Introduction to congenital immunodeficiency conditions

Immunodeficiency can be broadly classified as primary or secondary. Primary immunodeficiency results from inherited immune disorders associated with genetic mutations, usually present at birth and diagnosed in childhood. On the other hand, secondary immunodeficiency is also referred to as acquired immunodeficiency that results from disease or environmental factors, such as HIV, malnutrition, or medical treatment (e.g. chemotherapy). In the present discussion, we shall focus on the primary immunodeficiency. There are various disorders associated with primary immunodeficiency which can be broadly classified into two categories: congenital B-cell immunodeficiencies and congenital T-cell deficiency. Let us discuss them in detail,

Congenital B-cell immunodeficiency

  • Bruton’s agammaglobulinemia: This is X- linked disease so only males are affected. In this condition, all immunoglobulins are decreased two very levels and deficiency of B-cell is also there. Pre-B cells are present but they don’t form mature B-cell. This is due to the lack of enzyme Tyrosine Kinase. Cell-mediated immunity is normal. The patient starts having pyogenic infections after 6 months of birth as maternal IgG protection is reduced at this time.
  • Selective Immunoglobulin deficiency: Most commonly IgA is deficient. IgG and IgM deficiencies are very rare. Patient with IgA deficiency has recurrent sinus and lung infection.



Congenital T-Cell deficiency:

  • De’george Syndrome (Thymic Aplasia): This disease is due to a defect in the third and fourth pharyngeal arch due to which thymus and parathyroid glands fail to develop. Early in life patient suffer from severe viral, fungal or protozoal infections due to profound deficit in T-cell. Most common symptom is tetany due to hypocalcemia. Thymus transplant from a child less than 14 years cures a patient. Chronic mucocutaneous candidiasis occurs in severe T-cell deficiency.
  • Hyper IgM Syndrome: The patient has a high level of IgM but low levels of IgG, IgA, and IgE, etc. T and B-cells are normal. The disorder is characterized by defective CD40 signaling by B-cells affecting class switch recombination and somatic hypermutation. As a consequence, patients with this syndrome have decreased concentrations of serum IgG and IgA and normal or elevated IgM, leading to increased susceptibility to infections.
  • Combined B-cell and T-cell deficiencies/ Severe Combined Immunodeficiency Disease (SCID): Recurrent infections caused by fungi, bacteria, viruses, protozoans occur in early pregnancy because both B-cell and T-cell are defective. It is inherited as two types; X-linked and autosomal. Patients who have mutant tyrosine kinase gene ZAP-70 and adenosine deaminase and purine nucleoside P. phosphorylase can suffer from B-cells and T-cells deficiency.
  • Wiskott-Aldrich Syndrome: X-linked disease that occurs in male infants. The patient has the inability to mount the B-cell response. Basically, T-cell response is defective which is not able to provide help to B-cells proliferation.
  • Ataxia-Telangiectasia: Ataxia (staggering), telangiectasia (malformed in larger blood vessels). This condition is also referred to as Louis-Bar syndrome. It is caused by a defect in the ATM gene, which is responsible for managing the cell’s response to multiple forms of stress including double-strand breaks in DNA. In this condition, low levels of one or more classes of immunoglobulins (IgG, IgA, IgM or IgG subclasses) are observed. Also, low numbers of lymphocytes (especially T-lymphocytes) are present in the blood.

Conclusion

When we study the immune system, it becomes essential to know about those genetic diseases and conditions which are associated with defective functioning of the immune system. The above discussion was a brief description of these diseases. With this basic knowledge, now we shall study in detail the mechanism of functioning of various arms of the immune system.



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