IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

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

Dynamics of Leukocyte and Immunogram Parameters in Infectious Diseases

During The Development of immunopathological conditions, specific and nonspecific alterations in immune reactivity occur simultaneously, with the latter always predominating quantitatively and, in some cases, developing more rapidly. This is particularly evident during the development of inflammation.

The inflammatory process exhibits characteristic clinical stages accompanied by distinct shifts in the immunogram: a) incubation period; b) prodromal stage; c) onset and development of clinical symptoms; d) peak of the process; e) crisis; f) resolution of clinical manifestations; g) convalescence; h) recovery or transition of the disease into a chronic course (distinguishing between phases of remission and exacerbation).

Analyzing the dynamics of inflammatory stages across various immunogram parameters—specifically checking for the presence or absence of shifts characteristic of a given stage—can serve as a basis for predicting disease progression and adjusting therapeutic interventions. Studying the dynamics of key immunogram indicators during acute inflammation (Lebedev K.A., 1996) has demonstrated that under normal conditions, immunogram parameters form straight horizontal lines, whereas during inflammation, these lines become fluctuating.

During the incubation period, immunohemogram changes are minimal, with a drop in the percentage of T Cells occurring only at the very end of this period.

The prodromal stage is characterized by a moderate decrease in the percentage of eosinophils, a reduction in the relative and absolute basophil counts and the percentage of T cells, alongside an elevation in null lymphocytes.

The stage of fully developed clinical manifestations is marked by peak leukocytosis, increased monocyte levels, and—by the middle or end of the stage—normalization or reduction of the neutrophil percentage due to an increasing relative lymphocyte count. The left shift of the Blood formula persists or intensifies with the appearance of band/immature forms, indicating immune system activation. In cases of mounting intoxication, neutrophil phagocytic activity declines.

An extremely unfavorable sign is a further decrease in T-Cell and nucleated cell counts. Other poor prognostic indicators include an exacerbated left shift of the leukogram, an increase in immature neutrophil forms coupled with persisting leukopenia, an elevated T-suppressor-to-T-helper ratio, and reduced neutrophil phagocytic activity. Such conditions typically arise with highly pathogenic causative agents.

Table 43 illustrates the dynamics of immunogram parameters During the first three days of acute bacterial Pneumonia in comparison with the patient's immunogram obtained 2 months after recovery.

Class="center">Table 43. Dynamics of immunogram parameters during the development of bacterial pneumonia

Note: LI — load index (see text for details).

The crisis stage leading to subsequent recovery is characterized by the normalization of eosinophil counts, an increased percentage of B cells, a rise in T-suppressors relative to T-helpers, restoration of depleted T-cell counts, and normalization of nucleated cells. The general blood count reveals a drop in total leukocytes along with normalization of the neutrophilic nuclear shift (fewer immature forms) against the backdrop of a persistently high relative lymphocyte count. The favorable course of the recovery period is exemplified by the immunogram on day 7 of pneumonia (Table 39).

The transition of the process into a sluggish subacute course is accompanied by decreased eosinophil levels. Concurrently, There is a prolonged failure of T-lymphocytes and killers to recover, a trend toward increased monocyte counts amid lymphopenia, a persistent left shift characterized by juvenile neutrophil forms, and low neutrophil phagocytic activity coupled with high or reduced adhesive activity. Table 44 presents an immunogram reflecting protracted pneumonia in a patient with Diabetes Mellitus. The patient was admitted to the ICU for diabetic coma, and on day 8 developed bilateral pneumonia. Following antibiotic therapy, improvement was noted after 10 days, as confirmed by serial immunograms. However, 3 more days later, unfavorable trends appeared in The final stage of the process. Clinical Recovery was prolonged by 15 days.

Table 44. Immunogram reflecting a protracted course of pneumonia against the Background of diabetes mellitus (Lebedev K.A., 1996)

The convalescence stage begins as recovery concludes. A primary criterion for incomplete resolution is a reduced T-cell count combined with elevated null lymphocytes, whereas an increasing B-cell count confirms ongoing convalescence.

If a patient is prematurely returned to a full normal workload and all therapeutic measures are discontinued at this stage, either a disease relapse with clinical symptoms may occur or, much more frequently, a chronic process will develop following a variable period of remission. The clinician's objective at this stage is to differentiate between complete recovery and the transition into convalescence (once clinical symptoms have resolved). Analyzing the immunogram, particularly dynamically, helps the physician determine the exact endpoint of the inflammatory process, thereby guiding the appropriate timing for discontinuing Treatment.

A chronic inflammatory process in the remission phase is characterized by markedly reduced immunological regulation, high immunogram lability, and parameters frequently straying beyond normal limits.

An immunogram indicator pointing to the clinical remission of a chronic process is a load index (LI) significantly lower than that of a healthy individual. The load index (LI) represents The ratio of E-RFC/E-RFC(th) across a series of stress tests, such as following 30 minutes of lymphocyte incubation at 37°C or after incubation with theophylline. For middle-aged adults, normal LI values are below 2. A shifted LI—whether accompanied by clinical symptoms or not—reflects highly synchronized, active functioning of The Immune System regardless of the specific Site of Action. Consequently, a reduced LI can be detected in any chronic or unresolved acute process. For instance, a lowered LI may equally indicate the presence and persistence of chronic cholecystitis or tonsillitis if the patient has a history of these conditions. Nevertheless, if a clinically healthy patient's LI returns to normal, one can state with a high degree of certainty that all chronic inflammatory processes have ceased.

Table 45 shows the immunogram of a patient with chronic tonsillitis complicated by frequent acute respiratory infections (more than 6 episodes per year), obtained 36 days after the resolution of a recent tonsillitis episode against a background of complete clinical well-being. This immunogram exhibits a decreased LI value, indicating a chronic process in remission despite the apparent clinical health. Notably, the immunogram reveals a high level of T-suppressors, nearly matching the percentage of T-helpers, which is extremely rare in healthy individuals.

Table 45. Immunogram of a female patient with chronic tonsillitis complicated by frequent acute respiratory infections (>6 episodes per year), obtained 36 days after the resolution of a recent tonsillitis episode and following 2 years of prophylactic care against the background of complete clinical well-being (Lebedev K.A., 1996)

In chronic inflammatory processes during the acute phase, a distinct pattern is observed. The overwhelming majority of immunogram parameter shifts in this case resemble those seen in acute inflammation, although they are typically less pronounced. With mild inflammation, the degree of immunodeficiency decreases, while with significant inflammation, it increases. Abnormally high values of immune parameters indicate an unfavorable prognosis.

During a mild exacerbation of a chronic process, the II remains at the same level maintained throughout the entire flare-up. However, if the exacerbation is sufficiently intense, the II rises to values typical of the norm or even exceeds the levels usually found in healthy individuals. Extremely high II figures are an unfavorable sign, indicating a severe course of exacerbation against the background of reduced bodily resistance. Changes in the immunogram during the acute phase of a chronic process are presented in Table 46. The first immunogram was taken from a patient at the peak of a severe Exacerbation of chronic obstructive pulmonary disease, and the second was taken after treatment, upon discharge from the clinic in a satisfactory condition.

Table 46. Changes in the immunogram during the acute phase of a chronic process (Lebedev K.A., 1996)

Note: II - index of burden (see text for explanation).

Unlike acute inflammation, exacerbations of chronic inflammatory processes do not exhibit a decrease in blood eosinophil counts at the onset followed by normalization towards the end, which is attributed to the frequent presence of an allergic component in chronic conditions. Furthermore, during the flare-up of a chronic process, the ESR increases more frequently and persistently than in acute conditions. Similarly, the elevation of B-lymphocyte levels occurs earlier and reaches significantly higher values during chronic exacerbations compared to acute ones.