Combined Immunodeficiencies (B and T Cells Defects)
المؤلف:
APURBA S. SASTRY , SANDHYA BHAT
المصدر:
Essentials Of Medical Microbiology 2021
الجزء والصفحة:
3rd edition , p210-211
2025-09-29
423
Severe Combined Immunodeficiencies (SCID) SCID represents groups of genetically distinct syndromes; all having in common, defects in both humoral and cell mediated immune responses.
Types of Genetic Defect in SCID
- Mutation in cytokine receptor: Approximately 50–60% of the cases of SCID are X-linked (seen in males), resulting from mutations in the gene encoding the common γ chain shared by the cytokine receptors for IL-7 and others (IL-2, IL-4, IL-9, and IL-15)
* IL-7 being lymphopoietic growth factor, defective IL-7 receptor signalling leads to defect in survival and expansion of immature B and T cell precursors in the bone marrow
* Defect in IL-15 receptor signaling leads to deficiency of NK cell.
- The remaining cases of SCID are inherited as autosomal recessive manner include:
* Adenosine deaminase (ADA) deficiency: It is the most common type of autosomal recessive SCID. ADA is an enzyme required for purine degradation; its deficiency leads to accumulation of deoxyadenosine which is toxic to rapidly dividing immature T lymphocytes. B cell deficiency is not profound
* RAG Mutation: Recombinase-activating genes (RAG) are essential for somatic gene rearrangements of T cell receptor and immunoglobulins. Thus, defect in RAG blocks the development of T and B cells
* Jak3 mutation: Jak3, an intracellular kinase, is essential for signal transduction through the common cytokine receptor γ chain. Hence Jak3 mutation is another way of blocking the cytokine receptor signalling
* Class II MHC deficiency: Mutations that impair the expression of class II MHC molecules prevent the development of CD4+ T cells. This condition is also called the Bare lymphocyte syndrome.
Infections
Irrespective of the underlying genetic defect, the affected infants are susceptible to severe recurrent infections by a wide array of pathogens, including Candida, Pneumocystis, cytomegalovirus and Pseudomonas.
Treatment
Bone marrow transplantation is the mainstay of treatment. Gene therapy replacing the mutated genes has been successful in X-linked cases.
Wiskott–Aldrich Syndrome (WAS)
It is an X-linked recessive disease, characterized by immunodeficiency with thrombocytopenia, eczema, etc. The severity of WAS increases with age.
- It first manifests itself by defective responses to bacterial polysaccharides and by lower IgM levels. IgG levels are usually normal. Paradoxically the levels of IgA and IgE are often elevated
- Other T and B cell responses are normal initially, but with increase of age, there are recurrent bacterial infections and a gradual loss of humoral and cellular responses
- Patients are also prone to develop non-Hodgkin B cell lymphomas
- Patients may present with bloody diarrhea secondary to thrombocytopenia.
Pathogenesis
The underlying genetic defect is due to a mutation in the gene encoding Wiskott–Aldrich syndrome protein (WASP) present in precursor lymphoid cells of bone marrow. It is a cytoskeletal glycoprotein (sialophorin or CD43), required for actin polymerization.
Ataxia Telangiectasia
The syndrome is characterized by:
- Difficulty in maintaining balance while walking (cerebellar ataxia)
- Appearance of broken capillaries (telangiectasia) in the eyes and choreoathetoid movements (usually noticed in infancy)
- Deficiency of IgA and sometimes IgE
- Profound sinopulmonary infections.
Genetic defect: The primary defect appears to be in a kinase involved in regulation of the cell cycle. The relationship between the immune deficiency and the other defects in ataxia telangiectasia remains obscure.
Nezelof Syndrome
It is an autosomal recessive condition characterized by cellular immunodeficiency resulting from thymus hypoplasia. Affected individuals suffer from chronic diarrhea, viral and fungal infections, and failure to thrive.
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