IMMUNOLOGY TEXTBOOK - Mercury Podillya 2013

MECHANISMS OF IMMUNE DEFENSE IN BACTERIAL, VIRAL, FUNGAL, AND PROTOZOAN INFECTIONS

Features of Immunity in "Slow" Viral Infections

Despite the high efficacy of antiviral Immunity, viral infection can manifest through The Development of "slow infections," which pose a rather serious problem, for instance, in neuroinfections due to the high risk of complications: the development of demyelinating processes and hemorrhagic vasculitis against the Background of insufficient pathogen elimination, its high contagiousness, and aggressiveness.

According to virological and immunological examinations, the most frequent causes of viral meningitis, encephalitis, arachnoiditis, and Chronic Fatigue Syndrome are infections with herpes simplex Viruses type 1 and 2, cytomegalovirus, and Epstein-Barr virus, and less frequently, the persistence of herpes viruses type 6 and 8, which belong to the so-called slow infections. Furthermore, worldwide there are about 350 million people infected with hepatitis B and C viruses, with chronic hepatitis B and C being the main causes of cirrhosis and primary Liver Cancer. Pathogens of Viral Hepatitis are capable of affecting not only liver tissue but also the gastric mucosa and Pancreas, persisting for long periods in peripheral Blood mononuclear Cells. Thus, studying the immune status in viral infections is currently relevant for predicting the course of the infectious-inflammatory process and selecting Treatment tactics.

The Diversity of immune mechanisms involved in antiviral immunity, combined with varying degrees of immunological reactivity to viruses—including "slow" ones—leads to The formation of Different types of Immune Response. Data from immunological examinations allow us to distinguish three Variants of the immune response in patients with a positive virological history.

1. Activated variant of the Immune Response to viral infection (Table 36). It is characterized by the predominant activation of cellular immunity: marked lymphocytosis, high levels of cytotoxic lymphocytes (CD8 and CD16), activation of T-lymphocytes According to the lymphocyte blast transformation test (LBTT), activation of phagocytosis (high neutrophil engulfment activity and spontaneous bactericidal activity), and an elevated ERYTHROCYTE SEDIMENTATION RATE (ESR). In patients with the activated variant of the immune response to a viral infection, a moderate activation of the humoral link of immunity is detected, characterized by signs of an acute infectious process, specifically an increased concentration of IgM and elevated levels of circulating immune complexes (CIC). These patients exhibit a significant increase in specific IgM Antibodies against viruses of "slow" infections, such as HSV, CMV, EBV, etc. Given the pronounced activity of the immune response to the viral infection, the clinical viral process in such patients is characterized by an acute course.

As an example of the activated variant of the immune response to a viral infection, we present the medical history of patient V., 27 years old, suffering from an acute viral infection with clinical manifestations of acute herpes infection in the facial area. The patient was found to have elevated titers of antibodies specific to HSV type 1 and CMV viruses, and a positive PCR for the DNA of these same pathogens.

Immunogram (Table 36): lymphocytosis, a slight increase in ESR. Activation of the T-Cell link of immunity is observed, manifested by a high content of cytotoxic lymphocytes (CD8, CD16) and T-lymphocytes, along with activation of phagocytosis (neutrophil engulfment activity and spontaneous bactericidal activity). There is a moderate increase in the concentration of circulating immune complexes and Class M IMMUNOGLOBULINS.

Diagnosis: acute herpes virus infection of the face and Lips.

Conclusion: signs of an acute viral infection (activated variant of the immune response).

Based on the immunological status features of patient V., 27 years old, the following regimen of immunotropic and etiotropic therapy was prescribed to treat the clinical manifestations of the acute herpes virus infection:

1) specific Antiviral Therapy (immunotherapy with human anti-Herpes simplex virus type 1 immunoglobulin, 4.5 ml (3 amp.) once every 3 days intramuscularly, up to 5 injections);

2) valacyclovir 500 mg 2 times a day orally, for 7–10 days;

3) Viferon 150 thousand IU, every other day in suppositories, 10 administrations;

4) isoprinosine 500 mg, 2 tablets 3 times a day, for 7 days;

5) Herpevir ointment, apply to the Skin of the face and lips 3 times a day, for 7 days.

Immunorehabilitation:

6) cycloferon 12.5%, 1 ml once a day subcutaneously according to the basic schedule—on days 1, 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, and 29.

Monitoring of specific immunoglobulins and PCR for HSV type 1 and CMV in 6 months.

Table 36. Immunogram of patient V., 27 years old

2. Secondary immunodeficiency variant of the immune response of cellular type to viral infection. It is characterized by moderate lymphocytosis, multidirectional Changes in the level of cytotoxic lymphocytes (an increase in CD8 and normal or elevated CD16 content), and a significant decrease in the functional activity of T-lymphocytes according to the LBTT. Signs of marked dysregulation of neutrophil phagocytic activity are observed (decreased engulfment activity and functional reserve of the oxidation-reduction potential against the background of increased spontaneous bactericidal activity). In patients with the secondary immunodeficiency cellular-type variant of the immune response, just as in the activated variant, a moderate activation of the humoral link is detected, but it is characterized by signs of chronization of the infectious process—specifically, the presence in the blood of a high content of specific IgG antibodies to viruses (primarily CMV, HSV types 6 and 8, etc.). Given the decreased activity of predominantly the cellular link of The Immune System, the clinical viral process in such patients is characterized by a chronic relapsing course.

As an example of the secondary immunodeficiency cellular-type variant of the immune response to a viral infection, which has a chronic, relapsing course, we present the medical history of patient G., 35 years old, suffering from a chronic relapsing herpes virus infection of the face and lips; relapsing lymphadenopathy; and immune system dysfunction of the cellular type. The patient was found to have elevated titers of class G specific immunoglobulins to HSV types 6 and 8 and CMV viruses, and a positive PCR for the DNA of these same pathogens.

Immunogram: relative lymphocytosis with a decrease in the count of all types of T-lymphocytes (decreased counts of CD3, CD4, CD8, CD16), and a significant decrease in the functional activity of T-lymphocytes. Slight activation of the humoral link of immunity (increased levels of IgG and CIC). Neutrophil phagocytic activity is preserved (Table 37).

Diagnosis: Chronic recurrent herpes virus infection involving the facial and labial regions. Recurrent lymphadenopathy. Cellular-type immune system dysfunction.

Conclusion: Cellular-type immune system dysfunction.

Based on the immunological profile of patient H., aged 35, the following regimen of immunotropic and etiotropic therapy was prescribed to treat the clinical manifestations of chronic recurrent herpes virus infection:

1) valacyclovir 500 mg twice daily for 7–10 days;

2) viferon 150,000 IU rectally every other day, 10 administrations following the cessation of valacyclovir;

3) groprinosin 500 mg (2 tablets) 3 times daily for 7 days;

4) galavit 200 mg as a loading dose, followed by 100 mg once daily subcutaneously, n = 10;

5) herpevir ointment, apply topically to the skin of the face and lips 3 times daily for 7 days.

Immunorehabilitation:

6) immunofan 1 ml of 0.005% solution subcutaneously once daily, n = 10;

7) cycloferon 12.5%, 1 ml once daily according to the standard schedule on days 1, 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, and 29.

Follow-up assessment of specific immunoglobulins and PCR for HSV types 6, 8, and CMV in 6 months.

Table 37. Immunogram of patient H., aged 35

3. Secondary immunodeficiency variant of the cellular-type immune response accompanied by the activation of the humoral arm of the immune system in response to viral infection. It is characterized by the predominance of humoral immune reactions: a tendency toward eosinophilia, elevated levels of B lymphocytes, increased concentrations of immunoglobulins across all classes studied, and elevated circulating immune complexes, along with lymphopenia and decreased functional activity of T lymphocytes as determined by the lymphocyte blastogenesis test (LBT). Signs of dysregulation in neutrophil phagocytic and bactericidal activity are noted (decreased phagocytic activity and functional reserve of the oxidation-reduction potential against the background of elevated spontaneous bactericidal activity).

As an example of the secondary immunodeficiency variant of the cellular-type immune response with activation of the humoral arm of the immune system in response to a chronic, recurrent viral infection, we present the case history of patient P., aged 32, who presented with an Exacerbation of chronic infectious-allergic encephalitis against the background of a chronic recurrent herpes virus infection of the lips, cellular-type immune system dysfunction with humoral immunity activation, and phagocytosis dysregulation. The patient demonstrated elevated titers of specific class G immunoglobulins to HSV type 1 and a positive PCR test for HSV type 1 DNA.

Immunogram: marked activation of the humoral arm of immunity — a tendency toward eosinophilia, elevated B lymphocyte count, increased levels of IgM, IgG, and IgA, a sharp increase in circulating immune complexes, lymphopenia, and decreased functional activity of T lymphocytes according to LBT data. Signs of phagocytosis dysregulation (reduced engulfing activity and functional reserve of the neutrophil oxidation-reduction potential) against the background of increased spontaneous neutrophil bactericidal activity (Table 38).

Diagnosis: Chronic infectious-allergic encephalitis. Chronic recurrent herpes virus infection of the lips. Cellular-type immune system dysfunction with activation of the humoral arm of immunity. Phagocytosis dysregulation.

Conclusion: Cellular-type immune system dysfunction with activation of the humoral arm of immunity. Phagocytosis dysregulation.

Based on the immunological profile of patient P., aged 32, the following therapeutic regimen was prescribed for etiotropic treatment and immunological correction of clinical manifestations of chronic infectious-allergic encephalitis against the background of chronic recurrent labial herpes virus infection:

1) acyclovir 250 mg dissolved in 50 ml of diluent, administered intravenously as a drip twice daily for 7 days;

2) bioven mono 400 ml intravenously as a drip once daily for 3 days.

Immunorehabilitation:

3) cycloferon 12.5%, 1 ml once daily according to the standard schedule on days 1, 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, and 29.

Follow-up assessment of specific immunoglobulins and PCR for HSV type 1 in 6 months.

Table 38. Immunogram of female patient P., aged 32

Various patterns of immune response provide a rationale for tailored approaches to Immunomodulatory therapy in patients suffering from slow viral infections. Thus, changes in the immune status in the first pattern may indicate an adequate immune response accompanied by an acute inflammatory process during viral infection. In this situation, prophylactic immunomodulatory therapy is advisable only in the presence of clinical manifestations to prevent potential complications that could lead to an autoimmune process. In cases of an inadequate immune response (second and third patterns), patients require the inclusion of targeted immunotropic agents in their combination therapy. If suppression of cellular immune reactions is detected, therapy should involve agents aimed at stimulating cellular immunity; conversely, if a distorted immune response with predominant humoral activation is observed, agents that switch the immune response from a humoral to a cellular type are required to successfully mount anti-infectious immunity.

In addition to the most typical patterns of immune response to slow viral infections mentioned above, other immune system reactions may also occur.

As an example of immune system dysfunction against the background of chronic viral infection, we present the case history of patient I., aged 24, who suffers from chronic recurrent lymphadenitis accompanied by immune system dysfunction and functional deficiency of the neutrophil Lineage. Patient I. was found to have elevated titers of specific class G immunoglobulins to EBV, along with a positive PCR test for the DNA of this pathogen (Table 39).

Immunogram: relative CTL cytosis. Decreased functional reserve of the neutrophil oxidation-reduction potential (NBT res.). Increased spontaneous and antigen-induced activation of T-lymphocytes (LST spont., LST ind.).

Diagnosis: chronic recurrent lymphadenitis. Immune system dysfunction with functional deficiency of the neutrophil lineage.

Conclusion: signs of T-cell immunity activation, functional deficiency of the neutrophil lineage against the background of a possible intracellular infection.

Based on the immunological profile of patient I., aged 24, the following regimen of immunotropic and etiotropic therapy was prescribed to treat the clinical manifestations of chronic recurrent lymphadenitis caused by EBV infection:

1) acyclovir 250 mg dissolved in 50 mL of solvent, administered IV drip twice daily for 7 days;

2) galavit 200 mg - initial dose, followed by 100 mg once daily subcutaneously, no. 10;

3) polyoxidonium 6 mg subcutaneously once daily, no. 10.

Immunorehabilitation:

4) sodium nucleinate 0.1 orally 3 times daily for 2 weeks;

5) cyclferon 12.5% 1 mL once daily according to the baseline schedule - on days 1, 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, and 29.

Monitoring of specific immunoglobulins and EBV PCR after 6 months.

Table 39. Immunogram of patient I., aged 24