IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

CONCEPT OF IMMUNE STATUS AND IMMUNOGRAM: INTERPRETATION OF IMMUNOGRAMS

According to modern views, The Immune System is responsible for maintaining structural Homeostasis, providing defense against Bacteria, Viruses, and parasites, rejecting foreign Tissues and toxins, offering tumor surveillance, and ensuring tolerance to self-tissues. Structural homeostasis involves searching for, recognizing, binding, and destroying foreign agents, as well as memorizing foreign structures in the case of specific immune responses.

This is achieved by recognizing and neutralizing carriers of foreign Genetic information, or host Cells that have altered their antigenic Structure and become foreign, via effector and regulatory factors. Effector factors are those that directly destroy foreign or altered self-cells that have acquired antigenic properties and "become foreign".

Factors of innate Immunity:

a) cellular — Cells of the general inflammatory response and natural killer cells;

b) humoral — The Complement System, interferons, and acute-phase Proteins of inflammation.

Factors of adaptive immunity:

a) cellular — cytotoxic T lymphocytes;

b) humoral — specific Antibodies.

Regulatory factors — those that control the Specificity and strength of the Immune Response (T helpers, cytokines).

Immunodiagnostics serves as a vital methodological foundation of clinical immunology, allowing for the characterization of individual Links of the immune system and their functional state.

To objectively assess the state of the immune system, the Concept of Immune status has been introduced.

Immune status is a set of quantitative and qualitative characteristics reflecting the state of a person's immune system at a specific point in time.

When evaluating the immune system, it is essential to account for individual Variability in immune parameters and recognize that A change in one parameter triggers compensatory reactions in others. A defect in some components or links of the immune system — whether congenital and genetically determined, or acquired — can be quite fully compensated for by other components. If such a defective system adapts under favorable physiological conditions, homeostasis can stabilize sufficiently, establishing the necessary balance among the available components. Such a balanced system can function quite effectively even under extreme conditions, although the risk of failure remains significantly higher than in a system where all components are fully functional.

The functional activity of immunocompetent cells is constantly influenced by neuroendocrine factors (the neuro-endocrine-immune axis). There are also age-related differences in immune status parameters.

Seasonal fluctuations in the functional activity of the immune system have been identified. Specifically, peak values for T- and B-Cell immunity parameters are observed in winter. A decrease in the number and functional activity of T lymphocytes occurs in spring, whereas B lymphocytes decline in summer. Diurnal rhythms in immune status parameters have also been documented: the highest lymphocyte count is recorded at midnight (24:00), while the lowest is observed upon awakening.

Defects in the immune system become apparent during periods of its active operation. Thus, in summary, three MAIN TYPES OF active functioning of the immune system can be distinguished.

Type One is fundamentally normal functioning, which is observed in the majority of diseases (acute, chronic, recurrent). Within this normal functioning, temporary insufficiencies in the immune system's work may develop; however, they are transient, and once the underlying causes are eliminated, the system returns to normal operation.

Type Two is pathological functioning associated with disruptions in a specific link of the immune system in response to a particular antigen. Abnormal functioning in this case occurs because the specific link misdirects the immune response. This can manifest either as an uncontrolled Amplification of the immune reaction (allergies), a breakdown of tolerance to self-Antigens (autoimmune diseases), or a weakened response to foreign agents (oncological diseases).

Type Three is pathological functioning associated with a defect in any link or component of the immune system. This happens when compensation mechanisms fail for various reasons (e.g., a massive defect, adverse living conditions, etc.), leaving the system unbalanced and unable to adequately respond to foreign agents. Component defects can be congenital (Primary immunodeficiencies) or acquired (hematopoietic disorders associated with the malignant transformation of immunocompetent cells; AIDS, characterized by the selective destruction of T-helper cells by the virus).

An immunological examination requires addressing the following tasks: 1) a comprehensive health status assessment; 2) DETECTION OF IMMUNE system dysfunctions (Primary and secondary immunodeficiencies, autoimmune processes, allergies, etc.); 3) Determination of the severity of immune disorders; 4) identification of the impaired immune link; 5) identification of diseases in whose Pathogenesis immune disorders may be involved; 6) detection of genetically mediated immune system defects; 7) monitoring The impact of harmful factors; 8) assessing the status before and after vaccination in risk groups; 9) monitoring immunomodulatory, immunosuppressive, and cytostatic therapy; 10) evaluation and prognosis of immunotherapy efficacy; 11) Diagnosis of acute and chronic infections of various etiologies, including AIDS; 12) diagnosis of autoimmune, immune-complex, and allergic diseases; 13) diagnosis of lymphoproliferative and other malignant neoplasms; 14) evaluation of recipients before and after organ transplantation.

To establish an immunopathological diagnosis or draw Conclusions about The Role of immune disorders in the pathogenesis of various diseases, the following stages of investigation are recommended:

I. Anamnesis analysis

II. Clinical examination

III. Immuno-Laboratory examination.

1. Complete Blood count, ESR, C-reactive protein, rheumatoid factor.

2. Assessment of cellular (T-cell) immunity:

Screening Methods:

- determination of total lymphocyte count;

- determination of the percentage and absolute number of mature T-lymphocytes — CD3 (+) and the two main subpopulations: helper CD4 (+) and killer/suppressor CD8 (+). Attention should be paid to the count of "double negatives" — CD3 (+) CD4 (-) CD8 (-) and "double positives" — CD3 (+) CD4 (+) CD8 (+);

- investigation of lymphocyte response to the T-cell mitogen phytohemagglutinin (PHA) in the blast transformation test (LBT).

Confirmatory methods:

- determination of "activation markers" CD25 and HLA II on T-lymphocytes;

- Study of cytokine production — interferon-gamma, interleukin-2, -4, tumor necrosis factor-α (TNF-α), interleukin-6 in vivo and in vitro;

- analysis of proliferative response in LBT to a specific antigen;

- study of T-lymphocyte apoptosis processes by determining CD95.

3. Assessment of humoral (B-cell) immunity:

Screening methods:

- determination of the percentage and absolute count of B-lymphocytes — CD20 (+) or CD19 (+);

- measurement of serum levels of non-specific IMMUNOGLOBULINS A, M, G, E;

- determination of circulating immune complexes in the blood;

- investigation of lymphocyte response to the B-cell mitogen pokeweed mitogen (PWM) in LBT.

Confirmatory methods:

- determination of specific serum immunoglobulins A, M, G, E;

- assessment of IL-6 production in vivo and in vitro;

- determination of secretory IgA.

4. Assessment of the phagocytic system (neutrophils):

Screening methods:

- evaluation of the absolute neutrophil count;

- Study of the intensity of microbial engulfment by phagocytes (percentage of phagocytic cells and the average engulfment capacity of each phagocyte);

- assessment of the oxygen-dependent bactericidal mechanism of phagocytes using the NBT test.

Confirmatory tests:

- intensity of phagocyte chemotaxis (migration);

- neutrophil adhesion capacity to plastic and estimation of The Cell count with CD11/CD18 adhesion molecules on the membrane.

5. Assessment of the complement system:

- determination of total complement via CH50;

- determination of C1q, C3, C3a, C4, C5a, C1inh levels;

Given the multidirectional nature of immunological tests, their varying DIAGNOSTIC AND PROGNOSTIC significance, and levels of complexity, the set of standardized immunological methods can be divided into 2 tiers.

Tier I tests (screening tests). First-tier tests allow for the detection of gross defects in cellular and humoral immunity, as well as in the phagocytic system. Utilizing these tests in the routine practice of a clinical immunologist makes it possible to confirm or rule out suspected immune system dysfunction.

Tier II tests (analytical, confirmatory). Second-tier tests enable the identification of subtle defects in cellular and humoral immunity, as well as in the phagocytic system. Applying these tests in clinical immunology practice allows for determining the specific type of immunodeficiency and precisely identifying the disorders leading to immune system dysfunction.

After analyzing specific parameters and comparing them with clinical and anamestic data, the physician substantiates the need to proceed with a comprehensive immunological examination of the patient or concludes that the patient is immunologically healthy.

Presented below is an advanced immunogram form that incorporates both screening and confirmatory methods of immune assessment. It outlines the reference ranges for each panel of tests (Table 26).

IMMUNOGRAM

I. Patient Information

II. Diagnosis

III. Cellular Immunity Parameters

Class="center">Table 26. Immunogram and its characteristics

IV. Lymphocyte Functional Activity

V. Humoral Immunity Parameters

VI. Circulating Immune Complexes (CIC)

VII. Neutrophil Granulocyte System

VIII. Complement System

IX. Parameters of the Cytokine Immune Cascade

X. HLA System

HLA-A HLA-С

HLA-В HLA-DR

Interpretation of Immunograms

Evaluation of the leukogram. Assessment of the immune system status should begin with a leukogram, which allows determining the relative and absolute counts of cells involved in the systemic inflammatory response (monocytes, neutrophils, eosinophils, basophils, and large granular lymphocytes, which are morphological counterparts of natural killer cells; platelets can also be included here as they are directly implicated in non-specific immune responses and lymphocytes). Before assessing the Functional Properties of immune cells, it is necessary to evaluate the status of systemic inflammatory cells along with a description of their Morphology. Under normal conditions, these cells should be quiescent in the blood, showing no signs of activation.

This implies that a left shift indicates the activation stress of acute inflammatory response cells; toxic granulation of neutrophils reflects the release of IL-1 and TNF-α into Circulation, either together or separately. An indicator of neutrophil activation is their ability to form rosettes with autologous erythrocytes or other cells due to the upregulated expression of adhesion molecules, pointing to the circulation of proinflammatory cytokines such as IL-1 and TNF-α. Increased myeloperoxidase activity also points to neutrophil activation. The presence of cytoplasmic vacuolization in neutrophils and monocytes indicates that enzyme-containing granules have been released within the microvasculature of a specific organ, suggesting the potential formation of a Shock organ and The Development of a systemic inflammatory response. The formation of a shock organ is evidenced by an elevated level of middle molecules resulting from albumin proteolysis by neutrophil granule proteases. An increasing hematocrit reflects endothelial activation, which subsequently triggers primary platelet hemostasis. In such situations, it is essential to monitor not only dynamic platelet counts, but also to regularly assess fibrinogen levels and perform a coagulogram. Thus, evaluating immune status frequently extends beyond purely immunological investigations.

Monocyte morphology is evaluated using the same principles as that of neutrophils. However, it should be kept in mind that among all cells of the acute inflammatory response, monocytes represent the primary damaging factor for autologous tissues.

Evaluation of lymphocytes. Lymphocytosis is typically indicative of a viral infection. Infection with lymphotropic viruses leads to the appearance of atypical mononuclear cells in the circulation. Large lymphocytes with decondensed Chromatin in The Nucleus and prominent nucleoli serve as a sign of active immunogenesis. Large granular lymphocytes (LGLs) are primarily involved in the antiviral immune response (non-specific defense). The appearance of A large number of lymphocytes with degenerating nuclear forms in peripheral blood indicates massive apoptosis—which should not occur under normal conditions—and may result from prior lymphocyte hyperactivation, including the inappropriate use of immunostimulators. Medium-sized lymphocytes containing granules are morphological equivalents of cytotoxic lymphocytes bearing the CD8G phenotype.

The next stage in evaluating an immunogram is analyzing the leukocyte subpopulation composition, including their relative and absolute counts. As an example, let us examine how the leukogram changes during an acute inflammatory process against the Background of an initially normal immune system and a successful clinical resolution. Minimal clinical manifestations, which often escape the clinician's notice, begin during the prodromal stage when a sufficient antigen load is present in the body awaiting elimination. The immune system becomes activated: the peripheral blood eosinophil count drops as these cells migrate from the circulation into the inflammatory focus. By the end of the prodrome, a relative leukocytosis is observed. The peak of the disease is characterized by progressive leukocytosis, which correlates with the extent and severity of the inflammatory response. The relative neutrophil count increases, accompanied by a left shift in the leukocyte differential. At the height of clinical manifestations, leukocytosis reaches maximum values, the ERYTHROCYTE SEDIMENTATION RATE (ESR) increases, and monocytosis, a decreased relative neutrophil count, and an elevated percentage of lymphocytes are observed. Up to this point, the immune system has responded primarily through its non-specific branches and rapid-response mechanisms. A certain amount of time is required to mount a fully-fledged specific immune response. Within 4–5 days from disease onset, antigen-specific T-lymphocyte clones are generated, and the synthesis of antigen-specific immunoglobulins begins via B lymphocytes transforming into plasma cells. Under normal immune reactivity, this period marks the onset of the next stage of acute inflammation—the crisis. A critical sign of the beginning resolution is the normalization of the relative eosinophil count in peripheral blood, which early-century clinicians termed the "dawn of recovery." These events reflect the activation of type 2 T helper cells, which synthesize IL-4 and IL-5; these cytokines are essential for class switching in plasma cells (from IgM to IgG) and act as chemoattractants for eosinophils. For the physician, the normalization of circulating eosinophils is a vital prognostic sign, as it typically occurs 1–2 days before clinical signs of resolution, after which leukocyte counts begin to decline. Subsequently, the leukocyte count normalizes, while a high relative percentage (%) of lymphocytes persists.

Thus, the leukogram can provide valuable insight into the patient's condition and the course of the inflammatory process. Alterations in specific immune cell counts during inflammation are characterized by a decrease in the relative number of T lymphocytes beginning as early as the prodromal stage and persisting through the clinical phase. This is driven by the migration of cells into the inflammatory focus. The high sensitivity of circulating T-lymphocyte counts is due to the fact that the most active T lymphocytes rapidly mobilize toward the inflammatory site alongside granulocytes, whereas T cells with low metabolic activity (immature, senescent, or defective cells, as well as those with blocked receptors—i.e., temporarily inactive cells) remain in the bloodstream and are poorly detected by standard laboratory methods, thus falling into the category of "null cells." Consequently, laboratory analysis reveals a sharp drop in T-lymphocyte counts coupled with an elevation in null cells.

Congenital and acquired immunodeficiencies are likewise characterized by decreased blood lymphocyte counts, occasionally presenting as absolute lymphopenia, as seen in AIDS. However, for A number of congenital immunodeficiencies, reduced T-cell levels are not a typical feature (e.g., Louis-Bar syndrome / ataxia-telangiectasia, adenosine deaminase deficiency, and nearly all types of dys- and agammaglobulinemia).

An elevated relative lymphocyte count is quite frequently observed in Autonomic Nervous system disorders. The ratios of T, B, and null cells, as well as T-helper and T-suppressor subsets, remain unaltered in these cases, indicating that increased numbers of lymphocytes are released into the bloodstream simply in response to routine neural stimulation.

Conversely, an increase in lymphocyte counts associated with endocrine disorders—particularly thyrotoxicosis accompanied by leukocytosis—is characterized by a drop in T-lymphocyte numbers alongside elevated T-suppressors and null cells, indicating active involvement of the lymphocytic branch.

Lymphoproliferative disorders are characterized by a marked increase in lymphocyte counts, occurring against the background of either leukocytosis or leukopenia, depending on the disease subtype.

An increase in the relative number of B lymphocytes—at times quite pronounced—is observed during the crisis phase, when the humoral specific immune response is engaged. The recovery of T-lymphocyte counts generally coincides with clinical convalescence.

Nevertheless, the progression of an acute inflammatory process largely depends on the baseline status of the immune system—whether it is in a normal functional state or compromised, and whether it is influenced by prior or concurrent illnesses. The course and outcome of the disease heavily rely on the quantity and quality of the antigen, its invasiveness, aggressiveness, and toxicity, among other factors. Finally, the anatomical localization of the process can exert a significant influence on the course of acute inflammation.

During the latter half of the inflammatory process, an increase in the relative blood count of B lymphocytes is observed. This most commonly occurs in viral infections. Typically, this parameter rises in parallel with the enlargement of Lymph Nodes regional to the inflammatory focus. An elevated percentage of B lymphocytes is generally seen in protracted or chronic inflammatory processes. A persistently high B-lymphocyte level is characteristic of patients with thyrotoxicosis.

Acute and chronic leukemia are characterized in most cases by a pathological increase in blood B-lymphocyte counts, frequently in parallel with an elevated number of null cells. Such conditions are accompanied by leukocytosis with lymphocytosis. However, in aleukemic forms, particularly in the Cytology/cytology/16.html">Early stages of the process, blood leukocyte levels remain within the normal range, whereas the proportion of B cells is sharply elevated (up to 90%).

In congenital immunodeficiencies, an elevated relative count of B lymphocytes may be observed, which is most characteristic of Swiss-type agammaglobulinemia (a combined immunodeficiency characterized by depressed immunoglobulin levels across virtually all classes); it occurs in more than 60% of patients. In this pathology, B lymphocytes are defective and fail to differentiate into fully functional plasma cells that secrete immunoglobulins. An increased number of B lymphocytes is also frequently detected in Nezelof syndrome (the French type of immunodeficiency). Conversely, in polyimmunodeficiencies, particularly combined ones, the B-lymphocyte count is reduced as a consequence of a general decrease in the total blood lymphocyte pool.

The appearance of plasma cells in the peripheral blood indicates severe irritation of the lymph node tissue, triggering their hyperproduction and leading to an enhanced release of plasma cells into the bloodstream.

The detection of plasma cells in the blood of an adult (typically at 1–3%) is associated with specific underlying diseases: infections such as measles, rubella (up to 20% of cases), cholera (late stages), bacterial dysentery, as well as severe forms of malaria, epidemic typhus, and typhoid fever. Severe cases of Influenza in children may also be accompanied by the appearance of significant numbers of plasma cells in the blood. Furthermore, plasma cells can be found in the blood of patients suffering from severe forms of anemia.

Plasma cells are consistently identified in plasmacytoma (multiple myeloma) and plasma cell leukemia. They may also be detected in chronic B-cell leukemia, usually during the advanced Stages of the disease.

Phagocytic activity of leukocytes. The next stage in evaluating an immunogram is determining the phagocytic activity of leukocytes. Phagocytosis is a non-specific Immune Response to The entry of foreign entities into the body. The effectiveness of phagocytosis dictates whether antigen dissemination in the body is prevented and whether foreign agents are successfully eliminated during the initial phase of the immune response. Defects in the phagocytic system lead to the development of pathological conditions, such as frequent pyogenic infections, recurrent bacterial infections, recurrent purulent infections, and Chediak-Higashi syndrome. In chronic granulomatous disease, associated with an innate defect in H₂O₂ production within granulocytes, abscesses may form in the Lungs, Liver, intestines, and Skin As a result of incomplete phagocytosis. Below are several Examples of disease development associated with various acquired defects of the phagocytic system (Table 27).

Table 27. Characteristics of phagocytic system defects in certain diseases

Note: * impairment, blockade.

First-tier tests make it possible to identify defects in the phagocytic system based on the phagocytic number and phagocytic index. Given appropriate clinical manifestations and laboratory data indicating impaired phagocytic engulfment capacity or incomplete phagocytosis, the feasibility of performing second-tier analytical tests is considered to pinpoint the exact site of failure within the phagocytic link.

Complement system. The next stage of the immunological examination involves studying the hemolytic activity of the complement system—the humoral arm of the non-specific immune response. The complement system participates in the immune response through three effector mechanisms: lysis of bacterial cell walls, generation of chemoattractants for phagocytic cells, and opsonization.

Hemolytic complement activity is determined by the 50% lysis of sheep erythrocytes sensitized with rabbit antibodies. This method evaluates the functional activity of the Components of the classical complement activation pathway. During acute inflammatory processes, complement activity increases because complement components (C5a, C3a, C4a) function as acute-phase proteins of inflammation. Of greatest diagnostic significance is a decrease in complement activity. This occurs in congenital deficiencies of complement components or regulatory proteins, as well as in acquired defects such as mixed cryoglobulinemia, acquired C1-inhibitor deficiency, and membranoproliferative Glomerulonephritis, all of which can cause a significant reduction or complete absence of CH50. Complement consumption driven by immune complex disease, infectious processes, autoimmune diseases, malignancies, trauma, burns, hypocomplementemic urticarial vasculitis, partial lipodystrophy, and liver disease can likewise lead to decreased CH50 levels. If reduced hemolytic complement activity is detected, additional tier II analytical tests are performed to identify specific complement component deficiencies.

The complement system plays a role in the elimination of circulating immune complexes (CIC) formed after antigen binding by antigen-specific antibodies. Consequently, a close correlation exists between hemolytic complement activity and CIC levels. For instance, CIC levels rise during viral and bacterial infections. If the CIC level increases while complement activity drops, it indicates accelerated consumption of complement components, with the immune complexes being composed predominantly of IgG and IgM. If CIC levels rise while hemolytic complement activity remains normal, it signifies that the ICs are formed primarily of IgA, since immunoglobulins of this class do not activate complement. Another scenario is possible where complement activity decreases against the background of normal immune complex levels; in this case, the presence of fixed ICs should be suspected first. The rate of CIC formation depends on the type of infection, type 4 allergic reactions, and the presence of systemic disorders, whereas the clearance rate of CIC is impaired in the presence of defects in either the complement system or the phagocytic system.

The rapid-response mechanisms of the immune system during the initial stage of pathogen entry also include the synthesis of acute-phase inflammatory proteins. These encompass, alongside complement system proteins, C-reactive protein, Fibronectin, fibrinogen, and serum amyloid A protein, which are produced primarily by hepatocytes. Beyond their opsonizing role in facilitating phagocytosis, these proteins help restrict pathogen dissemination within the body and protect autologous tissues by acting as inhibitors of peroxidation products generated during neutrophil degranulation. Assessing acute-phase protein levels provides insight into the adequacy of the immune system's response to an acute inflammatory process.

In the absence of antigenic challenge, specific antibodies are not produced. Based on this feature, antibody genesis is classified as an inducible process, with the antigen acting as the inducer. Antibody production requires a secondary costimulatory signal, which the B lymphocyte receives through direct T-B cell contact. During the acute phase of a disease, even at the incubation stage, IgM levels rise due to polyclonal B-cell activation, independently of the Specificity of the B-cell receptor IgM. This occurs at high antigen concentrations. Subsequently, as mitogen concentrations decline, the Synthesis of specific immunoglobulins begins—initially IgM, followed by IgG, but possessing the same specificity. High IgG levels can persist for a prolonged period.

Thus, during an inflammatory reaction associated with a primary contact between the Organism and a given antigen, IgM levels rise in the early stages of inflammation, followed subsequently by a surge in IgG levels. Upon secondary exposure to the same antigen, an elevation in both IgG and IgA levels occurs even in the early Phases of the inflammatory response.

The immune system's response to the penetration of a foreign agent or physical trauma (a mild stress response) is frequently accompanied by an elevation in plasma immunoglobulin concentrations (predominantly classes G and A) due to their release from storage depots. Conversely, major surgical Procedures that elicit a severe stress response lead to a reduction in immunoglobulin levels across all classes as a result of their sorption onto cells and damaged tissues. Such shifts resolve relatively quickly.

Certain diseases are accompanied by profound alterations in blood immunoglobulin levels. These conditions include:

a) multiple myeloma (plasmacytoma) with monoclonal paraproteinemia, where various disease variants reveal hyperproduction of immunoglobulin clones of different classes, while the synthesis of normal immunoglobulins across all classes is suppressed, increasingly so as the disease progresses;

b) autoimmune chronic and Viral Hepatitis, characterized by elevated levels of immunoglobulins of all classes, particularly IgG;

c) elevated IgG levels observed during the chronic course of systemic lupus erythematosus;

d) decreased levels of all immunoglobulin classes seen in benign follicular lymphoblastoma and in the terminal phase of proliferative disorders affecting hematopoietic and Lymphoid Organs;

e) a marked increase in immunoglobulin levels occurring in liver cirrhosis;

f) diagnostic significance attributed to decreased levels of IgG and IgA (against a normal or elevated IgE count) in pathologies characterized by increased permeability of all Blood Vessels, notably Nephrotic Syndrome and numerous generalized skin disorders with exudative components;

g) elevated IgE levels observed in all allergic diseases or pathologies featuring an allergic component, particularly of the immediate type, especially during interictal periods and sluggish exacerbations;

c) an increase in immunoglobulin levels occurs in a number of infectious diseases, such as cholera (due to hemoconcentration);

i) inflammatory processes on mucous membranes predominantly proceed with an elevated count of IgA or, in the case of decreased body resistance, with suppressed IgA production. Table 28 presents the Diagnostic significance of immunoglobulin determination.

Table 28. Diagnostic significance of immunoglobulin determination

Assessment of specific links in the immune chain. To characterize the content of individual T-lymphocyte subpopulations and their functional activity, level II tests are used, which are available only in well-equipped laboratories. To assess the specific humoral link of the immune system, the determination of serum immunoglobulins is applied. The involvement of antibodies in the immune response manifests in 3 forms: neutralization of the pathogen and its toxins; complement activation; opsonization.

Above, we examined how the total content of T- and B-cells changes during the development of an acute inflammatory process. To characterize the content of individual T-lymphocyte subpopulations and their functional activity, level II tests are used, which are available only in well-equipped laboratories. To assess the specific humoral link of the immune system, the determination of serum immunoglobulins is applied. The involvement of antibodies in the immune response manifests in 3 forms: neutralization of the pathogen and its toxins; complement activation; opsonization.

Normal ranges for the percentage of T-helper cells (%), T-suppressor cells (%), and their ratio (determined by the theophylline rosette-forming test) in the blood of healthy individuals are characterized by the following values.

Middle-aged adults: T-helper cells - 70%-(40-62%); 90%-(35-70%); 95%-(28-76%); T-suppressor cells - 70%-(8-25%); 90%-(6-35%); 95%-(4-45%); Th/Ts - 70%-(2.5-5.0); 90%-(1.8-6.0); 95%-(1.3-7.5).

Young children: T-helper cells - 70%-(30-56%); 90%-(24-65%); 95%-(21-70%); T-suppressor cells - 70%-(7-20%); 90%-(5-30%); 95%-(3-40%); Th/Ts - 70%-(2.0-4.4); 90%-(1.5-5.5); 95%-(1.2-6.6).

At various stages of a normally progressing inflammatory process, the blood counts of T-helper and T-suppressor cells fluctuate, yet in such a way that T-suppressors do not significantly outnumber T-helpers.

In severe inflammatory processes, the Th/Ts ratio may drop below 1. Such a decrease is caused by the preferential production, differentiation, migration to the inflammatory focus, or redistribution into lymphoid organs of a specific T-lymphocyte subpopulation.

A separate issue is the Th/Ts ratio in Acquired Immunodeficiency Syndrome (AIDS). In this disease, the HUMAN IMMUNODEFICIENCY VIRUS selectively targets and destroys T-helper cells, causing the Th/Ts ratio to plummet well below 1.

In the absence of overt clinical AIDS, a Th/Ts ratio dropping below 1 merely raises the suspicion of potential HIV carriage. This probability increases in the presence of suggestive anamnestic data and a vague symptom complex—fatigue, night sweats, generalized or localized lymphadenopathy. However, a definitive diagnosis of AIDS in such cases can only be established upon detecting antibodies and, crucially, HIV antigens in the patient's blood.

Nosologies in which the inflammatory process is accompanied by a sharp decline in the Th/Ts ratio:

1) T-helper cells (%) ↓, T-suppressor cells (%) ↑;

a) T-helper cells (10⁹/L) ↓, T-suppressor cells (10⁹/L) normal: AIDS, paraproteinemia;

б) T-helper cells (10⁹/L) ↓, T-suppressor cells (10⁹/L) ↑: malaria; multiple myeloma; chronic viral hepatitis; common variable immunodeficiency;

в) T-helper cells (10⁹/L) normal, T-suppressor cells (10⁹/L) ↑: agammaglobulinemia (Bruton's disease); Ulcerative Colitis.

2) T-helper cells (%) normal, T-suppressor cells (%) ↑:

a) T-helper cells (10⁹/L) normal, T-suppressor cells (10⁹/L) ↑: Sepsis; hemophilia; Schistosomiasis; solid plasmacytoma; infectious mononucleosis; immunodeficiency with thymoma; lung or kidney abscess; measles.

б) T-helper cells (10⁹/L) ↓, T-suppressor cells (10⁹/L) ↑: Peritonitis.

An elevated Th/Ts ratio is observed in the acute phase of Inflammatory Diseases, as well as in autoimmune disorders: hemolytic anemia (induced by warm and cold antibodies), immune thrombocytopenia, Hashimoto's thyroiditis, pernicious anemia, chronic active hepatitis, Goodpasture syndrome, systemic lupus erythematosus, rheumatoid arthritis, and Pemphigus vulgaris.

During the Initial Stages of inflammation, there is typically a relatively high count of T-helper cells and a low number of T-suppressors, yielding a high Th/Ts ratio (usually well above 3). In the second half of the inflammatory process, approaching its resolution, an elevation in T-suppressor levels is observed alongside a relatively high count of T-helpers. Near the disappearance of clinical signs of inflammation—often even before the complete restoration of T-, B-, and null cell counts—a decrease in the Th/Ts ratio is noted. Such dynamics of the Th/Ts index in a normally resolving inflammatory process confirm the heightened activity of the body's immune system aimed at eliminating the foreign agent and serve as a positive prognostic sign.

A complicated course of inflammation is frequently accompanied by a sharp drop in the Th/Ts ratio below 1, driven by an increase in T-suppressor counts. Across virtually all inflammatory diseases, this is an unfavorable sign indicating disease severity. Such a decrease in the Th/Ts ratio is most commonly seen in severe septic inflammatory conditions and severe forms of infectious diseases.

In Conclusion, Diagnostics and prognosis must always rely on a comprehensive evaluation of changes across all parameters of the leukogram and immunogram. The same final outcome of an immune response under equal conditions can be achieved through various quantitative and qualitative combinations of the immune system components.