IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

ACQUIRED IMMUNODEFICIENCY STATES

Acquired (Secondary) Immunodeficiencies

Acquired (secondary) immunodeficiency refers to immune system disorders that develop in the postneonatal period or in adults and are not the result of genetic defects.

Thus, the term "secondary immunodeficiency" denotes immune disorders resulting from somatic and other diseases, as well as various external factors, accompanied by clinical manifestations (International Classification of Diseases, 10th Revision).

Acquired (secondary) immunodeficiency is a clinico-immunological syndrome: a) developing against the Background of a previously normally functioning immune system; b) characterized by a persistent and significant decline in quantitative and functional parameters of immune status; c) representing a risk factor for The Development of chronic infections, autoimmune disorders, allergic diseases, and malignancies.

Based on this definition of acquired (secondary) immunodeficiency, several key features follow.

1. First, The Immune System disorders are truly secondary, emerging against the backdrop of previously normal health in both clinical and immun Laboratory terms. This can be identified during the medical history interview.

2. The disruptions in the immune system must be persistent and pronounced. This is an important condition, as immune parameters are known to be labile and dynamic, allowing various components to Complement and buffer one another. Therefore, transient, temporary changes in immune parameters may simply reflect situational adaptation.

3. Immune system disorders should not be assessed solely by quantitative measures; cellular Functions must also be evaluated. Instances are known where a reduced count of specific Cells, such as NK cells, was compensated by their elevated functional activity. However, if a decrease in the number of certain immune cells is accompanied by a simultaneous impairment of their function, this is undeniably a critical laboratory marker of immunodeficiency.

4. Immune system impairments may affect indicators of both specific (adaptive) Immunity and nonspecific resistance, i.e., innate (natural) immunity.

5. Immune system disorders are typically characterized by the predominant impairment of a single arm of immunity (cellular, humoral, complement, or phagocytic), while other immunological changes are secondary and generally compensatory in nature. Combined immune disorders are also possible.

6. It is important to understand the following: generally, patients seek medical care when they already exhibit clinical signs of secondary immunodeficiency, such as chronic, Treatment-resistant infectious and inflammatory pathologies. In such cases, the active intervention of a clinical immunologist is required. Nevertheless, clinicians should be aware that some ostensibly healthy individuals may present with immuno-laboratory markers of secondary immunodeficiency accompanied only by indirect clinical signs, such as mild fatigue that has not yet become chronic. In these instances, it is more accurate to speak of transient immunogram alterations lacking clinical correlation, which often do not require immunotropic therapy. To clarify the situation, such patients require follow-up observation. It should be remembered that such individuals are at risk of developing secondary immunodeficiency-related pathologies, including infectious, autoimmune, allergic, or oncological disorders. At the same time, belonging to a "risk group" is fortunately a reversible state, and such patients can be helped through appropriate immunorehabilitation measures.

Below are the causes that can trigger the development of secondary immunodeficiency.

Class="center">Causes of Secondary Immunodeficiencies

I. Infectious Agents

1. Viral infections:

a) acute — measles, rubella, Influenza, mumps (epidemic parotitis), chickenpox, hepatitis, herpes, etc.;

b) persistent — chronic hepatitis B, subacute sclerosing panencephalitis, AIDS, etc.;

c) congenital — cytomegalovirus infection, rubella (TORCH complex).

2. Bacterial infections: staphylococcal, pneumococcal, meningococcal infections, tuberculosis, etc.

3. Protozoan and helminthic infestations (malaria, Toxoplasmosis, leishmaniasis, trichinosis, ascariasis, etc.).

II. Nutritional (Alimentary):

1. Protein-energy malnutrition.

2. Deficiency of Trace Elements (Zn, Cu, Fe) and Vitamins — retinol (A), ascorbic acid (C), alpha-tocopherol (E), Folic acid.

3. Exhaustion, cachexia, protein-losing enteropathy, nephropathy.

4. Inborn errors of METABOLISM.

5. Overnutrition, obesity.

6. Malabsorption syndrome.

III. Metabolic:

1. Chronic renal failure, uremia, Nephrotic Syndrome.

2. Chronic Liver diseases.

3. Diabetes Mellitus.

4. Hypercatabolism of IMMUNOGLOBULINS.

IV. Conditions leading to the loss of immunocompetent cells and immunoglobulins (Hemorrhage, lymphorrhea, Burns, nephritis).

V. Malignant neoplasms, particularly lymphoproliferative disorders.

VI. Autoimmune diseases.

VII. Exogenous and endogenous intoxications (poisoning, thyrotoxicosis, decompensated diabetes mellitus).

VIII. Immunodeficiency resulting from various factors:

1. Physical factors (ionizing radiation, microwaves, etc.).

2. Chemical factors (immunosuppressants, cytostatics, corticosteroids, drugs, herbicides, pesticides, etc.).

3. Adverse environmental factors.

4. Immunosuppressive treatments: medicinal products (immunosuppressants, glucocorticosteroids, cytostatics, Antibiotics, nonsteroidal anti-inflammatory drugs).

5. Occupational hazards, including X-ray radiation, radioactive exposure, biologically active and chemically aggressive substances.

6. Various types of stress (emotional, psychological trauma, physical stress, athletic overexertion, etc.).

IX. Various severe illnesses, surgery, anesthesia, burns.

X. Impairments of neurohormonal regulation.

XI. Age-related factors: early childhood, advanced age, Pregnancy.

It should be emphasized once again that clinical and laboratory

findings show striking similarities between secondary and Primary immunodeficiencies, to the extent that a correlation exists between The Nature of the immune disorders and the type of pathogen. The fundamental difference lies in the underlying cause of the immune impairment: congenital defects in primary immunodeficiencies versus acquired defects in secondary ones.

Just like primary immunodeficiencies, secondary immunodeficiencies can be caused by dysfunction in one of the primary immune systems: humoral (B-system), cellular (T-system), the phagocytic system, The Complement System, or multiple systems simultaneously (combined defects).

Among secondary immunodeficiencies, three forms are distinguished:

- acquired;

- induced;

- spontaneous (ICD-10 Code D.84.9).

The acquired form of secondary immunodeficiency is Acquired Immunodeficiency Syndrome (AIDS), which develops As a result of damage to the immune system by the HUMAN IMMUNODEFICIENCY VIRUS (HIV).

The induced form (ICD-10 Code D.84.8) of secondary immunodeficiency arises as a result of specific causative factors: X-ray irradiation, cytostatic therapy, corticosteroid administration, trauma and surgical interventions, as well as immune impairments developing secondary to an underlying disease (diabetes, liver and Kidney diseases, malignant neoplasms).

The spontaneous form (ICD-10 Code D.84.9) of secondary immunodeficiency is characterized by the absence of an obvious cause triggering the impairment of immune reactivity. Clinically, it manifests as chronic, recurrent infectious and inflammatory processes of the bronchopulmonary apparatus, Paranasal Sinuses, urogenital and gastrointestinal tracts, eyes, Skin, and soft Tissues caused by opportunistic (conditional-pathogenic) microorganisms. Therefore, chronic, frequently recurring, sluggish inflammatory processes of any localization in adults that are difficult to treat with conventional remedies are regarded as clinical manifestations of a secondary immunodeficiency state.

Quantitatively, the spontaneous form is the dominant form of secondary immunodeficiency.

Types of immunodeficiencies (depending on the etiological factor):

- specified (infectious, toxic, metabolic, physical, psychogenic, post-traumatic, with an indication of the specific Diagnosis or disease that caused it) (ICD-10 Code D.84.8);

- unspecified (cryptogenic, essential, idiopathic, or spontaneous — assigned in the absence of any identifiable etiological factor) (ICD-10 Code D.84.9).

Specified immunodeficiencies include the following types:

✵ infectious immunodeficiency develops as a result of the action of an infectious agent, including opportunistic pathogens (viral, bacterial, protozoal, fungal, helminthic);

✵ toxic immunodeficiency develops under conditions of prolonged exposure to exo- and endotoxins, xenobiotics, etc. (exogenous, drug-induced, occupational, endogenous, burn-related, etc.);

✵ metabolic immunodeficiency develops under conditions of prolonged metabolic disturbance, including acid-base balance disorders (nutritional, metabolic, due to Protein deficiency, malabsorption, etc.);

✵ physical immunodeficiency develops as a result of prolonged exposure of The Human Body to ionizing and ultraviolet radiation, high-frequency fields, etc.;

✵ psychogenic immunodeficiency develops under conditions of prolonged psycho-emotional overload, stress, CNS disorders, etc.;

✵ post-traumatic immunodeficiency (including surgical) develops in cases of severe extensive trauma, burns, extensive and prolonged surgical interventions, Blood loss, lymphorrhea, etc.

TYPES OF IMMUNE system defects:

✵ lymphocytic immunodeficiency is characterized by persistent quantitative and/or functional alterations in the T-Cell link of the immune system;

✵ humoral immunodeficiency is characterized by persistent quantitative and/or functional alterations in the B-cell link of the immune system, including immunoglobulin production;

✵ phagocytic immunodeficiency is characterized by persistent quantitative and/or functional alterations in phagocytic cells (monocytes/macrophages, granulocytes) of the immune system;

✵ complement immunodeficiency is characterized by persistent Changes in the level and activity of complement components;

✵ combined immunodeficiency is characterized by persistent quantitative and/or functional alterations in indicators of multiple (two or more) Links of the immune system. It is advisable to identify the leading immune system defect (for example, a combined defect with a prominent lymphocytic component).

Classification of secondary immunodeficiencies by clinical form:

✵ autoimmune form is characterized by relevant clinical and laboratory findings (hypergammaglobulinemia, elevated circulating immune complexes [CIC], etc.);

✵ allergic form (including IgE-dependent, reaginic) is characterized by relevant clinical findings (hypersensitivity of the skin and mucous membranes, primarily of the respiratory and gastrointestinal tracts) and laboratory findings (eosinophilia, elevated IgE levels, etc.);

✵ immunoproliferative form is characterized by The formation of tumors in various Organs and systems with the accumulation of tumor mass of lymphoid-monocytic-cellular composition, enlargement of the Spleen, Tonsils, adenoids, Thymus, Peyer's patches, etc.;

✵ paraneoplastic form is characterized by impaired immune system function in Cancer patients due to the tumor's systemic impact and damage to the immune system following anti-tumor therapy (cytotoxic therapy, irradiation, etc.);

✵ neurogenic form (Chronic Fatigue Syndrome, neuroimmunoendocrine syndrome, immunodeficiency in psychiatric disorders, etc.);

✵ mixed form is characterized by the presence of two or more forms in a patient; it is advisable to distinguish the primary form (e.g., mixed form with a predominance of autoimmunity).

Patterns of immunodeficiency progression

✵ Acute — clinical and laboratory signs of immunodeficiency develop and persist for up to 1 month.

✵ Subacute — clinical and laboratory signs of immunodeficiency develop and persist for up to 3 months.

✵ Chronic — clinical and laboratory signs of immunodeficiency develop and persist for up to 6 months.

✵ Recurrent — clinical and laboratory signs of immunodeficiency reappear earlier than 6 months after successful treatment.

Grades of immune deficiency (based on the absolute lymphocyte count; normal absolute lymphocyte count is 1.4–3.2 × 10⁹/L):

Grade 1 immune deficiency — minimal (ID-1) — absolute lymphocyte count is 1.4–1.2 × 10⁹/L; laboratory parameters are decreased by 15–30% of the mean normal value. Clinically, immunodeficiency may be asymptomatic (compensated form).

Grade 2 immune deficiency — moderate (ID-2) — absolute lymphocyte count is 1.1–0.9 × 10⁹/L; laboratory parameters are decreased by 35–55% of the mean normal value. Clinically, immunodeficiency may manifest as a single clinical syndrome or a combination of several syndromes, with a subacute or chronic course.

Grade 3 immune deficiency — severe (ID-3) — absolute lymphocyte count is less than 0.9 × 10⁹/L; laboratory parameters are decreased by more than 55% of the mean normal value. Clinically, immunodeficiency presents with pronounced symptoms.

Classification of secondary immunodeficiencies by functional disability (FD):

✵ FD I — the patient retains working capacity and requires outpatient treatment without issuing a sick leave certificate;

✵ FD II — the patient temporarily loses working capacity or has restricted working capacity, requiring outpatient treatment with a sick leave certificate;

✵ FD III — the patient experiences temporary or permanent loss of working capacity, requiring inpatient treatment and/or a disability assessment.

The main forms, types, and categories of immunodeficiencies, grades of immune system compensation and deficiency, clinical patterns, and immunopathological syndromes are presented in Table 69.

Table 69. Classification of secondary immunodeficiencies

The primary clinical manifestation of secondary immunodeficiencies is the presence and specific Clinical forms of infectious syndrome — relapses and exacerbations of Infections caused by opportunistic microorganisms, including Viruses, Bacteria, Fungi, and parasites.

The main condition for the onset of an infectious process is host susceptibility, i.e., impaired immunity (immunodeficiency), where even an opportunistic microorganism can cause infection. The Link Between infections caused by opportunistic pathogens and immunodeficiency is evident, as their expansion is only possible in the presence of such a deficiency.

Immunodeficiency — relative or absolute — is the primary cause of infections, whereas enhanced and stimulated immunity following vaccination provides resistance to many highly virulent pathogens. For instance, vaccination campaigns successfully eradicated smallpox, which claimed millions of lives, and currently induce immunity against measles, poliomyelitis, influenza, hepatitis B, tick-borne encephalitis, yellow fever, and other infections. This proves that even highly virulent pathogens cannot overcome pre-mobilized immune barriers of the Organism. Therefore, the virulence of infectious agents is not absolute, and an organism with a sufficiently high level of specific and non-specific immune activity — that is, an immune-competent one — is fully capable of resisting it.