Frequency of anergy in a group of patients with rheumatoid arthritis on immunosuppressive therapy / Frecuencia de anergia en un grupo de pacientes con artritis reumatoide y terapia inmunosupresora

ABSTRACT Background: Tuberculin is the globally accepted delayed cutaneous hypersensitivity test for the diagnosis of latent tuberculosis. The alteration of cellular immunity induced by disease-modifying drugs used in rheumatoid arthritis may give a false negative result, also known as cutaneous anergy. There are no studies that determine the frequency of anergy in patients with rheumatoid arthritis and on immunosuppressive therapy. Objective: To determine the frequency and possible factors associated with cutaneous anergy in a group of patients with rheumatoid arthritis and on immunosuppressive therapy. Methods: Cross-sectional analytical observational study including 100 patients with rheumatoid arthritis on immunosuppressive therapy. They were tested for delayed cutaneous hypersensitivity with tuberculin, and a control test with tetanus toxoid. The non-reactivity of both tests was defined as anergy. Results: The overall frequency of cutaneous anergy was 9% (n = 11). It occurred in 33% of men versus 6% of women. The mean age was 57 years, and 89% were over 50 years-old. Being female behaved as a protective variable for the generation of anergy, OR 0.795 [95% CI, 0.658 - 0.959, P<.05]. All patients with anergy were being treated with corticosteroids, 44% with methotrexate, and 33% with biological therapy. Treatment with moderate to high dose prednisone and biological therapy were independently associated as risk factors for presenting with anergy, OR 1.044 [95% CI, 1.008-1.080 P<.05] and OR 1.096 [95% CI, 1.016-1.182, P<.05], respectively. The overall positivity for tuberculin was 13%. Symptoms associated with disease activation were present in 38% of these. All cases (n= 1) of confirmed active tuberculosis were excluded. Conclusions: The high prevalence of cutaneous anergy in patients with RA in the present study, and the evidence presented here, supports the recommendation of a second diagnostic test (tuberculin booster or Interferon-Gamma Release Assays) for the diagnosis of latent TB in patients with RA on immunosuppressive therapy.

RESUMEN Antecedentes: La tuberculina es la prueba de hipersensibilidad cutánea tardía mundialmente aceptada para el diagnóstico de tuberculosis latente. La alteración de la inmunidad celular inducida por los fármacos modificadores de la enfermedad utilizados en la artritis reumatoide puede dar un resultado falso negativo, también conocido como anergia cutánea. No hay estudios que determinen la frecuencia de anergia en pacientes con artritis reumatoide y terapia inmunosupresora. Objetivo: Determinar la frecuencia y los posibles factores asociados con la anergia cutánea en un grupo de pacientes con artritis reumatoide y terapia inmunosupresora. Métodos: Estudio observacional analítico transversal que incluyó a 100 pacientes con artritis reumatoide con terapia inmunosupresora. Se les realizó una prueba de hipersensibilidad cutánea tardía con tuberculina y una prueba de control con toxoide tetánico. La no reactividad de ambas pruebas se definió como anergia. Resultados: La frecuencia general de anergia cutánea fue del 9% (n = 11). Ocurrió en el 33% de los hombres versus el 6% de las mujeres, la edad promedio fue de 57 anos y el 89% tenía más de 50 anos. El sexo femenino se comportó como una variable protectora para la generación de anergia (OR 0,795; IC 95%: 0,658-0,959; p < 0,05). Todos los pacientes con anergia usaron corticosteroides, el 44% fue tratado con metotrexato y el 33% con terapia biológica. El tratamiento con dosis de moderadas a altas de prednisona y terapia biológica se asoció de manera independiente como factor de riesgo para la presentación de anergia: OR 1,044 (IC 95%: 1,008-1,080; p < 0,05) y OR 1,096 (IC 95%: 1,016-1,182; p < 0,05), respectivamente. La positividad general para la tuberculina fue del 13%. Los síntomas asociados con la activación de la enfermedad estaban presentes en el 38% de ellos. Se excluyeron todos los casos de tuberculosis activa confirmada (n = 1). Conclusiones: La alta prevalencia de anergia cutánea en pacientes con artritis reumatoide en el presente estudio y la evidencia presentada respaldan la recomendación de una segunda prueba de diagnóstico (refuerzo de tuberculina o IGRA) para el diagnóstico de tuberculosis latente en pacientes con artritis reumatoide y terapia inmunosupresora.

Valoración de las pruebas diagnósticas para tuberculosis bovina en un rebaño bovino ubicado en zona de alta incidencia del estado Zulia Venezuela / Valuation of diagnostic tests for bovine tuberculosis in cattle herd located in a high incidence area of Zulia state Venezuela

Las pruebas de tuberculina son las de uso generalizado para el diagnóstico y el control de la tuberculosis (TBC) en el hombre y en los animales. Se caracteriza por una compleja mezcla de antígenos de mycobacterias capaces de inducir reacciones de hipersensibilidad en animales infectados, incluso con mycobacterias diferentes al Mycobacterium bovis, por efectos de reactividad cruzada. La preparación del derivado protéico purificado (PPD), es similar a la de la tuberculina, a diferencia de la concentración de proteínas, las cuales se separan por precipitación con agentes químicos y no por calor, aumentando su especificidad. Los primeros resultados obtenidos con las pruebas serológicas para el diagnóstico de tuberculosis bovina muestran que existe una gran reactividad antigénica cruzada entre las especies de mycobacterias, por lo que se requiere de antígenos más específicos. Se implementó un ELISA-TBC para la detección de anticuerpos anti M. bovis. El ensayo inmunoenzimático para el IFN-y bovino cuando se utilizó conjuntamente con el sistema de cultivo de sangre completa resultó en un ensayo in vitro rápido y sensible para detectar la reactividad de la inmunidad mediada por células al M. bovis en el ganado infectado. A partir de estas pruebas se compararon los resultados obtenidos para establecer la sensibilidad y especificidad utilizando como prueba oro, los datos obtenidos en el cultivo bacteriológico y la reacción en cadena de la polimerasa (PCR). Los animales reaccionantes a la tuberculina incluyeron animales positivos a PPD-B y PPD-A, así como animales negativos a cultivo bacteriológico y PCR. Los PPD-B positivos, no son en su totalidad, los mismos reaccionantes al IFN-y o al ELISA-TBC. Aún cuando su sensibilidad es baja, muestra mayor especificidad y concordancia que el resto de las pruebas utilizadas.

The tuberculin tests are widely used for diagnosis and control of tuberculosis (TB) in humans and animals. It is characterized by a complex mixture of mycobacteria antigens able to induce hypersensitivity reactions even in animals infected with mycobacteria other than M. bovis, for purposes of cross-reactivity. The preparation of purified protein derivative (PPD) is similar to the tuberculin, unlike the concentration of proteins which are separated by precipitation with chemical agents and not by increasing its specific heat. The first results obtained with the serological tests for diagnosis of bovine tuberculosis show that there is a great antigenic cross-reactivity between mycobacterias species so it requires more specific antigens. It implemented a cattle IFN-g test and ELISA-TBC to detect anti M. bovis activity. The immunoassay test for IFN-g used in conjunction with the cropping system of whole blood resulted in an essay in vitro rapid and sensitive to detect the reactivity of the cell-mediated immunity to M. bovis in livestock infected. Comparative test of the tuberculina, test of Gamma Interferon (INF-y) and a test ELISA-TBC, soon was taken to slaughter house to take linfoides weave samples and nodules, to which the test of chain reaction of Polimerasa was applied to them, to bacteriological culture and (PCR), for the identification from the pathogen. From these tests the patterns of immune response settled down and the obtained results of the different tests were compared to establish sensitivity and specificity using with t gold standard, the data collected in culture and PCR. The results were analyzed using the statistical method of analysis of variance for nonparametric tests. The PPD B-positive, are not the same reacting to IFN-y or at ELISA-TBC. Although its sensitivity is low, it shows greater specificity and consistency as the rest of the tests used.

Caracterización de la respuesta inmunitaria de bovinos infectados con Mycobacterium bovis en condiciones de campo en el municipio Colón estado Zulia Venezuela / Characterization of the immune response of bovines with Mycobacterim bovis field infection in an area with high incidence of bovine tuberculosis in Venezuela

La tuberculosis bovina es una enfermedad crónica, zoonótica, infecciosa y contagiosa teniendo como agente causal al Mycobacterium bovis inductor de una respuesta inmunitaria diversa. Esta abarca, desde una respuesta celular capaz de controlar la infección, pasando por una potente, más no eficiente respuesta humoral, hasta un estado de no respuesta o anergia, coadyuvante de la diseminación de la micobacteria. En este estudio se evaluaron animales seleccionados por el Instituto Nacional de Salud Agrícola Integral (INSAI), como reactores a la prueba simple de la Tuberculina en una finca con antecedentes de tuberculosis por más de 20 años. A estos animales se le aplicaron las siguientes pruebas: Comparativa del PPD (PPD-B y PPD-A), prueba de Interferón Gamma (INFy) y un ensayo inmunoenzimático para TBC (ELISA-TBC), seguidamente se realizó la inspección post morten en el frigorífico donde se evaluaron y clasificaron las lesiones macroscópicas compatibles con tuberculosis. Los tejidos seleccionados fueron utilizados para estudios bacteriológicos, extracción de ADN y posterior amplificación secuencia específica con cebadores y oligonucleótidos IS6110 específicos para el complejo M. tuberculosis, aplicando la prueba de Reacción en Cadena de la Polimerasa (PCR-SSP) para la identificación definitiva del patógeno. El resultado de estas pruebas permitió observar diferentes patrones de respuesta inmunitaria: celular (PPD+/IFN-y-, PPD+/IFNy+, PPD-/IFNy+), mixto (PPD+ o IFN-y+/ELISA-TBC+) y humoral (ELISA-TBC+). Igualmente se detectaron animales anérgicos, negativos a todas las pruebas inmunológicas, positivos en bacteriología y PCR-SSP. Se pudo establecer la progresión de la enfermedad a partir de la severidad de las lesiones y la edad de los animales. Estos patrones pueden aparecer al inicio de la infección o ser el resultado de la progresión crónica de la enfermedad. Estas diferentes respuestas inmunitarias pueden explicar la permanencia de la infección...

The bovine tuberculosis is a chronic, zoonótic infectious disease and contagious having as causal agent to the Mycobacterium bovis inductive of a diverse immune response. This sandal, from an answer cellular, able to control the infection, happening through powerful, but a nonefficient one, humoral response to a state of not response or anergia, facilitating the dissemination of mycobacteria. In this study animals selected by the Venezuelan National Institute of Integral Agricultural Health (INSAI), like reactors to the simple test of the Tuberculina in a property with antecedents of tuberculosis by but of 20 years. To these animals the following tests were applied: Comparative of the tuberculina (PPD-B and PPD-A), test for Gamma Interferon (INF-y) and a Immun-enzimatic Test for TBC (ELISA-TBC), next was made the inspection post morten in the refrigerator where the compatible macrocospic injuries with tuberculosis were evaluated and classified. The selected weaves were used for bacteriological studies, DNA extraction and later amplification specific sequence with specific boots IS6110 for tuberculoso complex M., applying the test of Chain Reaction of Polimerasa (PCR-SSP) for the definitive identification of the pathogen. The result of these tests allowed to observe different patterns from immune response: cellular (PPD+, PPD+ - INF-y + or INF-y +), mixed (PPD+ and/or INF-y, ELISA-TBC+) and humoral (ELISA-TBC). Also anérgics animals detected themselves, negatives to all the immunological tests, positive in bacteriology and PCR-SSP. It was possible to be established the progression of the disease from the severity of the injuries and the age of the animals. These different immune responses may explain the persistence of infection in farm notwithstanding the implementation of the resolution of official control and eradication of Bovine Tuberculosis in the region.

Maintenance of CD8+T-cell anergy by CD4+CD25+ regulatory T cells in chronic graft-versus-host disease

In a murine model of systemic lupus erythematosus (SLE)-like chronic graft-versus-host disease (cGVHD), donor CD8+T cells rapidly fall into anergy to host cells, while donor CD4+T cells hyperactivate B cells and break B-cell tolerance to self-Ags in the recipient mouse. The functional recovery of donor CD8+T cells can result in the conversion of cGVHD to acute GVHD (aGVHD), indicating that donor CD8+T-cell anergy is a restriction factor in the development of cGVHD. In this report, we present evidence that donor CD4+CD25+regulatory T cells (T(reg) cells) are critical in maintaining the donor CD8+T-cell anergy and thus suppressing the development of aGVHD in mice that are naturally prone to cGVHD. Our results provide a novel insight into the role of T(reg) cells in determining cGVHD versus aGVHD.

The Effects of Maturation Resistant Donor Dendritic Cells on Alloimmune Response in Mice / 대한신장학회잡지

BACKGROUND: Although dendritic cells (DCs) are the most influential antigen presenting cells maturation of DC is the critical control point toward either activation or regulation of immunity. We hypothesized that pretreatment with donor DCs, if which were maturation-resistant in vivo, could enhance engraftment by inducing inactivated state for allo- reactive T cell clones. METHODS: Immature DCs were prepared by 6- day culture of BM cells and we used paraformaldehyde for locking the DCs as immature phenotypes. We did in vitro and in vivo MLR to evaluate the effect of maturation resistant DCs on alloreactive T cells and we confirmed the effect of DCs in MHC full mismatched skin and islet transplantation model. RESULTS: Fixed DCs in immature state were resistant to maturation stimuli and weak stimulator for allo-reactive T cells (CB6F1-->C3H). In contrast, fixed DCs in mature state stimulated allogeneic T cell proliferation effectively. Splenocytes isolated from mice 2 weeks after maturation resistant DC injection could not be reactivated and maintained naive phenotype when cocultured with allogeneic splenocytes (BALB/c-->C57BL6). Consistent with this finding maturation resistant DC treatment suppressed MLR-driven T cell division (CB6F1-->C3H) as assessed by CFSE analysis. But, CD25+ T cells depletion by treatment with anti-CD25 prior to DCs transfer attenuated this regulatory effect of DCs. In a MHC mismatched transplantation model (CB6F1-->C3H), treatment with maturation-resistant DCs 2 weeks before operation, markedly prolonged skin and islet graft survival. But C3H mice pretreated with CB6F1 DCs rejected DBA1 (H-2q) skin graft within 14 days. CONCLUSION: These findings suggest the maintenance of immaturity of DCs is a key factor in modulating alloimmune responses through dendritic cells.

Anergy testing in patients with head and neck cancer.

Patients with head and neck cancer were found to be deficient in were not clear [correction] Possible explanations include a change in T-lymphocyte numbers, particularly the helper/suppressor T-cell ratio, with the cause of this change still unknown. Tumor immunosuppressing factors and cancer-induced immunosuppression are proposed to be such causes. The deficiency of T cells resulted in an impaired cell-mediated immune response (CMIR), which lowered the host resistance, such facilitating the tumor to spread. As the CMIR can be evaluated by delayed hypersensitivity skin testing (= anergy screen), the objective of this study was to compare the CMIR function of patients with head and neck cancer to a non-cancer control group using this anergy screen. The study group consisted of 20 patients (17 males, 3 females, age range 10-76 years) with head and neck cancer, which were anti-HIV negative and had not received any therapy yet. The control group consisted of another 20 persons (17 males, 3 females, age range 21-72 years) without any cancer and who were also anti-HIV negative. Exclusion criteria were (1) eczema or skin disease in the area to be tested, (2) having received oral prednisolone within the last week and (3) an anti-HIV positive immune status. The antigens used in this study consisted of PPD (5 IU), tetanus toxoid (TT) (0.8 LF/ml and 1.6 LF/ml, Candida albicans (20 PNU/ ml and 200 PNU/ml), mumps-measles-rubella (MMR) vaccine (1:10 v/v and 1:5 v/v). The test was done by intradermal injection of 0.1 ml of each antigen. The anergy screen was considered positive when the test resulted in an erythema or induration larger than 5 mm at 72 hours after the injection. Complete anergy was diagnosed when there was no skin reaction at all, partial anergy when only 1 antigen tested positive and no anergy when there were positive skin reactions to two or more antigens. In the study group, 9 (45%) patients were diagnosed with complete anergy, 11 (55%) with partial anergy and none with no anergy, while in the control group, none were complete anergic, 3 (15%) were partially anergic and 17 (85%) had no anergy. There was a statistically significant difference (p < 0.01) between these two groups. In conclusion, patients with head and neck cancer seemed to have an impaired CMIR, with at least the partial anergy being statistical significantly different compared to the non-cancer group.

Differential susceptibility of naïve versus cloned CD4+ T cells to antigen-specific and MHC-restricted anergy induction / 生理学报

T cell anergy has been successfully induced under different conditions in cloned CD4(+) T cells, but induction of T cell anergy in vivo has been difficult and controversial. Due to the low frequency of naturally occurring T cell population with specificity to a defined antigen, it is very difficult to study anergy of naïve T cells without prior in vivo priming which complicates the interpretation of experimental data. To solve this problem, we adopted the HNT-TCR transgenic mice which have homogeneous antigen specific CD4(+) T cell population. In this study, we generated an influenza virus hemagglutinin (HA) peptide-specific CD4(+) T cell clone from the HNT-TCR transgenic mice and induced anergy using APCs which were treated with the crosslinker, ECDI (1-ethyl-3-3(3-dimethylaminopropyl) carbodiimide). The proliferative response of the cloned or freshly purified naïve CD4(+) transgenic T cells after treatment with ECDI-treated APCs and the HA peptide antigen was monitored as the index of anergy induction. The results showed that anergy was successfully induced in the cloned HNT-TCR transgenic CD4(+) T cells. It was determined that the induced anergy was antigen- and MHC-specific. By contrast, anergy was not observed in freshly purified naïve CD4(+) transgenic T cells under the same conditions. The results suggest that naïve CD4(+) T cells may have different anergy inducing requirements, or that cloned CD4(+) T cells may have certain priming or in vitro cloning artifact which makes them more susceptible to anergy induction. We propose that induction of T cell anergy may depend on the T cell growth, activation and differentiation state or cloning conditions. The results from the present study may have important implications for the study of the mechanism(s) underlying T cell anergy induction in vivo and for applications of immune tolerance based therapy.

Anergy and chemokine receptors.

The human immunodeficiency virus (HIV) induces a spectrum of immune abnormalities in the host by binding to CD4 molecules and chemokine receptors. Anergy, apoptosis, and immune activation are among the diverse immunological changes observed in the host. Chemokines, being the natural ligands for the chemokine receptors, block the entry of a retroviral strain, which exhibits tropism for the given receptor. This opens new therapeutic strategies and intervention possibilities for treating HIV infected individuals.

Respuesta inmunitaria y anergia. Estudio en pacientes tuberculosos del Hospital Universitario de Maracaibo, Venezuela / Immunitary response and anergy. Study in tuberculosis patients from the Universitary Hospital, Maracaibo, Venezuela

RESUMEN: Con el objeto de evaluar la anergia en individuos infectados con el Mycobacterium tuberculosis se estudiaron 57 pacientes y 15 controles sanos de ambos sexos y edades diferentes, a los cuales se les practicó cultivo bacteriológico de esputo (BK) y la intradermoreacción con el PDD. La prueba de tuberculina en piel fue realizada inoculando 0.1 ml de PPD vía intradérmica con resultados evaluados a las 72 horas. Un total de 28 pacientes resultaron BK+ y 29 BK-. Del grupo BK+, 15 resultaron PPD+ y 13 PPD-, estos últimos fueron clasificados como pacientes anérgicos (BK+PPD-). De los 29 pacientes restantes (BK-), 20 fueron PPD+ y 9 PPD-. Todos los controles resultaron BK- PPD-. Solamente se evaluó la anergia en pacientes BK+ (28 individuos).Los pacientes fueron clasificados desde el punto de vista clínico en tres series: Serie N: 27 pacientes TBC + BK-, Serie P: 28 pacientes TBC + BK+ y Serie EP: 2 pacientes con TBC extra pulmonar. Según el grado de complicación pulmonar, los pacientes se separaron en dos grupos, de acuerdo a la extensión y tipo de lesión encontrados en la evaluación con rayos X. El ôgrupo 1ö con 9 pacientes (32.14 %) presentó lesiones unilaterales con o sin cavernas y el ôgrupo 2ö con 19 pacientes (67.85 %) con lesiones bilaterales con o sin cavernas. Se realizó el Test de transformación linfoblástica (TTL) estimulando con PHA y/o PPD, para lo cual se recolectaron muestras de sangre periférica con heparina. Las concentraciones de IL-4, IL-6 INF-gama obtuvieron por ensayos inmunoenzimáticos en sobrenadante de cultivos y en plasma, posterior a la estimulación con el PPD. El análisis estadístico se realizó utilizando el Test T de Student pareado, Análisis de Varianza y el Chi cuadrado. Sólo los controles y los pacientes BK-, mostraron respuesta normal a la PHA, en contraste, los pacientes BK+ PPD+ presentaron una supresión de la respuesta frente a la PHA de aprox. 90 %. Los pacientes PPD+ mostraron una respuesta superior en cultivo que los pacientes PPD-. La concentración de IL-4 en el plasma de los pacientes anergicos (PPD-) mostró una diferencia significativa (P<0.05) con respecto al grupo PPD+. La concentración de INF-gama fue inferior en los pacientes anérgicos mas no significativamente diferente a la de los pacientes PPD+. Similar resultado se obtuvo en la medición de IL-4 INF- en sobrenadante de cultivo. Se pudo observar la presencia de pacientes con IL-4 + INF-gama, INF-gamao IL-4 solamente...

From clone selection to danger model / 中国医学科学院学报

How is the balance between immune response and immune tolerance dynamically kept in the complicated immune system of human body? To answer this question, many scientists have proposed various models since 1950's. A brief introduction to these models is given in this mini-review, which might reflect the historical process in the development of immunology in the past half century.

Valor de la prueba cutánea tardía en pacientes de la tercera edad / Value of the cutaneous late test in patients of the third age

Antecedentes: la hipersensibilidad cutánea retardada a diversos antígenos se ha estudiado en humanos de diversas edades y se ha observado que en individuos mayores de 60 años de edad existe una disminución en la respuesta a las pruebas que miden la hipersensibilidad retardada. Objetivo: determinar el patrón de respuesta a las pruebas de hipersensibilidad retardada en una muestra supuestamente sana de la población cubana residente en Ciudad de La Habana, mediante la aplicación de una batería de pruebas cutáneas con antígenos nacionales. Material y método: se aplicaron pruebas intradérmicas a 87 personas (69 mujeres y 18 hombres) entre 60 y 89 años de edad, sin antecedentes de infecciones frecuentes. A todos los sujetos de estudio se les hizo historia clínica y análisis clínicos para descartar padecimientos que pudieran desviar el propósito del estudio. Se determinó el grado de respuesta mediante la suma de las medias de los diámetros de las induraciones, misma que se denominó puntuación media total. Resultados: en todos los grupos de edades la puntuación media total fue ligeramente superior en las mujeres, tanto en el grupo control como en el de estudio, excepto en el grupo de edades entre 80 a 89 años. Conclusión: en virtud de que existen pocos indicadores de salud para las personas ancianas la batería de pruebas aquí propuesta pudiera ser un buen indicador predictivo de morbilidad y mortalidad en pacientes de la tercera edad.

Valoración de la respuesta inmune retardada en pacientes sanos de la tercera edad / Assessment of the delayed immune response in sound aged patients

Se utilizo una batería de pruebas demoradas (estafilococo, estreptococo, toxoide tetánico , Proteus mirabilis, candidina y tricofitina) con el objetivo de evaluar la inmunidad celular in vivo en 87 personas de más de 60 años supuestamente sanas. Se determinó el grado de respuesta mediante la sumade las medias de los diámetros de las induraciones a lo que se denominó puntuación media total (PMT)que fue para los hombres 14mm y para las mujeres 12mm. Los resultados se compararon por sexos y grupos etáreos

Nutrients as modulators of anergy in acquired immune deficiency syndrome.

Malnutrition induces a spectrum of immune abnormalities including a state of anergy in the host. This state is due to a decrease in CD4 + helper cells, diminished cytotoxic cell activity and reduction in production of lymphokines required for signal transduction. Human immunodeficiency virus (HIV), the retrovirus known to cause acquired immune deficiency syndrome (AIDS), leads to a state of anergy by causing similar immunological changes. Micronutrient abnormalities, concomitant infections and genetic factors, etc., are some of the compounding co-factors which further contribute to the deterioration of the immune functions in AIDS patients. Reversal of these immune abnormalities would improve the quality of life of HIV-infected individuals.

Mecanismos gerais de tolerância imunológica e auto-imunidade / General mechanisms of immunologic tolerance and autoimmunity

A tolerância imunológica a antígenos próprios do organismo é um estado fisiológico, adquirido ao longo do desenvolvimento, envolvendo vários mecanismos, para preservar os tecidos do indivíduo. Ambos repertórios, de linfócitos T e B, sao tolerizados por mecanismos interconectados, que ocorrem em dois níveis: 1) órgaos linfóides primários (tolerância central), e 2) órgaos linfóides periféricos e sangue circulante (tolerância periférica). A deleçao, por apoptose, de clones Te B imaturos, em timo e medula óssea, respectivamente, constitui o principal mecanismo de tolerância, através da seleçao negativa de células com potencial de auto-reatividade. Este processo é influenciado por diversos fatores: grau de afinidade, pelo ligando, do receptor específico para o antígeno, dos linfócitos T e B; concentraçao e natureza do antígeno reconhecido; interaçao de co-receptores e de moléculas de adesao. A detecçao de clones T e B auto-reativos, no repertório periférico normal, confirma a possibilidade de escape à deleçao clonal. Por um lado, linfócitos maduros podem ser potencialmente auto-agressivos, e ainda tolerizados, em periferia, através de mecanismos descritos principalmente para o compartimento T: deleçao clonal, anergia clonal (ocupaçao do receptor, em ausência de co-estimulaçao) e imunossupressao (por células ou citocínas). Por outro lado, o conceito de auto-reatividade fisiológica é introduzido, para se diferenciar de doença auto-imune (auto-reatividade patológica). As doenças auto-imunes se desenvolvem por falhas na manutençao da tolerância, cujas causas sao múltiplas: terreno genético individual, sobretudo genes que regulam a apresentaçao e reconhecimento antigênicos, e fatores ambientais (dieta, infecçoes virais ou bacterianas).

Correlaçäo entre a infecçäo pelo HIV, anergia cutânea e alteraçöes oculares observadas entre pacientes com sorologia positiva para o HIV ou de risco para a infecçäo: parte II / Correlation of HIV infection, anergy and ocular manifestations observed in patients with or at risk of HIV infection: part II

Uma série de 203 pacientes ambulatoriais com sorologia positiva para o HIV ou de risco para a infecçäo foram examinados para determinar a frequência das manifestaçöes oftalmológicas e correlacioná-las com a imunodeficiência. O estado imunológico foi pesquisado através de testes cutâneos utilizando os antígenos: PPD, candidina, tricofitina e estreptoquinase. Observou-se que existe uma forte associaçäo entre a infecçäo pelo HIV, a energia cutânea e as alteraçöes oculares. O paciente infectado e anérgico apresenta um risco 22 vezes maior de desenvolver alteraçöes oculares (p=0)