PRINCIPLES OF THERAPY OF IMMUNODEFICIENCES

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General tactics

1. Treatment is determined by the type of immunodeficiency.

2. In severe T-cell pathology, bone marrow transplantation is indicated.

3. With IgG deficiency, intravenous administration of solutions containing Ig.

4. Do not administer live vaccines to immunocompromised patients and their families. When cellular immunodeficiency is contraindicated, transfusion of fresh blood and blood products. Ig and plasma should not be administered to patients with selective IgA deficiency. In thrombocytopenia, intramuscular injections should be avoided. Before the surgical or dental procedures, antibiotics should be prescribed.

Drug therapy

1. Practically for all forms it is necessary to appoint:

- Antibiotics (for prevention and immediate treatment of infections).

- Immunostimulants (eg, levamisole, ascorbic acid, to improve the function of neutrophils).

2. For humoral and combined immunodeficiencies - Ig substitution therapy.

3. In case of adenosine deaminase deficiency, substitution therapy with enzyme conjugated with polyethylene glycol (Adagen). Gene therapy (corrected T-lymphocytes of the patient) is also performed.

Complications of immunodeficiencies

1. Autoimmune diseases.

2. Development of serum sickness in treatment with γ-globulin.

3. Development of malignant neoplasms (eg, with hypogammaglobulinemia, thymoma may develop).

4. Severe infections.

5. "Graft versus host" reaction (usually as a result of blood transfusion in patients with severe combined immunodeficiency).

Prevention

At primary immunodeficiencies it is necessary mediko-genetic consultation.

Pathological tolerance

Immunological tolerance is a condition characterized by the "tolerance" of the immune system in relation to foreign AIs. Immunological tolerance is divided into physiological, pathological and artificial.

Physiological tolerance

Physiological tolerance implies the "tolerance" of the IBN system to its own AG.

The main mechanisms of development of physiological tolerance:

1. Clonally selective

2. Insulation »

3. Elimination of autoaggressive T-lymphocytes in the thymus ("central selection")

4. Anergy of T-lymphocytes not exposed to the action of costimulatory molecules ("clonal anergy")

5. Depression of T-killers by T-suppressors

6. Apoptosis of lymphocytes, activated by endogenous antibodies ("clonal deletion")

- Elimination in the antenatal period (when the immune system is not yet ripe enough) of those clones of lymphocytes that have undergone antigenic overload - the massive effect of their own hypertension. This position was put forward by M. Bernet and F. Fenner in the clonal-selection hypothesis formulated by them. In the laboratory, this phenomenon is reproduced by replanting the embryo and the fetus of the animal tissue or organ of another animal of the same species (allograft). Repeated transplantation to an adult animal of the same transplant does not lead to its rejection - tolerance develops to it. Such animals (in the body of which there is genetically and antigenically a foreign tissue or organ) are called chimeras. Similar chimerism develops in the twins and twins, which during the prenatal period are exchanged by different blood. In the adult state, they can freely transfuse the blood of both groups.

- Isolation of AG of a number of organs from contact with immunocytes by structural and physiological barriers. These organs include the brain, eyes, testes, thyroid gland, which are separated from the internal environment of the body by hemato-tissue barriers (hemato-encephalic, hemato-ophthalmic, hemato-thyroid). This kind of tolerance is called insulating.

- Suppression of proliferation and differentiation of autoaggressive (acting against own cells) T-lymphocytes in the central organ of the immune system - thymus. This phenomenon is called the central selection and elimination of autocytotoxic lymphocytes.

- Death (apoptosis) of clones of lymphocytes activated by autoantigens. In such a situation, T-lymphocytes, responsive to the AG of their own organism, express Fas-receptors, which are acted upon by Fas ligands of normal cells, which activates the apoptosis program.

Pathological tolerance

In this case, we are talking about the "tolerance" of the system of IBS of foreign AG, most often - bacteria, viruses, parasites, malignant tumor cells or a transplant.

The main mechanisms of pathological tolerance:

1) Immunodeficiency states and immunodeficiencies.

2) Excessive increase in activity of T-suppressors. The latter is characterized by inhibition of the maturation of the effector cells of the immune system: T-killers, natural killers, plasma cells.

3) Inhibition or blockade of cytotoxic reactions of cellular immunity to the corresponding AH (most often tumor cells, grafts or virus-containing cells) as a result of "screening" of antigens with antibodies.

4) Overload of immunocytes by excess of foreign AGs formed in the body or introduced into it from outside. This can be observed in the synthesis of abnormal proteins in the liver, amyloidosis, denaturation of protein molecules with massive burns, the introduction of a large number of protein-containing solutions (whole blood, plasma).

5) Death of cytotoxic T-lymphocytes with the development of T-cell immunodeficiency. This is observed when other cells (eg, tumor cells) express Fas ligands. The latter, interacting with Fas-receptors of cytotoxic T-lymphocytes, activate the program of their apoptosis.

Artificial Tolerance

Induced (artificial, medical) tolerance is reproduced by means of influences that suppress the activity of the immune system. Usually, ionizing radiation, high doses of cytostatics and immunosuppressants are used for this purpose. To create a state of artificial tolerance, special cells (impermeable to immunocytes) implanted under the skin, mucous membrane, into muscles or body cavities are also used. A homogenate or fragments of foreign tissue (for example, the endocrine gland to eliminate the deficiency of endogenous hormone) are placed in the chamber. This kind of tolerance is called insulating.

The state of induced tolerance is used to increase the success of organ and tissue transplantation, allergy treatment, immune auto-aggression diseases, endocrine insufficiency and some other conditions.

The "graft versus host" reaction

The "graft versus host" reaction develops when the donor tissues containing immunocytes (for example, bone marrow, spleen, leukocyte mass) are transplanted to the recipient (the "host").

Conditions for the development of "graft versus host" reactions

- Genetic alienity of the donor and recipient.

- The presence of a large number of lymphocytes in the transplant.

- Inability of the recipient to destroy or reject this transplant.

Manifestations

The "graft versus host" reaction is characterized by the defeat of the immune system of the recipient and the development of immunodeficiency in connection with it. In addition to the immune system, other organs are always damaged: skin, muscles, gastrointestinal tract, liver, kidneys.

The lesions of these organs and tissues are manifested by necrotic and dystrophic changes, the development of deficiency of their functions, lymphopenia, anemia, thrombocytopenia, dyspeptic disorders (nausea, vomiting, diarrhea), liver enlargement.

- In adults, the described condition is called homologous or transplantation disease.

- Wound disease develops in children - a small-growth disease (from English, runt, the smallest individual). The latter is associated with a violation of the child's physical development, multiple organ failure, a tendency to develop infectious diseases and neoplasms.