State Immunity in Patients with Herpes

State immunity in patients with herpes

State immunity in patients with herpes - Clinical outcome of first GI is primarily determined by immune status. At the same time it should be noted that the nature of the pathogenetic changes in the body of patients with herpes is mainly due to the possibility of integration of the genome of the virus into the host cell genome, particularly in the paravertebral ganglia, as well as trails, completely HSV and other herpes viruses in blood cells and immunocytes (red cells, platelets, granulocytes, macrophages, lymphocytes) - It promotes lifelong Percy stentsii structures of HSV in the human body and causes changes in cellular and humoral immunity.

Moreover, today, GM is regarded as infectious (acquired) immune system disease (Barinskaja JF et al, 1986), in which long-term persistence of the virus in some cases accompanied by productive HSV infection in virtually all cells of the immune system that manifests their functional impairment and promotes the formation of immunodeficiency (Barinskaja JF, 1988, Kolomiets. A. et al., 1992). Us, as well as other researchers, have shown that the leading role in the formation of antiherpetic immunity cellular mechanisms, the state which mainly determines both the outcome of the initial infection and the frequency and intensity of relapses (Barinskaja JF et al., 1986; Isakov VA et al., 1993). The duration of immunodeficiency in viral infections is primarily determined by the properties of both the virus and the type of responses the patient.

It is believed that a high level of specific antibodies in the blood of patients with recurrent herpes stabilizes the persistence of the virus, but does not prevent recurrences (Bocharov AF et al., 1982; Semenova TB et al., 1987). TB Semenova et al. (1987) showed that in severe recurrent GI lesions with skin and mucous membrane disease is on the back of high titers of antibodies komplementsvyazy-tries with a decrease in the quantitative content of leukocytes and lymphocytes, while the correlation of population lymphocytes.

Numerous researchers (Barinskaja JF et al, 1986, Isakov VA, and others, 1991.1997; Prigogine, VK et al, 1990; Rakhmanov AG et al, 1995) showed that GM reduced the total to * lichestvo CD3 + cells (T lymphocytes general), CD4 + (T helper cells), decreased immunoregulatory index (CD4: CD8).

Reduced activity of natural killer and antibody-cell chi-totoksichnost, inhibited the ability of leukocytes to the synthesis of endogenous interferon. Revealed changes were typical for patients with moderate and severe recurrent herpes. They are registered in a phase of relapse, in remission, the positive dynamics of the studied immunological parameters, but remained below average.

We conducted a comprehensive immunological study of 148 patients with genital herpes (GH) due to HSV. In 42% patients had a severe course of TT (relapse at least 1 per month), 33% had moderate (1 recurrence in 2 - 3 months) and 25% - a latent form of HS. Both monoinfection HS proceeded in 22% of patients in the remaining cases were identified different microbial associations.

In the peripheral blood was determined by the number of competent immunocompetent cells (CD3, CD4, CD8 T-cells and CD22 for B cells), proliferative activity of lymphocytes under the action of T-and B-cell mitogens in the RBTL, the activity of NK-cell anti- telozavisimuyu cytotoxic lymphocytes (AZTSTL). Investigated the phagocytic and metabolic activity of leukocytes in spontaneous and induced NBT test (test Nitroblue Tetrazolium), the level of cationic proteins (CB), lactoferrin (LF) and myeloperoxidase (MPO), the performance tserulop-lazmina (CPU), transferrin (TF) immunoglobulins and circulating immune complexes (CIC). The level of interleukins 1 and 2 (Table No 12).

A survey of patients with acute exacerbation GM found that the level of phagocytic activity of leukocytes was usually normal or tended to increase (Fig. 2). Marked reduction in the number of phagocytic cells (less than 30% at a rate of 52.5%) occurred in a few patients (frequency - 0,1). At the same time, the exacerbation of a chronic process revealed a significant increase in performance oxidase activity of leukocytes in both spontaneous and induced to test the NST compared with the control group (CNT spontaneous = 38.0 7.6%; NST induced = 60.0 + 6,9% against 18,4 ± 2,1% and 36,9 ± 3,6% in the control, P <0.05).

High values of the induced NBT test accompanied by the presence of more highly of cells: the activity index ranged from 0.6 to 1.0 vs. 0.5 -0.75 in the control group. Improved performance of spontaneous and induced NBT-te-hundred and indicates an increase in the redox potential of cells, which correlates with higher values of CEC, identified in patients in acute phase {Figure 3). At the same time growing the number of high-level cells (induced by NBT-test) can be interpreted as an increased expression of Fc-and csh-receptor on the membrane of cells involved in phagocytosis (Noseson MW, 1982). Changes in the levels of major classes of immunoglobulins have been minimal, only in few cases, the concentration of IgG increased to 14,0 - 15,5 g / l (at 11.5 g / L in healthy individuals), against the backdrop of high values of CEC, which requires further study.

When remission 2-3 weeks after exacerbation in patients observed decline in stimulated NBT-test (up to 27,6 ± 2,9% vs. 36,9 ± 3,6% in controls). In some cases (frequency - 0.3) occurred in reducing the number of phagocytic cells, T ca. The percentage of phagocytosis was 16 -30% -68% versus 41 in the control group.

With the reduction of functional activity of leukocytes were detected in the blood increase in IgA (2,47 ± 0,19 g / L vs. 1.90 0.08 g / L in controls, P <0.05), in some cases, the reduction of IgG to lower limit of normal, equal to 7.0 g / l (frequency - 0.2) coincided with clinical remission.

Also of interest to analyze the state of the phagocytic and oxidative function of leukocytes in 40 patients with recurrent genital herpes (WPG), depending on the duration and phase of the disease, as well as the frequency of relapses (Fig. 4), * Patients were divided into two groups: the first consisted of patients with disease duration up to 2 years and with the frequency of recurrence is not more than 2 times a year.

The second group consisted of persons who are suffering from herpes for over two years and with the frequency of exacerbation of the disease for more than three times a year.

It is shown that in acute infection, usually, a decrease of phagocytic activity and an increase in the number of cells capable of restoring Nitroblue tetrazo of effort regarding stimulation of neutrophils and PHA in the spontaneous NBT-test. Apparently, the observed changes are due to a large number of viral antigen in the inflammation and intense increase in leukocytes of reactive oxygen species.

For the period of clinical remission in patients with the first group level study defense reactions was within the bounds defined in healthy subjects (Fig. 4). At the same time the second group of patients in remission, there was a distinct increase in indices of spontaneous and induced NBT-test, which proved to be somewhat lower than the values characteristic of the period of exacerbation (see Fig. 4). During the period of remission in patients suffering from HS for over two years, phagocytosis was more active than in the acute phase but significantly lower than in healthy individuals. The changes revealed in our opinion, are due to chronic antigenic load and reflect the state of functional overstrain of phagocytes in patients in remission.

The study of cell activity monotsitaryao macrophagolimphoid-dimensional system (MMS) is of interest to clinicians because MMC cells are involved in many phases of the immune response, primarily interact with T cells during antigen recognition and processing of antigenic information. Directly or indirectly activated T-lymphocytes cells MMC play an essential role in the effective acceptor phase of the immune response (cytotoxic effects, uptake of immune complexes).

In this regard, we also investigated the characteristics of macrophage responses and functional activity of T lymphocytes in vivo in a test on Rebuck skin window (Rebuck F., Gromnley F., 1925) in patients with herpes simplex in the acute stage of illness.

Previously it was shown that the activity of immune cells of the dermal layer could be determined by the output of macrophages in the area of aseptic inflammation (in the daily dermogramme) and their response to mitogen-NY tuberculin, PHA (T-cell mitogens), as well Pee rogenal (mitogen 6-lymphocytes and macrophages) (Golzand IV et al, 1984).

In daily dermogramme, we studied 15 patients during the recurrence of HS, showed inhibition of spontaneous migration of macrophages (MF), the increased output of lymphocytes (LF) and neutrophil (NP), as well as a decline in the (MH + MF): NP compared with control group of healthy subjects {Table. 13),

The introduction of tuberculin into the zone box accompanied by a moderate yield of lymphocytes in the inflammatory focus (11.9%), decreasing the number of neutrophils (34.5%). Migration of macrophages was higher than in healthy individuals (53,7% and 36,4% respectively). Ratio (MH + MF): FN was significantly higher than in the control group. Obviously, this reflects the redistribution of immune cells of the dermis, migrating into the inflammatory focus under the influence of mitogens.

In formulating the intradermal tuberculin test in 3 of 15 patients, the result was negative in 12 - moderately positive (induration diameter - 11 mm in healthy individuals - 7 mm, P <0.05).

Introduction to the area of the skin window pyrogenic accompanied by some reduction in the yield of lymphocytes, the significant increase in monocyte-macrophage cell line and a decrease in yield of neutrophils. Ratio (MH + MF): FN was equal to 1.28, whereas in healthy individuals -0.7 (P <0,001).

Thus, in patients with RGI in a phase of relapse had a substantial change in the ratio of cells identified in dermogramme and their response to mitogens. B-cell-ki actively responds to pirogenal than T cells to tuberculin, which confirms the functional deficiency of T-cell immunity in the patients examined.

Increased in recent years the interest of scientists to study the role of factors of nonspecific resistance in antiviral immunity is not accidental. As a phylogenetically more ancient mechanism protecting the organism, the immune system, the various components of nonspecific resistance contribute to the complex responses of the body to viral infection. It should be emphasized that in time these events precede the development of specific immune response (Masing A., Danilova MA, 1989).

Critical factors of nonspecific defense, along with the above, are cationic proteins (KB) of neutrophil granulocytes (NG). Secret enzymes (myeloperoxidase, lysozyme, cathepsin 6, elastase) and non-enzymatic (difensiny, bactericidal permeability increasing protein, lactoferrin), cationic proteins (Kokryakov VN et al., 1989). In the literature available to us we did not encounter reports that examine the dynamics of CB in patients with herpes. The activity of CB, we determined the reaction lysosomal-cation test (LKT) (Bryazzhiko-vaT. C, 1995).

Established that the granules contained in NG cationic proteins have diverse functions in the inflammatory reaction (inflammatory mediators, non-specific opsonins for phagocytosis, modulators of blood coagulation and fibrino-lease, etc.). Cationic proteins provide a powerful antimicrobial potential of NG due to the combined effect on the structure and metabolism of microorganisms. Low molecular weight CB - difensiny, being highly basic surface compounds inhibit reproduction of HSV, acting on the shell of the virus and depriving him of membranotropic-surface.

Consequently, they are active in the free and sorbed on cell virus (Kokryakov VN, 1988) and are factors readjustment of the body against viruses and suppress the infection. We have shown that the acute phase of HS accompanied by a decrease of the total content of CB, as defined in LKT, which might suggest that an intensive secretion of LH and the active involvement of these cells in the system of host defense reactions. Further positive dynamics of the infectious process accompanied by an increased content of CB, respectively, and the restoration of indicators LKT to average values. Nevertheless, high levels of serum myeloperoxidase (MPO) for the entire cycle of the disease may be indicative of a constant voltage of secretion of LH, provided by accelerating the circulation of NY and a more rapid upgrade a pool of these cells in the blood. Indicators of NBT-test and phagocytosis NG further evidence of active involvement in the pathological process of NG, which is accompanied by depletion of the functions of these cells in remission.

Specific interest is metalloproteins chain-ruloplazmin (CPU), transferrin (TF) and lactoferrin (LF), which are acute phase proteins of inflammation, the primary symptom of which - a rapid and significant change in concentration due to the violation of homeostasis irrespective of the nature and location of the stimulus causing it. As is known, the mechanism ostrofaznoy reaction is that under the action of damaging factors are distinguished biologically active substances that contribute to the increased synthesis of IL-1 and other cytokines. Stimulates the protective response of the body and enhances the synthesis of liver acute phase proteins of inflammation - in particular CPU. Therefore, in severe inflammatory reaction observed higher concentration medsvyazyvayuschego blood protein.

It is considered that zhelezosodezhaschy protein belongs to the toxic ostrofaznym proteins whose concentration decreases at the beginning of the disease.

Lower content of HF in patients with uncomplicated and oeobenno complications of influenza and herpes simplex * acute phase of illness confirm this position at this, we have shown that the easier it is for a viral infection, the less significant decrease in FF, the more massive the clinical course of influenza and herpes viruses, the stronger reduces the value of TF in the blood serum (Isakov VA et al., 1996).

The mechanism of reduction of FF is the same - the development of acute-phase inflammatory response. Increased levels of IL-1 enhances the release of LF neutrophils, it captures the LF iron and leads to gshyusideremii. It can be assumed that lowering of serum iron, accompanying the development of many inflammatory diseases, and reduces the concentration of HF. Perhaps, medsvyazyvayuschy protein is involved in this process, since it has expressed enzyme roksidaznymi properties: it oxidizes Fe2 * -> Fe3 +, which is built in a molecule apotransferina.

Lactoferrin (LF) plays a vital role in intercellular cooperation of phagocytic cells. LF receptors found on monocytes, macrophages, NY, activated T-lymphocytes and B lymphocytes (Naidu AS, 1991). Absorption LF mononuclear phagocytes inhibit their ability to form hydroxyl radical and protect cells from an autoperoksidatsii membrane. Increased LF in the serum of patients with GI can be considered as antioxidant protection dantnuyu undertaken NY, and a favorable prognostic sign, indicating the occurrence of remission (Bryazzhikova TS et al., 1995).

Lactoferrin is a marker of specific granules NY, on the inner membrane, which is a set of receptors in these cells. LF secretion of particular granules is accompanied by activation of the receptor cells of the field due to the incorporation of protein receptors in the outer membrane NG. In dynamics, we see a significant increase in LF, reaching maximum values in remission, this can be accompanied by an increased functional activity of LH with subsequent activation of cells of mononuclear phagocytes carrying elimination of the pathogen.

Nevertheless, we see increased levels of CEC in remission, suggesting the inferiority of MMC cells, since HSV has a tropism for these cellkam and can hurt them. Thus, there is a failure of effector cells in the acute stage and remission of herpes simplex, which in this case is only the unstable equilibrium between the host and pathogen, accumulating the potential for the next cycle of the disease.

It is known that phagocytosis is accompanied by the formation of reactive oxygen species (ROS) generated neytrofilamn in significant quantities in the initial stages of stimulation of immune cells. ROS formation is an important point, providing the phagocytic activity of neutrophils, eosinophils, monocytes. However, excessively high concentrations of ROS have a destabilizing effect on the cell membranes, initiate the process of le-rekisnogo lipid oxidation, may cause depression of the phagocytic activity of cells. For the inactivation of the negative impact of ROS on cells and tissues in the latter, there is a system of antioxidant protection (AOP). The primary enzyme specific AOD in the body is superoxide dismutase (SOD). Along with the SOD active components of AOP are catalase, ceruloplasmin, deep-tation peroksyadaza, glutathione, ascorbic acid and uric acid, glucose, mannitol, etc.

The main copper-containing protein of blood plasma is ceruloplasmin (Cp). It connects 95% of all copper, and it is used for the enzymatic activity in the oxidation of Fe2 + to Fe3 +, after which the iron-bound transferrin. It is essential that the oxidation of Fe2 + to Fe3 +, in contrast to non-enzymatic oxidation of Fe2 * in the presence of oxygen is not accompanied by the formation of superoxide anion (02). Therefore, the oxidative reactions involving Fe2 + ions is the primary antioxidant ceruloplasmin plasma, a kind of trap for ROS (Loginov C Matyushin BN, 1994; Gutteridge J. MS et al., 1979).

In the sera of patients with chronic GH level, CP was significantly higher than those of healthy individuals, indicating that the increase in antioxidant capacity of blood serum in acute illnesses * lower concentrations of CP characterized phase of clinical remission, but its level was still significantly higher than in healthy individuals. It indicates that the voltage of AOS and in reduction GM, which is apparently due to the need of inactivation increased concentrations of ROS.

An essential role in the enzymatic production of ROS play a variable valency metals (iron and copper). The primary purpose of transferrin and lactoferrin in the organism is the acceptance of free iron, which prevents the development of the reactions of the hydroxyl radical (OH), catalyzed by iron ions.

IV Drobot (1992) and Turkin VV (1994) showed that children with pseudotuberculosis and infectious mononucleosis (Epstein - Barr virus) increased the level of not only them-munoreaktivnoy forms of CP, significantly increased blood levels of the enzymatically active fraction of this protein. The latter suggests an essential protective role of this particular type of CKD, which is apparently due to the ability medoksidazy inactivate free radicals that are available in abundance in the inflammation. Besides, CP enhances the production of antibodies, improves the production of IL-1 by activated macrophages, increases the proliferation of cytotoxic T cells and K cells. Thus, we studied metalloproteins (CPU, TF, and LF) possess not only antioxidant but also are essential components of nonspecific re-zistentnosti, providing resistance to bacterial and viral infections (Isakov VA et al., 1996; Turkin VV, 1994).

In conclusion, it should be noted that for recurrent GI depressed and unbalanced system of T-and B-cell immunity, which plays a decisive role in antiviral defense. However, there is a functional deficiency of many factors of a nonspecific-resistant surface of the body. Moreover, the violations recorded in the immune homeostasis in the phase of relapse and remission of the disease, thus significantly prejudice and explaining the development of long-term persistence of herpesvirus in the organism with the establishment of relapsing disease course. The above facts should undoubtedly be taken into account clinicians in treating patients with various forms of herpes infection.

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