**1. Introduction**

[26] Reed, L., Muench, H.A. (1938). A Simple Method of Estimating Fifty Per Cent End‐

[27] Rubin, S.G., Chumakov, M.P. (1980). New data on the antigenic types of tick-borne encephalitis (TBE) virus. Arboviruses in the Mediterranen Countries. – Stutgart, New

[28] Tamura, K, Peterson, D, Peterson, N, Stecher, G., Nei, M, and Kumar S. MEGA5: Mo‐ lecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods. Molecular Biology and Evolution.

points. Am. J. Hyg.. № 27. pp. 493-497.

2011. V. 28. №10. pp. 2731-2739.

York, pp. 231-236.

112 Encephalitis

In the 1990s, both in the Far East and other regions of Russia, has intensified the incidence of tick-borne encephalitis (TBE), which reached the 1940-1950s, with widespread worsening of clinical signs of infection (Mamunts, 1993, Zlobin & Gorin, 1996; Leonova, 1997; Erman et al., 1999, etc.). The Far Eastern version of the tick-borne encephalitis has long been known as a heavy neuroinfection clinically flows mainly in the focal paralytic forms with residual symptoms, high mortality rate reaching 30-35%, and sometimes a progressive transition to a chronic form.

Well-known in the literature, the classical data on the pathological anatomy and pathogene‐ sis of human tick-borne encephalitis, date back to the early period of the study of this infec‐ tion on Far East in 1940 - 1950's, given the generalized idea of the nature and location of the morphological changes in the central nervous system (Robinson & Sergeeva, 1939, 1940; Kastner, 1941; Panov, 1956; Shapoval, 1961; Belman, 1960).

In 1960 - 1990-s the study of pathology of tick-borne encephalitis occurred mainly in the experimental-morphological terms, and was aimed to clarify issues of pathogenesis and immunogenesis, the study of viral neurovirulence strains, and their differentiation to find high-performance candidates for the preparation of vaccine against tick-borne encephalitis (Rozina, 1972; Frolova, 1965, 1967, 1973, 1975; Konev, 1982, 1995; Kvetkova, 1984; Erman et al., 1999, etc.).

The experience 75- years of the study showed that the tick-borne encephalitis is not mono‐ lithic and heterogeneous infection, including several subspecies: the Far-Eastern, the Sibe‐

© 2013 Somova et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

rian and other variants, which differ in the clinic, the severity and outcome of disease, as well as antigenic and genetic structure of pathogens, habitats and mechanisms of trans‐ mission (V.I. Votyakov et al., 1978; A.A. Smorodintsev, A. Dubov, 1986; V.I. Zlobin et al., 1996; M.P. Isaeva, 1998; Y.P.Dzhioev, 2000, G.N. Leonova, 2009; H. Holzmann et al., 1991; G.N. Leonova et al, 1999).

with severe exudative phenomena with the formation of perivascular infiltrates consisting of lymphocytes, monocytes, plasma cells, histiocytes, as well as with diffuse proliferative glial response. As pointed out by Kestner (1941), the pathological process can be described as an acute non-purulent meningo-polioencephalomyelitis involving all sections of the cen‐ tral and peripheral nervous system. Pathological changes are found in sensory and vegeta‐ tive nodes, as well as in peripheral nerves (Semenov-Tien Shansky & Shapoval, 1949;

The Pathomorphology of Far Eastern Tick-Borne Encephalitis

http://dx.doi.org/10.5772/53449

115

In the pia mater and vascular plexuses of brain ventricles observed redness, swelling, and stratificatione, perivascular infiltrates of lymphocytes and histiocytes, to a lesser extent – leukocytes and plasma cells. Revealed the destruction and proliferation of ependyma cells of the ventricles, subependimar glia cells, as well as the central gray matter of the Sylvius

The permanent feature of TBE pathomorphology are the vasomotor disturbances. There has been a dramatic expansion and vascular hyperemia until capillary stasis, diapedetic hemor‐

Nerve cells in the affected area are in a state of acute swelling, vacuolization, the perinuclear or the total chromatolysis, kariocytolisis, cytolisis elting, neuronophagia. It is characteristic

The destructive changes occur in hematogenous cells of inflammatory infiltrates and in proliferating glial cells with the expressed klasmatodendrosis. In the subsequent forma‐ tion of multiple foci of softening, localized in the varoliav pons, medulla oblongata, bain legs, hypothalamic area, basal ganglia and spinal cord. The deep destructive changes also occur in the vascular wall and in the white matter of the brain with signs of myelin and

The most mobile part of the pathological process are inflammatory changes that already in the acute stage are not always identical. In most cases, there is an abundant infiltration of vessels wall, perivascular infiltration of lymphocytes and histiocytes with an admixture of polymorphonuclear leukocytes and a small amount of plasma cells. With the prolongation of infection the infiltration of lymphocytes and plasma cells increases, the massive perivas‐

There is the focal and diffuse proliferation of microglia, astrocytes and oligodendroglia (Sha‐ poval, 1961; Zlotnik, 1968; Zlotnik et al., 1976). There are formed numerous glial nodules,

Thus, the preferential injury of Varoliy pons, medulla oblongata nuclei and the motor neu‐ rons of the anterior horn of the cervical spinal cord is the main feature of the topography of

Sometimes the inflammation in the brain at TBE passes in atypical with little or no produc‐ tive and exudative changes. The perivascular infiltration is isinsignificant, the inflammatory response is expressed in the form of microglial nodules. In these cases, you should empha‐ size the discrepancy between the severity of the clinical course and low severity of inflam‐

rhages, coagulation thrombi, sometimes fibrinoid necrosis of vessel walls.

of the TBE the piknomorfic (hyperchromic) changes of nerve cells.

granulomas in place the dead nerve cells and around capillaries.

Dekonenko et al., 1994).

axons disintegration.

cular infiltrates as a muffs appeared.

the histo-pathological changes typical for TBE.

aqueduct.

It is shown that the disease is characterized by polymorphism of clinical manifestations from inapparent to severe fever and focal forms, from the acute to progressive chronic course, from the complete recovery to the serious residual effects and death.

Characteristic features of the pathogenesis of tick-borne encephalitis are: the presence of two phases of infection - visceral and neural; hematogenous, lymphogenous, and neural pathes the generalization of infection and penetration of the pathogen in the central nervous system (CNS); the marked tropism of the virus to lymphoid tissue, an early and active involvement of the immune system in the process of reproduction of the virus and the patholigical proc‐ ess; the pronounced neurotropizm and the diffuse spread of the virus in the CNS. The incu‐ bation period for TBE is an average of 7-14 days.

The well-known in the literature, the classical description of the pathomorphology of acute TBE in human is mainly characterized by the stage of maximum expression of the pathologi‐ cal process in the CNS. The evaluation of encephalitic changes carried out in accordance with general pathological knowledge that existed in the mid-twentieth century and up until the last decade (Erman et al, 1999; Ierusalimsky, 2001) did not undergo correction in terms of immunopathogenesis.

On examination of the dead peoples they often have a strong constitution and good phys‐ ical development (Shapoval, 1980). Macroscopic changes appear only hyperemia and ede‐ ma of the meninges and brain substance. There are a small subarachnoid and subpial hemorrhages. The figure matter of the spinal cord is blurred, especially in the neck and shoulder level. In the anterior horns of the spinal cord revealed small foci of hemorrhage, and softening. In the internal organs is determined the congestive hyperemia and degen‐ erative changes. The serous and mucous membranes often have pinpoint hemorrhages. The spleen is usually hyperplasive. Some of the dead people have the thinning of the cort‐ ical layer of the adrenal glands.

The histopathological picture of acute tick-borne encephalitis is characterized by diffusely distributed in the central nervous system inflammatory changes that are made up of altera‐ tive, exudative and proliferative effects. The most severe changes with necrosis and massive deposition of motor nerve cells observed in the indicator areas (Nathanson et al., 1966): in anterior horns of the cervical and thoracic spinal cord, the nucleus of the hypoglossal and the vagus nerves, the reticular formation and inferior olive of the medulla oblongata as well as its own nucleus Varoliy pons, red nucleus and substantia nigra of the brain legs and in the cortex and nuclei of cerebellum (Robinson & Sergeeva, 1940). The pathological process with necrobiosis of nerve cells is also observed in the thalamus, caudate and lenticular nu‐ clei, and diffusely in the cerebral cortex of the brain. The degree of severity of the process decreases in the oral direction of CNS. Alterative changes in the nerve cells are combined with severe exudative phenomena with the formation of perivascular infiltrates consisting of lymphocytes, monocytes, plasma cells, histiocytes, as well as with diffuse proliferative glial response. As pointed out by Kestner (1941), the pathological process can be described as an acute non-purulent meningo-polioencephalomyelitis involving all sections of the cen‐ tral and peripheral nervous system. Pathological changes are found in sensory and vegeta‐ tive nodes, as well as in peripheral nerves (Semenov-Tien Shansky & Shapoval, 1949; Dekonenko et al., 1994).

rian and other variants, which differ in the clinic, the severity and outcome of disease, as well as antigenic and genetic structure of pathogens, habitats and mechanisms of trans‐ mission (V.I. Votyakov et al., 1978; A.A. Smorodintsev, A. Dubov, 1986; V.I. Zlobin et al., 1996; M.P. Isaeva, 1998; Y.P.Dzhioev, 2000, G.N. Leonova, 2009; H. Holzmann et al., 1991;

It is shown that the disease is characterized by polymorphism of clinical manifestations from inapparent to severe fever and focal forms, from the acute to progressive chronic

Characteristic features of the pathogenesis of tick-borne encephalitis are: the presence of two phases of infection - visceral and neural; hematogenous, lymphogenous, and neural pathes the generalization of infection and penetration of the pathogen in the central nervous system (CNS); the marked tropism of the virus to lymphoid tissue, an early and active involvement of the immune system in the process of reproduction of the virus and the patholigical proc‐ ess; the pronounced neurotropizm and the diffuse spread of the virus in the CNS. The incu‐

The well-known in the literature, the classical description of the pathomorphology of acute TBE in human is mainly characterized by the stage of maximum expression of the pathologi‐ cal process in the CNS. The evaluation of encephalitic changes carried out in accordance with general pathological knowledge that existed in the mid-twentieth century and up until the last decade (Erman et al, 1999; Ierusalimsky, 2001) did not undergo correction in terms

On examination of the dead peoples they often have a strong constitution and good phys‐ ical development (Shapoval, 1980). Macroscopic changes appear only hyperemia and ede‐ ma of the meninges and brain substance. There are a small subarachnoid and subpial hemorrhages. The figure matter of the spinal cord is blurred, especially in the neck and shoulder level. In the anterior horns of the spinal cord revealed small foci of hemorrhage, and softening. In the internal organs is determined the congestive hyperemia and degen‐ erative changes. The serous and mucous membranes often have pinpoint hemorrhages. The spleen is usually hyperplasive. Some of the dead people have the thinning of the cort‐

The histopathological picture of acute tick-borne encephalitis is characterized by diffusely distributed in the central nervous system inflammatory changes that are made up of altera‐ tive, exudative and proliferative effects. The most severe changes with necrosis and massive deposition of motor nerve cells observed in the indicator areas (Nathanson et al., 1966): in anterior horns of the cervical and thoracic spinal cord, the nucleus of the hypoglossal and the vagus nerves, the reticular formation and inferior olive of the medulla oblongata as well as its own nucleus Varoliy pons, red nucleus and substantia nigra of the brain legs and in the cortex and nuclei of cerebellum (Robinson & Sergeeva, 1940). The pathological process with necrobiosis of nerve cells is also observed in the thalamus, caudate and lenticular nu‐ clei, and diffusely in the cerebral cortex of the brain. The degree of severity of the process decreases in the oral direction of CNS. Alterative changes in the nerve cells are combined

course, from the complete recovery to the serious residual effects and death.

G.N. Leonova et al, 1999).

114 Encephalitis

of immunopathogenesis.

ical layer of the adrenal glands.

bation period for TBE is an average of 7-14 days.

In the pia mater and vascular plexuses of brain ventricles observed redness, swelling, and stratificatione, perivascular infiltrates of lymphocytes and histiocytes, to a lesser extent – leukocytes and plasma cells. Revealed the destruction and proliferation of ependyma cells of the ventricles, subependimar glia cells, as well as the central gray matter of the Sylvius aqueduct.

The permanent feature of TBE pathomorphology are the vasomotor disturbances. There has been a dramatic expansion and vascular hyperemia until capillary stasis, diapedetic hemor‐ rhages, coagulation thrombi, sometimes fibrinoid necrosis of vessel walls.

Nerve cells in the affected area are in a state of acute swelling, vacuolization, the perinuclear or the total chromatolysis, kariocytolisis, cytolisis elting, neuronophagia. It is characteristic of the TBE the piknomorfic (hyperchromic) changes of nerve cells.

The destructive changes occur in hematogenous cells of inflammatory infiltrates and in proliferating glial cells with the expressed klasmatodendrosis. In the subsequent forma‐ tion of multiple foci of softening, localized in the varoliav pons, medulla oblongata, bain legs, hypothalamic area, basal ganglia and spinal cord. The deep destructive changes also occur in the vascular wall and in the white matter of the brain with signs of myelin and axons disintegration.

The most mobile part of the pathological process are inflammatory changes that already in the acute stage are not always identical. In most cases, there is an abundant infiltration of vessels wall, perivascular infiltration of lymphocytes and histiocytes with an admixture of polymorphonuclear leukocytes and a small amount of plasma cells. With the prolongation of infection the infiltration of lymphocytes and plasma cells increases, the massive perivas‐ cular infiltrates as a muffs appeared.

There is the focal and diffuse proliferation of microglia, astrocytes and oligodendroglia (Sha‐ poval, 1961; Zlotnik, 1968; Zlotnik et al., 1976). There are formed numerous glial nodules, granulomas in place the dead nerve cells and around capillaries.

Thus, the preferential injury of Varoliy pons, medulla oblongata nuclei and the motor neu‐ rons of the anterior horn of the cervical spinal cord is the main feature of the topography of the histo-pathological changes typical for TBE.

Sometimes the inflammation in the brain at TBE passes in atypical with little or no produc‐ tive and exudative changes. The perivascular infiltration is isinsignificant, the inflammatory response is expressed in the form of microglial nodules. In these cases, you should empha‐ size the discrepancy between the severity of the clinical course and low severity of inflam‐ mation in the presence of the intensive dystrophic and destructive changes in neurons (Robinson & Sergeeva, 1939; Kastner, 1941; Belman, 1960; Somova, 2010). In the early occur‐ rence of deep disturbances of consciousness (coma) in the cerebral cortex and other parts of the brain observed the common hyperchromatosis of neurons with a peculiar dark staining and wrinkling their (Shapoval, 1980).

ed of immune system organs and the development in these proliferative processes. A num‐ ber of authors (Spindles, 1969; Vargin & Semenov, 1980; Konev, 1982; Alexandrov & Kislitsyna, 1982; Kvetkova & Shmatko, 1983; Webb & Smith, 1966) suggest that the failure of

The Pathomorphology of Far Eastern Tick-Borne Encephalitis

http://dx.doi.org/10.5772/53449

117

For tick-borne encephalitis has been shown experimentally that the virus from the primary foci of multiplication in the skin and subcutaneous fat is distributed in the body with lym‐ phogenous and hematogenous routes (Pogodina et al., 1986; Albrecht, 1968). The penetra‐ tion of the virus in the brain associated with overcoming the blood-brain barrier through the wall of blood capillaries located in the parenchyma of the nervous tissue. This barrier is a complex system of defense mechanisms, including vascular plexus, the meninges, the wall

Pogodina et al. (1986), summarizing data on the immunopathogenesis of the disease, indi‐ cates that the TBE holds a pronounced immune response, characterized by a deficiency of Tlymphocytes, B-lymphocyte proliferation, macrophage reaction, the appearance of antibodies in the blood and cerebrospinal fluid, cellular immune responses in brain tissue,

Thus, by the early 2000s, the accumulated extensive experimental material has prepared the basis for the specification of views on the nature of the pathological process in the CNS in human tick-borne encephalitis. On the basis of modern ideas that the inflammatory re‐ sponse, which is realized hematogenous elements, provides a basal level of immunity, we saw fit to approach the study of the pathology of tick-borne encephalitis in terms of immu‐

The main goal of our research was focused on an integrated assessment of the nature of the pathological process in the central nervous system in tick-borne encephalitis and identifica‐ tion of clinical and morphological variants of the disease caused her immunopathogenetic mechanisms. An important aspect of the study, in our opinion, was the distinction, on the one hand, the primary damage to tissue-structural elements of the CNS, directly related to the cytopathic effect and intracellular reproduction of the TBE virus, on the other hand, reac‐ tive and immunopathological changes with the definition of pathogenetic importance of the last in the development of various clinical and morphological forms of encephalitis. The study was based on the autopsy material from 35 patients aged 4 to 68 years old, ill tickborne encephalitis in different parts of the Primorye Territory in the 1990s and died in dif‐

Date of death from the disease ranged from 3 to 28 days. The duration of hospital stay ranged from 1 hour to 25 days. The incubation period from the time of tick suction on bite before the first symptoms of the disease lasted from 7 to 23 days, an average of 15 days. In 6 cases there were multiple bites of ticks, so specify the duration of the incubation period was impossible. In two cases, infection occurred in the crushing ticks with the aid of arms.

For pathohistological study samples from different parts of the central nervous system were dissected: the anterior central gyrus, stem sections at the levels of the brain legs, Varolii pons

and medulla, as well as the cortex and the vermis of cerebellum, cervical spinal cord.

the immune system is an important factor in the pathogenesis of TBE.

which in general have both protective and pathologic effects.

nopathological nature of central nervous system damage.

of blood vessels and glial elements.

ferent periods from the onset.

The lack of etiotropic treatment of TBE dictated the need to further develop the issues on pathogenesis and morphogenesis of infection with the calculation of the especial feature of regional TBE strains, in order to support more efficient methods of pathogenetic therapy.

In the 1980-1990-s there is evidence of the involvement of lymphoid organs (thymus, spleen, lymph nodes) in the TBE virus reproduction, which greatly complement the information on the pathogenesis of acute and chronic processes during this infection (Pogodina et al., 1986; Rychkov et al., 1989, 1990; Karmysheva & Pogodina, 1990, 1991; Leonova &. Isachkova, 1995; Malkova & Frankova, 1959; Malkova & Smetana, 1966; Kopecky, 1987).

Using highly specific method of molecular hybridization of nucleic acids in cryostat sections of lymph nodes, spleen and brain of experimental animals (Zinoviev et al., 1990; Konev et al., 1991; Rychkov, 1992 ) it is found that on acute and chronic TBE is resettlement and virus replication in cells of the sinuses and T-dependent areas of lymphoid organs at the same time with the development of these reactions, reflecting the formation of an immune re‐ sponse. In the dynamics of the incubation period the TBE virus is accumulated in the lym‐ phoid organs, especially the regional to the site of infection lymph nodes, and subsequently recorded in the area of vascular lesions of the brain, where the beginning of clinical manifes‐ tations of the disease the virus is detected by IFA and electron microscopy.

It is determined that the damage of the lymphoid organs with subsequent development of the immune deficiency leads to the development of inflammation in the brain with a quick invasion of his virus, and the degree of damage of lymphoid organs is an important criteri‐ on for prediction of viral infection (Konev, 1994, 1995). According to the author, in an ex‐ periment on animals the dependence of TBE morphogenesis and relationships in the "brain lymphoid organs" from the degree of susceptibility of the host to the virus, the causative agent, take a place. In a susceptible animal the necrotic reaction develops in the lymphoid organs with subsequent formation of encephalitis in the background of secondary immuno‐ deficiency, and in insensitive animal the damage of lymphoid organs and, accordingly, the immunodeficiency are absent, and encephalomyelitis does not develop.

Karmysheva and Pogodina (1991) in experiments on hamsters received the evidence about the active involvement of the thymus in the infectious process in the tick-borne encephalitis, with nature and extent of lesions of the thymus is heavier under the introduction of highly virulent strains than for infection caused fainly virulent strains. Immunological methods is shown that a severe course of TBE is associated with the expressive delay hypersensitivity (DH) under a weak antibody production, and asymptomatic infection – with a weak sensiti‐ zation, an early and strong reaction of antibody-forming cells and increased nonspecific re‐ sistance (Perehodova et al., 1976; Pogodina et al., 1984). A more favorable prognosis when infected by fainly virulent strains, apparently, to a large extent dependent on the less affect‐ ed of immune system organs and the development in these proliferative processes. A num‐ ber of authors (Spindles, 1969; Vargin & Semenov, 1980; Konev, 1982; Alexandrov & Kislitsyna, 1982; Kvetkova & Shmatko, 1983; Webb & Smith, 1966) suggest that the failure of the immune system is an important factor in the pathogenesis of TBE.

mation in the presence of the intensive dystrophic and destructive changes in neurons (Robinson & Sergeeva, 1939; Kastner, 1941; Belman, 1960; Somova, 2010). In the early occur‐ rence of deep disturbances of consciousness (coma) in the cerebral cortex and other parts of the brain observed the common hyperchromatosis of neurons with a peculiar dark staining

The lack of etiotropic treatment of TBE dictated the need to further develop the issues on pathogenesis and morphogenesis of infection with the calculation of the especial feature of regional TBE strains, in order to support more efficient methods of pathogenetic therapy.

In the 1980-1990-s there is evidence of the involvement of lymphoid organs (thymus, spleen, lymph nodes) in the TBE virus reproduction, which greatly complement the information on the pathogenesis of acute and chronic processes during this infection (Pogodina et al., 1986; Rychkov et al., 1989, 1990; Karmysheva & Pogodina, 1990, 1991; Leonova &. Isachkova,

Using highly specific method of molecular hybridization of nucleic acids in cryostat sections of lymph nodes, spleen and brain of experimental animals (Zinoviev et al., 1990; Konev et al., 1991; Rychkov, 1992 ) it is found that on acute and chronic TBE is resettlement and virus replication in cells of the sinuses and T-dependent areas of lymphoid organs at the same time with the development of these reactions, reflecting the formation of an immune re‐ sponse. In the dynamics of the incubation period the TBE virus is accumulated in the lym‐ phoid organs, especially the regional to the site of infection lymph nodes, and subsequently recorded in the area of vascular lesions of the brain, where the beginning of clinical manifes‐

It is determined that the damage of the lymphoid organs with subsequent development of the immune deficiency leads to the development of inflammation in the brain with a quick invasion of his virus, and the degree of damage of lymphoid organs is an important criteri‐ on for prediction of viral infection (Konev, 1994, 1995). According to the author, in an ex‐ periment on animals the dependence of TBE morphogenesis and relationships in the "brain lymphoid organs" from the degree of susceptibility of the host to the virus, the causative agent, take a place. In a susceptible animal the necrotic reaction develops in the lymphoid organs with subsequent formation of encephalitis in the background of secondary immuno‐ deficiency, and in insensitive animal the damage of lymphoid organs and, accordingly, the

Karmysheva and Pogodina (1991) in experiments on hamsters received the evidence about the active involvement of the thymus in the infectious process in the tick-borne encephalitis, with nature and extent of lesions of the thymus is heavier under the introduction of highly virulent strains than for infection caused fainly virulent strains. Immunological methods is shown that a severe course of TBE is associated with the expressive delay hypersensitivity (DH) under a weak antibody production, and asymptomatic infection – with a weak sensiti‐ zation, an early and strong reaction of antibody-forming cells and increased nonspecific re‐ sistance (Perehodova et al., 1976; Pogodina et al., 1984). A more favorable prognosis when infected by fainly virulent strains, apparently, to a large extent dependent on the less affect‐

1995; Malkova & Frankova, 1959; Malkova & Smetana, 1966; Kopecky, 1987).

tations of the disease the virus is detected by IFA and electron microscopy.

immunodeficiency are absent, and encephalomyelitis does not develop.

and wrinkling their (Shapoval, 1980).

116 Encephalitis

For tick-borne encephalitis has been shown experimentally that the virus from the primary foci of multiplication in the skin and subcutaneous fat is distributed in the body with lym‐ phogenous and hematogenous routes (Pogodina et al., 1986; Albrecht, 1968). The penetra‐ tion of the virus in the brain associated with overcoming the blood-brain barrier through the wall of blood capillaries located in the parenchyma of the nervous tissue. This barrier is a complex system of defense mechanisms, including vascular plexus, the meninges, the wall of blood vessels and glial elements.

Pogodina et al. (1986), summarizing data on the immunopathogenesis of the disease, indi‐ cates that the TBE holds a pronounced immune response, characterized by a deficiency of Tlymphocytes, B-lymphocyte proliferation, macrophage reaction, the appearance of antibodies in the blood and cerebrospinal fluid, cellular immune responses in brain tissue, which in general have both protective and pathologic effects.

Thus, by the early 2000s, the accumulated extensive experimental material has prepared the basis for the specification of views on the nature of the pathological process in the CNS in human tick-borne encephalitis. On the basis of modern ideas that the inflammatory re‐ sponse, which is realized hematogenous elements, provides a basal level of immunity, we saw fit to approach the study of the pathology of tick-borne encephalitis in terms of immu‐ nopathological nature of central nervous system damage.

The main goal of our research was focused on an integrated assessment of the nature of the pathological process in the central nervous system in tick-borne encephalitis and identifica‐ tion of clinical and morphological variants of the disease caused her immunopathogenetic mechanisms. An important aspect of the study, in our opinion, was the distinction, on the one hand, the primary damage to tissue-structural elements of the CNS, directly related to the cytopathic effect and intracellular reproduction of the TBE virus, on the other hand, reac‐ tive and immunopathological changes with the definition of pathogenetic importance of the last in the development of various clinical and morphological forms of encephalitis. The study was based on the autopsy material from 35 patients aged 4 to 68 years old, ill tickborne encephalitis in different parts of the Primorye Territory in the 1990s and died in dif‐ ferent periods from the onset.

Date of death from the disease ranged from 3 to 28 days. The duration of hospital stay ranged from 1 hour to 25 days. The incubation period from the time of tick suction on bite before the first symptoms of the disease lasted from 7 to 23 days, an average of 15 days. In 6 cases there were multiple bites of ticks, so specify the duration of the incubation period was impossible. In two cases, infection occurred in the crushing ticks with the aid of arms.

For pathohistological study samples from different parts of the central nervous system were dissected: the anterior central gyrus, stem sections at the levels of the brain legs, Varolii pons and medulla, as well as the cortex and the vermis of cerebellum, cervical spinal cord.
