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Secondary immunodeficiencies

Secondary immunodeficiency conditions (SIDS).

Immunodeficiency states are permanent (persistent) or temporary (transient) conditions characterized by an inadequate immune response to antigens of microbial or other origin.

Immunodeficiencies are divided into primary (congenital), physiological and secondary (acquired). Primary immunodeficiency conditions are genetically determined and manifest themselves at the genotype level. Secondary immunodeficiency states are formed in populations with an initially normal immune system under the influence of the environment or other factors. They manifest themselves at the phenotypic level.

Secondary immunodeficiencies arising from infectious diseases.
Infections are the most common causes of secondary immunodeficiencies.

Viral and other infections.
In accordance with WHO criteria, secondary immunodeficiencies can form during acute viral infections - measles, rubella, influenza, mumps, chickenpox, viral hepatitis, persistent viral infections - chronic hepatitis B, C, CMV, herpes infection, congenital viral infections - rubella, CMV , herpes, also toxoplasmosis, etc.

Mechanisms of formation: some viruses have tropism for immunocompetent cells - lymphocytes and macrophages. By multiplying in T- and B-lymphocytes, viruses suppress their functional activity, the ability to synthesize cytokines, antibodies, and destroy target cells. By infecting macrophages, viruses disrupt the processes of antigen presentation, as well as the ability of macrophages to absorb and digest foreign antigens.
The immunocompetent cells themselves can serve as a reservoir for the proliferation of viruses.

The most common causes of viral infections are disorders of the T-cell component of immunity. A decrease in the number of T-lymphocytes and their functional activity can be observed with measles, rubella, infectious mononucleosis, influenza, MS infection, polio, hepatitis B, and HIV infection. An immunodeficiency state can last from several weeks (flu, rubella) to several months (measles, hepatitis B) and even years (infectious mononucleosis).
With HIV infection, immunological disorders gradually progress and become the cause of death of the patient.

Expressed disorders T-cell immunity occurs in chronic and long-persistent viral infections (herpes, CMV, chronic hepatitis B, C, D). In some cases they persist for life.
Some viruses have the ability to cause defects in neutrophil granulocytes, reduce their bactericidal and digestive activity, which is observed with influenza, parainfluenza, MS infection, CMV, herpes, chickenpox, hepatitis B, rubella, HIV infection. The role of neutrophils in protection against these infections is not decisive. However, these cells provide the body's main defense against bacterial and fungal antigens and their defects are main reason bacterial complications due to viral infections (otitis media, pneumonia, toxic shock syndrome, sepsis, meningitis).
Deficiencies of the humoral immunity (hypogammaglobulinemia) are often associated with intrauterine infections (rubella, CMV, herpes). Children with IUI may experience a decrease in immunoglobulins up to the formation of primary humoral deficiencies. Such children are characterized by selective IgA deficiency and a late “immunological start.”

Bacterial infections

In accordance with WHO criteria, secondary immunodeficiencies can develop with leprosy, tuberculosis, syphilis, pneumococcal, meningococcal, and staphylococcal infections.

Mechanisms of development: Acute bacterial infections rarely lead to the development of persistent immune deficiency. The resulting disorders are most often transient in nature and reflect the activity of bacterial inflammation. In chronic and recurrent bacterial infections, accompanied by the accumulation of a large number of bacterial antigens in the body, toxic-infectious overloads, depletion of components of the complement system, immunoglobulins, and a decrease in the functional activity of phagocytic cells may be observed.
Chronic bacterial infections may be accompanied by a decrease in the activity of the complement system, its individual components, and the level of properdin. A decrease in the absorption activity of phagocytes during bacterial processes is rarely observed and occurs mainly in generalized infections, sepsis, and peritonitis.
The bactericidal activity of blood phagocytes decreases during prolonged bacterial infections. The weakening of oxygen-dependent bactericidal activity predisposes to secondary infection of the skin and mucous membranes with staphylococcus, Escherichia coli, Aspergillus fungi, and Candida albicans.
A decrease in the digestive activity of neutrophils and incomplete phagocytosis are associated with the ability of a number of bacteria to multiply inside phagocytic cells. This is typical for salmonellosis, yersiniosis, typhoid fever, paratyphoid fever, meningococcal, staphylococcal and streptococcal infections. It is one of the main causes of protracted and chronic forms of bacterial infections and long-term bacterial carriage.
In acute bacterial infections, violations of the T-cell component of immunity, as a rule, do not occur. The exception is intracellular bacterial infections (salmonellosis, tuberculosis, listeriosis, brucellosis, tularemia). In the immunological status during these infections, the following may be observed: a decrease in the number of T-lymphocytes (CD3), an increase in the level of T-cytotoxic (CD8), NK cells (CD16). A decrease in the level of T-helper cells (CD4) is characteristic of pneumococcal and meningococcal infections.

Fungal infections
Almost all mucocutaneous and visceral mycoses occur against the background of insufficiency of the T-cell component of immunity and/or insufficiency of phagocytic cells. The progression of fungal infections can cause a further decrease in the number of T lymphocytes and their functional activity.

In general, immunological disorders are an important link in the pathogenesis of infectious diseases. Maximum changes in the immunological status, as a rule, correspond to the acute period of the disease and normalize to the period of clinical recovery. However, recovery immune status may take months. The consequence of emerging immunological deficiency is the protracted nature of infectious diseases, the tendency to relapse, chronicity, and prolonged release of microbial agents. Immunological disorders are also associated with the development of secondary infectious complications, the causative agents of which are often opportunistic microorganisms of different classes: bacteria, viruses, fungi, protozoa. Secondary infections manifest themselves in the form of otitis media, sinusitis, pneumonia, toxic shock syndrome, meningitis, and sepsis. Often they determine the clinical course and outcome of the infectious process.

Protein deficiency(nephrotic syndrome, enteropathy, malabsorption syndrome).
In young children, poor nutrition leads to a decrease in thymus mass, often with absent or thinning of the cortex. There may be a disruption in the normal development of immunological reactivity.
Protein loss leads to a decrease in the level of immunoglobulins, components of the complement system. With malabsorption syndrome, a decrease in the number of T-lymphocytes and their functional activity may be observed.

Micronutrient deficiency.
Zinc and iron deficiency often cause T-cell immunodeficiency. Magnesium deficiency can cause a decrease in the number of NK cells, disrupt adhesion and interaction processes immunocompetent cells. Selenium deficiency leads to the formation of T-cell failure. Selenium is an important antioxidant; its deficiency can cause various disorders of nonspecific protective factors, cellular and humoral immunity.

Oncological diseases.
Inductors tumor growth there may be unfavorable physical, chemical, radiation factors. However, with adequate functioning of the immune system, a powerful immunobiological surveillance system operates, the main components of which are natural killer cells and tissue macrophages. They have the ability to quickly eliminate tumor, mutant, destroyed cells of the body. The tumor, as a rule, occurs against the background of violations of immunobiological surveillance. On the other side, oncological diseases(especially tumors of lymphoid tissue) themselves have a powerful immunosuppressive effect, aggravating the existing immunodeficiency.
Tumors of lymphoid tissue:
In case of oncological diseases, a violation of all parts of the immune system can be observed: a decrease in the number of T-lymphocytes and their subpopulations, a decrease in the functional activity of T-lymphocytes, a decrease or increase in the level of immunoglobulins, a decrease in nonspecific protection factors.
Secondary IDS in tumors manifest themselves in the form of bacterial, mycotic, and viral infections with predominant damage to the skin, mucous membranes, respiratory organs, and gastrointestinal tract. Very often, an immunocompromised host develops recurrent pneumonia, mucocutaneous candidiasis, gastrointestinal infections, and sepsis. The development of opportunistic infections is typical.

Emotional stress, depression, stress.
They have a depressing effect on most indicators of cellular and humoral immunity. Clinically, this is manifested by a decrease in resistance to infections and the development of tumors.

Post-traumatic and postoperative periods.
Often complicated by the development of a secondary immunodeficiency state. Predominantly nonspecific protective factors are disrupted (barrier function of the skin, system of phagocytic cells). The result of emerging immunosuppression is the development of postoperative suppuration and postoperative sepsis. The causative agents of purulent infection, as a rule, are representatives of opportunistic microflora.
Splenectomy is accompanied by the development of a secondary immunodeficiency state. After splenectomy, there is a violation of the filtering function of spleen macrophages, a decrease in serum IgM (a significant part of serum IgM is synthesized in the spleen), a violation of the mechanisms of activation of the complement system, and the activity of natural killer cells. Removal of the spleen in childhood often contributes to the development of septic infections.

Burns.
Dysfunction of the immune system in burn disease is caused by the following factors:
-damage to border tissues (impairment of the barrier functions of the skin and mucous membranes)
-powerful stressor
-increased antigenic load due to denatured and dehydrated tissue proteins and enzymatic tissue autolysis.
-intensive loss of immunoglobulins in plasma.

At stage 1, due to the loss of immunoglobulins, B-cell immunodeficiency develops with increased sensitivity to bacterial infections. Secondary T-cell deficiency develops with a large area of ​​burn damage (more than 30% of the skin surface). Against the background of burns, a decrease in the function of neutrophil granulocytes and a decrease in the opsonizing activity of serum due to the loss of immunoglobulins and complement components may be observed. The consequence of this is the addition of infections.

Ionizing radiation.
The severity of secondary post-radiation immunodeficiency is associated with the high sensitivity of lymphocytes and their bone marrow precursors to the damaging effects of ionizing radiation. Under the influence of irradiation, a violation of all parts of the immune system can be observed: nonspecific protective factors, the system of T- and B-lymphocytes, and macrophages.

Polluting effect of the environment chemicals .
Exposure to harmful chemicals causes damage to the immune system and forms IDS, which reduces the body's resistance to infections, disrupts the course of inflammatory and reparative processes, disrupts metabolism, and increases the risk of malignant neoplasms, allergic and autoimmune diseases. Different parts of the immune system have different sensitivity to environmental influences. First of all, nonspecific forms of defense are damaged; later, against the background of developing intoxication, insufficiency of the T-system of immunity may occur.

Other reasons.
Diabetes mellitus is accompanied by suppression of the T-cell component of immunity, disturbances in the complement system, phagocytic cells, which is accompanied by the development of frequent suppurations, and the unfavorable course of chronic infections.

Uremia leads to the development of T-cell immunosuppression (reduction in the number of T-lymphocytes, impairment of their functions). The digestive activity of phagocytic cells is also impaired due to a decrease in the production of reactive oxygen species.

Liver diseases (acute and chronic hepatitis, cirrhosis) are accompanied by impaired synthesis of complement components, a decrease in the number of T-lymphocytes, their functional activity, and a decrease in the digestive activity of phagocytic cells.

Immunomodulatory drugs.
Drugs that act predominantly on nonspecific protective factors.
1. Lysozyme. Used for replacement purposes to increase the antibacterial activity of blood serum and secretions. Indications for use: chronic focal infections, especially infections of the oral mucosa and ENT organs (stomatitis, rhinitis, sinusitis, otitis); wounds, burns. Prescribed intramuscularly at 2-3 mg/kg 2-3 times. per day for 2-6 weeks, more often - inhalation or intranasal 0.2% solution - 15 procedures.
For the treatment of infectious and inflammatory diseases of the ENT organs, drugs containing lysozyme in combination with antiseptics are used: hexalize, lysobact, laripront.

2. Interferon preparations.
Interferon-alpha preparations:
egiferon (Hungary)
Reaferon (Russia)
intron-A (USA)
realdiron (Lithuania)
roferon-A
welferon

Interferon-beta preparations
rebif (Switzerland)
feron (Japan)
fron-Switzerland
betaferon (England)

Interferon-gamma preparations
Mega-D-gamma interferon (England)
gamma interferon recombinant (“Biomed”, “Interkor”-Russia)

Mechanism of action:
-direct antiviral
-increase the number of HLA molecules by various types cells, enhance the function of antigen-presenting macrophages
-stimulate the activity of natural killer cells
-increase the mobility and digestive activity of macrophages
-increases antibody synthesis

General indications for intramuscular and subcutaneous administration:
1. Diseases of viral etiology
-severe viral infections (influenza, adenovirus, enterovirus, herpetic, mumps)
-acute, recurrent and chronic keratoconjunctivitis caused by adenovirus, herpes virus
-viral-bacterial and mycoplasma meningoencephalitis
-genital herpes
-shingles
- pappilomatosis of the larynx
-squamous and genital warts
-acute viral hepatitis B (severe forms)
-chronic hepatitis B
-chronic hepatitis C
-HIV
2. some malignant neoplasms
-melanoma, non-Hodgkin's lymphoma, osteosarcoma, breast cancer, squamous cell carcinoma skin, basal cell skin cancer, kidney and bladder carcinoma, etc.).

Interferon preparations for local use:
1. Human leukocyte interferon (nasal drops, eye drops, suppositories). For the prevention of ARVI: 1 ampoule of interferon for intranasal use is diluted in 2 ml of boiled water. Instill 0.25 ml (5 drops) into each nasal passage 4-5 times a day. Use while the risk of infection remains. For the treatment of ARVI: instill 5 drops. in each nasal passage for 2 hours 2-3 days. Can be used as an aerosol: the contents of the ampoule are dissolved in 10 ml of water, 1-2 ampoules are used per session, the frequency of inhalations is 2 times. in a day.
KIP-feron ointment. Contains A2 interferon and complex immunoglobulin preparation.
For influenza, ARVI, lubricate the nasal cavity 2-3 times a day. 5-7 days, for other diseases 1-2 times a day. 7-14 days.
Preventatively: 2 times a day and before visiting child care institutions, public places.
Indications for use:
-flu, ARVI, prevention and treatment
- herpes simplex of the skin and mucous membranes, herpes zoster
- genital warts and papillomas
-chlamydia
-urogenital mycoplasmosis
- vaginal dysbiosis, vulvovaginitis, cervicitis
-eczema of bacterial-viral etiology
- long-term non-healing wounds, fistulas, trophic skin ulcers
- anal fissures
-furunculosis
-pyoderma

2. Viferon (suppositories, ointment). A complex preparation including recombinant interferon, vitamin E, ascorbic acid.
In the treatment of newborns and children under 7 years old, Viferon-1 (150,000 IU) is used, for children over 7 years of age and adults - Viferon-2 (500,000 IU) and Viferon-3 (1,000,000 IU). The drug was obtained by genetic engineering and is not a blood product. Initial course: 1 candle - 2 rubles/day for 5-10 days.
Maintenance therapy: 1 suppository - 2 r/day - 3 times a week from 1 to 12 months.

Indications for use:
- ARVI, pneumonia, meningitis, sepsis, chlamydia, herpes, CMV, ureaplasmosis, mycoplasmosis in newborns, including premature ones
- ARVI, pyelonephritis, bronchopneumonia, nonspecific diseases lungs, urogenital infections in pregnant women
-acute and chronic viral hepatitis B, C in children and adults
-prevention and treatment of postoperative purulent complications
-mumps
-herpes, chlamydia, CMV, ureaplasmosis in children and adults
-virus-associated glomerulonephritis in children
- complex therapy of prostatitis, endometriosis and chronic vulvovaginitis
- dysbacteriosis in children and adults

Interleukin preparations
Roncoleukin. Recombinant form of human interleukin-2 Method of administration: intravenous drip from 1 to 2 million IU. In 400 ml of isotonic NaCl solution, 2-3 injections with a break of 3 days.
Mechanism of action:
-stimulates proliferation, differentiation, activation of T-killers, NK cells, B-lymphocytes.
Strengthens antibacterial, antiviral, antifungal, antitumor immunity.

Indications for use:
- post-traumatic, surgical,
-obstetric and gynecological burn, wound sepsis
-acute destructive peritonitis, osteomyelitis, endometritis, sinusitis, abscess, phlegmon
-chronic hepatitis C
-superficial and systemic mycoses
-herpes
-chlamydia
-melanoma, bladder cancer, colorectal cancer

Betaleikin. Recombinant human IL-1 preparation.
Directions for use: IV drip of 5-10 ng/kg in 500 ml of isotonic NaCl solution - 5 days
Mechanism of action:
-induces the synthesis of colony-stimulating factors
-stimulation of proliferation and differentiation of T- and B-lymphocytes
-activation of neutrophils
-increased resorption of damaged tissues, activation of regeneration

Indications for use:
-stimulation of leukopoiesis during toxic leukopenia (as leukomax) during chemoradiotherapy of tumors, to protect leukopoiesis during chemotherapy against the background of leukopenia

Interferon inducers

1.Dibazol (Russia)
Directions for use: adults: 0.02 g - 3 r. per day - 12 days children - 1 mg ha year of life once 3-4 weeks
Mechanism of action:
-increases interferon synthesis
-stimulates phagocytosis
Indications for use:
prevention of acute respiratory viral infections

Neovir
Directions for use: 250 mg (4-6 mg/kg body weight) 5-6 IM or IV injections with an interval of 48 hours.

Cycloferon
Directions for use: 250-500 mg IM or IV 5-7 injections with an interval of 48 hours. In children: 6-10 mg/kg IM – 2 days, then 5 injections every other day. Orally: 4-6 years, 150 mg (1 t.), 7-11 years, 300 mg (2 t.), over 12 years - 450 mg (3 t.) 1 r/day for 30 minutes. before meals, without chewing. Prophylactically: 1,2,4,6,8, then 5 doses with an interval of 72 hours.

Amiksin
Method of administration: 0.125-0.250 g after meals per day - 2 days, then 0.125 g at intervals of 48 hours. In children from 7 to 14 years old, 0.06 g. For influenza and ARVI, the course of treatment is 2 weeks, hepatitis B -3 weeks, neuroinfections - 3-4 weeks, herpes, CMV, chlamydia - 4 weeks. For the prevention of ARVI and influenza - 0.125 g - 1 r. per week - 4 weeks.

Mechanism of action of interferon inducers:
-induce the synthesis of interferons
-activate bone marrow stem cells, T-lymphocytes, macrophages, NK cells
-stimulates the synthesis of IgA, IgM, IgG.

Indications for use:
1. Prevention and treatment of severe forms of influenza, acute respiratory infections in persons with signs of immune deficiency
2. Infections caused by H. simplex, H. soster, H. Varicella zoster
3. Severe forms of genital herpes
4. Chronic hepatitis B
5. Chronic hepatitis C
6. CMV
7. Encephalitis of herpetic etiology
8. Severe forms of acute viral hepatitis B and C
9. Urethritis, prostatitis, cervicitis, salpingitis of chlamydial etiology
10. Radiation immunodeficiencies
11. Acquired immunodeficiencies with inhibition of the interferon system
12. Candidiasis of the skin and mucous membranes
13. Neuroviral infections

Metabolic drugs:

Methyluracil (Russia).
Directions for use: adults - 0.5 g (1t) - 3 rubles. per day after meals for 4 weeks, children 3-8 liters - 0.25 g - 3 rubles. per day, children over 8 years old - 0.3 g - 3 rubles. in a day

Pentoxyl (Russia)
Directions for use: adults 0.2-0.4 g - 3 r. day after eating
up to 1 g - 0.015 g - 3 r. day
up to 8 years - 0.05 g - 3 r. day
up to 12 years - 0.075 g - 3 r. day
over 12 years old - 0.1-0.2 g per day

Mechanism of action:

- enhance the absorption and digestion of microorganisms by phagocytic cells
-stimulate the synthesis of lysozyme, fibronectin, interferons

Indications for use:
1.Chronic bacterial infections occurring with neutropenia, suppression of leukocytosis
2.Intensive antibacterial, radio, chemotherapy
3. Agranulocytic tonsillitis
4. Mild forms of leukopenia
5.
6. Long-term non-healing burns and wounds

Activators of nonspecific protective factors are adaptogens (small immunocorrectors).

Echinacea preparations.
Immunal (echinacea preparation, contains lipopolysaccharides of plant origin). Directions for use: Adults 30 drops. 3 times a day from 1 to 8 weeks, children 1-6 years old, 5-10 drops. 3 times a day, 6-12 years 10-15 drops. 3 times a day from 1 to 8 weeks.
Echinabene. Adults and adolescents for the prevention of infections, 20 drops. 3 times a day. For acute diseases, first 30 drops. then 15 drops. every hour. Children for the prevention of infections, 10 drops. 3 times a day. For acute diseases, first 20 drops, then half 10 drops. every hour after eating. The course of treatment is 8 weeks.
Echinacea decoction. Adults: 1/3 cup 3 times a day (decoction at the rate of 1 tablespoon per 1 glass of water), children: 1 table. spoon 3 times a day. Course of treatment: 2-3 months.

Mechanism of action:
-stimulate bone marrow hematopoiesis, increase the number of neutrophils and macrophages
-increase chemotaxis, absorption, digestive activity of neutrophils
-increase the synthesis of cytokines

Indications for use:
1.Prevention of colds and flu
2.Chronic inflammatory diseases nasopharynx and oral cavity
3. Chronic nonspecific inflammatory diseases of the lungs and urinary tract
4.Secondary deficiencies of phagocytic cells arising under the influence of ionizing radiation, UV rays, chemotherapy, long-term antibacterial therapy, toxic air compounds, pesticides.

Eleutherococcus (adults - 2 ml of alcohol solution 30 minutes before meals - 3 rubles per day, children - 1 drop per 1 year of life - 1-3 rubles per day - 3-4 weeks). Alcohol extract or water extract of ginseng ((adults - 2 ml of alcohol solution 30 minutes before meals - 2 rubles per day, children - 1 drop per 1 year of life - 1-2 rubles per day - 3- 4 weeks).
Tonsilgon (adults, 2 tablets (25 drops), infants and children under 5 years old - 1 drop per kg of weight, children 5-10 years old - 10-15 drops, 10-16 years old - 20 drops or 1 pills Take 5-6 rubles a day for 4-6 weeks.
Radiola rosea (golden root). Taken in the form of aqueous and alcohol infusions. Directions for use: start with 5 drops. with the addition of 1 drop. for each subsequent dose (up to 30 drops). After reaching the maximum dose, the number of drops is reduced by 1 drop. at each dose and bring it to the initial dose - 5 drops. Take 3 rubles. a day before meals. The course is repeated 2 times a year at the beginning of winter and spring. Aralia Manchurian. Daily dose 10-20 drops, take 2-3 r. per day - 2-4 weeks.
Garlic extract, first 6 weeks. 5 g per day, in the next 6 weeks 10 g.
Tincture of Katian lemongrass. 20-30 drops. before meals 3 r. per day for 3-6 months Apilak. 1 tablet inside. 3-5 times a day under the tongue until complete resorption for 20-30 days, repeat the course after 10 days.
Aloe, PHYBS. 1 ml IM for up to 20 days.
Esberitox. Adults: 1 tablet. 3 times a day after meals. Course 1-2 months Children 1/4-2/3 table. 3 times a day after meals. Course 1-3 weeks. Apilak. Orally, 1 tablet 3-5 times a day under the tongue until completely dissolved, 20-30 days.

Preparations of microbial origin.
Sodium nucleinate (Russia). Yeast RNA.
Mode of application. Adults: 0.1-0.5 g of dry powder 3-4 times a day after meals for 10-20 days or 5-10 ml of 2% novocaine solution IM or SC 1 time a day. The course of treatment is 10 days. children under 1 year - 0.01 g. 2-5 years 0.01-0.05 g. 5-7 years 0.05-0.1 g. after 7 years - adult dose. Sodium nucleinate is taken 3-4 times a day after meals with plenty of liquid. The course of treatment is 10 days.

Mechanism of action:
-increases the number of leukocytes
-strengthens the main phases of phagocytosis: chemotaxis, absorption, digestion
-increases antibody synthesis
-increases the synthesis of lysozyme, interferons, complement components.

Indications for use:
1. Chronic bacterial and, to a lesser extent, viral infections, accompanied by leukopenia and decreased phagocytosis rates.
2. Chronic bronchitis.
3.Chronic parotitis.
4. Intensive antibacterial, radio, chemotherapy.
5.Mild forms of leukopenia.
6.Acute and chronic radiation sickness

Likopid (Russia).
Mechanism of action:
-increase the number of leukocytes
-increase the absorption and digestive activity of neutrophils and macrophages
- enhance the processing and presentation of antigens
- enhance antibody formation
-act on the central mechanisms of thermoregulation, create a temperature optimum for the functioning of immunocompetent cells.

Indications for use:
1. Chronic infections of the upper and lower respiratory tract 1 mg (1 tablet) 1 time per day - 10 days
2. Pustular skin lesions 1 mg 1 time per day - 10 days
3. Herpesvirus infections 1 mg 3 times a day - 10 days
4. Chronic hepatitis B and C 1 mg 3 times a day - 20 days
5. Protracted infections in newborns (pneumonia, bronchitis, enterocolitis, sepsis) 0.5 mg (1/2 tablet) 2 times a day - 10 days.

Polyoxidonium (Russia).
Mechanism of action:
-increases the functional activity of tissue macrophages, blood monocytes
-enhances the processing and presentation of antigens
-increases antibody synthesis
-has detoxifying properties

Indications for use:
1. Local and generalized purulent-septic diseases

2. Chronic and recurrent purulent-inflammatory diseases of any etiology that cannot be treated traditional therapy, including recurrent herpes, urogenital infections.

3. Chemotherapy and radiation therapy for tumors, 6 mg 2 times a week. The course is 2-3 months.

4. Activation of regenerative processes (fractures, burns, necrosis).

5. Prevention of postoperative complications in surgical patients.

6. Correction of secondary immunodeficiencies resulting from aging or exposure to adverse factors.

Stimulators of T-cell immunity.
1. Thymus hormones.
1. Taktivin (Russia). Use 100 mcg IM N10, in children 1-2 mcg/kg for 4-5 days
2. Timalin (Russia) - 1 ml of 0.01% solution IM N10, in children 0.1-0.2 mg/kg for 5 days
3. Timoptin (Russia) 100 mcg IM with an interval of 4 days N4-5
4. Timaktide sublingually 250 mcg, with an interval of 3-5 days N4, then 2 times with an interval of 2 days, then 3 times with an interval of a week.
5. Thymogen 100 mcg IM N10 or intranasally 100 mcg in 3-4 doses for 10 days. In children - up to 1 year - 20 mcg, 1-3 years - 20 mcg, 3-5 years - 30 mcg. Intranasally (1 drop per 1 year of life) – 1 time per day – 10 days.
6. Mega-Reakim (Germany-Ireland) - 100 mcg subcutaneously 2 times a week N8-10 or 0.25 g per day, dissolve for 15-30 minutes. at intervals of 4 days N-7.
7. TP-1-Serono (thymostimulin, Switzerland) - 1 mg/kg IM daily N7, then 1 mg/kg 2 times a week. The duration is individual.
8. Tim-vocal
9. Thymomodulin (Europe, Germany).

Mechanism of action:
They have a predominant effect on the T-immune system:
-increase proliferation and differentiation of T-lymphocytes
-increase the number of T-lymphocytes
-increase the functional activity of T-lymphocytes
-increase the activity of T-killers
- normalize T-B cell interactions.

Indications for use:
hemorrhagic chickenpox
2.chronic and sluggish infections, accompanied by disorders of the T-cell immunity: pulmonary tuberculosis, leprosy, pneumonia, Chronical bronchitis, indolent infections genitourinary system, purulent-inflammatory diseases of the maxillofacial area.
3. for prophylactic purposes after surgical interventions, during radiation and chemotherapy of tumors, during the period of convalescence after severe infections.

Thymogen in intranasal form is used for the treatment and prevention of acute respiratory viral infections and influenza infections.

Immunofan. It is an immunoregulatory peptide in combination with an antioxidant.
Directions for use: subcutaneously or intramuscularly, 1-2 mcg/kg body weight once a day.

Mechanism of action:
-normalizes the ratio of T-lymphocyte subpopulations
- restores humoral immunity, enhances the production of specific antibodies - increases the functional activity of phagocytic cells
-increases the excretion of CECs, reduces the intensity of allergic inflammation.

Indications for use:
1. ARVI (prevention and treatment)
2. Chronic viral and bacterial infections (chronic hepatitis B, yersiniosis, brucellosis, tuberculosis)
3.Radiation sickness
4. Chemoradiation therapy
5.Drug and substance abuse.
6. Atopic and infectious-allergic bronchial asthma
7.Rheumatoid arthritis
The drug does not combine well with other immunocorrectors.

Synthetic stimulators of T-cell immunity.
Levamisole (Dekaris, Hungary)
Directions for use: adults - 150 mg 3 times a week for a month, children - 2.5 mg/kg 3 times a week for 2-3 weeks.
Mechanism of action:
-increases the functional activity of T-helpers
-increases antibody formation
-stimulates phagocytosis
-increases complement activity

Indications for use:

1. Acute and chronic viral infections: chronic persistent hepatitis, chronic active hepatitis, viral bronchopulmonary infections, viral encephalitis, hemorrhagic chickenpox, recurrent herpes simplex, viral superinfections in malignant neoplasms.
2. Rheumatoid arthritis, Crohn's disease, SLE, tumors of the bronchi, colon, and mammary glands.

Diutsiphon (Russia)
Directions for use: Adults - 0.3 g, children 1-2 years old - 0.1 g, 3-4 years old - 0.15 g, 5-7 years old 0.2 g. Take orally 1 time per day after day N10.
Mechanism of action:
-increases the number of T-lymphocytes and their functional activity
-increases the synthesis of cytokines

Indications for use:
1.Chronic infections accompanied by insufficiency of T-cell immunity.
2. Rheumatoid arthritis, systemic scleroderma.

Isoprinosine (Israel)

Directions for use: 50 mg/kg body weight in 3-4 doses for 5-7 days. In the acute period of severe infections, 100 mcg/kg in 3-4 doses - 5 days.

Mechanism of action: antiviral and immunomodulatory
-increases the production of interleukins
-increases the chemotactic and phagocytic activity of monocytes and macrophages
-increases the proliferation of T-lymphocytes, T-helpers, natural killer cells
-increases antibody synthesis

Indications for use:
1. Influenza and ARVI, herpes types 1 and 2, herpes zoster, viral meningoencephalitis, human papillomavirus infection, vulgar warts, molluscum contagiosum.
2.Chronic infections accompanied by insufficiency of T-cell immunity.

Stimulators of humoral immunity:
Myelopid (Russia). Bone marrow preparation.
Directions for use: 0.04-0.06 mg/kg IM, SC, IV every other day N3-5.
Mechanism of action:
-restores the quantitative and functional indicators of the T- and B-immune systems
-stimulates the humoral immune system, enhances antibody formation
-stimulates the functional activity of macrophages and neutrophils

Indications for use:
1. Purulent and septic processes accompanied by a decrease in the level of immunoglobulins
2. Chronic nonspecific diseases of the lungs and urinary tract, occurring against the background of insufficiency of the humoral immunity.
3. Prevention of infectious complications in severe burns, injuries, and surgeries.
4. Complex therapy leukemia

Immunoglobulin preparations (replacement therapy).

Venoglobulin (France)
Intraglobin (Germany)
Human immunoglobulin (Austria)
Sandoglobulin (Switzerland)
Octagam (Austria, Switzerland, Israel)
Normal human immunoglobulin (Nizhny Novgorod, Russia)
Endoglobin (Austria)

These drugs contain 90-99% IgG
Pentaglobin (Germany) enriched with IgM
Immunoglobulin preparations contain a wide range of specific antimicrobial antibodies, including antiviral antibodies - against measles, rubella, chickenpox, influenza, polio, mumps, hepatitis B, C, etc.), antibacterial antibodies - antistaphylococcal, antistreptococcal, antimeningococcal, etc. d.) KIP (Russia). The complex immunoglobulin preparation is available in tablets for enteral use and in suppositories for rectal and intravaginal use. The drug contains IgA, IgM, IgG. Contains high titers of antibodies to Shigella, Escherichia, Salmonella.

Mechanism of action of immunoglobulin preparations:
Replacement therapy, administered immunoglobulins perform the function of normal antibodies in the body.

Indications for use:
1.Primary immunodeficiencies with damage to the humoral immune system (Bruton's disease, CVID)
2. Severe systemic infectious diseases: septicemia of newborns, septic shock, infectious-toxic shock in children and adults and other septic and septic-pyemic conditions.
3. Severe CNS infections.
4. Severe viral infections (measles, influenza, hepatitis)
5. Prevention of infections in premature infants with low birth weight (less than 1500 g or less)
6. Deficiency of immunoglobulins in lymphocytic leukemia, AIDS, nephrotic syndrome, burn disease, severe diarrhea.

CIP is used in children older than 1 month and adults in the treatment of acute intestinal infections, dysbiosis (especially during treatment with antibiotics, chemotherapy and radiotherapy). For the prevention of intestinal infections in immunodeficiencies, the elderly, and weakened children.
Apply orally 30 minutes before meals, 5 doses for 5 days.

There are preparations of immunoglobulins with specific actions: Specific immunoglobulins are a source of ready-made antibodies to the infectious agent that caused the infectious process.

Cytotect (Germany)
The drug is enriched with antibodies to CMV and is used for the treatment of acute CMV, for the prevention and treatment of CMV in patients with immunosuppression.

Antistaphylococcal immunoglobulin (Russia)
Measles immunoglobulin
antidiphtheria
antiherpetic

Mucosal vaccines. (Bacterial preparations).
Mucosal vaccines are drugs that are administered not parenterally, but through the mouth, aerosol or instillation. They have the most active effect on local immunity. They combine the properties of multicomponent vaccines and nonspecific immunocorrectors.

Mechanism of action:
-contain specific antigens pathogens, most often causing infections mucous membranes and form specific immunity to these infections.
-effectively stimulate nonspecific protective factors

Polyvaccines for the treatment of the respiratory tract:
VP-4 (Russia). The vaccine contains antigens of staphylococcus, pneumococcus, Proteus, Escherichia coli

Ribomunil (France).
The drug contains ribosomal antigens of Klebsiella, pneumococcus, pyogenic streptococcus, and Haemophilus influenzae.
Directions for use: 3 tablets each. on an empty stomach - 4 days in a row every week - 3 weeks. Then 3 tables. on an empty stomach - 4 days in a row at the beginning of each month - 5 months.

Bronchomunal (Yugoslavia)
Bronchomunal-P (children's form).
Contains antigens of pneumococcus, Haemophilus influenzae, Neisseria, Staphylococcus aureus, pyogenic streptococcus.
Directions for use: take 1 capsule orally for the first 10 days of each month - 3 months.

IRS19 (IRS19).
Lysate of inactivated bacteria for intranasal use. Contains 19 antigens.
Directions for use: In order to prevent respiratory infections of the upper respiratory tract - 1 dose of the drug intranasally in each nasal passage - 2 times a day - 14 days. In the acute phase of the disease, one dose of the drug is injected into each nasal passage 2 to 5 times a day until the symptoms of infection disappear.

Mechanism of action of mucosal vaccines:
-increase the functional activity of phagocytic cells of local and systemic immunity,
-increase the amount of lysozyme, secretory IgA in bronchial secretions, nasal mucus, and gastrointestinal tract secretions.
-increase the number of CD3, CD4, CD8 cells.

Indications for use:
Prevention and treatment of chronic and recurrent infectious and inflammatory diseases of the ENT organs, upper and lower respiratory tract (rhinitis, sinusitis, pharyngitis, laryngitis, tracheitis, bronchitis, pneumonia).

Polyvaccines for the treatment of the genitourinary tract
Solkotrichovak
Mixture of lyophilized lactobacilli.
Directions for use: 0.5 ml intramuscularly three times with an interval of 2 weeks. Revaccination is carried out once every year.
Indications for use: trichomoniasis, nonspecific bacterial vaginitis.

Solkourovak
The composition includes inactivated Escherichia coli, Proteus, Klebsiella, Streptococcus. Directions for use: 0.5 ml intramuscularly three times with an interval of 2 weeks. Children 5-14 years old: 0.25 ml. Revaccination is carried out once every year.
Indications for use: treatment of chronic and recurrent urogenital infections caused by microorganisms included in Solcourovac.

PRINCIPLES FOR DETECTING CHILDREN WITH IMMUNOLOGICAL DEFENSE.

They are based on the analysis of data from the medical history of the current disease, life history, results of clinical, laboratory and immunological examinations.

The purpose of diagnosing immunodeficiency states: prognosis and prevention in children at risk of developing immunopathological conditions, timely prescription of immunomodulatory drugs, monitoring their effectiveness, conducting anti-relapse therapy.

The first stage of the immunological examination is to identify clinical signs of immunodeficiency in the patient. This requires: a general assessment of the patient’s clinical condition, a thorough collection of anamnesis of the current illness and life history, an objective examination, including a thorough examination of the lymph nodes, tonsils, and spleen.

Recording an examination of a patient to identify his immune deficiency:
1. Complaints at the time of inspection.
2. History of the present disease.
When analyzing an. morbi, it is necessary to pay attention to the etiology of the current infectious process. Measles, infectious mononucleosis, hepatitis, herpes, CMV, influenza, chicken pox are accompanied by transient immunodeficiency, since the causative agents of these infections infect cells of the immune system and reduce their functional activity. Severe immunodeficiency is accompanied by intrauterine infections, chronic and persistent infections (chronic hepatitis, herpes, chlamydia), recurrent fungal infections.
Immunodeficiency may be indicated by:
-severe and complicated forms of infectious disease,
-the occurrence of superinfections caused by opportunistic, nosocomial flora
-protracted forms of the infectious process, resistant to antibacterial therapy.
- chronic and recurrent forms of infectious diseases.

3. Life history.
When collecting a life history, the following is taken into account:
A.
- unfavorable course of pregnancy (early and late gestosis, anemia, bacterial and viral infections in the mother, occupational hazards, threat of miscarriage, chronic diseases in the mother)
-birth: urgent, premature, late, naturally, by caesarean section.
- complications during childbirth
-weight, body length at birth
- was there intrauterine damage to the central nervous system, impaired hemolytic fluid dynamics, asphyxia, birth trauma, prematurity, hemolytic disease
-whether pathology was noted in the neonatal period:
-breastfeeding until how many months?
- presence of constitutional anomalies: exudative, lymphatic-hypoplastic, neuro-arthritic
B.
Vaccination history
WITH.
the presence in the anamnesis is specified:
1) infectious diseases
-chronic and recurrent diseases of the ENT organs, upper and lower respiratory tract (purulent sinusitis, otitis, sinusitis, bronchitis, pneumonia)
-recurrent bacterial infections of the skin and subcutaneous tissue (pyoderma, furunculosis, abscesses, cellulitis, septic granulomas, bacterial and fungal skin lesions)
- repeated lymphadenitis, lymphadenopathy
-chronic and recurrent urogenital infections (pyelonephritis, cystitis)
-generalized bacterial infections (meningitis, meningoencephalitis, sepsis)
-tuberculosis
-gastroenteropathy with persistent diarrhea, dysbacteriosis
-severe and/or atypical measles, rubella, mumps, chicken pox
-chronic viral hepatitis B, C, D
-recurrent herpes of the skin and mucous membranes
-intrauterine infections (CMV, herpes, rubella, chlamydia)
-slow infections of any localization caused by opportunistic pathogens
- ARVI more than 6-7 times a year

2) allergic diseases:
-bronchial asthma
-atopic dermatitis
-hay fever
-recurrent angioedema
- chronic and recurrent urticaria
-drug allergy

3) autoimmune diseases:
-juvenile rheumatoid arthritis
-dermatomyositis
-systemic vasculitis
-glomerulonephritis
-autoimmune hemolytic anemia, thrombocytopenia, neutropenia

4) immunoproliferative diseases:
-acute and chronic lymphocytic leukemia
-myeloid leukemia
-tumors of any localization

5) as well as diseases such as
-insulin-dependent diabetes mellitus
-uremia

Taken into account:
-age of the patient (1st year of life and puberty correspond to physiological immunodeficiency)
- low birth weight and prematurity
- long-term effect on the patient of chemicals, carcinogens, irradiation, herbicides.
- long-term use of corticosteroid, cytostatic, antibacterial drugs by patients
- history of splenectomy, appendectomy and tonsillectomy
- repeated blood transfusions
-recent exposure to injuries, burns, major operations

4.Objective examination

Based on the medical history, the presence of one or more immunological deficiency syndromes in the patient is determined: infectious, allergic, autoimmune, immunoproliferative.

Scheme for justifying a preliminary conclusion in a patient with immunological deficiency: Taking into account the history of the present disease: severe form, resistance to antibacterial therapy, prolonged course (long-lasting symptoms of intoxication, hepatomegaly, pathological stool, cough with sputum, nasal discharge, etc., lack of positive dynamics of physical and paraclinical data), generalization of infection, formation of complications, addition of superinfections,

Life history data (presence of infectious and inflammatory diseases in the patient, rheumatoid arthritis, dermatomyositis, systemic vasculitis, glomerulonephritis, etc.), as well as the patient’s age corresponding to the period of physiological immunodeficiency, it can be assumed that the patient has a secondary (primary, transient) immunodeficiency state with a leading infectious, allergic, autoimmune, immunoproliferative syndrome.

Stage II of the immunological examination is laboratory test immune status (immunogram), necessary to confirm the diagnosis and establish the level of the immunological defect.

After performing an immunogram, a laboratory syndrome of immune deficiency is identified: insufficiency of the T-cell component of immunity, the system of phagocytic cells, the humoral component of immunity, insufficiency of nonspecific protective factors, and the NK cell system.

Rationale for the final conclusion: Taking into account the opinion expressed in the preliminary conclusion (the patient belongs to the risk group for immune deficiency with leading infectious-inflammatory, allergic, autoimmune syndrome), immunogram data (signs of insufficiency of nonspecific protective factors -, T-cell -, humoral - immunity, phagocytic cell system), a diagnosis can be made: Secondary immunodeficiency state (secondary immune deficiency) with a violation of nonspecific protective factors, phagocytosis system, T- cellular, humoral immunity.
Urology:

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Secondary (acquired) immunodeficiencies

Secondary (acquired) immunodeficiencies are more widespread compared to congenital immunodeficiencies. Acquired immunodeficiencies can result from exposure to environmental factors and endogenous substances. Factors responsible for the induction of secondary immunodeficiencies include pathogens of infectious and invasive diseases, pharmacological substances, and endogenous hormones. They can be the result of splenectomy, aging, poor diet, tumor development, and radiation exposure.

Infectious agents. Canine distemper virus, canine parvovirus, feline panleukopenia virus, feline leukemia virus, feline immunodeficiency virus and other viruses induce suppression of the cellular component of the immune response. Diseases such as demodicosis, ehrlichiosis and systemic fungal diseases are also accompanied by profound immunosuppression.

Pharmacological substances. Corticosteroids and various antineoplastic drugs are the most common pharmacological agents that induce immunosuppression. Drugs such as chloramphenicol, sulfamethoxypyridazine, clindamycin, dapsone, lincomycin, griseofulvin are also associated with immunosuppression.

Endogenous hormones. Hyperadrenocorticism, growth hormone deficiency, diabetes mellitus and hyperestrogenism are associated with acquired immunodeficiency diseases. Hyperadrenocorticism is manifested by suppression of immune functions due to an increase in glucocorticoids, while growth hormone deficiency causes an immunodeficiency state associated with inhibition of T-lymphocyte maturation due to suppression of thymic development. Patients with diabetes mellitus show a predisposition to cutaneous, systemic and genitourinary tract infections, which may be directly related to decreased serum insulin concentrations or glycemia. The immunosuppressive effect of hyperestrogenism is similar to that of leukopenia.

3.1. IMMUNOSUPRESSION INDUCED BY VIRUSES

That viruses can influence immune parameters was discovered by von Pirquet as early as 1908, when he showed that measles infection delayed the development of delayed-type hypersensitivity in patients who had a normal response to the introduction of antigens from mycobacteria. Thus, von Pirquet was the first to introduce an immunological aspect of the explanation for the manifestation of increased sensitivity to superinfections in patients with viral diseases. The next report (1919), which confirmed this hypothesis, was that the influenza virus also suppresses the body's response to tuberculin. Over the next 40 years, there were no publications on the effects of viruses on the immune system. Since the beginning of 1960, evidence has emerged that oncogenic viruses have an immunosuppressive effect. Old et al pioneered this issue, and then five years later Good et al presented the first systematic assessment of antibody suppression caused by murine leukemia virus. During the late 1960s and early 1970s there was a boom in this field, with a large number of reports emerging supporting the concept of immune suppression by oncogenic viruses. Moreover, it has been shown that both humoral and cellular immunity are inhibited. Studies of many non-oncogenic viruses have shown that they also exhibit immunosuppressive activity. Many researchers have considered immunosuppression caused by viruses as an important factor causing persistent infections leading to chronic diseases and tumor formation. However, in the mid-70s, the number of studies in this area of ​​virology declined sharply, and their revival dates back to the 80s. At the same time, the authors tried to elucidate the molecular mechanisms causing virus-induced immunosuppression. Thus, the “science” of studying the relationship between virus and immunity is not new. Research in this area has become more active in last years. This was facilitated by the discovery and study of the human immunodeficiency virus.

Viruses can interfere with the development of an immune response in several ways:

• directly lyse lymphoid cells (for example, measles virus and canine distemper virus);
• infect lymphocytes and disrupt their functions in various ways (for example, bovine leukemia virus);
• produce viral substances that can directly interfere with antigenic recognition or cellular cooperation (for example, feline leukemia virus);
• secondary to induce immunosuppression by the formation of a large number of immune complexes (for example, feline infectious peritonitis virus).

Canine distemper virus (CDV), feline leukemia virus (FeLV), and parvoviruses cause virus-induced immune dysfunction through different mechanisms.

Measles viral infection in humans can induce a temporary state of immunosuppression due to the destruction of T-lymphocytes in the T-dependent zones of lymphoid structures. This is due to the presence of specific measles virus receptors on the surface of T cells.

Canine distemper virus is closely related to measles virus, and although the presence of equivalent viral receptors on the surface of canine T cells has not been demonstrated, there is compelling clinical and experimental evidence showing that this virus also causes a state of temporary immunosuppression. As a result of infection of gnotobiotic dogs with it, thymic atrophy with generalized lymphoid depletion is observed, leading to lymphopenia. In this case, blast transformation of lymphocytes in vitro is disrupted, but the ability to reject an allogeneic skin graft does not change. The degree of lymphoid depletion, and therefore the occurrence of T-cell immunosuppression, correlates with disease outcome. Animals that do not respond to intradermal injection of PHA are more severely affected and quickly die from encephalitis, while animals that maintain a T-cell immune response often recover.

Distemper of dogs causes immunosuppression primarily due to the cytotoxic effect during early replication of the virus in lymphoreticular tissue. As a result, necrosis of lymphocytes occurs in the lymph nodes, spleen, thymus and lymphopenia. In addition, there is a decrease in T-cell response to mitogens in vitro and a decrease in the humoral immune response during infections associated with CDV. This is observed in the early stage of the disease, followed by secondary development of bacterial infections.

Other mechanisms underlie the immunosuppression caused by feline leukemia virus.

The disease caused by FeLV is probably the most studied in veterinary medicine. Infection of kittens leads to virus-induced destruction of lymphoid tissues, followed by their atrophy and increased sensitivity to infections. At the same time, most immune parameters are reduced, and the ability of animals to reject an allogeneic skin graft is impaired. Typically, infection leads to immunosuppression without obvious destruction of lymphoid tissues. This is due to the production of excessive amounts of the viral envelope protein p15E. The exact mechanism of action of this excess is unclear, but it has been suggested that it interferes with lymphocyte activation and antigen recognition. The literature describes immunosuppression caused by a defectively replicated mutant of feline leukemia virus that occurs during natural disease. Although FeLV is often referred to as AIDS in cats because of its similarity to HIV infection, a more appropriate animal model may be the described feline T-lymphotropic lentivirus.

FeLV infection is characterized by thymic atrophy, lymphopenia, low levels of complement in the blood, and high level immune complexes. At the same time, cats have an increased sensitivity to various infections, including infectious peritonitis, herpes viral rhinitis, viral panleukopenia, hemobartonellosis and toxoplasmosis. Further development These diseases are caused by a fundamental defect in T cells, which manifests itself in vitro as a marked reduction in T cell response to mitogens. The primary T-cell defect is accompanied by a secondary functional defect of B-cells. But the B cell defect may not be related to the T cell defect. B cells are unable to produce IgG antibodies in the absence of T helper cells, but can retain the ability to synthesize IgM antibodies through T cell-independent mechanisms. Therefore, B cell activity is only partially impaired during FeLV infection.

The manifestation of a T cell defect is due to the lack of the required stimulation for T cell activation. A related problem is disruption in the production of interleukin-2, a lymphokine necessary to preserve and support T-cell activation, proliferation, and T-helper cell production, which favorably influences antibody production by B cells. Two serum factors are likely involved in the immunosuppressive effect of FeLV infection. The viral envelope protein p15E directly causes immunosuppression of lymphocytes and abolishes the response of lymphocytes to various mitogenic stimuli in vitro. This action may be due to its ability to block the response of T-41 lymphocytes to interleukin-1 and interleukin-2 and abolish the synthesis of interleukin-2. When p15E is administered to cats concomitantly with the FeLV vaccine, there is no formation of protective antibodies to the feline oncornavirus membrane cell antigen. Thus, p15E plays a central role in FeLV-induced immunosuppression both in vivo and in vitro. In addition, affected cats have high levels of circulating immune complexes, which are themselves immunosuppressive.

FeLV can directly impair the migration of T cells from the bone marrow to peripheral lymphoid tissues, reducing the number of normal T cells in the thymus, spleen and lymph nodes. Apparently, several different mechanisms of B and T cell injury may contribute to the immunosuppression of FeLV-infected cats.

Parvovirus infection of many animal species leads to immunosuppression due to the mitolytic effect of the virus on the division of stem cells in the bone marrow. Therefore, lymphopenia and granulocytopenia are a consequence of the direct effects of infection caused by this virus. Canine parvovirus infection is also accompanied by immunosuppression, and encephalitis due to distemper vaccination has been described in dogs experimentally infected with parvovirus.

Feline panlepcopene virus, like parvovirus, has a less potent immunosuppressive effect, which is more limited by the temporary depletion of T cells. The possible immunosuppressive effect of live attenuated vaccines, particularly canine parvovirus vaccine, remains questionable, but simultaneous immunization with attenuated parvovirus and distemper virus is believed to be safe and effective.

Infection of pregnant mares conditional equine herpesvirus, can cause abortions in the last third of pregnancy. If the foal is carried to term, it is susceptible to severe infections, which are caused by virus-induced atrophy of all lymphoid structures.

Bovine viral diarrhea - another example of virus-induced immunosuppression, which is accompanied by damage to T- and B- cellular immunity. This contributes to the development of chronic wasting syndrome with persistent infection. This virus is also able to cross the placenta, causing immunological tolerance and decreased immune response in calves.

Bovine leukemia virus- exhibits tropism for B cells, in which it causes proliferation and sometimes neoplastic transformation. Its effect on immunological parameters depends on the type and stage of the disease. Lymphocytosis is usually observed with an increase in the number of B cells expressing surface immunoglobulins.

3.2. IMMUNOSUPRESSION CAUSED BY BACTERIA

Compared to viral infections, in which the immunosuppressive effect is usually associated with direct infection of lymphoid tissues, the mechanism of secondary immunosuppression in bacterial diseases is not well understood.

With Jonah's disease, a paradox is observed in which, despite a pronounced cellular immune response to the pathogen, the corresponding reaction to other antigens may be impaired or not appear at all. Thus, affected cattle do not develop a skin reaction to tuberculin. The same situation is observed in chronic mycobacterial diseases in humans, in which a state of anergy is noted. At the same time, lymphocytes do not undergo transformation in response to PHA in vitro; the number of suppressor cells increases in the presence of a soluble factor that prevents the manifestation of cellular reactions.

Towards the end of the last decade, it became obvious that the lack of stimulation of lymphocytes in vitro is associated with many chronic diseases of infectious and non-infectious origin. Lymphocytes are unable to respond to mitogens in the presence of homologous normal serum or fetal bovine serum. In other cases, lymphocytes exhibit a reaction that occurs when they are isolated from autologous serum. Suppression in this case is associated with the action of suppressive serum immunoregulatory factors. The involvement of these substances in the immune response in vivo remains unclear. It is only known that substances with such properties are found in many sera obtained from normal and diseased animals, but the nature of these substances has not been established. It is also unclear whether they are the cause of the disease, or are formed during the disease process, participating in the mechanism by which the microbial agent subsequently manifests its pathogenicity. Experiments are needed to show the increased pathogenicity of microorganisms under the influence of these factors, since it is possible that they do not play any role in these cases.

3.3. IMMUNODEFICIENCY ASSOCIATED WITH DEMODECOSIS IN DOGS

The special genetic sensitivity of dogs, which predetermines the development of demodicosis, is determined by their inability to develop delayed-type hypersensitivity upon intradermal injection of tick-borne antigen. The molecular basis of this defect remains unclear.

Many researchers are studying the role of immunosuppression as an etiological factor in demodicosis in dogs with varying results, which are far from convincing and each side has its opponents. The following observations support the hypothesis that demodicosis is a result of T cell immunodeficiency:

• lymphocytes obtained from animals with demodicosis exhibit a weak blast transformation reaction in vitro under the influence of PHA;
• intradermal test with PHA in Doberman pinschers severely affected by demodicosis is significantly reduced in comparison with healthy animals of the same age.

Other evidence argues against the proposed role of immunodeficiency in demodicosis:

• immunosuppression disappears when the mite population is destroyed;
• immunostimulation of animals with levamisole leads to reversal of immunosuppression;
• factors that suppress blastogenesis are detected in demodicosis only in the presence of secondary staphylococcal infection, and are not detected in the serum of dogs with the scaly form of the disease, in which there is no association with secondary bacterial infections. Therefore, the suppression of T cell function is not due to proliferation of Demodex mites, but is most likely the result of a secondary staphylococcal infection.

Most evidence suggests that the immunosuppression observed in demodicosis is a result of secondary pyoderma and does not have an etiological role in the proliferation of Demodex mites. If in fact the immune response is related to the etiology of demodicosis, one hypothesis is that there is a primary defect in antigen-specific T cells that gives rise to the initial proliferation of mites.

Despite the possibility that immunosuppression is not the cause of demodicosis, it must be remembered that animals with a generalized form of the disease still have a state of immunosuppression. As a result, their immunoprophylactic measures are not effective enough.

Generalized canine demodicosis leads to the development of immunosuppression. The functions of T cells, as shown by the results of studies of blast transformation of lymphocytes under the influence of mitogens in vitro, and the delayed-type hypersensitivity reaction to concavalin A are sharply reduced. Interestingly, suppression of the lymphocyte response to mitogens in vitro occurs only in the presence of serum from affected dogs. If lymphocytes from the patient are washed and incubated with normal dog serum, then the blast transformation process proceeds normally. These results suggest the presence of a mite population-induced suppression factor in the serum. This position is supported by the fact that lymphocytes from normal dogs have a reduced response to mitogens when incubated with serum from dogs with demodicosis. The suppression factor is located in the beta-globulin fraction of the patient's serum, and some researchers suggest that it actually represents an antigen-antibody complex consisting of tick antigen and host antibodies. Therefore, the immunosuppressive effect of circulating immune complexes is reflected in a decrease in T-cell function, which is characteristic of many diseases such as feline leukemia virus. If such a situation occurs, the T cell defect should be considered as a result of the disease, or it is associated with the formation of pyoderma. It is unlikely that there are any other reasons at play here. This position is confirmed by observations where the destruction of the mite population and the pyodermal effects caused by them, returns the ability to a normal T-cell response to mitogens. Humoral immunity, neutrophil function, and T-cell counts remain normal in dogs with demodicosis.

In conclusion, demodicosis is most likely the result of a congenital T cell defect that allows the Demodex canis mite to infect its host. The presence of large numbers of mites further reduces T-cell function through the production of serum suppressive factor, leading to generalized immunodeficiency.

3.4. IMPAIRMENT OF PASSIVE ANTIBODY TRANSMISSION

Impaired passive transmission of maternal antibodies is one of the most common examples of acquired immunodeficiency in veterinary medicine, which is the main cause of neonatal infection and early mortality primarily in foals, calves, kids, lambs and piglets. Failure to obtain colostrum causes omphalophlebitis, septic arthritis, septicemia, pneumonia and diarrhea in newborns. Increased sensitivity to infection results from the absence of maternal immunoglobulins, which are necessary for direct bactericidal action on pathogens and for their opsonization.

The importance of this point depends on the relative contribution of placental versus colostral transfer of antibodies in the protection of newborns, which is a reflection of placental formation. The placenta of mares, donkeys, cows, sheep and pigs prevents the transfer of immunoglobulins from mother to offspring, while the endothelial placenta in dogs and cats provides limited transplacental transfer. It is believed that intestinal absorption of immunoglobulins occurs only in the first 24 hours, and one author notes that in dogs no absorption occurs after this time. Absorption is most effective in the first 6 hours.

Maternal colostrum deficiency does not have a significant effect on puppies as long as hygienic conditions are maintained, however there are reports that suggest that colostrum deficiency in cats contributes to increased morbidity and mortality in kittens. Of course, the lack of passive transfer of antibodies through colostrum is important in cows, horses, sheep and pigs, and it is very difficult to raise newborn calves, foals, lambs and piglets even under ideal conditions in the complete absence of colostrum.

Foals are usually born essentially agammaglobulinemic with only a small amount of IgM detectable in their serum. On the other hand, lambs are capable of producing low levels of IgG1 and IgM in late pregnancy, but lack IgG2 and IgA at birth. In both cases, newborn protection depends on receiving colostrum. The absence of maternal antibodies in newborns prevents the body from fighting infectious agents that it encounters in life. early life.

Receipt of colostrum by newborns results in intestinal absorption of large amounts of intact maternal immunoglobulins during the first 6-8 hours of life. Trypsin inhibitors in colostrum prevent the destruction of globulins in the newborn's stomach. Absorption of these globulins occurs through receptors for the Fc fragment of immunoglobulin located on the surface of intestinal epithelial cells. These cell properties that mediate intestinal absorption of maternal antibodies decline rapidly after 12 hours; Between 24 and 48 hours after birth, the intestine is unable to absorb immunoglobulins, despite the high concentration of immunoglobulins in the intestinal contents. The cessation of absorption is associated with the replacement of specialized immunoabsorbent enterocytes by mature epithelium. Typically, absorbed maternal antibodies gradually disappear over 6-8 weeks of life as newborns begin to synthesize their own antibodies.

Disorders of passive transmission of maternal antibodies can occur in any species of domestic animal, but are best documented in horses. Reports indicate that maternal antibody transmission may be impaired in up to 24% of foals. Impaired transmission can be determined by maternal factors, as well as the condition of the newborns themselves and environmental factors. Some mothers may not be able to produce colostrum with sufficient concentrations of immunoglobulins, mainly due to a genetic deficiency. On the other hand, mothers with normal colostrum production lose immunoglobulins due to premature lactation. Premature lactation is a major cause of impaired passive transmission and is associated with placentitis, twin pregnancies and premature separation of the placenta in the horse. The concentration of colostral immunoglobulins is lower than Umg/ml, indicating abnormal production or premature lactation, causing a disturbance in passive transmission.

The foal should receive an adequate amount of colostrum during the first 12 hours of life. Weak or maladjusted foals may not receive the required amount. Slippery floors make it difficult to ingest colostrum. In these cases, it is necessary to feed it from a bottle. Some newborn foals are not designed to drink well from a bottle, so they may not receive sufficient quantity colostrum. If the foal has received an adequate amount of colostrum, the intestinal epithelium should absorb the immunoglobulins, with the rate of absorption varying between foals. Endogenous glucocorticoid production associated with stress may lead to decreased absorption of IgG by specialized immunoabsorbent enterocytes. Thus, failure of passive transfer may occur for the following reasons: the quantity and quality of maternal colostrum, the foal's ability to consume sufficient amounts of colostrum, and the foal's ability to absorb immunoglobulins.

In recent years, the literature has widely presented data on immunodeficiencies in calves, piglets and lambs associated with untimely and insufficient receipt of colostrum after birth. It has been shown that the process of absorption of immunoglobulins by the intestines of newborn animals is influenced by various environmental factors and economic activities. At the same time, the morbidity and mortality of young animals are directly dependent on the time of receiving the first colostrum.

The diagnosis of impaired passive transmission of antibodies is based on determining the concentration of IgG in the blood serum of newborn animals during the first 12 hours of life. For this, 3 methods are used: zinc sulfate turbidity test, radial immunodiffusion or latex agglutination. The turbidity test is quick simple method, in which zinc sulfate (in foals), sodium sulfate (in calves) or ammonium sulfate (in piglets) is added to the test serum. The resulting immunoglobulin precipitates can be qualitatively measured colorimetrically at 485 nm. Foals that have more than 8 mg/ml serum immunoglobulins have good maternal transmission. A value between 4 and 8 mg/ml indicates partial disruption of transmission, and a level below 4 mg/ml indicates significant disruption of colostral absorption. The meanings for each type are different. Calves with immunoglobulin levels greater than 16 mg/ml have good absorption, levels between 8 and 16 mg/ml show reduced absorption, and impaired maternal transmission is evident when levels are below 8 mg/ml. The zinc sulfate turbidity test is semiquantitative and tends to overestimate serum IgG levels. Therefore, actual serum IgG concentrations below 4 mg/mL may appear higher in the opacification test, and these immunologically deficient foals may not receive appropriate treatment. The reaction with zinc sulfate depends on factors such as temperature, shelf life and preparation of the zinc sulfate solution.

A more accurate method by which the level of IgG in the blood serum of animals is determined is simple radial immunodiffusion. This test is commercially available, but the incubation time (18–24 hours) required to establish a reaction limits its use for diagnosing passive transmission during the first critical 12 hours of life. Latex agglutination is a commercially available test in practice for diagnosing passive transmission and is more accurate than the turbidimetric test. Latex agglutination data are 90% consistent with RID data in determining an IgG level of less than 4 mg/ml. The latex test requires a mixture of 5 µl of test serum with an appropriately diluted kit, followed by visual assessment of agglutination. The main disadvantage of this test is that it does not differentiate between 4 mg/mL and 8 mg/mL concentrations in foals.

Once a violation of passive transmission is established, to correct the deficiency it is necessary to drink colostrum from a bottle or intravenous administration of immunoglobulins (depending on the age of the newborn). Administration of 4 L of plasma over 2-5 days is necessary to ensure reliable IgG levels. Plasma donors should be free of anti-erythrocyte lysines and agglutinins and kept under the same conditions as foals for at least several months. Commercially available equine plasma certified as erythrocyte alloantibody negative can also be used in the equine industry to treat passive transmission disorder.

3.5. PREGNANCY AND LACTATION

3.6. OTHER FACTORS CONTRIBUTING TO IMMUNOSUPRESSION

Candidiasis of the skin and mucous membranes. The causative agent of candidiasis is the opportunistic yeast-like fungi Candida albicans. Immunodeficiencies, usually involving defects in T cells, may predispose to diseases that cause ulcerative lesions skin and mucous surfaces. This condition is sometimes seen in dogs and should be distinguished from autoimmune skin diseases. It is not determined in which cases this disease is the result of primary or secondary immunodeficiencies, or both. Experiments show that the immunological state is altered by stimulation with levamisole.

Microelements and vitamins. Their role in the immune response is obvious, although the influence of many agents and their mechanism of action is not always clear. Zinc is the most important micronutrient and its association with the lethal trait A46 (congenital immunodeficiency) has been established. In addition, vitamin E and selenium have an important role in the formation of a normal immune response, and the immunostimulating effect of vitamin E is used in adjuvants. Dogs consuming food deficient in vitamin E and selenium have severe immune system damage. Restoration of a normal immune response occurs as a result of vitamin E supplementation, but not selenium.

Environmental contaminants. Environmental contaminants, including heavy metals such as lead, cadmium, mercury, various industrial chemicals and pesticides, have a negative impact on the immune response. Fungal metabolites that contaminate feed are also important; There is evidence of the immunosuppressive effect of aflatoxins secreted by Aspergillus spp.

Therapeutic drugs. The list of therapeutic substances that have undesirable effects on the immune system is quite long. However, in general their impact is insignificant, otherwise the medicines will not be allowed on the market. The effect of anesthetic drugs on nonspecific defense is known; a noticeable disturbance in the blastogenic response of lymphocytes in dogs after anesthesia with methoxyfluorane has been shown. Although this may not have any practical significance, it does at least imply that caution must be exercised in interpreting the results obtained when studying lymphocyte function after anesthesia.

Table 2. The main causes of secondary immunodeficiencies in animals

DISORDERS OF PASSIVE TRANSMISSION OF ANTIBODIES (mother - fetus - newborn) all types VIRUSES: canine distemper virus, canine parvovirus, feline leukemia virus, feline panleukopenia virus, equine herpesvirus 1, bovine viral diarrhea MEDICATIONS: immunosuppressive/cytotoxic therapy, amphotericin B METABOLISM DISORDERS: zinc deficiency, iron deficiency, vitamin E deficiency DIABETES, HYPERADRENOCORTICISM, UREMIA, PREGNANCY BACTERIA: Mycobacterium paratuberculosis (Johne's disease) TOXINS: mycotoxin bracken trichlorethylene soybean extract RADIATION ENDOCRINE SYSTEM DISORDERS: growth hormone deficiency, estrogen toxicity TUMORS: lymphoma, multiple myeloma

Table 4. Immunosuppressive effect of lymphoid tumors

Tumor	Cell type	Manifestation of immunosuppression	Mechanism
Feline leukemia	T cells	lymphopenia, delayed rejection of skin grafts, increased sensitivity to infections, lack of response to mitogens	Suppressive viral proteins, p15E, cell suppression
Marek's disease	T cells	lack of response to mitogens, suppression of cellular cytotoxicity, suppression of IgG production	macrophage suppression
Avian lymphoid leukemia	B cells		lymphocyte suppression
Bovine leukosis	B cells	suppression of serum IgM synthesis	soluble suppressor factor
Myeloma	B cells	increased sensitivity to infections	soluble tumor cell factor
Malignant lymphoma of dogs	B cells	Predisposition to infections associated with autoimmune disorders	unknown
Equine lymphosarcoma	T cells	increased sensitivity to infections	suppressor cell tumor

Immunodeficiency states or immunodeficiency are a group of various pathological conditions characterized by disruption of the human immune system, against the background of which infectious and inflammatory processes recur much more often, are difficult, and last longer than usual. Against the background of immunodeficiency in people, any age group Serious diseases are formed that are difficult to treat. Due to this process, cancerous tumors can form that pose a threat to life.

This condition, depending on the causes, can be hereditary or acquired. This means that the disease often affects newborn babies. Secondary immunodeficiency is formed against the background of many factors, including trauma, surgery, stressful situations, hunger and cancer. Depending on the type of disease, they may manifest various symptoms, indicating defeat internal organs and human systems.

Diagnosis of immune dysfunction is based on general and biochemical blood tests. Treatment is individual for each patient, and depends on the factors that influenced the occurrence of this state, as well as the degree of manifestation of characteristic signs.

Etiology

There are many causes of immunodeficiency, and they are divided into several groups. The first consists of genetic disorders, and the disease can manifest itself from birth or at an early age. The second group includes complications from a wide range of pathological conditions or diseases.

There is a classification of immunodeficiency states, divided depending on the factors that caused this condition to form:

• primary immunodeficiency – caused by a genetic disorder. It can be transmitted from parents to children or occurs due to a genetic mutation, which is why there is no hereditary factor. Such conditions are often diagnosed in the first twenty years of a person’s life. Congenital immunodeficiency accompanies the victim throughout his life. Often leads to death due to various infectious processes and complications from them;
• Secondary immunodeficiency is a consequence of many conditions and diseases. A person can get this type of immune disorder for the reasons mentioned above. It occurs several times more often than the primary one;
• severe combined immunodeficiency is extremely rare and is congenital. Children die from of this type diseases in the first year of life. This is due to a decrease in the number or disruption of the functioning of T and B lymphocytes, which are localized in the bone marrow. This combined condition differs from the first two types, in which only one type of cell is affected. Treatment of such a disorder is successful only if it is identified in a timely manner.

Symptoms

Since the classification of the disease includes several types of disorder, the expression will differ depending on the form specific symptoms. Signs of primary immunodeficiency are frequent damage to the human body by inflammatory processes. Among them:

• abscess;

In addition, immunodeficiency in children is characterized by digestive problems - lack of appetite, constant diarrhea and vomiting. There are delays in growth and development. The internal manifestations of this type of disease include the spleen, changes in the composition of the blood - the amount of and decreases.

Despite the fact that primary immunodeficiency is often diagnosed in childhood, there are several characteristic signs that indicate that an adult may have this type of disorder:

• frequent attacks of purulent otitis media and sinusitis more than three times a year;
• severe inflammatory process in the bronchi;
• recurring skin inflammations;
• frequently recurring diarrhea;
• the occurrence of autoimmune diseases;
• undergoing severe infectious processes at least twice a year.

Symptoms of secondary immunodeficiency are those signs that are characteristic of the disease that provoked it. In particular, the symptoms of the lesion are noted:

• upper and lower respiratory tract;
• upper and deeper layers of the skin;
• gastrointestinal organs;
• genitourinary system;
• nervous system. In this case, a person feels chronic fatigue, which does not go away even after a long rest.

Often people experience a slight increase in body temperature, seizures, as well as the development of generalized infections that affect several internal organs and systems. Such processes pose a threat to human life.

Combined immunodeficiencies are characterized by the presence in children of delayed physical development, a high level of susceptibility to various infectious and inflammatory processes, and chronic diarrhea.

Complications

Depending on the type of disease, different groups of consequences of untimely treatment of the underlying disorder may develop. Complications of immunodeficiency in children may include:

• repeating with high frequency various infectious processes of a viral, fungal or bacterial nature;
• the formation of autoimmune disorders, during which the immune system acts against the body;
• high probability of occurrence various diseases heart, gastrointestinal tract or nervous system;
• oncological neoplasms.

Consequences of secondary immunodeficiency:

• pneumonia;
• abscesses;
• blood poisoning.

Regardless of the classification of the disease, when late diagnosis and treatment, death occurs.

Diagnostics

People with immunodeficiency conditions have clear signs that they are sick. For example, sickly appearance, pale skin, presence of diseases of the skin and ENT organs, coughing, inflamed eyes with increased tear production. Diagnosis is primarily aimed at identifying the type of disease. To do this, the specialist needs to conduct a thorough interview and examination of the patient. After all, treatment tactics depend on whether the disease is acquired or hereditary.

The basis diagnostic measures make up various blood tests. General analysis provides information about the number of cells of the immune system. A change in the amount of any of them indicates the presence of an immunodeficiency state in a person. To determine the type of disorder, a study of immunoglobulins is carried out, i.e. the amount of proteins in the blood. The functioning of lymphocytes is being studied. In addition, an analysis is carried out to confirm or deny genetic pathology, as well as the presence of HIV. After receiving all the test results, the specialist makes a final diagnosis - primary, secondary or severe combined immunodeficiency.

Treatment

To choose the most effective tactics for treating primary immunodeficiency, it is necessary to determine at the diagnostic stage the area in which the disorder has occurred. In case of immunoglobulin deficiency, patients are prescribed injections (for life) of plasma or serum from donors that contain the necessary antibodies. Depending on the severity of the disorder, the frequency of intravenous treatments can range from one to four weeks. For complications of this type of disease, antibiotics are prescribed in combination with antibacterial, antiviral and antifungal medications.

Prevention

Since congenital immunodeficiency is formed against the background of genetic disorders, it is impossible to avoid it with preventive measures. People need to follow several rules to avoid recurrence of infections:

• do not use antibiotics for a long time;
• undergo vaccinations recommended by specialists in a timely manner;
• carefully follow all personal hygiene rules;
• enrich the diet with vitamins;
• Avoid contact with people who have a cold.

Prevention of secondary immunodeficiency includes vaccination, depending on the doctor’s prescription, protected sexual contact, timely treatment of chronic infections, moderate exercise, a balanced diet, and taking courses of vitamin therapy.

If any manifestations of immunodeficiency conditions occur, you should immediately seek advice from a specialist.

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Antibodies to p24

Antibodies to gr120

Rice. 4.49. Dynamics of the content of the virus itself and antibodies to its two proteins in the blood of people infected with human immunodeficiency virus

T cells, which allows them to escape pressure from T cell immunity. Thus, the cellular immune response is not able to eliminate the virus from the body due to the high adaptability of the virus, based on variability. NK cells are also ineffective, although they are not directly infected by the virus.

The relationship between HIV infection and the macroorganism is reflected in the dynamics of the content of viral antigens in circulation

And antiviral antibodies (Fig. 4.49). A surge of antigenemia in the early period of development HIV infection (2–8 weeks after infection) reflects intensive replication of viruses that have entered cells. When the host's immune system is intact, this causes the production of neutralizing antibodies (mainly to the surface proteins gp120, gp41, and the group-specific gag antigen p17), which can be detected by an increase in the titer of serum antibodies to these antigens, starting from the 8th week from the moment of infection. This change from the circulation of antigen to the presence of antibodies in the bloodstream is referred to as “seroconversion”. Antibodies to envelope (env) proteins persist stably throughout the disease, whereas gag-specific antibodies disappear at certain stages of disease development, and viral antigens reappear in the bloodstream. Simultaneously with the accumulation of antibodies to viral antigens in the blood serum, the concentration of all serum immunoglobulins, including IgE, increases.

Circulating antibodies are able to neutralize free virus

And bind its soluble proteins. In response to gp120, this is most true for antibodies specific to the immunodominant epitope 303–337, localized in the 3rd hypervariable domain (V3) of the molecule. This is supported by the fact that passively administered antibodies can protect against HIV infection. Neutralizing antibodies, especially those directed against gp120, are able to block infectious

cell formation. This probably plays a role in the initial containment of HIV infection and, to some extent, accounts for the long latent period characteristic of HIV infection. of this disease. At the same time, the effector activity of these antibodies is limited and their protective role in HIV infection cannot be considered proven.

Formation of immunodeficiency in acquired immunodeficiency syndrome

(see table 4.20)

The main cause of immunodeficiency in AIDS is the death of CD4+ T cells. The obvious reason for the death of infected cells is the cytopathogenic effect of the virus. In this case, the cells die through the mechanism of necrosis due to a violation of the integrity of their membrane. Thus, when blood cells are infected with HIV, the number of CD4+ T cells, starting from the 3rd day, sharply decreases simultaneously with the release of virions into the medium. The population of CD4+ T cells in the intestinal mucosa is most affected.

In addition to this mechanism of death of infected cells in AIDS, a high level of apoptosis is detected. The damage to the T-cell component of the immune system significantly exceeds what would be expected based on an estimate of the number of infected cells. In lymphoid organs, no more than 10–15% of CD4+ T cells are infected, and in the blood this amount is only 1%, but a much larger percentage of CD4+ T lymphocytes undergo apoptosis. In addition to those infected, a significant portion of cells not infected with the virus apoptote, primarily CD4+ T-lymphocytes specific to HIV antigens (up to 7% of these cells). The inducers of apoptosis are the gp120 proteins and the Vpr regulatory protein, which are active in soluble form. The gp120 protein reduces the level of the anti-apoptotic protein Bcl-2 and increases the level of the pro-apoptotic proteins p53, Bax, and Bak. The Vpr protein disrupts the integrity of the mitochondrial membrane, displacing Bcl-2. Cytochromas exits the mitochondria and activates caspase 9, which leads to apoptosis of CD4+ T cells, including uninfected, but HIV-specific ones.

The interaction of the viral protein gp120 with the membrane glycoprotein of CD4+ T lymphocytes causes another process that occurs during HIV infection and is involved in the death and functional inactivation of host cells - the formation of syncytium. As a result of the interaction of gp120 and CD4, cell fusion occurs with the formation of a multinuclear structure that is unable to perform normal functions and doomed to death.

Among the cells infected with HIV, only T-lymphocytes and megakaryocytes die, undergoing cytopathogenic effects or entering apoptosis. Neither macrophages nor epithelial or other cells infected with the virus lose viability, although their function may be impaired. Dysfunction can be caused not only by HIV as such, but also by its isolated proteins, for example, gp120 or the p14 gene product. Although HIV is not capable of causing malignant transformation of lymphocytes (unlike, for example, the HTLV-1 virus), the tat protein (p14) is involved in the induction of Kaposi's sarcoma in HIV infection.

A sharp decrease in the content of CD4+ T-lymphocytes is the most striking laboratory sign of HIV infection and its evolution into AIDS. Conditional

4.7. Immunodeficiencies

the boundary of the contents of these cells, which is usually followed by clinical manifestations AIDS, - 200–250 cells in 1 μl of blood (in relative figures - about 20%). The CD4/CD8 ratio at the peak of the disease decreases to 0.3 or lower. During this period, general lymphopenia appears with a decrease in the content of not only CD4+, but also CD8+ cells and B-lymphocytes. The response of lymphocytes to mitogens and the severity of skin reactions to common antigens continue to decline to complete anergy. Added to the various reasons for the inability of effector T cells to eliminate HIV is the high mutability of HIV with the formation of ever new epitopes that are not recognized by cytotoxic T cells.

Naturally, among the immunological disorders in AIDS, disorders of T-cell and T-dependent processes dominate. Factors that determine these violations include:

– decreased CD4 count+ T-helpers due to their death;

– weakening of CD4 functions+ T cells influenced by infection and the action of soluble HIV products, especially gp120;

– population imbalance T cells with a shift in the Th1/Th2 ratio towards Th2, while Th1-dependent processes contribute to protection against the virus;

– induction of regulatory T cells by the gp120 protein and the HIV-associated protein p67.

A decrease in the body's ability to immune defense affects both its cellular and humoral factors. As a result, a combined immunodeficiency is formed, making the body vulnerable to infectious agents, including opportunistic ones (hence the development of opportunistic infections). Deficiency of cellular immunity plays a certain role in the development of lymphotropic tumors, and the combination of immunodeficiency and the action of certain HIV proteins plays a role in the development of Kaposi's sarcoma.

Clinical manifestations of immunodeficiency in human immunodeficiency virus infection and acquired immunodeficiency syndrome

The main clinical manifestations of AIDS are the development of infectious diseases, mainly opportunistic ones. The following diseases are most characteristic of AIDS: pneumonia caused by Pneumocystis carinii; diarrhea caused by cryptosporidium, toxoplasma, giardia, amoeba; strongyloidiasis and toxoplasmosis of the brain and lungs; candidiasis of the oral cavity and esophagus; cryptococcosis, disseminated or localized in the central nervous system; coccidioidomycosis, histoplasmosis, mucormycosis, aspergillosis of various localizations; infections with atypical mycobacteria of various localizations; Salmonella bacteremia; cytomegalovirus infection of the lungs, central nervous system, digestive tract; herpetic infection skin and mucous membranes; Epstein–Barr virus infection; multifocal papovavirus infection with encephalopathy.

Another group of pathological processes associated with AIDS are tumors, which differ from those not associated with AIDS in that they develop at a younger age than usual (up to 60 years). With AIDS, Kaposi's sarcoma and non-Hodgkin's lymphomas, localized mainly in the brain, often develop.

The development of the pathological process is facilitated by certain macroorganism reactions provoked by HIV infection. Thus, activation of CD4+ T cells in response to the action of viral antigens contributes to the implementation of the cytopathogenic effect, especially the apoptosis of T lymphocytes. Most of the cytokines produced by T cells and macrophages favor the progression of HIV infection. Finally, the autoimmune component plays an important role in the pathogenesis of AIDS. It is based on homology between HIV proteins and some body proteins, for example between gp120 and MHC molecules. However, these disorders, aggravating immunodeficiency, do not form specific autoimmune syndromes.

Already at the preclinical stage of HIV infection, there is a need to use immunological diagnostic methods. For this purpose, enzyme-linked immunosorbent test kits are used to determine the presence of antibodies to HIV proteins in blood serum. Existing test systems are based on enzyme-linked immunosorbent antibody testing (ELISA). Initially, test kits were used using viral lysates as antigenic material. Later, for this purpose, recombinant HIV proteins and synthetic peptides were used that reproduce epitopes with which serum antibodies of HIV-infected people interact.

Due to the extremely high responsibility of doctors who make a conclusion about HIV infection based on laboratory tests, the practice of repeating antibody tests (sometimes using alternative methods, such as immunoblotting, see section 3.2.1.4), as well as determining the virus using polymerase chain reaction.

Treatment of AIDS is based on the use of antiviral drugs, the most widely used of which is zidovudine, which acts as an antimetabolite. Progress has been made in controlling the course of AIDS, significantly increasing the life expectancy of patients. The main therapeutic approach is the use of antimetabolites nucleic acids in the variant of highly active antiretroviral therapy ( High active antiretroviral therapy- HAART). An effective addition to antiretroviral therapy is the use of interferon drugs, as well as the treatment of concomitant diseases and viral infections that contribute to the progression of AIDS.

The mortality rate from AIDS is still 100%. Most common cause deaths are due to opportunistic infections, especially Pneumocystis pneumonia. Other causes of death are concomitant tumors, damage to the central nervous system and digestive tract.

4.7.3. Secondary immunodeficiencies

Secondary immunodeficiency conditions - these are violations of the body’s immune defense due to the action of non-hereditary inductor factors (Table 4.21). They are not independent nosological forms, but only accompany diseases or the action of immunotoxic factors. To a greater or lesser extent, immune disorders

4.7. Immunodeficiencies

theta accompanies most diseases, and this significantly complicates determining the place of secondary immunodeficiencies in the development of pathology.

Table 4.21. The main differences between primary and secondary immunodeficiencies

Criterion	Primary	Secondary
	immunodeficiencies	immunodeficiencies
Presence of genetic
defect with installed
ny type of hereditary
The role of the inducer
Early manifestation	Expressed	Time of manifestation of the immune system
immunodeficiency		but the deficit determines-
		due to the action of induc-
		factor
Opportunistic	Develop primarily	Develop after action
infections		Via inducing
	Substitute, anti-	Elimination of induction
	infectious therapy.	influencing factor.
	Gene therapy	Substitute, anti-
		war-infectious therapy

It is often difficult to differentiate the contribution to the development of immune disorders from hereditary factors and inductive influences. In any case, the reaction to immunotoxic agents depends on hereditary factors. An example of the difficulties in interpreting the basis of immunity disorders can be diseases classified as “frequently ill children”. The basis of sensitivity to infection, in particular respiratory viral infection, is a genetically (polygenically) determined immunological constitution, although specific pathogens act as etiological factors. However, the type of immunological constitution is influenced by factors external environment and previous diseases. The practical significance of accurately identifying the hereditary and acquired components of the pathogenesis of immunological deficiency will increase as methods for differentiated therapeutic effects on these forms of immunodeficiency are developed, including methods of adaptive cell therapy and gene therapy.

The basis of immunodeficiencies not caused by genetic defects can be:

– death of cells of the immune system - total or selective;

– dysfunction of immunocytes;

– unbalanced predominance of the activity of regulatory cells and suppressor factors.

4.7.3.1. Immunodeficiency conditions caused by the death of immunocytes

Classic examples of such immunodeficiencies are immunity disorders caused by the action of ionizing radiation and cytotoxic drugs.

Lymphocytes are one of the few cells that respond to a number of factors, in particular those damaging DNA, by developing apoptosis. This effect manifests itself under the influence of ionizing radiation and many cytostatics used in treatment malignant tumors(for example, cisplatin, which inserts into the DNA double helix). The reason for the development of apoptosis in these cases is the accumulation of unrepaired breaks, registered by the cell with the participation of ATM kinase (see section 4.7.1.5), from which the signal arrives in several directions, including to the p53 protein. This protein is responsible for triggering apoptosis, the biological meaning of which is to protect a multicellular organism at the cost of the death of single cells that carry genetic disorders that carry a risk of cell malignancy. In most other cells (usually resting), this mechanism is counteracted by protection from apoptosis due to increased expression of the Bcl-2 and Bcl-XL proteins.

Radiation immunodeficiencies

Already in the first decade after the discovery of ionizing radiation, their ability to weaken resistance to infectious diseases and selectively reduce the content of lymphocytes in the blood and lymphoid organs was discovered.

Radiation immunodeficiency develops immediately after irradiation of the body. The effect of radiation is mainly due to two effects:

– disruption of natural barriers, primarily mucous membranes, which leads to increased access of pathogens to the body;

– selective damage to lymphocytes, as well as all dividing

cells, including immune system precursors and cells involved in the immune response.

The subject of study of radiation immunology is mainly the second effect. Radiation cell death is realized by two mechanisms - mitotic and interphase. The cause of mitotic death is unrepaired damage to DNA and the chromosomal apparatus, which prevents the implementation of mitoses. Interphase death affects resting cells. Its cause is the development of apoptosis via a p53/ATM-dependent mechanism (see above).

If the sensitivity of all cell types to mitosis is approximately the same (D0 - about 1 Gy), then in sensitivity to interphase death lymphocytes are significantly superior to all other cells: most of them die when irradiated at doses of 1–3 Gy, while cells of other types die at doses exceeding 10 Gy. The high radiosensitivity of lymphocytes is due, as already mentioned, low level expression of anti-apoptotic factors Bcl-2 and Bcl-XL. Different populations and subpopulations of lymphocytes do not differ significantly in sensitivity to apoptosis (B cells are somewhat more sensitive than T lymphocytes; D0 for them is 1.7–2.2 and 2.5–3.0 Gy, respectively). In the process of lymphopoiesis, sensory

4.7. Immunodeficiencies

susceptibility to cytotoxic effects changes in accordance with the level of expression of anti-apoptotic factors in cells: it is highest during periods of cell selection (for T-lymphocytes - the stage of cortical CD4+ CD8+ thymocytes, D0 - 0.5–1.0 Gy). Radiosensitivity is high in resting cells; it further increases in the initial stages of activation and then sharply decreases. The process of proliferative expansion of lymphocytes is characterized by high radiosensitivity, and upon entering proliferation, cells that were previously exposed to radiation and that carry unrepaired DNA breaks may die. Formed effector cells, especially plasma cells, are resistant to radiation (D0 - tens of Gy). At the same time, memory cells are radiosensitive to approximately the same extent as naive lymphocytes. Innate immune cells are radioresistant. Only periods of their proliferation during development are radiosensitive. The exception is NK cells, as well as dendritic cells (they die at doses of 6–7 Gy), which, in terms of radiosensitivity, occupy an intermediate position between other lymphoid and myeloid cells.

Although mature myeloid cells and the reactions they mediate are radioresistant, early dates After irradiation, it is the deficiency of myeloid cells, primarily neutrophils, caused by radiation disruption of hematopoiesis that is maximally manifested. Its consequences affect neutrophil granulocytes early and most severely, as the cell population with the most rapid turnover of the pool of mature cells. This causes a sharp weakening of the first line of defense, the load on which increases significantly during this period due to the breakdown of barriers and the uncontrolled entry of pathogens and other foreign agents into the body. The weakening of this part of the immune system is the main cause of radiation death in the early stages after irradiation. At a later date, the effects of damage to innate immune factors are much less pronounced. The functional manifestations of innate immunity themselves are resistant to the action of ionizing radiation.

3–4 days after irradiation at doses of 4–6 Gy, more than 90% of the lymphoid cells in mice die and the lymphoid organs are devastated. The functional activity of surviving cells decreases. The homing of lymphocytes is sharply disrupted - their ability to migrate during the process of recycling to secondary lymphoid organs. Adaptive immune responses when exposed to these doses are weakened in accordance with the degree of radiosensitivity of the cells that mediate these reactions. Those forms of the immune response, the development of which requires the interactions of radiosensitive cells, suffer the most from the effects of radiation. Therefore, the cellular immune response is more radioresistant than the humoral one, and thymus-independent antibody production is more radioresistant than the thymus-dependent humoral response.

Radiation doses in the range of 0.1–0.5 Gy do not cause damage to peripheral lymphocytes and often have a stimulating effect on the immune response due to the direct ability of radiation quanta,

generating reactive oxygen species, activate signaling pathways in lymphocytes. The immunostimulating effect of radiation, especially in relation to the IgE response, naturally manifests itself during irradiation after immunization. It is believed that in this case the stimulating effect is due to the relatively higher radiosensitivity of the regulatory T cells that control this form of the immune response compared to effector cells. The stimulating effect of radiation on innate immune cells is manifested even at high doses, especially in relation to the ability of cells to produce cytokines (IL-1, TNF α, etc.). In addition to the direct stimulating effect of radiation on cells, the stimulation of these cells by products of pathogens entering the body through damaged barriers contributes to the manifestation of an enhancing effect. However, increased activity of innate immune cells under the influence of ionizing radiation is not adaptive and does not provide adequate protection. In this regard, the negative effect of radiation prevails, manifested in the suppression (at doses exceeding 1 Gy) of the adaptive antigen-specific immune response (Fig. 4.50).

Already during the period of developing devastation of lymphoid tissue, restoration processes are activated. Recovery occurs in two main ways. On the one hand, the processes of lymphopoiesis are activated due to the differentiation of all types of lymphocytes from hematopoietic stem cells. In the case of T-lymphopoiesis, the development of T-lymphocytes from intrathymic precursors is added to this. In this case, the sequence of events repeats to a certain extent,

7 Dendritic

Medullary 3 thymocytes

1 Cortical

thymocytes 0.5–1.0 Gy

Answer: T cells

IgM: antibodies to

in SCL - 1.25 Gy

EB - 1.0–1.2 Gy

Answer B: cells

Education

in vitro on LPS -

IgG: antibodies to

EB - 0.8–1.0 Gy

Rice. 4.50. Radiosensitivity of some cells of the immune system and the reactions mediated by them. The values ​​of D0 are presented . EB - sheep red blood cells

4.7. Immunodeficiencies

characteristic of T-lymphopoiesis in the embryonic period: first, γδT cells are formed, then αβT cells. The recovery process is preceded by rejuvenation of thymic epithelial cells, accompanied by an increase in their production of peptide hormones. The number of thymocytes increases rapidly, reaching a maximum by the 15th day, after which secondary atrophy of the organ occurs due to the depletion of the population of intrathymic progenitor cells. This atrophy has little effect on the number of peripheral T-lymphocytes, since by this time the second source of restoration of the lymphocyte population is turned on.

This source is the homeostatic proliferation of surviving mature lymphocytes. The stimulus for the implementation of this mechanism of lymphoid cell regeneration is the production of IL-7, IL-15 and BAFF, which serve as homeostatic cytokines for T-, NK- and B-cells, respectively. The recovery of T lymphocytes occurs most slowly, since contact of T lymphocytes with dendritic cells expressing MHC molecules is necessary for the implementation of homeostatic proliferation. The number of dendritic cells and the expression of MHC molecules (especially class II) on them are reduced after irradiation. These changes can be interpreted as radiation-induced changes in the microenvironment of lymphocytes - lymphocyte niches. This is associated with a delay in the restoration of the lymphoid cell pool, which is especially significant for CD4+ T cells, which is not fully realized.

T cells formed during the process of homeostatic proliferation have the phenotypic characteristics of memory cells (see section 3.4.2.6). They are characterized by recycling pathways characteristic of these cells (migration into barrier tissues and non-lymphoid organs, weakening of migration into the T-zones of secondary lymphoid organs). That is why the number of T-lymphocytes in the lymph nodes is practically not restored to normal, while in the spleen it is restored completely. The immune response developing in the lymph nodes also does not reach normal levels when it is completely normalized in the spleen. Thus, under the influence of ionizing radiation, the spatial organization of the immune system changes. Another consequence of the conversion of the T-lymphocyte phenotype in the process of homeostatic proliferation is an increase in autoimmune processes due to an increased likelihood of recognizing autoantigens during migration to non-lymphoid organs, facilitating the activation of memory T-cells and lagging regeneration of regulatory T-cells compared to other subpopulations. Many of the changes in the immune system induced by radiation resemble those of normal aging; This is especially evident in the thymus, the age-related decline in activity of which is accelerated by irradiation.

Variation of the radiation dose, its power, the use of fractionated, local, internal irradiation (incorporated radionuclides) gives a certain specificity to immunological disorders in the post-radiation period. However, the fundamental principles of radiation damage and post-radiation recovery in all these cases do not differ from those discussed above.

The effect of moderate and small doses of radiation has acquired particular practical significance in connection with radiation disasters, especially

but in Chernobyl. It is difficult to accurately assess the effects of low doses of radiation and differentiate the effects of radiation from the role of external factors (especially stress). In this case, the already mentioned stimulating effect of radiation may appear as part of the hormesis effect. Radiation immunostimulation cannot be considered as a positive phenomenon, since, firstly, it is not adaptive, and secondly, it is associated with an imbalance of immune processes. It is still difficult to objectively assess the impact on the human immune system of the slight increase in natural background radiation that is observed in areas adjacent to disaster zones or associated with the characteristics of industrial activities. In such cases, radiation becomes one of the unfavorable environmental factors and the situation should be analyzed in the context of environmental medicine.

Immunodeficiency conditions caused by non-radiation death of lymphocytes

Mass death of lymphocytes forms the basis of immunodeficiencies that develop in a number of infectious diseases of both bacterial and viral nature, especially with the participation of superantigens. Superantigens are substances that can activate CD4+ T lymphocytes with the participation of APCs and their MHC-II molecules. The effect of superantigens differs from the effect of normal antigen presentation.

Superantigen is not cleaved into peptides and is not integrated into anti-

gene-binding cleft, but is connected to the “side surface” of the β-chain of the MHC-II molecule.

Superantigen is recognized T cells by their affinity not to the antigen-binding center TCR, but to the so-called 4th hypervariable

mu region - sequence 65–85, localized on the side surface of TCR β-chains belonging to certain families.

Thus, superantigen recognition is not clonal, but is determined by the TCR belonging to certain β-families. As a result, superantigens involve a significant number of CD4+ T lymphocytes in the response (up to 20–30%). Thus, the response to staphylococcal exotoxin SEB involves CD4+ T cells from mice expressing TCRs belonging to the Vβ7 and Vβ8 families. After a period of activation and proliferation, accompanied by hyperproduction of cytokines, these cells undergo apoptosis, which causes a significant degree of lymphopenia, and since only CD4+ T cells die, the balance of lymphocyte subpopulations is also disturbed. This mechanism underlies T-cell immunodeficiency, which develops against the background of certain viral and bacterial infections.

4.7.3.2. Secondary immunodeficiencies caused by functional disorders of lymphocytes

It is likely that this group of secondary immunodeficiencies is predominant. However, at present, there is virtually no accurate data on the mechanisms of decreased lymphocyte function in various somatic diseases and exposure to harmful factors. Only in isolated cases is it possible to establish the exact mechanisms

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Immunodeficiency - what is it?

Doctors note that patients are increasingly being diagnosed with serious diseases that are difficult to treat. Immune deficiency, or scientifically known as immunodeficiency, is a pathological condition in which the immune system does not work properly. Both adults and children experience the described disorders. What is this condition? How dangerous is it?

Immunodeficiency is characterized by a decrease in activity or the inability of the body to create a protective reaction due to the loss of the cellular or humoral immune component.

This condition can be congenital or acquired. In many cases, IDS (especially if not treated) is irreversible, however, the disease can also have a transitive (temporary) form.

Causes of immunodeficiency in humans

The factors causing IDS have not yet been fully studied. However, scientists are constantly studying this issue to prevent the onset and progression of immunodeficiency.

Immunodeficiency, causes:

The cause can only be identified through a comprehensive hematological diagnosis. First of all, the patient is sent to donate blood to assess cellular immunity indicators. During the analysis, the relative and absolute number of protective cells is calculated.

Immunodeficiency can be primary, secondary or combined. Each disease associated with IDS has a specific and individual severity.

If pathological signs occur, it is important to promptly consult your doctor to receive recommendations for further treatment.

Primary immunodeficiency (PID), features

It is a complex genetic disease that manifests itself in the first few months after birth (40% of cases), in early infancy (up to two years - 30%), in childhood and adolescence (20%), less often - after 20 years (10%).

It should be understood that patients do not suffer from IDS, but from those infectious and concomitant pathologies that the immune system is unable to suppress. In this regard, patients may experience the following:

• Polytopic process. This is multiple damage to tissues and organs. Thus, the patient may simultaneously experience pathological changes, for example, in the skin and urinary system.
• Difficulty in treating a particular disease. The pathology often becomes chronic with frequent relapses (repetitions). Diseases are rapid and progressive.
• High susceptibility to all infections, leading to polyetiology. In other words, one disease can be caused by several pathogens at once.
• The usual therapeutic course does not give the full effect, so the dosage of the drug is selected individually, often in loading doses. However, it is very difficult to cleanse the body of the pathogen, so carriage and a latent course of the disease are often observed.

Primary immunodeficiency is a congenital condition, the beginnings of which were formed in utero. Unfortunately, screening during pregnancy does not detect severe anomalies at the initial stage.

This condition develops under the influence of an external factor. Secondary immunodeficiency is not a genetic disorder; it is first diagnosed with equal frequency in both childhood and adulthood.

Factors causing acquired immunodeficiency:

• deterioration of the ecological environment;
• microwave and ionizing radiation;
• acute or chronic poisoning with chemicals, heavy metals, pesticides, low-quality or expired food;
• long-term treatment medicines affecting the functioning of the immune system;
• frequent and excessive mental stress, psycho-emotional stress, worries.

The above factors negatively affect immune resistance, therefore, such patients, in comparison with healthy ones, will more often suffer from infectious and oncological pathologies.

Main reasons, which may cause secondary immunodeficiency are listed below.

Errors in nutrition - The human body is very sensitive to a lack of vitamins, minerals, proteins, amino acids, fats, and carbohydrates. These elements are necessary to create a blood cell and maintain its function. In addition, the normal functioning of the immune system requires a lot of energy, which comes with food.

All chronic diseases negatively affect the immune defense, worsening resistance to foreign agents penetrating into the body from the external environment. In case of chronic course infectious pathology the hematopoietic function is inhibited, so the production of young protective cells is significantly reduced.

Adrenal hormones. An excessive increase in hormones inhibits the function of immune resistance. A malfunction occurs when material metabolism is disrupted.

A short-term condition, as a defensive reaction, is observed due to severe surgical procedures or severe injury. For this reason, patients undergoing surgery are susceptible to infectious diseases for several months.

Physiological characteristics of the body:

• prematurity;
• children from 1 year to 5 years;
• pregnancy and lactation period;
• old age

Features in people of these categories are characterized by suppression of immune function. The fact is that the body begins to work intensively in order to bear additional load to perform its function or survive.

Malignant neoplasms. First of all, we are talking about blood cancer - leukemia. With this disease, there is an active production of protective non-functional cells that cannot provide full immunity.

Also a dangerous pathology is damage to the red bone marrow, which is responsible for hematopoiesis and replacement of its structure with a malignant focus or metastases.

Along with this, all other oncological diseases cause a significant blow to protective function, but disorders appear much later and have less pronounced symptoms.

HIV – human immunodeficiency virus. By suppressing the immune system, it leads to a dangerous disease - AIDS. All the patient's lymph nodes are enlarged, oral ulcers often recur, candidiasis, diarrhea, bronchitis, pneumonia, sinusitis, purulent myositis, and meningitis are diagnosed.

The immunodeficiency virus affects the defense response, so patients die from diseases that a healthy body can hardly resist, and even more so when weakened by HIV infection (tuberculosis, oncology, sepsis, etc.).

Combined immunodeficiency (CID)

Is the heaviest and rare disease which is very difficult to cure. CID is a group of hereditary pathologies that lead to complex disorders of immune resistance.

As a rule, changes occur in several types of lymphocytes (for example, T and B), whereas with PID only one type of lymphocyte is affected.

CID manifests itself in early childhood. The child does not gain weight well and is delayed in growth and development. These children are highly susceptible to infections: the first attacks may begin immediately after birth (for example, pneumonia, diarrhea, candidiasis, omphalitis).

As a rule, after recovery, a relapse occurs after a few days or the body is affected by another pathology of a viral, bacterial or fungal nature.

Treatment of primary immunodeficiency

Today medicine has not yet invented universal medicine, helping to completely overcome all types of immunodeficiency conditions. However, therapy is proposed aimed at relieving and eliminating negative symptoms, increasing lymphocyte protection and improving quality of life.

This is a complex therapy, selected on an individual basis. The patient's life expectancy, as a rule, depends entirely on the timely and regular use of medications.

Treatment of primary immunodeficiency is achieved by:

• prevention and concomitant therapy of infectious diseases in the early stages;
• improving protection by bone marrow transplantation, immunoglobulin replacement, neutrophil mass transfusion;
• increasing lymphocyte function in the form of cytokine treatment;
  introduction of nucleic acids ( gene therapy) in order to prevent or stop the development of a pathological process at the chromosomal level;
• vitamin therapy to support immunity.

If the course of the disease worsens, you should inform your doctor about this.

Treatment of secondary immunodeficiency

As a rule, the aggressiveness of secondary immunodeficiency states is not severe. Treatment is aimed at eliminating the cause of IDS.

Therapeutic focus:

• for infections - elimination of the source of inflammation (with the help of antibacterial and antiviral drugs);
• to increase immune defense - immunostimulants;
• if IDS was caused by a lack of vitamins, then a long course of treatment with vitamins and minerals is prescribed;
• human immunodeficiency virus - treatment consists of highly active antiretroviral therapy;
• for malignant tumors - surgical removal of a focus of atypical structure (if possible), chemotherapy, radiotherapy,
• tomotherapy and other modern methods of treatment.

In addition, when diabetes mellitus You should carefully monitor your health: stick to a low-carbohydrate diet, regularly test your sugar levels at home, take insulin tablets or administer subcutaneous injections in a timely manner.

Treatment of CID

Treatment for primary and combined forms of immunodeficiency is very similar. Most effective method The treatment is considered to be a bone marrow transplant (if T-lymphocytes are damaged).

• Today, transplantation is successfully carried out in many countries to help overcome an aggressive genetic disease.

Prognosis: what awaits the patient

The patient must be provided with high-quality medical care in the early stages of the disease. If we are talking about a genetic pathology, then it should be identified as early as possible by taking many tests and undergoing a comprehensive examination.

Children who suffer from PID or CID from birth and do not receive appropriate treatment have a low survival rate to two years.

In case of HIV infection, it is important to regularly test for antibodies to the human immunodeficiency virus in order to control the course of the disease and prevent sudden progression.