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immunologic aspects of a HIV-infection, sochetannoj with a tuberculosis

The leading mechanism in HIV-infection development is the lesion of immune system (Pantaleo G., Graziosi S, Fauci A, 1993).

Immunopatogenez the HIV-infection is a difficult process of interaction of a virus with a human body.

By various researches it is established, that, having got into a human body, a virus by means of a cover glycoproteid gp 120 it is fixed on a membrane of the cells having a receptor - fiber CD4. Receptor CD4 cells of nervous system (neuroglia) have, mainly, T-limfotsity helpers (Т4), playing the central role in the immune answer, and also, monocytes, macrophages, an endothelium of vessels, etc. Formation of a molecular complex gp 120 CD4 are activated by process of development of cytokines (Fauchi E, Lejn K, 1998; Smirnov V. S, Frejdlin I.S., 2000). The carried out researches have established, that linkage gp 120 with CD4 leads to an induction of synthesis FNOa which in turn, promotes replikatsii a virus which is in the "dozing" condition (Butera S.T., 1993). Was besides, open specific for T-helperov hemotaksichesky the factor produced CD8 - the lymphocytes, named ИЛ-16 (Baler M, Wener A. Bannert et al., 1995). A receptor for it also is CD4 the molecule. The virus merges with a cell membrane, there is a decomposition of a virus kernel and emission RNK a HIV in a cytoplasma. By means of enzyme revertazy RNK is exposed to transcription in dvuhnitevuju DNA which is built in in a gene of a cell with the help integrazy.

In 1996-1998 one more mechanism of penetration of a HIV in a cell-owner has been opened. It is shown, that receptors for chemokines are to - receptors for a virus (Alkhatib G., Locafi M, Hennedy River E et al., 1997;

Clapham P.R., Weiss R.A., 1997). There is a virus tropism to concrete types of cells which is provided corresponding hemokinovymi with receptors.

Change from party T-limfotsitov at a HIV-infection is shown by depression of a proliferation and klonoobrazovanija, and also reactance oppression in the admixed culture of lymphocytes and disturbance of process of differentiation CD4 and CD8 subpopulations. All ■ these disturbances are caused by ability loss to produce ИЛ-2. In process of HIV-infection advance deficiency interlejkina accrues, that in turn, is accompanied by subpopulation reduction GD4 - lymphocytes, their oppression helpernoj activity, ability to react to repeated influence of an antigen in reaction of the admixed culture of lymphocytes: and: proliferations, in reply to FGA (phytohemagglutinin). Except, deficiency ИЛ-2 there is a mass of other reasons of depression of quantity СД-4 of cells.

, First, it is immediate  destruction of cells as a result of action: a virus (Gandhi R., Chen V, Straus S. et al., 1998). After translation of the information with RNK a virus in cell DNA, process replikatsii and the subsequent  destruction of a cell, in this case С04-лимфоцита is started. It is established, that the molecule gpl20 contains alloepitopy which are identical to epitopes of molecules of II class of HLA-system, receptor ИЛ-2, Timosinum and of some others. alloepitopy, a virus cover allow a HIV to leave from epidemiological supervision and free to get into target cells - (Smirnov V. S, Frejdlin I.S., 2000).

Secondly, the  destruction of lymphocytes can occur as a result of formation of the sincytium consisting of virus particles and lymphocytes. These conglomerates can thrombose capillaries, and the lymphocytes which have got to this thrombus perish.

Thirdly, on the cells infected with a virus the specific immune answer including cytotoxic lymphocytes is formed,
Natural killers and the antibodies participating in  destruction CD4 - lymphocytes both direct, and mediated (antitelozavisimaja cytotoxicity) by. Natural cells-killers can learn a HIV-infected of a cell and destroy them (Karpas A., Gilson W., Bevar River S et al., 1985).

Fourthly, a certain role plays and programirovannaja  destruction of cells - an apoptosis. The basic part of these cells after a becoming infected perishes owing to a necrosis (Gandhi R., Chen V, Straus S. et al., 1998). HIV - the infected lymphocytes can perish owing to cytotoxic action FIO which induces lizis zlokachestvenno the transformed cells and as the cells infected with intracellular microorganisms. Cytotoxic action of the factor is realised by means of an apoptosis.

At a HIV-infection disturbance and in a humoral link is observed. So, it has been shown, that at acute development of an infection number of the cells cosecreting antibodies, it is sharply enlarged, however it is not accompanied by augmentation of development of immunoglobulins while at a chronic current against small, numbers antiteloprodutsirujushchih cells there is a distinct

Hypergammaglobulinemia (Lane N.S., Masur N, Edgar L.C. et al., 1983). These data testify that at a HIV-infection is observed inverse mutual relations between level of immunoglobulins in blood serum and number of circulating cells of producers. Thus, the virus influences functional activity V-limfotsitov and at a chronic current enlarges development of immunoglobulins and especially Ig G (Lane N.S., Masur EL, Edgar L.C. et al., 1983). Thus 95 % of immunoglobulins despite virus presence are nonspecific.

The HIV-infection is accompanied by the nonspecific polyclonal activation V-limfotsitov caused by influence of the virus, and as other factors (other microorganisms, CYTOKINES - loss T - helpernogo the control, etc.). The chemotherapy promotes normalisation
Mutual relations between antiteloprodutsirujushchimi cells and an antiserum capacity (Smirnov V. S, Frejdlin I.S., 2000). The persons infected with a HIV - 1, have high level of neutralised antibodies against a virus, unlike sick of AIDS which have lost ability to develop an antibody (Karpas A., Gilson W., Bevar River S et al., 1985).

Besides, the virus is capable to induce production of set of various factors, which can block functional activity of lymphocytes and macrophages and by that to promote unobstructed replikatsii virions in cells (Saidov M. Z, Esedov E.M., Aliev T.S., 1996; Smirnov V. S, Frejdlin I.S., 2000).

Cells Langergansa are as cells-targets for a HIV. In dendritic cells Langergansa the virus is taped only in 2-3 years after a becoming infected, that is their becoming infected occurs much later, than lymphocytes (Pantaleo G., Grasiosi S, Fauci A, 1993).

The big role in the antiviral immune answer is played by cytotoxic lymphocytes - CD8 (TSTL). They cause lizis a HIV - of the infected cells. In a late stage of disease depression of activity TSTL is observed. There is variety of the reasons of depression of activity TSTL: loss T-helpernoj of activity in connection with sharp falling of their quantity; switching YOU on Th2 and reduction of development ИЛ-2 and IFNu as the factors supporting a differentiation and activity TSTL, becoming infected CD8 of lymphocytes; depression of activity TSTL can be induced by various subpopulations of T-cages, a HIV the infected apoptosis, absence of CD of 8-cells carrying receptors to ИЛ-7, disturbance of presentation of an antigen owing to mutations in immunodominantnyh peptides (Smirnov V. S, Frejdlin I.S., 2000).

In clinical practice by a reliable marker of advance of disease is СО4-лимфоциты. At all patients with again taped by a HIV-infection should be defined С04-лимфоциты.

At sick HIV-infections deficiency of only separate subpopulations of lymphocytes (СИ4-клеток-Т-хелперов/индукторов, V-limyofotsitov) while the quantity of CDS-cages (T-T/killers) increases develops, that leads to expressed depression CD4/CD8. Simultaneously register rising of concentration IgA, IgM, IgG and circulating immune complexes (Central Electoral Committee) (Gabrilovich D.I., Serebrovskaja L.V., Habarova V.V., etc., 1994; Yurin O. G, Irova T.I., Gabrilovich D.I., etc., 1992; Mitin J.A., 1997). At sick HIV-infections damage of the polymorphonuclear neutrophils playing the important role in antimicrobial and anti-virus protection of an organism (Gabrilovich D.I., Vasilev V. B, V.V. Nouses, etc., 1995 becomes perceptible; Pantaleo G., Graziosi S, Fauci A, 1993). At definition of levels of cytokines (IL2, FIO, interferons) at sick HIV-infections also are registered the expressed changes aside both augmentations, and depressions of their concentration (Kalinin N.M. 1996; Chaisson R.E., 1996). Therefore

Disturbances in system of immunity at sick HIV-infections it is possible to characterise as disbalans systems, instead of deficiency (Kravchenko A.V., Serebrovskaja L.V., Shagildjan V. I, 1999, Milochkina J.N., Papuashvili M. N, 2003).

Development of opportunistic diseases in a HIV-infected of persons depended on degree of depression of quantity С04-лимфоцитов in peripheric blood: the tuberculosis arose at quantity less than 200 in 1 мм3, sarcoma Kaposhi - less than 100 in 1 мм3, demonstrative tsitomegalovirusnaja an infection - 50 in 1мм3 and less. At patients with a tuberculosis observed disturbance agregatsionnoj activity of cells in the absence of a thrombocytopenia. At the majority sick of a tuberculosis (63 %) level CD4 - cells was above 100 in 1 мм3. Maintenance CdS-limfotsitov was raised. Quantity СО22-лимфоцитов was in 3 times below value of healthy faces. Essential rising of the maintenance of the Central Electoral Committee was registered. The anaemia was observed in 56,3 % of cases, an average haemoglobin content at
Patients 112,4±6,8 a g/l, quantity of erythrocytes - 3,54±0,19 h 10 12/l. (Kravchenko A.V., Poljakova A.M., Serebrovskaja L.V., etc., 1997).

Disturbance of immune functions under the influence of a HIV consists in attrition of subpopulations of T-cages CD4 and oppression of their reactions to antigens, mitogeny, alloantigeny and antibodies anti-SiZ with parallel depression of production IL-2 and other changes of production of cytokines. As a result of these disturbances ability cytotoxic T - cells to a HIV-specific to the answer and some antigenprezentirujushchie cellular functions is lost. The number activated and areaktivirovannyh T-cages CD8 thus increases, maintenance RoYOmi kroglobulina and a neopterine in Serum raises, occurs polyclonal In - cellular activation with the advent of V-limfotsitov, unreceptive to action of T-independent V-cellular activators, formation of autoantibodies and immune complexes (Rahmanova A.G., Sizova N.V., Moskvina E.A., 2002 increases; I.V.Isakov, 2004, Rosenberg V. JA, Butylskij A.N., 2004).

Development of a tubercular infection also is accompanied by a syndrome of a secondary immunodeficiency and (on immunologic indicators) is taped at 98 % sick of a pulmonary tuberculosis. Thus patients with the fibrous-kavernoznoj form of the disease, prevailing have 2nd type of an immunodepression characterised by deeper oppression of immunity. Depression of relative quantity CD4 - CD8 - and С072-лимфоцитов, the monocytes expressing antigens gistosovmestimosti of II class (DR) is observed. At sick the tuberculosis taps oppression of proliferative activity of T-cages and production ИЛ-2, moderate depression of production ИЛ-1 and the raised level of secretion FNO. At fibro-kavernoznoj form more expressed depression of quantitative maintenance DR + - monocytes and production of proinflammatory cytokines (ИЛ-2, ИЛ-1) is registered, than at

infiltrativnoj to the pulmonary tuberculosis form (Honina N.A., Nikonov S.D.,

Shpilevskij S.V., etc., 2000; Adambekov D.A., Litvinov V. I, Mambetov K.B., 1998; Bloom B.R., Flynn J., McDonough K., 1994; Huygen K., Lozes E., Gilles B., 1994).

S.Yamamoto, M.Wada, I.Toida (1993) recommend to spend monitor tracking level T-limfotsitov CD4 + as the given indicator allows to prognosticate a current of a tuberculosis and to correct treatment. According to I.M. Orme, etc. (1993) depression of number CD4 of lymphocytes leads to weighting of tubercular process as CD4 in regular intervals allocate ravnonapravlennye against micobacteria of a tuberculosis cytokines, providing possible completeness of interaction of cellular and humoral immunity.

According to A.G.Homenko (1988), the condition of immune system is of great importance in tuberculosis clinic. There is an assumption, that occurrence and reproduction in the course of treatment of lekarstvenno-steady forms of micobacteria of a tuberculosis serve as the proof of weakening of natural protective forces of an organism. According to A.S.Sadykov (1990), lekarstvenno-steady forms of micobacterium TB meet at patients various complications TB is more often. At comparison of groups of a HIV positive and a HIV of negative patients it is taped, that at a HIV - of the revealings infected frequency lekarstvenno steady forms of micobacteria it has appeared higher (Chukanov V. I, Kuzmina N.V., 1996).

As show virologic researches, the tubercular infection accelerates replikatsiju a HIV, this acceleration is stimulated directly with micobacteria of a tuberculosis and oposredovanno cytokines. Active tubercular process, unlike a latent infection conducts to cellular activation and emission of cytokines which in turn accelerates replikatsiju a virus. Unlike other opportunistic infections which complicate a HIV-infection current, a tuberculosis practically unique infection which it is dangerous to the people who have been not infected with a HIV (Skrjagina E.M., Kolomiets A.G., Grits M. A.i other, 1999). The tuberculosis possesses
Activating and disregulirujushchim influence on tsitokinovuju and hemokinovuju systems, promoting diffusion and virus reproduction. At patients of a HIV-infection, sochetannoj with a tuberculosis the virus load and heterogeneity of a virus is enlarged in case of an active tuberculosis (Bocchino M, Sanduzzi A., Bariffi F., 2000, Toossi Z., 2003).

Immunodeficiency development occurs at the expense of acceleration of processes of the programmed  destruction of immune cells that is known under the term "apoptosis". Last is seldom observed in infected CD4 the T-cages producing a HIV, but the located normal cells are subject to this process by a number. The above-stated testifies to complexity of a pathogenesis sochetannoj infections and necessities of working out of various ways of early diagnostics of a HIV-infection (Ismailov SH. SH, Alenova A.H., CHaklikov I.e., etc., 2001; Kuzmin O. A, Sergeeva E.G., 2003).

The becoming infected an immunodeficiency virus also essentially influences and a tuberculosis pathogenesis. Absolute and relative depression of quantity T-limfotsitov of helpers changes mutual relation in system of the cellular immunity having essential value at a tuberculosis: the differentiation of macrophages and formation specific granuljatsionnoj tissues are broken. And if at early stages of a becoming infected of a HIV the morphology of a tubercular inflammation essentially changes, during the late period of AIDS - specific granulomas simply are not formed. It is known, that at the heart of AIDS pathogenesis the selective becoming infected of virus T-helpernyh of lymphocytes against which various infectious processes (on early AIDS - more often a tuberculosis free develop lays, on late - usually pnevmotsistnaja the pneumonia and is more rare malignant neoplasms (sarcoma Kaposhi).

From humoral factors of protection change of maintenance Ig And at all stages of a tubercular infection becomes perceptible, after carrying out lechebnoyoprofilakticheskih actions frequency of depression of level Ig And decreases. Level Ig M at different stages of a tubercular infection is in
Norm limits, except for persons with for the first time taped spontaneous clinically cured tuberculosis. Quantity Ig G at different stages of a tubercular infection did not differ from that at persons of control group (Knorin B.E., 1996, Sirenko I. A, 2001).

One of implications of defect of cellular immunity at sick of a pulmonary tuberculosis is dermal tuberkulinovaja the anergy caused by oppression of reaction of hypersensitivity of slowed down type (GZT) on a specific antigen - tuberkulinovyj the cleared albuminous derivative (purified protein derivative, PPD). Dermal areactivity on tuberculin introduction is often taped at sick of a tuberculosis against serious accompanying diseases, such as a diphtheria, a measles, a HIV - an infection, oncologic diseases, and also can develop at patients with the active form of the tuberculosis which has been not complicated by serious somatopathies (Honina N.A., Sahno L.V., Norkin M. N, etc., 2001; Zumla F., Grand J., 1998; I-Isieh S.M., Hung C.C.; Pan S.C.; Wang J.T. et al., 2000).

As a result of E.E.Komogorovoj, E.V.Kostenko, V.A.Stakhanov's researches, etc. (2005) gross infringements both cellular, and humoral immunity at patients with various forms of a pulmonary tuberculosis are taped. The most expressed changes of indicators of immunity nabljuyodalis at patients with the serious forms of disease characterised by a dissimination of process and destructive changes of a pulmonary tissue.

Definition of antituberculous antibodies and antigenemii can be the important component of complex inspection of patients for the purpose of differential diagnostics of a tuberculosis and netuberkulezpoj pathologies (Adambekova D.A., Kurmanov R. A, Baenskij A.V., etc., 1997).

The tuberculosis and HIV-infection are two diseases which mutually burden each other. The HIV-induced immunosupressija considerably raises risk to be ill with a tuberculosis owing to both reactivations latent mikobakterialnoj infections, and fresh infection (the exogenous

Reinfections). In the conditions of raised infektsionnosti environment, for example in ITU, the second mechanism of development of a tuberculosis (ShChelkanova A.I., Kravchenko A.V., 2004) most likely is realised.

The tuberculosis also adversely influences advance of a HIV - of an infection. In vitro the augmentation of ability of a HIV to replikatsii under the influence of MBT-ANTIGENES which proved to be true augmentation of number of spears RNK of a virus in peripheric blood (Goletti D has been shown., Weissman D., Jackson R.W. etal., 1996).

At late stages of a HIV-infection, at level CD4 less than 200 cells in 1 мм3 bloods (AIDS, according to criteria SDS), develop opportunistic diseases, which morses lead if in due time not to prevent them by means of highly active antiretrovirusnoj therapy, and also specific preventive maintenance and treatment. For lack of specific therapy and in the presence of a deep immunodeficiency there is fast hematogenic generalisation MBT as a sepsis, and illness comes to an end with a lethal outcome. Sick of a chronic tuberculosis, having caught a HIV, the same patients, but without a HIV-infection (ShChelkanova A.I., Kravchenko A.V., 2004) have smaller survival rate, than.

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A source: HAMZINA Ruzalija Vagizovna. CLINICAL AND IMMUNOLOGICAL PECULIARITIES OF HIV INFECTION COMBINED WITH TUBERCULOSIS DISSERTATION for the degree of candidate of medical sciences. St. Petersburg - 2005. 2005

More on topic immunologic aspects of a HIV-infection, sochetannoj with a tuberculosis:

  1. Immunologic features of a HIV-infection, sochetannoj with a tuberculosis, depending on time of revealing of a HIV-infection and an active tuberculosis
  2. Chapter 4 the Comparative characteristic clinico-immunologicheskih HIV-infection indicators, sochetannoj with a tuberculosis and a HIV-infection without a tuberculosis
  3. Clinical aspects of a HIV-infection, sochetannoj with a tuberculosis
  4. Clinical features of a HIV-infection, sochetannoj with a tuberculosis
  5. modern approaches to HIV-infection treatment, sochetannoj with a tuberculosis
  6. Immunologic features of a HIV-infection in a combination to a tuberculosis at their simultaneous revealing
  7. immunologic features of the HIV-infection, taped against an active tuberculosis
  8. Chapter 5 Clinico-Immunologichesky indicators of a HIV-infection, sochetannoj with a tuberculosis against antiretrovirusnoj therapies
  9. Immunologic features of a HIV-infection at revealing of an active tuberculosis (SH group)
  10. the Comparative characteristic of a current of tubercular process at patients of the basic group (a tuberculosis in a combination to a HIV-infection) and in control group (a tuberculosis without a HIV-infection)
  11. CHAPTER 3 Clinico-Immunologichesky features of a HIV-infection, sochetannoj with a tuberculosis
  12. HAMZINA Ruzalija Vagizovna. CLINICO-IMMUNOLOGICHESKY FEATURES of a HIV-INFECTION, SOCHETANNOJ With the TUBERCULOSIS the DISSERTATION on competition of a scientific degree of the candidate of medical sciences. St.-Petersburg -,