Immunologic diagnosis of tuberculosis - Research Paper Example

? The issue of TB vaccination Catherine Skinner Mohammed Alotaibi Wordcount: 2560 Keywords: tuberculosis , vaccination, revaccination, immunization. Introduction All people have natural immunity to tuberculosis. The attempts to find a correlation between sensitivity to tuberculosis and HLA phenotype have produced conflicting results. Although sensitivity to tuberculosis is associated with race, the evidence is largely unconvincing. Age is an important determinant of natural resistance to tuberculosis. Although there is no specific data concerning the relationship of nutritional status and immunity against tuberculosis, it is clear that malnutrition and tuberculosis are related in some way. Primary tuberculous infection is associated with the development of acquired immunity. Tuberculosis which is caused by exogenous reinfection in North America and Europe are rare. Much more often it is registered among the population with a high incidence of tuberculosis, where there is a high risk of reinfection. It would be appropriate to note that the immune system in the classic sense of the word means resistance to infection, whereas hypersensitive means a state of the damaged host's reactivity. In this sense, immunity may be the result of infection caused by other mycobacteria, or the result of vaccination of bacillus Calmette-Guerin (BCG), or the result of natural infection with mycobacteria, which common in the environment. This acquired non-specific immunity can be regarded as a reflection of the primary activation of macrophages. (Chan, 2000, 134) Topic 1. M Tuberculosis Antigen-specific immunity is mediated by T-lymphocytes and can be adapted by them. Antigen-specific immunity is strongly correlated with delayed-type hypersensitivity. It can act as an independent factor, but it is believed that functional expression of cellular hypersensitivity is the most efficient. Tuberculin sensitivity is antigen-specific in nature and develops after the primary infection. It is directed mainly against protein antigens. Mycobacterial antigens are the subject of diverse immunochemical studies. (Smith, 2005). It is quite clear that there is no single dominant antigen, and in any microorganism which is artificially infected or sensitized hypersensitivity to the set of mycobacterial proteins develops. Tuberculin purified protein derivative (PPD) is antigen preparation which is most often used in clinical and epidemiological practice in order to identify the tuberculin hypersensitivity and it is a mixture of crude largely denatured antigens and poorly reflects the character of the natural antigens. (Brennan, 2009, 335) In the case of infection in organism the protein antigen mycobacteria are always present in association with this set of adjuvants. In vitro studies have shown that the purified arabynogalactan is a potent immunosuppressive agent. (Chan, 2000, 134) The recognition of antigen which is sensitized by macro-processing is accompanied by macrophages and it depends on the expression of macrophages on their surface of antigen-specific epitopes associated with the Ia-antigen gene product of histocompatibility. This complex is recognized by specific T lymphocytes. For the development of the response of T lymphocytes to antigen presentation also requires macrophage synthesis and secretion of interleukin-1. (Chan, 2000, 137) The immunoreactive cells secrete mediators that can cause activation of macrophages. The macrophages as the main effectors cells of tuberculin hypersensitivity. The peripheral blood monocytes of TB patients have some properties which are the characteristic of activated macrophages, including enhanced activity against hecsomonophosphatus, increased ability to to the surface adhesion, expression of specific membrane structures and increased bactericidal activity. However in some cases of tuberculosis it is possible to observe the deviation from the state of hypersensivity (Chan, 2000, 137). Such cases formed the basis for the assumption that TB can develop in the presence of immunological spectrum in the organism similar to that in leprosy, but expressed somewhat weaker. Thus on the one hand there are patients with chronic process regarding chronicity and pronounced tuberculin hypersensitivity. And on the other - much less identify patients with cutaneous anergy, and some of them do not have formed granulomas, and all other manifestations of cellular hypersensitivity, but at the same time revealed pancytopenia, disseminated common process. Although best known manifestation of tuberculin hypersensitivity is delayed skin reaction to tuberculin, its main and the most important expression, apparently, and the formation of which is an important mechanism to contain the spread of infection. Studies on tuberculin antigens on the surface of bentonite or agarose particles show that the formation of granulomas in response to antigen presented in a certain way, has all the characteristic features of the immunological reactions of hypersensitivity. (Chan, 2000, 137) In recent years Chan E. D., Heifets L., Iseman M. D paid their attention to the role of dendritic cells in the formation of granulomas. Dendritic cells are considered to be the number of antigen presenting cells, they play a central role in the initiation of primary immune response. However, their role in the formation of granulomatous inflammatory response remains largely unexplored area of ??immunity in tuberculosis. The focus of current researches is also to establish the role of neutrophils in the formation of anti-tuberculosis immunity. The activation of circulating polimorphonuclears obtained from patients with active tuberculosis is associated with induced apoptosis. The biological effects of tuberculosis occur in the accelerated apoptosis of polymorphonuclear cells. It must be emphasized that the accelerated apoptosis can be observed from the other cells, particularly macrophages, gdT-lymphocytes, which is also associated with the process of colonization of Mycobacterium tuberculosis. (Kaufmann, Hussey, Lambert, 2010, 12) However, it should be recognized that the substantial number of scientific data is accumulated on the role of lymphocytes and macrophages in the formation of immunity in tuberculosis. Cellular intereaction between T-lymphocytes and macrophages plays an important role in granuloma formation and protection of anti-colonization by Mycobacterium tuberculosis. The establishing an effective immunological protection depends on the cell interaction, which is defined as cellular immunity. It should be emphasized that the role of T-lymphocytes in the formation of cell-mediated immunity is the focus of many researches and is constantly updated with new scientific facts. The preconditions for activing scientific investigation of the role of T-lymphocytes in the formation of immunity in tuberculosis is their ability to synthesize IFN g and TNF-a. T-lymphocytes attributed the development of protection mechanisms in mycobacterial infection. These cytokines play an important role in the activation of macrophages, thus they have a pathogenic effect on the formation of immunity during infection with Mycobacterium tuberculosis. Over the past two years there were some researches to establish the role of CD8 + T-lymphocytes. Thus, studies in recent years established the role of CD8 T lymphocytes in the pathogenesis of tuberculosis, evidence of their active participation in the formation of the immunological reactions. These data allow considering new approaches to designing vaccines against tuberculosis. This fact is of great importance in planning for new approaches in designing new generation vaccines. Great importance should be given to the factor of the ability of CD8 T lymphocytes recognize macrophages that phagocytosed tuberculosis, and lead them to death directly at the source of the inflammatory response. However, there remain a large number of unexplored issues that include the interaction of different populations of lymphocytes, immune resistance, especially in the later periods of observation, evaluation of the effectiveness of the strategy to develop a new generation of vaccines. (Kaufmann, Hussey, Lambert, 2010, 14) Of great interest is caused by the role of nitric oxide in the pathogenesis of tuberculosis. Interest has increased particularly after the facts have been established, which demonstrated the ability of nitric oxide exhibit antibacterial properties. The genetic studies have shed light on the nature of the increased susceptibility to the pathogen. In recent years there have been launched a series of studies on different genes, which could be attributed to the increased sensitivity of tuberculosis. These studies were undertaken to further explore the relationship of the microorganism and host in the development of an infectious process. More data has been accumulated for the study of genes regulating the synthesis of interferon-g path in the human body susceptible to Mycobacterium tuberculosis. The first gene, which is related to metabolic disorder interferon g, controls the functional activity of the receptor. The deficit appears to reduce the ability of the receptor to bind to the ligand. This defect is transmitted in an autosomal recessive way. Another genetic defect in interferon-sharing refers to the complete loss of the ability of the receptor to transmit biological signals. Autosomal dominant type of genetic disorder in the regulation of the exchange associated with infringement of interferon signal transduction and activation of the transcription process. Interleukin-12 stimulates the production of interferon-g, which occurs with the participation of lymphocytes. Topic 2. TB vaccination The search for a protective vaccine against tuberculosis has a long history. Since the discovery by Robert Koch (1882), causative agent of tuberculosis the attempts to create such a vaccine began. This problem was solved by a French microbiologist, a student of Pasteur - A. Calmette. According to the results of experiments carried out jointly with K. Guerin, he proved that a single infection with weakly virulent, but live Mycobacterium tuberculosis infection leads to the infection resistance to subsequent reinfection. The vaccine BCG (Bacillus Calmette et Guerin) was called in honor of these scholars. The first experience of a newborn child vaccination was carried out in France in 1921. After successful testing of this vaccine the strain was given many countries. Over the next 85 years, the vaccination is carried out by hundreds of millions of people to this day is one of the priority in the prevention of tuberculosis in children and adolescents. Immunization against tuberculosis is mandatory in 64 countries and is recommended in 118 countries. (Mart?n, 2005) Tactics of Bacillus Calmette et Guerin Vaccination varies in different countries: In some countries the vaccination is made only at birth. This approach is consistent with WHO recommendations and the tactics is used in the largest number of countries, especially developing ones. WHO experts in recent years insisted on the use of this tactic is due to clear evidence that BCG vaccination protects against serious forms of TB. Sometimes BCG vaccination is made once for a child. The repeated vaccination / revaccinations BCG are used in some countries. Non-routine use of BCG vaccine is maintaining. Despite much progress in TB control achieved by the vaccine and chemotherapy, a number of issues are not yet resolved. Ongoing debate about the essence of immunological reactions and changes in the organism under the influence of BCG vaccination, its efficacy and safety. According to the controlled trials, vaccine efficacy ranged from 80 to 0%. It is recognized that the BCG vaccine does not always prevent diseases, but it provides protection against the most dangerous forms of tuberculosis (miliary and generalized tuberculosis, tuberculous meningitis), prevents the development of severe progressive forms of the disease in children. One of the most debated issues today is the need for repeated vaccination with BCG boosters. The changes in the immune response to repeated administration of the vaccine are of wave-like nature: along with the ability to stimulate antibody production, phagocytosis, and cytotoxic cellular immune response may cause the BCG vaccine and the development of immunosuppression. Evidence of such suppression were obtained in experimental conditions, after intravenous administration of high doses of a vaccine that may have clinical implications for vaccination in neonates with immature immune system or its defects. (Girard, Fruth, Kieny 2005) The BCG vaccine introduced in the infant behaves like a virulent substance and quickly gets to the regional lymph nodes, blood and scattered in various organs and tissues. Major changes occur in the lymph nodes of the reticuloendothelial apparatus of liver and spleen are possible reaction from the blood and changes neurohumoral regulation. The neurohumoral changes begin in the first weeks after vaccine and are increasing by 3-4 months. The specific phase that occurs at the peak of vaccine response, characterized by the formation of a rudimentary primary tuberculosis, while in the immune organs may appear bumps dissemination, and in the lungs - symptoms of alveolitis. The residual virulence of the strain of BCG mycobacteria can vegetate in the body of the child in the form of L-forms, causing specific morphological changes limited to the subsequent resorption and formation of non-sterile TB immunity. (Mart?n, 2005, 166) Intrauterine infection and immunodeficiency are contraindications to vaccination with BCG and BCG-M. It is not always possible to identify the primary immunodeficiency, intrauterine infection or all fermentopathy in the first 3-4 days after birth, so in some cases, BCG vaccination is the "screening" to identify children with defective immune systems. Furthermore, early vaccination, according to some researchers, violates the basic procedure for the formation of immune reactions, "ripening" of the immune system of the newborn. Thus, it becomes clear that mass BCG vaccination gave rise to serious problems of post-vaccination complications. Complications of BCG are attached to it from the very beginning of application, with a change in method of administration (oral, subcutaneous, intradermal) the frequency and structure of complications was changed. According to the WHO classification the complications of BCG vaccination are classified into four categories: local skin lesions (subcutaneous infiltration, cold abscesses, ulcers), and regional lymphadenitis; persistent and disseminated BCG infection is not fatal (lupus, osteitis); disseminated BCG infection and generalized lesion with a fatal outcome, which is noted in congenital immunodeficiency; post-BCG syndrome (manifestation of the disease that emerged shortly after BCG vaccination, mainly allergic: erythema nodosum, annular granuloma, rash, etc.). To the 4th type of complications the aggravation of existing and new development of chronic diseases on the background of BCG vaccination or revaccination due to underestimation of contraindications are also included. In recent years there is an increasing number of scientific publications, showing how the vaccine is connected with diseases such as autism, diabetes, rheumatoid arthritis. (Olsen, 2003, 208) Conclusion It is known that the incidence of these illnesses is growing rapidly in the countries with high levels of vaccination and the "drug-loading" of the population. The properties of the vaccines used play a significant role in the development of complications. The use of BCG-M with reduced antigenic load has reduced the number of BCG lymphadenitis by 3-5 times. (Olsen, 2003, 208) The cause of complications after immunization with the TB vaccine may be the wrong intradermal injection technique, comorbidities in children vaccinated before and during the development of local vaccination reactions. The increase their numbers in recent years may be associated with increased immunodeficiency and related disorders in children, more than busy schedule of immunization in the first year of life, the wrong selection of children. In addition, the number of complications increases with the improvement of their registration. The disturbing fact is the increase in the number of BCG osteitis (osteomyelitis or BCG). The problem of complications of BCG vaccination, and their early detection and prevention, is very relevant, especially because of the effectiveness of BCG vaccination in a wide spread of drug-resistant strains is reduced. All the above allows to offer the activities that improve the efficiency and reduce the risk of complications of BCG vaccination: wider (or solid) attenuated BCG vaccination-M; vaccination of infants against hepatitis B and tuberculosis in groups at risk for these diseases, in cases where it is impossible to exclude primary immunodeficiency, postpone BCG-M until the child is 1 month or clarify the diagnosis; carrying out other shots after local reaction to BCG vaccination, ie after falling brown. If the crust is preserved in the 3 months following an immunization should be delayed; training medical staff (30-35% of post-vaccination reactions are due to a violation of intradermal vaccine administration technique). Thus, BCG vaccination is certainly needed all over the world and it should become safer for children. Individual approach to estimate the ratio of "risk / performance" allows to select the correct time, a vaccine to every child, to prevent serious complications of vaccination, and thus do not discredit the method immunization of tuberculosis. Bibliography Brennan P J. “Tuberculosis: Molecular Basis of Pathogenesis”, Colorado State University, Fort Collins, CO, US (2009): 333 – 339. Chan E. D., Heifets L., Iseman M. D. Immunologic diagnosis of tuberculosis. Tubercle and Lung Disease (2000) 80(3): 131–140. Kaufmann Stefan H E, Hussey Gregory, Lambert Paul-Henri. “New vaccines for tuberculosis”. Lancet 2010; 375: 2110–19. Mart?n C. “The dream of a vaccine against tuberculosis; new vaccines improving or replacing” BCG? Series ‘‘Controversial Issues in Tuberculosis” ed. by A. Torres and J. Caminero, Number 8, 2005; 26: 162–167. Olsen Anja W., Peter Andersen. “A novel TB vaccine; strategies to combat a complex pathogen” . Immunology Letters 85 (2003): 207 - 211. Read More