Immunodeficiencies due to insufficiency of the cellular system of the immune system

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As a rule, insufficiency of the cellular part of the immune system has more severe consequences in comparison with the inferiority of the functioning of the humoral link. Most of the genetically caused disorders of the cellular system of the immune system have a poor prognosis. Persons with disorders of the cellular system of the immune system are susceptible to diseases caused by intracellular pathogens (bacteria, viruses), protozoa and fungi. Opportunistic infections are common. In persons with this pathology, hyperergic reactions are almost never observed, most skin tests with allergens, including Candida fungi, as well as tuberculin test are negative, due to pronounced T-lymphocyte anergy.

A. Primary cellular immunodeficiency

1. Di Georgi syndrome is characterized by pronounced impairment of T-Lymphocyte differentiation due to thymus epithelial dysgenesis and its hypoplasia due to a defect of 3-4 gill arches. As a result, the thymus is not populated by lymphoid precursors and T-Lymphocyte does not develop. The defect of the T-cell link of the immune system is also combined with developmental defects of histogenetically related organs (parathyroid gland, heart and vessels), which leads to cardiac pathology, hypoparathyroidism and severe hypocalcemia.

2. Adenosine deaminase (ADA) and purine nucleotide phosphorylase (PNP) deficiency. ADA catalyze the conversion of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively, and PNP is the conversion of deoxyguanosine and guanosine to guanine, as well as inosine and deoxyinosine into hypoxanthine. The basis of the pathogenesis of these conditions is poisoning by purine metabolites resulting in a steady decrease in immunocompetent cells. In the absence of ADA, deoxyadenosine, adenosine, deoxy ATP and cAMP are accumulated (the first one is the most toxic), which leads to the death of both T and B cells, especially developing developing thymocytes. With deficiency of PNP, deoxyguanosine, GTP and deoxy GTP accumulate, toxic only for T-series lymphocytes.

3. The "bare lymphocyte" syndrome is an autosomal recessive disease that is a consequence of a violation of the formation of transcription factors (CIITA, RFX-S, etc.), which leads to the absence of expression of all histocompatibility (MHC) genes of classes I and II on the surface of T- and B-lymphocytes and antigen-presenting cells (macrophages, dendritic cells). As a result, positive selection of CD4 + cells can not be performed, and this population is not formed.

B. Secondary immunodeficiency of the cell link can occur as a result of the following causes:

1. Virus infections (viruses of measles, herpes, human immunodeficiency, cytomegalovirus, etc.). Deficiency of the cellular part of the immune system is caused both by the cytopathogenic effect of viruses and by the hyperactivation of cells, leading to their death by the mechanism of apoptosis (characteristic of HIV infection).

2. Mycobacterial and protozoal infections lead to immunodeficiency of the cell link as a result of damage to cells of the immune system by microbes and toxins, which causes anergy and death of T cells, as well as activation of macrophage suppressor factors.

3. Suppression of the cellular system of the immune system in uremia is due to the presence of toxic metabolites and developing acidosis, which causes lymphopenia, by activating suppressor effects in relation to maturation and differentiation of different populations of Lymphocyte.

4. Suppression of the cellular part of the immune system in case of burn disease is caused by toxic factors and the formation of autoantibodies, which contributes to suppression of phagocytosis, deficiency and suppression of CD4 + T-LYMPHOCYTE functions and hyperactivation of B-LYMPHOCYTE.

5. Tumors cause immunodeficiency of the cell link also through toxic and immunosuppressive factors leading to T-LYMPHOCYTE hypofunction, development of blocking effects of antibodies and activation of the suppressor link of the immune system.