Immunodeficiencies and its Types

115

Immunodeficiencies and its Types

According to their origin, all immunodeficiencies are divided into primary and secondary.

Primary immunodeficiencies are the hereditary diseases originated from various genetic abnormalities.

Secondary immunodeficiencies arise as the result of deleterious influences of various external or internal factors (starvation, severe acute and chronic diseases, unfavourable environmental conditions – chemical and radiation pollution, low-quality foodstuffs, etc.)

Immunodeficiencies can affect any part of the immune system. Most important are the immunodeficiencies of the lymphoid system. Likewise, they can affect mononuclear phagocytes and granulocytes, complement system and many other subsets of immunity. In the large number of cases the combined immune disturbances occur.

However, in many cases, immunodeficiencies remain latent owing to the great reserves and cross-reactivity between the links within the immune network.

Primary Immunodeficiencies

Severe combined immunodeficiency syndrome (SCID)

  • This state is characterized by profound impairment of differentiation of various immune cell precursors, including lymphoid stem cells. There are several SCID variations.
  • The main variant of SCID is based on gene abnormality localized in X-chromosome. It impairs the synthesis of IL-2 receptor gamma-chain. This common chain is also the obligate constituent of IL-7 receptor molecule. As IL-7 is one of the major differentiation factors for blood cells, the maturation of T- and B cells is ceased.
  • SCID emerges also in case of several enzyme deficiencies, where the cells are lack of production adenosine deaminase or purine nucleoside phosphorilase. This leads to the accumulation of toxic metabolites of nucleic acids degradation within immune cells.
  • The prognosis of SCID is very poor, and patient survival is possible only owing to advanced treatment methods, including gene therapy or bone marrow transplantation.

Ataxia-telangiectasia or Louis-Bar’s syndrome

  • It is a human autosomal recessive disorder associated with chromosome impairment in genes of the Ig heavy chains and T cell receptors.
  • It is characterized by progressive cerebellar ataxia with Purkinje cells degeneration, high incidence of cancer, greater susceptibility to respiratory infections, microcirculation disturbances. The process is followed by profound combined T- and B cell deficiency.

Wiskott-Aldrich syndrome

  • Patients suffering from Wiskott-Aldrich syndrome possess immunodeficiency with thrombocytopenia and eczema. Immune cells, in that case, lack a surface molecule sialophorin (CD43), which is a ligand for adhesion molecule ICAM-1.
  • Wiskott-Aldrich syndrome is associated with a low IgM and a poor response to many polysaccharides due to the dysfunctions of T- and B cells cooperation.

Immunodeficiencies and its Types

T cell immunodeficiencies

DiGeorge syndrome

  • This disease is evolved due to severe disorders in thymus development (thymus dysgenesis) from the third and fourth pharyngeal pouches in embryogenesis. The sick children also lack parathyroid glands and have severe cardiovascular abnormalities.
  • Thymus dysgenesis (aplasia or hypoplasia) results in the block of T cell precursor differentiation. The cell-mediated immune response is absent. Antibody response can appear but it is impaired against the majority of antigens because of T helper depletion.
  • Treatment by transplantation of thymus may perform the restoration of immunocompetence, but this method is being only worked out.

B cell immunodeficiencies

Bruton’s syndrome

  • Bruton’s syndrome or Bruton’s congenital agammaglobulinemia is developed in males and affects B cells maturation on the level of pre-B cells differentiation. The disease is associated with X-chromosome.
  • The main cause of it is the failure of variable genes rearrangement due to tyrosine kinase gene mutations. Serum immunoglobulin levels are negligible. The cell-mediated immune response is normal.
  • These children are very susceptible to infections caused by pyogenic bacteria. In case of adequate substitutive therapy with intravenous immunoglobulin (IVIG), the patients with Bruton’s syndrome can survive.

Common variable immunodeficiency

  • It pertains to the most common primary immunological disorders. It comprises a number of related syndromes resulted from B cell dysfunction, T helper insufficiency, dysregulation of cytokines and costimulatory molecules.
  • This ailment is usually manifested at the age of 25-30 years by lymphadenopathy, splenomegaly, recurrent infections of the respiratory and gastrointestinal tract. The patients demonstrate the elevated risk of lymphoid-derived tumours. Blood concentrations of all immunoglobulin classes are seriously reduced.

Selective IgA deficiency

  • It is the most frequent variant of disimmunoglobulinemia, where only one or a few Ig classes are decreased or absent.
  • The incidence of this syndrome is about 1:700. Sometimes it comes without manifestations but usually, patients are susceptible to respiratory and enteric infections.

Immunodeficiencies of mononuclear phagocytes and granulocytes

  • These disturbances can impair any stage of phagocytosis. The first group comprises the disorders in phagocyte chemotaxis, the second one – in opsonin functions, the third – in surface receptor expression, and one more includes the defects in a respiratory burst with impaired microbial killing.
  • An example is a chronic granulomatous disease, where granulocytes are lack of functional NADPH oxidase for respiratory burst activation. Phagocytes ingest microbes normally, but subsequent microbial killing is slow or absent. These patients suffer from different bacterial infections.

Chediak–Higashi syndrome

  • It is a rare disease inherited by autosomal recessive type. It is characterized by mutations affecting lysosomal trafficking regulator protein.
  • This is followed by the formation of giant vesicles within phagocytes incapable of fusion with lysosomes due to cytoskeleton impairment. The dampening of phagocytosis results in recurrent opportunistic bacterial infections.
  • The disease is manifested by fever, low neutrophil and platelet count; the patients demonstrate partial albinism with photophobia and bleedings.

Leukocyte adhesion deficiency or LAD syndrome

  • It is also a rare autosomal recessive disease. Several clinical variants of this disorder include the deficiency of beta-chain (CD18) of leukocyte integrin molecules and the lack of expression of leukocyte selectins.
  • The disturbances in leukocyte chemotaxis, adhesion, migration to inflammatory focus and extravasation lead to severe bacterial infections; their treatment ultimately requires bone marrow transplantation.

Immunodeficiencies in the complement system

  • Levels of any complement component may be decreased in case of primary complement immunodeficiency.
  • Patients with C1, C2, C4 and C5 deficiency develop a lupus-like state that affects microcirculation, whereas C3 deficiency is characterized by recurrent bacterial infections.

Hereditary angioedema

  • It is the result of Cl inhibitor deficiency. The disease has the dominantly autosomal inheritance.
  • Non-inflammatory edema of tongue, pharynx, and neck tissues appears by action of excess of vasoactive C2 fragment.
  • These patients are usually heterozygotic and may synthesize small amounts of the inhibitor. Its concentration can be raised to sub-normal levels by androgen steroidal treatment. For the urgent treatment of the disease, C1 inhibitor concentrate isolated from a donor’s blood is used.

Secondary immunodeficiencies

  • Secondary immunodeficiencies evolve under the pressure of different environmental conditions. They develop with a far greater rate comparing with primary ones. Secondary immunodeficiencies are followed by multiple viral and bacterial acute and chronic infections of respiratory, urogenital and digestive tracts.
  • These disorders are not inherited. They usually have a specific cause, which provokes the immune system dysfunction, but the immune changes retain even after the causative factor disappearance.
  • Many infectious and non-infectious factors can trigger secondary immunodeficiencies.
  • Infectious agents can directly suppress immune cells. Many viral, fungal, parasitic and bacterial diseases stimulate secondary immunodeficiency. The most severe secondary immunodeficiency develops in the course of HIV-infection resulting in AIDS progression.
  • Non-infectious factors include immunosuppressive therapy, starvation, any severe chronic diseases (diabetes, cancer, cardiovascular or pulmonary failure, etc.), stresses, burns, post-operative traumas, intoxications, drug abuse, or unfavourable external factors (chemical and radiation pollution, low-quality food-staffs and others).
  • Any part of the immune system can be affected with secondary immunodeficiency.