IMMUNOTHERAPY (Latin immunis free, saved from something + grech, therapeia treatment) — the type of treatment influencing immune system of an organism for recovery of an immunological homeostasis, regulation or temporary substitution of function of separate links of immunity.
The concept «immunotherapy» is treated as impact on immune system, function a cut is broken as a result of various reasons: genetic (inborn immunodeficiency), tumors, organ transplantation and fabrics, infectious diseases, etc., and also as influence on the activator or its toxins.
And. it is applied independently or in a complex with other types of treatment: And. and antibioticotherapia, And. and surgical treatment, And. and the dosed gamma irradiation, And. and chemotherapy in oncology etc.
Immunotherapeutic impact on an organism of the patient is conducted in the directions of stimulation, suppression, correction or passive completion of products of activity of separate links of immunocompetent system at its functional insufficiency (e.g., administration of immunoglobulins at certain immunodeficiency).
And. can have also negative effect on various systems and bodies: the immunosuppression promotes development of various infectious processes, activation of already available centers which in usual conditions do not cause patol, reactions, and also to emergence of neoplastic processes. Some medicines in itself possess an immunodepressive effect (antibiotics in high doses, anesthetics, etc.) that needs to be considered at their appointment with immunodepressants not to gain the undesirable summing-up effect. And. it is carried out to a wedge, conditions under control immunol, reactions and systematic gematol, researches.
And. it began to be used since the end of 19 Century. Scientific basis And. fundamental opening in L. Pasteur (1885) medicine which were a basis for introduction of inoculations against rage were; cellular theory of immunity and I. I. Mechnikov's tsitstoksin (1883): detection of diphtheritic and tetanic antitoxins E. Beringom (1890); production to E. R (1894) horse antidiphtherial serums, and later G. Ramone (1923) of a diphtherial anatoxin. And. it was applied with different success first of all at infectious diseases: serotherapy of tetanus, acute dysentery of Shigi, typhoid, spotted fever and other diseases; treatment of the people bitten by venomous snakes (F. Krauss, 1914).
After opening of antibiotics the serotherapy of infectious diseases was limited separate nozol, forms (see. Serotherapy ).
Broad use methods I. received from 60th 20 century in connection with development of various sections of immunology of an iimmunogenetika: justification of existence of T - and the V-lymphocytes responsible for formation and implementation of immune responses (see. Immunocompetent cells ); development of tests of quantitative and quality standard of these cells in clinic; development of bases of atrepsy (see. atrepsy ); definition of various classes immunoglobulins (see) and establishment of the sequence of their emergence in an organism; the characteristic of histocompatibility antigens (see. Immunity transplant ) and their genetic control; receiving and use of various immunodepressants (see. Immunodepressive substances ), etc.
Immunotherapeutic actions are divided into specific — specific impact on systems cellular (T lymphocytes) or humoral (V-lymphocytes) of an immune response and the pursuing aim to strengthen or weaken formation of immunity to this antigen or a difficult antigenic complex (the activator, a transplant); nonspecific, based on ability of immune system to react to many nonspecific stimulators or depressors. Both groups I. are subdivided on active, passive and adoptive.
Drugs for an immunotherapy
the Majority of the drugs used for these purposes is either immunodepressants, or immunostimulators. In immunodepressive therapy apply as biol, drugs (e.g., anti-lymphocytic serum — ALS, antibody-containing, directed against lymphocytes), and chemical synthetic connections (an imuran, Cyclophosphanum, tsitozin-arabinozid, etc.). Stimulators of immunity also happen biological (e.g., vaccine BTsZh) and chemical (e.g., levamisole). Apply to replacement and adoptive therapy biol, drugs — immunocompetent cells and their components.
The mechanism of action
the Main feature of the mechanism of effect of the drugs used for And., the fact that they carry out the action through immunocompetent cells (or accessory factors of immunity — macrophages, system of a complement) is. Each drug used for And., in addition to the main direction of action (tab.), has also other effects (e.g., corticosteroids which mechanism of action on immune system consists in disturbance of interaction between lymphocytes and macrophages possess also antiinflammatory action; immunoglobulins, in addition to the main replaceable effect, have also promoting effect on synthesis of antibodies etc.). For the characteristic of all means applied for And., two parameters are main: 1) the direction of action — stimulation, suppression or substitution of immune system; 2) points of application of action — T - and V-lymphocytes.
So, stimulating And. can strengthen the speed of proliferation and a differentiation of immunocompetent cells, and this effect can be as specific — involvement only of clones of the cells capable to react to this antigen (tuberculine, etc.), and nonspecific when a considerable part of population of immunocompetent cells is involved in reaction. At the same time some drugs stimulate preferential T lymphocytes (levamisole, etc.), others — B-lymphocytes (poliadinit: poliuridinovy to - that, etc.). Overwhelming therapy can influence as separate clones of cells (tolerance induction, desensitization), and the whole populations (immunosuppression). Immunodepressants can have preferential effect on T lymphocytes (e.g., ALS) or on V-lymphocytes (e.g., tsitozin-arabinozid). Special look And. is passive And., when to the recipient needing the corresponding treatment transfer ready protective factors or cells, specifically sensibilized to a certain antigen, or immune serum, or the cells replacing activity of the whole population (T or In), or immunoglobulins. One of types I. — adoptive And. — by means of products of cells of sensibilized donors or just by means of extracts of immunocompetent cells of a cell of the recipient are allocated with immune properties (so, e.g., at introduction of «transfer factor» — extract of the cells reacting to a certain antigen — the cells of the recipient which were earlier not reacting to this antigen recover the reactivity).
And. apply at the diseases which were result inborn (immunodeficiency) or acquired (e.g., as a result of an immunosuppression at organ transplantation) defeats of immune system, and also at various diseases in which development such defeats arise and cause the adverse course of a disease, development of a recurrence and complications.
At immunological insufficiency, in genesis the cut lies defeat of immunocompetent systems of the inborn or acquired character (see. Immunological insufficiency ), And. it is directed to recovery (substitution) of the available defect in a certain link of immune system. So, at preferential defeat of T-system (Di George's syndromes, Nezelofa) therapy by means of the T lymphocytes processed by various stimulators, surgical change of a thymus, treatment by Timosinum, «transfer factor» is shown (see. Immunity transplant ). At different agammaglobulinemias where the B-system is struck preferential, therapy is shown by immunoglobulins, transplantation of marrow (see). Researches Yu. M. Lopukhina, etc., 1974; R. V. Petrova, 1976; Fudenberg (H. H. Fudenberg, 1974) was shown, as. by the available methods and means gives temporary effect, especially at various inborn aplasia of a thymus and the combined immunodeficient defeats.
At tumors And. quite often has the combined character — it is combined with surgical treatment, gamma irradiation, chemotherapy. And. at tumors stimulates immune system of an organism of the patient (preferential T lymphocytes). For this purpose apply opukholespetsifichesky antigens, allogenic lymphocytes; the lymphocytes processed fitogemagtlyutininy, «transfer factor» (including and opukholespetsifichesky). For treatment of acute leukoses, some melanomas carry out nonspecific active And. vaccine BTsZh [V. I. Govallo, 1974; I. F. Lancius, 1974; J. N. Thomas, 1975]. It is applied also retikulostimulin — a product of synthesis of Corynebacterium anaerobies — in a combination with cyclophosphamide [Prevo (A. - R. Prevot), 1972]. Optimum results And. are reached in a condition of the remission caused by radiation, reception of tsitostatik, surgical treatment, etc.
At organ and tissue transplantation a task And. — to promote engraftment of a transplant by suppression of ability of an organism to its rejection. First look And. — the immunodepressive therapy (the x-ray radiation, drugs possessing cytotoxic action, corticosteroids) which is quite often causing complications owing to suppression of immunocompetent systems of an organism and posing hazard to life (suppression of reactions to alien antigens, development of infectious complications, hl. obr. a bacterial origin, up to sepsis). Other look And. at organ transplantation and fabrics there can be an administration of the serums containing the blocking factors (usually antibodies against graft-specific antigens) for creation of a so-called phenomenon of strengthening when serum, blocking antigens determinants, interferes with action on a transplant of immune lymphocytes of the owner. Third look And. there can be preliminary tolerance induction to antigens of future transplant — to graft-specific antigens (see. unresponsiveness ).
At autoimmune diseases of the purpose I. suppression of reactions of immunity against own fabrics by means of immunodepressive drugs (is at autoimmune hemolitic anemia, a system lupus erythematosus, etc.).
At allergic diseases among which bronchial asthma, hay fever, a medicinal allergy have the greatest value use the hyposensibilizing therapy by the corresponding allergen or automonovaktsina (see. Desensitization ) or nonspecific immunodepressive therapy by corticosteroids.
At infectious diseases of the indication for And. are defined by a combination of several factors: features of a pathogeny nozol, forms, weight and stage of disease, state specific (immunity) and nonspecific protective factors (complement, lysozyme, etc.), premorbidal status, allergic background. Efficiency And. also depends on etiopatogenetichesky treatment and properties of the activator. Early And. specific immune serums — immunoglobulins (see. Immunoglobulins ) plays a crucial role in the outcome, napr, botulism, diphtheria, tetanus. At these diseases speed is of great importance, about a cut there is a contact in a blood-groove of toxic products of the activator and anti-toxic antibodies, and also their neutralization and the subsequent elimination from an organism (a way of introduction, a dose, activity of drugs). After binding of toxins fabrics I. it is not effective any more. Within one nozol. forms, napr, the dysentery caused by different activators, the serotherapy renders different effect. If at dysentery Fleksnera it is not effective, then at the toxic dysentery caused by Grigoriev's stick — Shigi, is possible. For treatment of infectious diseases it is reasonable to use those types I. (stimulating, adoptive, passive) which pathogenetic influence mechanisms of this infection. T lymphocytes play a crucial role in development and an outcome of a number of the viral and some bacterial infections differing in the preferential intracellular nature of parasitism of the activator (a leprosy, tuberculosis, a brucellosis, a tularemia), V-lymphocytes at the majority of other bacterial and viral infectious diseases. Therefore at diseases of the first group the drugs stimulating T lymphocytes (Timosinum, levamisole) are recommended, and at diseases of the second group — the drugs stimulating or replacing function of B-lymphocytes (polyadenylic, poliuridilovy to - you, immunoglobulins).
Slow and hron, forms of infectious diseases (tuberculosis, some fungus diseases) are followed by oppression of immunity. In such cases it is shown specific stimulating or replaceable And. («transfer factor», Timosinum, immunoglobulins etc.). At some infectious diseases there is a dangerous giperergichesky reaction, edge demands desensitization or use of immunodepressants, is more often than corticosteroids. Special difficulties arise at multi-infection. In these cases consider actual state of cellular and humoral immunity to each of activators at this patient.
In surgical practice And. apply the patient with burns. Its main objective — fight against infectious complications (staphylococcal sepsis, etc.), postoperative suppurations when an antibioticotherapia is powerless. Apply anti-staphylococcal plasma, gamma-globulin, etc., stopping the arisen complication after 1 — 2 administrations of drug.
In obstetrics And. use for the prevention a Rhesus factor conflict at pregnant Rh-negative women, especially at repeated pregnancy by a Rh-positive fruit. In these cases anti-Rh antibodies of the person — immunoglobulin of anti-RhO (D) give good effect.
Contraindications to And. their influences on the general condition of an organism of the patient, portability, etc.
the Table are defined individually with the used drugs. Main types of an immunotherapy, drugs and their clinical use =
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V. I. Litvinov, I. V. Rubtsov.