Submandibular and sublingual glands involvement in advanced acquired immunodeficiency syndrome (AIDS): an autopsy-based study

Objective. To assess the histopathological, immunohistochemical (IHC), and in situ hybridization (ISH) features found in the submandibular (SM) and sublingual (SL) glands of 105 acquired immunodeficiency syndrome (AIDS) patients at autopsy. Study design. Gender, age, CD4 cell level, and clinical histories were obtained from clinical charts (SM: n = 103; SL: n = 92). Histologic analysis of hematoxylin and eosin, Gomori-Grocott, and Ziehl-Neelsen stained tissues, IHC to detect infectious agents and characterize inflammatory cells in sialadenitis, and ISH for EBER-1/2 were performed. Results. The mean age of the patients and CD4 cell count were 36 years and 76 cells/mu L, respectively. Fifty-eight cases (SM: n = 51 [49%]; SL: n = 54 [59%]) were considered to be microscopically normal. The most common infectious conditions were mycobacteriosis (SM: n = 11 [10%]; SL: n = 7 [7%]), followed by cytomegalovirus (CMV) (SM: n = 14 [13%]; SL: n = 2 [2%]), and cryptococcosis (SM: n = 3 [3%]; SL: n = 4 [4%]). Human immunodeficiency virus (HIV) p24 (SM: n = 2 [2%]; SL: n = 1 [1%]) and EBER-1/2 (SM: n = 9 [39%]; SL: n = 4 [20%]) were seen only in macrophages and lymphocytes, respectively. The most prevalent cells seen in chronic nonspecific sialadenitis (SM: n = 25; SL: n = 25) were CD8+ T lymphocytes, whereas CD68+ macrophages were predominant in the mycobacteriosis-associated granulomatous and nonspecific diffuse macrophagic sialadenitis. Concomitant infections occurred in 5 cases (SM: n = 4; SL: n = 1) and non-Hodgkin lymphoma in 1 case. Conclusions. Infectious diseases and chronic nonspecific sialadenitis were the main alterations found in the SM and SL glands. These alterations were greater in the SM than in the SL glands. CD8+ T lymphocytes and CD68+ macrophages might be relevant to the pathogenesis of the sialadenitis. Clinicians should consider these diseases when assessing the major salivary glands in advanced AIDS patients and follow biosafety procedures to avoid contamination by HIV, CMV, mycobacteriosis, and cryptococcosis. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: 216-226)

Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice

Vaccines capable of inducing mucosal immunity in early postnatal life until adulthood, protecting early sexual initiation, should be considered as strategies to vaccination against HIV. The HIV-1 GAG protein as a chimera with the lysosome-associated membrane protein (LAMP/gag), encoded by a DNA vaccine, is targeted to the endosomal/lysosomal compartment that contains class II MHC molecules and has been shown to be immunogenic in adult mice. Assuming that one such strategy could help to overcome the immunological immaturity in the early postnatal period, we have evaluated the systemic and mucosal immunogenicity of LAMP/gag immunization in neonatal mice. Intranasal immunization with LAMP/gag vaccine induced higher levels of sIgA and IgG anti-GAG antibodies in intestinal washes than did the gag vaccine. The combination of ID injections and the IN protocol with the chimeric vaccine promoted the increase of Ab levels in sera. Both vaccines induced splenic IFN-gamma- secreting cells against GAG peptide pools, as well as in vivo cytotoxic T lymphocyte (CTL) function, and increased the percentage of CD8+ T cells to the immunodominant class I peptide in gut and spleen. However, only the chimeric vaccine was able to enhance Th1/Th2 cytokine secretion in response to class II GAG peptide and to enhance IL-4-secreting cells against GAG peptides and p24 protein stimuli. Long-lasting humoral and cellular responses were detected until adult age, following neonatal immunization with the chimeric vaccine. The LAMP/gag vaccination was able to induce potent GAG-specific T and B cell immune responses in early life which are essential to elicit sustained and long-lasting mucosal and systemic humoral response. (C) 2010 Elsevier GmbH. All rights reserved.

Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment

Dendritic cells (DCs)-based vaccine was demonstrated to increase HIV specific cellular immune response; however, in some HIV-infected patients, the response to the vaccine resulted to be not effective. In order to understand if the outcome of the vaccination may be influenced by the host`s genome and natural immunity, we studied the innate immune genome of HIV-infected patients previously vaccinated with DCs. We identified 15 SNPs potentially associated with the response to the immuno-treatment and two SNPs significantly associated with the modulation of the response to the DC vaccine: MBL2 rs10824792 and NOS1 rs693534. These two SNPs were also studied in different ethnic groups (Brazilians, African and Caucasian) of HIV-infected, exposed uninfected and unexposed uninfected subjects. The HIV positive Caucasian patients were also characterized by different disease progressions. Our findings suggest that, independently and/or in addition to other variables. the host`s genome could significantly contribute to the modulation of the response to the DC vaccine. (C) 2009 Elsevier Ltd. All rights reserved.

Comparative Study of the Standard Fluorescent Antibody to Membrane Antigen (FAMA) Assay and a Flow Cytometry-Adapted FAMA Assay To Assess Immunity to Varicella-Zoster Virus

A flow cytometry-adapted fluorescent antibody to membrane antigen (FAMA) assay to detect IgG antibodies against varicella-zoster virus (VZV) was developed and tested in 62 serum samples, showing 90.32% accuracy obtained from a receiver operating characteristic (ROC) curve with a 0.9125 (95% confidence interval [CI], 0.829 to 1.00) area below the curve compared to the result with standard FAMA.

Relationship between serum and saliva antibodies to Candida and isolation of Candida species from the mucosa of HIV-infected individuals

Colonisation and infection by Candida species occur frequently in acquired immunodeficiency syndrome (AIDS), but their relationship to the humoral immunity against candidiasis is controversial. To evaluate the levels of antibodies to Candida in the serum and in the saliva of HIV-1-infected patients in relation to the presence of immunodeficiency, oral candidiasis and Candida colonisation, Candida was investigated in the urine and in the oral and anal mucosae of HIV-1-infected patients, AIDS patients and healthy controls. The levels of IgG, IgM and IgA antibodies to Candida were determined in the serum and in the saliva by immunoassay. Candida species were detected in 76% of the patients. Mucosal yeast colonisation and the levels of serum and saliva antibodies to Candida were similar between asymptomatic HIV-infected and non-infected patients. Mucosal colonisation was highest in AIDS patients, who also had higher serum IgA and saliva IgG antibodies. Antibody levels were similar in patients with and without candidiasis oral lesions. Asymptomatic HIV-infected individuals are similar to non-infected individuals with respect to mucosal colonisation as well as serum and saliva levels of antibodies to Candida. The higher mucosal colonisation and clinical candidiasis observed in the AIDS patients apparently stimulated a more intense humoral response to the yeast.

Modulation of mucosal immunity in a murine model of food-induced intestinal inflammation

Background Hypersensitivity or uncontrolled responses against dietary antigens can lead to inflammatory disorders like food allergy and current models reflect a variety of causes but do not reveal the detailed modulation of gut immunity in response to food antigens after breakdown in mucosal tolerance. Objective To develop and characterize a murine model for food-induced intestinal inflammation and to demonstrate the modulation of gut immune response by dietary allergenic antigens. Methods C57BL/6 mice were sensitized with peanut proteins, challenged with peanut seeds and their sera and gut segments were collected for subsequent analyses. Results Sensitization and challenged with peanut seeds led to alterations in gut architecture with inflammatory response characterized by oedema in lamina propria and cell infiltrate composed mainly by eosinophils, mast cells, phagocytes, natural killer and plasma cells, together with low percentage of gamma delta(+) and CD4(+)CD25(+)Foxp3(+) cells in Peyer`s patches. These animals also presented high levels of specific IgE and IgG1 in sera and modulation of mucosal immunity was mediated by increased expression of GATA-3, IL-4, IL-13 and TNF-alpha in contrast to low IFN-gamma in the gut. Conclusion A murine model for food-induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T-helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food-related enteropathies like food allergy, focusing on gut-specific immune response.

Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population

OBJECTIVE: To determine contribution of reinfection with new strains of cytomegalovirus in cytomegalovirus seromimmune women to incidence of congenital cytomegalovirus infection. STUDY DESIGN: In 7848 women studied prospectively for congenital cytomegalovirus infection from a population with near universal cytomegalovirus seroimmunity, sera from 40 mothers of congenitally infected infants and 109 mothers of uninfected newborns were analyzed for strain-specific anticytomegalovirus antibodies. RESULTS: All women were cytomegalovirus seroimmune at first prenatal visit. Reactivity for 2 cytomegalovirus strains was found in 14 of 40 study mothers and in 17 of 109 control mothers at first prenatal visit (P=.009). Seven of 40 (17.5%) study women and 5 of 109 (4.6%) controls (P=.002) acquired antibodies reactive with new cytomegalovirus strains during pregnancy. Evidence of infection with more than 1 strain of cytomegalovirus before or during current pregnancy occurred in 21 of 40 study mothers and 22 of 109 controls (P<.0001). CONCLUSION: Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.

Case Report: Esophageal Histoplasmosis Associated with Disseminated Tuberculosis in Acquired Immunodeficiency Syndrome

Bacterial and fungal infections are common in acquired immunodeficiency syndrome (AIDS). Histoplasmosis is a common fungal disease in severely immunocompromised patients infected with human immunodeficiency virus (HIV) in endemic areas. In this population the most frequent form of presentation of histoplasmosis is disseminated, with the clinical manifestations being similar to those of disseminated tuberculosis. Esophageal histoplasmosis and the association of histoplasmosis with tuberculosis are infrequent. We report here a rare Case of esophageal histoplasmosis associated with disseminated tuberculosis in AIDS.

Cytokine Signatures of Innate and Adaptive Immunity in 17DD Yellow Fever Vaccinated Children and Its Association With the Level of Neutralizing Antibody

Background. The live attenuated yellow fever (YF) vaccines have been available for decades and are considered highly effective and one of the safest vaccines worldwide. Methods. The impact of YF-17DD-antigens recall on cytokine profiles of YF-17DD-vaccinated children were characterized using short-term cultures of whole blood samples and single-cell flow cytometry. This study enrolled seroconverters and nonseroconverters after primovaccination (PV-PRNT(+) and PV-PRNT(-)), seroconverters after revaccination (RV-PRNT(+)), and unvaccinated volunteers (UV-PRNT(-)). Results. The analysis demonstrated in the PV-PRNT(+) group a balanced involvement of pro-inflammatory/regulatory adaptive immunity with a prominent participation of innate immunity pro-inflammatory events (IL-12(+) and TNF-alpha(+) NEU and MON). Using the PV-PRNT(+) cytokine signature as a reference profile, PV-PRNT(+) presented a striking lack of innate immunity proinflammatory response along with an increased adaptive regulatory profile (IL-4(+) CD4(+) T cells and IL-10(+) and IL-5(+) CD8(+) T cells). Conversely, the RV-PRNT(+) shifted the overall cytokine signatures toward an innate immunity pro-inflammatory profile and restored the adaptive regulatory response. Conclusions. The data demonstrated that the overall cytokine signature was associated with the levels of PRNT antibodies with a balanced innate/adaptive immunity with proinflammatory/regulatory profile as the hallmark of PV-PRNT(MEDIUM+), whereas a polarized regulatory response was observed in PV-PRNT(-) and a prominent proinflammatory signature was the characteristic of PV-PRNT(HIGH+).

Anandamide prior to sensitization increases cell-mediated immunity in mice

The endocannabinoid system has become a topic of great interest in pharmacology due to its remarkable distribution in mammal organisms and capacity to play a modulatory role on several physiological systems, including modulation of immunity. Many studies have shown that administration of cannabinoids causes inhibitory effects on immune cells, including decreased proliferation and antigen-presenting cell (APC) costimulatory activity. In contrast, other groups have shown that some cannabinoids might present stimulatory actions on macrophage activity and T cell activation. Therefore, we aimed to investigate whether a treatment in vivo with a low dose of anandamide (0.1 mg/kg) immediately prior to sensitization would have an immunosuppressive or immunostimulatory effect on cell-mediated immunity (Th1 response) in mice. We report here that anandamide, prior to sensitization, was able to increase the Th1 response to ovalbumin in vivo and ex vivo. Anandamide increased delayed type hypersensitivity (DTH), splenocyte proliferation, and IFN-gamma production in a co-culture of adherent and non-adherent splenocytes. Moreover, anandamide prior to sensitization increased both the expression of DC co-stimulatory molecules (CD80/CD86) and IL-12/IL23 (p40) production ex vivo. We have also assessed direct effects of anandamide in the IFN-gamma/IL-4 balance of ConA-stimulated splenocytes in vitro. Anandamide at nanomolar concentrations increased the production of IFN-gamma, while such production decreased at micromolar range. Thus, anandamide induced both the increment of DC activation and IFN-gamma production, which are likely the mechanisms involved in the increase of Th1 response reported here. (C) 2010 Elsevier B.V. All rights reserved.

Effects of type II pyrethroid cyhalothrin on rat innate immunity: A flow cytometric study

Synthetic type II pyrethroids induce anxiety, immunosuppresion or, alternatively, immunostimulatory effects in laboratory animals. Macrophages and neutrophils are known to be key elements in cellular immune responses. The present study was designed to investigate the in vivo effects of cyhalothrin (1.0 and 3.0 mg/kg/once daily for 7 days) on macrophage and neutrophil activities, using a flow cytometry method. Results showed that cyhalothrin treatment decreased the percentage and intensity of phagocytosis performed by macrophages, but did not alter these parameters in neutrophils: and also decreased basal neutrophil oxidative burst and increased S. aureus-induced neutrophil oxidative burst, but did not alter these responses in macrophages. The present results are discussed in the light of a possible indirect action of cyhalothrin on macrophage and neutrophil activities via hypothalamic pituitary adrenal (HPA) axis activation. A possible direct effect of cyhalothrin on macrophage and neutrophil activities is also considered. (C) 2008 Elsevier B.V. All rights reserved.

Evaluation of colostral immunity in swine with commercial anti-leptospira polyvalent whole-bacteria vaccine

The intensity and duration of passive immunity against swine leptospirosis were investigated by the microscopic agglutination test and in vitro leptospira growth inhibition. Twenty-one females at first parturition were divided into three groups: Group A (n = 08): received two doses with 30 days interval of the commercial anti-leptospira bacterin A. Group B (n = 06) received two doses with 30 days interval of the commercial anti-leptospira bacterin B and Group C (n = 07) was the control. In all groups the colostrums were collected. Blood collection of piglets was performed in four different ages. Agglutinin antibodies were equally detected in sera and colostrums for serovars Canicola, Grippotyphosa, Copenhageni, Icterohaemorrhagiae and Pomona (Group A) and Canicola, Copenhageni, Icterohaemorrhagiae, Pomona and Hardjo (Group 13). Mean neutralizing antibodies titers were low. Passive immunity was low duration. (C) 2007 Elsevier Ltd. All rights reserved.