IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

ACQUIRED IMMUNODEFICIENCY STATES

Secondary Immunodeficiencies in Certain Clinical Cases

Acquired immunodeficiencies in purulent-septic infections. Secondary immunodeficiencies accompanied by the Clinical presentation of a purulent-septic (surgical) infection are typically triggered by opportunistic endogenous microorganisms, which frequently invade the lesion site via translocation from the intestine. Immunodeficiency induced by surgery or anesthesia is generally of a combined nature. The Development of the infection depends on the pathogen load entering a susceptible host, whereas the ratio between this load and the strength of the defense response dictates the timeline and clinical trajectory of the disease.

Immunological mechanisms. The mechanisms underlying immune suppression in purulent-septic infections may include antigen competition, enhanced activation of T-suppressors (in numerous infections), and the modulation of Immune Response pathways by various Bacterial toxins and Antigens. At the peak of Sepsis, an imbalance occurs within T- and B-lymphocyte populations, lymphocyte differentiation is impaired, and functional insufficiency ensues. The proportion of undifferentiated "null" lymphocytes increases, the Ts/Th ratio rises, dysimmunoglobulinemia develops, and the levels of natural and specific Antibodies decline. Consequently, the purulent-septic process elicits a polyvalent infectious effect characterized by disruptions across multiple Branches of the immune response; marked deficiencies in these pathways serve as DIAGNOSTIC AND PROGNOSTIC markers for sepsis. During Clinical Recovery, immunoglobulin levels normalize, whereas the composition of T-lymphocyte subpopulations does not. This persistence of abnormal lymphocyte receptor profiles conceals a risk of infection relapse and constitutes a secondary immunodeficiency.

Therefore, alongside the surgical removal of purulent foci and antibacterial therapy, immunotherapy represents an indispensable component of management both during the acute phase of the illness and throughout convalescence, while anti-relapse immunorehabilitation is required in A number of cases.

Regimen and types of immunotherapy are contingent upon the form and severity of the condition. In cases of sepsis and generalized infections, intravenous immunoglobulin preparations are utilized, along with plasmapheresis, hemoperfusion, and other detoxification modalities that simultaneously facilitate the clearance and neutralization of excess pro-inflammatory cytokines generated during the initial stage of the process. IgM-enriched IMMUNOGLOBULINS (pentaglobin) exhibit superior endotoxin neutralization and offer distinct advantages in the management of sepsis and septic Shock. The administration of cytokine-blocking antibodies (anti-TNF, anti-IL-1, etc.) may improve the clinical course of the disease. Subsequently, the hyperproduction of pro-inflammatory cytokines driven by bacterial endotoxins induces immunosuppression and the onset of immunological paralysis accompanied by multiple organ dysfunction syndrome—representing the Second Stage of the septic process, during which the removal or suppression of inflammatory cytokines is no longer effective.

Thymomimetic agents such as tactividin and thymalin reduce the incidence of postoperative infectious complications and accelerate recovery by normalizing the immune status.

Likopid administered in 10 mg tablets or via intramuscular injections of 0.125 mg daily for 10 days is prescribed for purulent-septic complications.

Myelopid is indicated for patients following cardiac surgery, jaw fractures, and other pathologies characterized by combined common variable immunodeficiency.

Immunofan is administered subcutaneously or intramuscularly at a dose of 1 ml per day of a 0.009% solution for 7–10 days in patients with infective endocarditis, severe purulent-septic postoperative complications, septic Pneumonia, or Peritonitis.

Polyoxidonium is utilized in cases of sepsis, peritonitis, abscesses, and other purulent-Inflammatory Diseases, with a Treatment course ranging from 15 to 45 mg of the drug.

Plasmapheresis eliminates pro-inflammatory cytokines in purulent-septic processes, while replacement immunotherapy with exogenous immunostimulatory cytokines beneficially modulates the cytokine profile.

Roncoleukin (recombinant IL-2) is administered at a dose of 0.25–1 mg (25,000–1,000,000 IU) in 200–400 ml of 0.9% sodium chloride solution via intravenous drip at a rate of 1–2 ml/min over 4–6 hours daily. The treatment course consists of 3–8 intravenous infusions.

Betaleukin (recombinant IL-1β) stimulates T- and B-lymphocytes as well as Bone Marrow hematopoiesis. It has proven beneficial in purulent-destructive conditions, peritonitis, and abscesses. It is administered subcutaneously or intravenously (by drip) to stimulate leukopoiesis at a dose of 15–20 ng/kg and Immunity at 58 ng/kg once daily for 5 days; if necessary, the course can be repeated after 2 weeks.

Leukinferon, a complex cytokine preparation with a high interferon content (IFN-α), normalizes sharply reduced levels of T-lymphocytes and T-helper-1 Cells and enhances phagocytosis. Leukinferon is administered intramuscularly at 10,000 IU (1 ampoule) every other day for 3–5 doses in severe Influenza, peritonitis, or sepsis complicated by multiple organ dysfunction syndrome. The administration of Leukinferon 1–2 days prior to surgery accelerates the normalization of BODY Temperature AND hemogram parameters in patients, while enhancing anti-bacterial and anti-viral immunity.

Combined immunocorrection is the preferred approach for chronic purulent diseases, given that they are underpinned by an acquired combined immunodeficiency. Immunostimulatory agents should be employed in conjunction with antibacterial therapy as early as the preoperative preparation stage. In cases of leukopenia, agents that stimulate leukopoiesis are required: methyluracil, cytokines (Leukinferon), granulocyte-macrophage colony-stimulating factor (GM-CSF)—such as Leukomax (molgramostim) at a dose of 1–10 µg/kg/day or Granocyte (lenograstim) at 2–10 µg/kg/day for 6 days, tactividin (1.0 ml/day) intramuscularly, Leukinferon (1 ampoule every other day intramuscularly), and, upon clinical indication, Roncoleukin at 1 mg (1 million IU) in 400 ml of 0.9% sodium chloride solution via intravenous drip at a rate of 1–2 ml/min for 4–6 hours, alongside the cytoprotector glutoxim (1%, 2 ml intramuscularly once daily for 10 injections).

Novikov et al. proposed combining levamisole, dimexide, and heparin for immunodeficiencies accompanied by purulent-inflammatory clinical manifestations, as dimexide counteracts the negative effects of levamisole on neutrophils, whereas intradermal heparin enhances lymphopoiesis. Administration of a 30% dimexide solution was performed via Electrophoresis using standard methodology up to 7 days postoperatively, after which dimexide was applied topically to the inflammatory focus until patient discharge from the hospital. Levamisole was prescribed at 25–50 mg every other day for 15 days. Alternatively, tactividin (thymalin), polyoxidonium, or other immunomodulators may be used in place of levamisole. In the presence of a bacterial infection, they should be combined with antibacterial agents that also enhance immune responses—such effects have been demonstrated for metronidazole, which stimulates antibody synthesis, phagocytosis, and interferon production.

Passive immunotherapy involves human antistaphylococcal globulin (10 IU per kg of body weight for 10 days), homologous immune antistaphylococcal plasma (intravenous drip daily at 30 IU per kg of body weight), heterologous antistaphylococcal globulin administered according to Besredka's method (intramuscularly, 10 ml daily, total of 10 injections), and staphylococcal intravenous phage (40 ml intravenously, total of 10 injections). For severe cases, intravenous immunoglobulins containing IgG and IgM are indicated.

Active immunotherapy, provided the body possesses sufficient reserve capacity, utilizes staphylococcal toxoid, autovaccine administration, or leukocyte suspension.

Enhancing non-specific immune activity via ultraviolet Blood irradiation.

As an example of granulocytic and B-Cell type immunodeficiency, we present the case history of patient V., a 54-year-old male who underwent treatment in the surgical department with a Diagnosis of chronic sepsis (staphylococcal), interloop abdominal abscesses, and septicopyemia. Patient history: surgical management for purulent-destructive appendicitis performed 6 months prior, with clinical deterioration over the preceding 2 weeks.

Immunogram (Table 71): leukopenia, neutropenia, relative Th-cytosis. Decreased levels of B-lymphocytes and reduced production of IgG and IgM immunoglobulins. Diminished neutrophil phagocytic capacity (phagocytic index, phagocytic number). Reduced spontaneous bactericidal activity (NBT test, spontaneous), decreased functional reserve of the phagocyte oxidation-reduction potential (NBT test, reserve), and elevated Complement levels (CH-50). Signs of intoxication ( medium molecular weight toxins / TZN).

Diagnosis: chronic sepsis, interloop abdominal abscesses, septicopyemia, granulocytic and B-cell immunodeficiency (D 84.9).

Conclusion: evidence of an evolving immunodeficiency state affecting the granulocytic and B-cell lineages, accompanied by decreased phagocytic activity resulting from a chronic inflammatory process—likely of a septic nature—that is complicated by severe intoxication and low immune system reactivity.

Staphylococcus aureus with high hemolytic activity was cultured from the patient's blood analysis.

Class="center">Table 71. Immunogram of patient V., 54 years old

Final diagnosis: chronic sepsis, interloop abdominal abscesses, septicopyemia, granulocytic and B-cell immunodeficiency (D 84.9).

The patient underwent Surgical treatment, and the Abdominal cavity was drained. Based on the immunological status of patient V., the following immunotropic therapy regimen was prescribed for the treatment of chronic sepsis:

Stage I of therapy (inpatient)

1) specific antibacterial therapy (immunotherapy with human anti-staphylococcal globulin 10 mL IM for 10 days);

2) etiotropic antibacterial therapy - sulperazone 1.0 g in 200 mL of 0.9% sodium chloride solution IV drip twice daily; zyvox (linezolid) 0.6 g IV drip twice daily;

3) detoxification - rheopolyglucin 400 mL IV drip; 400 mL of 0.9% sodium chloride solution IV drip, 5% glucose 400 mL + Insulin 4 IU IV drip.

4) plasmapheresis 400 mL of plasma twice a week, 6 sessions.

5) direct anticoagulants clexane 40 mg twice daily subcutaneously;

6) recombinant IL-2 roncoleukin 1 mg (1 million IU) in 400 mL of 0.9% sodium chloride solution IV drip once daily, 5 infusions;

7) granulocyte colony-stimulating factor filgrastim (neupogen) 60 million IU (2 mL, 10 mcg/kg/day) SC once daily. If the neutrophil count remains above 1x109/L for 3 consecutive days, the dose is reduced to 30 million IU (1 mL, 5 mcg/kg/day). The drug is discontinued after the neutrophil count exceeds 1x109/L for an additional 3 days.

8) cytoprotector glutoxim 1% 2 mL IM once daily, 10 injections.

9) probiotic linex 2 caps. 3 times daily.

Stage II of therapy (outpatient)

10) polyoxidonium 6 mg IM twice a week, no. 10;

11) likopid 1 mg, 1 tab. once daily, 10 days;

12) linex 2 caps. 3 times daily, 20 days.

Immunorehabilitation:

13) viferon 150 thousand IU, every other day in suppositories, 10 administrations;

14) sodium nucleinate 0.1 g 3 times daily, 20 days.