IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

CORE PRINCIPLES IN THE MANAGEMENT OF IMMUNE DEFICIENCY

The immunotropic EFFECTS OF ENVIRONMENTAL factors, Bacteria, and Viruses induce transient immunomodulation in healthy individuals and provoke persistent immunomodulation in patients, manifesting as immunodeficiencies (allergies, autoimmune diseases). In patients with Primary and secondary immunodeficiencies, such exposures lead to severe clinical manifestations and even fatal outcomes. Consequently, developing Methods to correct immune system Functions using immunotropic medicinal products is a primary focus of clinical immunology. Deteriorating environmental conditions in urban and rural residential areas necessitate The Development of population-wide immunorehabilitation strategies.

Principles of Immunotherapy, Immunocorrection, and Immunomodulation

Impairments in immune mechanisms play a critical role in the Pathogenesis of primary and secondary immunodeficiencies, immune complex-mediated disorders, autoimmune diseases, and lymphoproliferative processes. There are approaches for selectively targeting Cells of The Immune System, as well as suppressing and stimulating immune responses, which can be applied in immunotherapy, immunocorrection, and immunomodulation.

✵ Immunotherapy refers to therapeutic interventions targeting the immune system to halt a pathological process.

✵ Immunocorrection encompasses therapeutic modalities that arrest or rectify defects within the immune system, specifically correcting impaired components of Immunity.

✵ Immunomodulation is the temporary enhancement or suppression of specific immune parameters. Immunotherapy may be local or systemic, combination-based, or monotherapy.

Goals of immunotherapy: stimulating diminished immunoreactivity; suppressing heightened immunoreactivity (in allergies and autoimmune diseases); and replacing deficient immune factors.

Given the specific requirements of immunotherapy across various diseases, the following categories must be distinguished:

✵ immunotherapy for disorders characterized by heightened immunoreactivity;

✵ immunocorrection of primary and secondary immunodeficiencies;

✵ immunotherapy for tumors and lymphoproliferative diseases;

✵ immunotherapy for post-transplantation reactions;

✵ immunocorrection of reproductive disorders.

Based on the MECHANISM OF ACTION on the immune system, the following types of immunotherapy are distinguished:

- stimulating - used to activate immune responses in a healthy Organism to prevent infectious diseases and treat immunodeficiencies;

- suppressive - employed to inhibit immune responses in allergies and autoimmune (autoallergic) diseases.

- specific - utilizes antigen or antibody preparations specific to the pathogen or antigen;

- nonspecific - involves the action of chemical agents, physical factors, and Antigens on the immune system that are nonspecific to the arising pathological process;

✵ in systemic therapy, the administered agent acts uniformly across all lymphoid tissue;

✵ local (regional) therapy - such as Electrophoresis, inhalation, or irrigation - targets the specific site of the lesion. This minimizes systemic side effects and maximizes the impact on local immune factors, which frequently play a leading role in the pathological process;

✵ combination therapy - the concurrent use of multiple drugs acting on different Links of the immune system, combined with various systemic and local administration routes.

Successful immunotherapy is impossible without the Structure/175.html">Implementation of immunodiagnostics. A given therapeutic agent should only be prescribed after a thorough Assessment of the nature of immunoreactivity disorders. Prior to initiating immunostimulation or immunosuppression, the prescribed agents must be pre-tested via Skin tests or in vitro assays to determine their efficacy for a specific patient. This approach allows clinicians to predict drug effectiveness and prevent complications. Immunodiagnostics also facilitates the adjustment of Treatment regimens if initial efficacy is insufficient.

Clinical criteria for prescribing immunostimulatory therapy: chronic purulent infections; poor response of the primary underlying disease (inflammatory process) to conventional treatments; administration of high doses of immunosuppressants; and prolonged glucocorticosteroid, antibacterial, or Radiation therapy.

Immunological criteria for prescribing immunostimulatory therapy (in the presence of clinical signs of immunodeficiency): a decrease in lymphocyte count and functional activity, reduced levels of serum IMMUNOGLOBULINS and Complement, and a drop in phagocytic activity (incomplete phagocytosis) by at least 30–50%.

Clinical criteria for prescribing immunosuppressive therapy: severe forms of allergy with renal involvement, Organ and tissue transplantation, and systemic Connective Tissue diseases.

Immunological criteria for prescribing immunosuppressive therapy: the appearance of high titers of autoantibodies in the Blood.

When prescribing immunotherapy, it should be clinically justified and a treatment plan must be developed.

Specific active stimulating immunotherapy is associated with the immunoprophylaxis of infectious diseases. It utilizes Vaccines, toxoids, and antigens. An example is The Use of staphylococcal toxoid and vaccines for the treatment and Prevention of Staphylococcal infections. The staphylococcal vaccine (toxoid) is used to increase the level of anti-staphylococcal Antibodies. It activates phagocytosis and stimulates antibody production. Indications for use include chronic relapsing staphylococcal infection. Contraindications involve severe allergic diseases and Primary immunodeficiencies. The efficacy of staphylococcal toxoid and vaccine administration is monitored by initial and subsequent determination of antibody titers.

Nonspecific active stimulating immunotherapy activates the Immune Response. Three types of influences are employed: biological, chemical, and physical.

1. Biological influences

Adjuvants are nonspecific enhancers of immunological reactions. They boost the Immune Response to a specific antigen, create an antigen depot, and facilitate its slow release into the bloodstream to achieve the most effective stimulation of the immune response. These include lipopolysaccharides from certain bacteria. They stimulate B lymphocytes, phagocytosis, and The production of interleukin-1 and lymphokines. Examples are Freund's adjuvant, BCG vaccine (used to stimulate Antibody production in humans), and bacterial products such as prodigiosan and pyrogenal. Their use is indicated in cases of immunoglobulin deficiency and impaired B-lymphocyte functional activity. It is advisable to prescribe them concurrently with macrolides during inflammatory processes. Conversely, their simultaneous use with Cephalosporins and beta-lactams is contraindicated due to antagonism.

Nucleic Acids, their salts, and polynucleotides activate various links of the immune response. They are most effectively administered together with an antigen during the Cytology/cytology/16.html">Early stages of immunogenesis. At low doses, they stimulate immunogenesis, whereas at high doses, they suppress it. Sodium nucleinate, a sodium salt of Yeast RNA, stimulates the migration of stem cells, the cooperation of T AND B lymphocytes, the functional activity of their populations, and antibody genesis. It is effective in secondary immunodeficiencies.

Vitamins are regulators of biochemical processes within Cells and Tissues, particularly in the immune system. Vitamin C exhibits antioxidant activity and stimulates phagocytosis, migration, and the differentiation of T and B lymphocytes. In high doses (1–3 g per day), it exerts anti-allergic and anti-inflammatory effects. Vitamin E enhances T-helper activity and antibody synthesis. Vitamin A possesses adjuvant properties, stimulates The activity of complement and properdin, enhances antibody genesis and antitumor immunity, and reduces the immunosuppressive effects of glucocorticosteroids and Antibiotics.

2. Chemical influences include artificial polyelectrolytes: pentoxil, methyluracil, dibazole, tuftsin, and diucifon. They activate B lymphocytes and antibody production against an antigen present in the body.

3. Physical influences, depending on the type and dose of energy, can either stimulate immunological reactions or suppress immunoreactivity. Ultrasound stimulates phagocytosis and chemotaxis, and increases the concentration and affinity of receptors on activated lymphocytes. This property forms The basis of its medical Applications. Transcutaneous sonication of the Spleen leads to a reduction in allergic manifestations in Bronchial Asthma and increases the number of T-suppressors. Sonication of the Thymus in children with low T-lymphocyte levels (down to 25%) yields positive results, increases their count, and restores The ratio of Th/Ts populations.

Adaptive stimulating immunotherapy is based on the application and reception of nonspecific stimuli by immunocompetent cells from exogenous thymic Hormones and other immune factors. These effects are characteristic of hormones derived from the thymus, Bone Marrow, spleen, and Lymph Nodes. Thymosin, thymalin, and T-activin are used to treat primary and secondary immunodeficiencies as well as tumors. They restore impaired immune links and T-lymphocyte counts, stimulate cellular immunity, phagocytosis, tissue regeneration, and hematopoiesis, and improve METABOLISM.

Nonspecific passive replacement immunotherapy is characterized by the administration of preformed nonspecific immune factors and immunocompetent cells to a patient in cases of deficiency. Examples include bone marrow or lymphoid tissue transplantation for severe immunodeficiencies; blood transfusions and blood products (effective only when Histocompatibility Antigens match the donor's, otherwise ineffective due to rapid Cell elimination); administration of immunoglobulins for passive therapy; administration of purified gamma globulins of various classes to compensate for deficiencies; and the administration of complement and Lysozyme to enhance anti-infective defense.

Nonspecific passive suppressive immunotherapy targets various links of the immune system. It requires specific indications and careful monitoring of the patient's immunological status alongside clinical and laboratory data. An absolute indication for its prescription is organ and tissue allotransplantation.

Glucocorticosteroids (prednisolone, methylprednisolone, dexamethasone, hydrocortisone, kenacort, triamcinolone) suppress reactions in allergic diseases, transplant rejection, and systemic connective tissue diseases. They inhibit inflammatory reactions, stabilize leukocyte membranes and the release of neutrophils from the bone marrow, prolong their Circulation time in the blood, and block migration, adhesion, and accumulation at inflammation sites. They inhibit all Phases of the immune response, induce lymphocytolysis, suppress phagocytosis, lymphocyte proliferation, and their interaction with other cells, and impair the effector function of lymphocytes.

Cytostatic drugs:

✵ antimetabolites:

- purine antagonists (mercaptopurine, azathioprine, imuran) inhibit DNA and RNA Synthesis and block cell proliferation;

- Folic acid antagonists (methotrexate) inhibit DNA Synthesis AND Replication.

- alkylating agents (cyclophosphan, cyclophosphamide, melphalan, myleran) disrupt the DNA molecule and inhibit Protein Synthesis; leukeran acts selectively on lymphoid tissue;

✵ antibiotics (actinomycin D and C, puromycin) inhibit RNA and Protein synthesis;

✵ Alkaloids (vincristine) block mitosis in metaphase and inhibit protein synthesis;

✵ metabolites (cyclosporine A) selectively inhibit T helpers, suppress T-cell-mediated delayed-type hypersensitivity and antibody production. It is effective in organ transplantation, though accompanied by a pronounced nephrotoxic side effect. The suppressive effect on the immune system is reversible.

Nonsteroidal anti-inflammatory drugs (aspirin, diclofenac) inhibit prostaglandin synthesis, exhibit antihistamine activity, suppress leukocyte migration, reduce chemotaxis and phagocytosis, and disrupt the cooperation of T and B lymphocytes.

Quinoline derivatives (delagil, plaquenil) inhibit the activity of Enzymes, inflammatory and allergic mediators, and suppress DNA synthesis. They are most commonly used in systemic connective tissue diseases (such as systemic lupus erythematosus, rheumatoid Arthritis, etc.).

Antilymphocyte globulin destroys lymphocytes and induces lymphopenia.

Monoclonal Antibodies targeting CD20+ T lymphocytes (rituximab), TNF-α (adalimumab), activated lymphocytes (leflunomide), interleukin-1 receptors (anakinra), and IgE (omalizumab).

Physical factors (X-ray and ultraviolet radiation) act as suppressors;

Plasmapheresis and hemadsorption involve the removal of immunological factors from the blood (lymphocytes, circulating immune complexes, antigens, antibodies, and mediators), producing a temporary suppressive effect and restoring immune status, particularly in allergic conditions.

Any immunosuppressive therapy must be administered alongside broad-spectrum antibiotics and gamma globulin preparations, while keeping the patient in aseptic conditions.

Transfusion methods of immunotherapy in intoxication. During the toxic phase of diseases, the potential for immunocorrection is limited by the immunosuppressive effects of intoxication, which play a significant role in systemic immunosuppression and the suppression of T-lymphocyte function and phagocytosis. Compensation for toxigenic immunosuppression is possible through the infusion of low-molecular-weight polyvinylpyrrolidone solutions, such as polyglucukin, rheosorbilact, polyoxidonium, etc.

The detoxifying mechanism of polyglucukin and rheosorbilact is based on their ability to bind toxins within the bloodstream and facilitate their elimination from the body. They protect immunocompetent cells from the immunosuppressive effects of intoxication. These agents should be used in combination with other medications required during the toxic phase, such as antibacterial and cardiovascular drugs, with polyglucukin and rheosorbilact further enhancing the efficacy of antibacterial therapy.

Blood Plasma exhibits significant antitoxic activity. The Effect of native concentrated plasma on the immune system manifests as replenishing deficiencies in immunoglobulins, mediators, cytokines, and complement components. Its use has helped restore the functional activity of T-lymphocytes, particularly during high inflammatory activity. The positive immunomodulatory effect of plasma is observed exclusively during the toxic phase. The immunocorrective action of plasma lies in countering the immunosuppressive factors present in the acute phase of inflammation, including microorganisms, secondary inflammatory products, and pharmacological agents. The immunocorrective impact of plasma is transient. Laboratory criteria indicating The Need for native concentrated plasma transfusion include deficiencies in cellular immunity and immunoglobulins.