be associated with or secondary to other diseases. Patients have severe symptoms and the condition can be fatal unless properly treated. Early and reliable diagnosis is in many instances crucial for the efficient treatment of these diseases as delayed diagnosis and management can cause severe and irreversible complications, even the death of the patient. Combined immunodeficiencies, which are a heterogeneous disease group, appear throughout the immune system and affect several crucial genes and proteins. The symptoms and signs vary significantly between the different forms of combined immunodeficiencies. Despite variations in single factors, both B‐ and T‐cell responses are affected in these diseases.

Key Concepts

  • Combined immunodeficiency affects both B and T cells.
  • Lymphocytes are white blood cells including B and T cells.
  • Haematopoietic stem cell transplantation, the intravenous infusion of autologous or allogeneic stem cells collected from bone marrow, peripheral blood or umbilical cord blood, re‐establishes haematopoietic function in patients.
  • V(D)J recombination is genetic recombination which randomly selects and assembles segments of genes encoding specific proteins in the immune system.

Keywords: adaptive immunity; immunodeficiency; immune system; B cell; T cell; severe combined immune deficiency

Figure 1. V(D)J recombination process. (a) Recombination of the immunoglobulin or TCR gene by random combination of individual regions. (b) Detailed description of the stages where recombination deficiency proteins are involved. Note that a number of other factors are also involved but not shown in the figure.
Figure 2. Simplified schematic view of the common IL2RG–Janus kinase (JAK) 3 signalling pathway. Binding of an interleukin 2 (IL2) to the receptor on the cell surface triggers cellular signalling reactions in which JAK3 is involved. The signal is further transmitted by signal transducers and activators of transcription (STATs) which, when activated and dimerised, can translocate to the nucleus, where they effect the transcription of genes responsive to cytokines by binding to the γ activation sequence (GAS) motif.


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Further Reading

IDbases. http://structure.bmc.lu.se/idbase

Samarghitean C, Väliaho J and Vihinen M (2007) IDR knowledgebase for primary immunodeficiencies. Immunome Research 3: 6. ImmunoDeficiency Resource, http://structure.bmc.lu.se/idbase/idr/

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

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Vihinen, Mauno(Jun 2015) Mixed T‐ and B‐Lymphocyte Deficiency Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002167.pub4]