Comparative Histopathology and Immunohistochemistry of QX-like, Massachusetts and 793/B Serotypes of Infectious Bronchitis Virus Infection in Chickens

The aim of this study was to compare experimentally the pathogenicity and tissue distribution of the recently emerged QX-like strain of infectious bronchitis virus (IBV) with the widespread M41 and 793/B serotypes of the virus. Histopathological and immunohistochemical methods were employed to define the main sites of virus replication. One-day-old specific pathogen free chickens were inoculated with five different QX-like strains, or with the M41 and 793/B IBV strains and monitored for 42 days post-infection. Tracheal lesions developed in all infected birds, confirming the ability of all of the tested strains to induce respiratory disease. Replication of the isolates in the alimentary tract was detected, but the infection did not cause significant gut lesions. Four of the five QX-like IBV strains induced severe kidney lesions. Dilation of the oviduct with accumulation of serum-like fluid in the lumen of this structure, reported previously from field cases of QX-like IBV infection, was observed following experimental infection with all of the five QX-like strains. Microscopical and immunohistochemical examination of the affected oviducts did not help to elucidate the pathogenesis of this lesion.     

Anti‐transglutaminase antibodies in non‐coeliac children suffering from infectious diseases

Anti‐transglutaminase antibodies are the diagnostic markers of coeliac disease. A role is suggested for infectious agents in the production of anti‐transglutaminase antibodies. The aim was to measure positive anti‐transglutaminase antibody levels in children with infectious diseases and to compare immunological and biological characteristics of the anti‐transglutaminase antibodies derived from these children with that from coeliac patients. Two hundred and twenty‐two children suffering from infectious diseases were enrolled prospectively along with seven biopsy‐proven coeliacs. Serum samples were tested for anti‐transglutaminase antibodies and anti‐endomysium antibodies; positive samples were tested for coeliac‐related human leucocyte antigen (HLA)‐DQ2/8 and anti‐viral antibodies. Purified anti‐transglutaminase antibodies from the two study groups were tested for urea‐dependent avidity, and their ability to induce cytoskeletal rearrangement and to modulate cell‐cycle in Caco‐2 cells, using phalloidin staining and bromodeoxyuridine incorporation assays, respectively. Nine of 222 children (4%) tested positive to anti‐transglutaminase, one of whom also tested positive for anti‐endomysium antibodies. This patient was positive for HLA‐DQ2 and was diagnosed as coeliac following intestinal biopsy. Of the eight remaining children, two were positive for HLA‐DQ8. Levels of anti‐transglutaminase returned to normal in all subjects, despite a gluten‐containing diet. Purified anti‐transglutaminase of the two study groups induced actin rearrangements and cell‐cycle progression. During an infectious disease, anti‐transglutaminase antibodies can be produced temporarily and independently of gluten. The infection‐triggered anti‐transglutaminase antibodies have the same biological properties as that of the coeliacs, with the same in‐vivo potential for damage.     

Human migration and infectious diseases

Emerging infectious diseases (EID) are defined as diseases that have appeared recently or that have recently increased in their frequency, geographical distribution or both. Commercial globalisation, population movements and environmental changes are the main factors favouring the international spread of microorganisms. Transport and communication development constitutes also a remarkable factor in the worldwide dispersion of microorganisms. The mass movement of large numbers of people creates new opportunities for the spread and establishment of common or novel infectious diseases. A surveillance system to detect emergent and re-emergent infections, a rapid responsiveness of healthcare systems and laboratories, vector control, and the provision of healthcare education programmes to inform the population of how to avoid infections are needed in order to stop the spread of infectious diseases.     

CD122+CD8+ Treg suppress vaccine‐induced antitumor immune responses in lymphodepleted mice

Lymphodeleption prior to adoptive transfer of tumor‐specific T cells greatly improves the clinical efficacy of adoptive T‐cell therapy for patients with advanced melanoma, and increases the therapeutic efficacy of cancer vaccines in animal models. Lymphodepletion reduces competition between lymphocytes, and thus creates “space” for enhanced expansion and survival of tumor‐specific T cells. Within the lymphodepleted host, Ag‐specific T cells still need to compete with other lymphocytes that undergo lymphopenia‐driven proliferation. Herein, we describe the relative capacity of naïve T cells, Treg, and NK cells to undergo lymphopenia‐driven proliferation. We found that the major population that underwent lymphopenia‐driven proliferation was the CD122⁺ memory‐like T‐cell population (CD122⁺CD8⁺ Treg), and these cells competed with Ag‐driven proliferation of melanoma‐specific T cells. Removal of CD122⁺CD8⁺ Treg resulted in a greater expansion of tumor‐specific T cells and tumor infiltration of functional effector/memory T cells. Our results demonstrate the lymphopenia‐driven proliferation of CD122⁺CD8⁺ Treg in reconstituted lymphodepleted mice limited the antitumor efficacy of DC vaccination in conjunction with adoptive transfer of tumor‐specific T cells.     

Emerging infectious diseases and blood donation

Emerging infectious diseases (EIDs) require vigilance from blood banks everywhere. As EIDs spread to new areas and populations, blood banks are forced to re‐evaluate safety measures continually. Screening, pathogen inactivation and deferral policies must be balanced against supply, safety and cost‐effectiveness. One size does not fit all, and blood banks must adjust to local needs and conditions when considering initiation or halting of screening, pathogen inactivation or deferral procedures to balance between demand/supply, safety and economy.     

Immunization delivered by lentiviral vectors for cancer and infectious diseases

The increasing level of understanding of the lentivirus biology has been instrumental in shaping the design strategy of creating therapeutic lentiviral delivery vectors. As a result, lentiviral vectors have become one of the most powerful gene transfer vehicles. They are widely used for therapeutic purposes as well as in studies of basic biology, due to their unique characteristics. Lentiviral vectors have been successfully employed to mediate durable and efficient antigen expression and presentation in dendritic cells both in vitro and in vivo, leading to the activation of cellular immunity and humoral responses. This capability makes the lentiviral vector an ideal choice for immunizations that target a wide range of cancers and infectious diseases. Further advances into optimizing the vector system and understanding the relationship between the immune system and diseases pathogenesis will only augment the potential benefits and utility of lentiviral vaccines for human health.     

Toll‐like receptor polymorphism in host immune response to infectious diseases: A review

Immunopolymorphism is considered as an important aspect behind the resistance or susceptibility of the host to an infectious disease. Over the years, researchers have explored many genetic factors for their role in immune surveillance against infectious diseases. Polymorphic characters in the gene encoding Toll‐like receptors (TLRs) play profound roles in inducing differential immune responses by the host against parasitic infections. Protein(s) encoded by TLR gene(s) are immensely important due to their ability of recognizing different types of pathogen associated molecular patterns (PAMPs). This study reviews the polymorphic residues present in the nucleotide or in the amino acid sequence of TLRs and their influence on alteration of inflammatory signalling pathways promoting either susceptibility or resistance to major infectious diseases, including tuberculosis, leishmaniasis, malaria and filariasis. Population‐based studies exploring TLR polymorphisms in humans are primarily emphasized to discuss the association of the polymorphic residues with the occurrence and epidemiology of the mentioned infectious diseases. Principal polymorphic residues in TLRs influencing immunity to infection are mostly single nucleotide polymorphisms (SNPs). I602S (TLR1), R677W (TLR2), P554S (TLR3), D299G (TLR4), F616L (TLR5), S249P (TLR6), Q11L (TLR7), M1V (TLR8), G1174A (TLR9) and G1031T (TLR10) are presented as the major influential SNPs in shaping immunity to pathogenic infections. The contribution of these SNPs in the structure‐function relationship of TLRs is yet not clear. Therefore, molecular studies on such polymorphisms can improve our understanding on the genetic basis of the immune response and pave the way for therapeutic intervention in a more feasible way.     

Translational Mini‐Review Series on Vaccines for HIV: T lymphocyte trafficking and vaccine‐elicited mucosal immunity

Many pathogens use mucosal surfaces to enter and propagate within the host, making particularly desirable vaccines that target immune responses specifically to mucosal compartments. The majority of mucosal vaccine design strategies to date have been empirical in nature. However, an emerging body of basic immunological knowledge is providing new insights into the regulation of tissue‐specific lymphocyte trafficking and differentiation. These insights afford the opportunity for the rational design of vaccines that focus immune responses at mucosal surfaces. Mucosal cellular immunity may prove critical for protection in the context of HIV infection, and thus there has been considerable interest in developing vaccines that target HIV‐specific cellular immune responses to the gastrointestinal and vaginal mucosa. However, the optimal strategies for eliciting mucosal cellular immune responses through vaccination remain to be determined. Here, we review both recent vaccine studies and emerging paradigms from the basic immunological literature that are relevant to the elicitation of potent and protective mucosal cellular immune memory. Increasing the synergy between these avenues of research may afford new opportunities for mucosal vaccine design.     

Parainfluenza virus 5–vectored vaccines against human and animal infectious diseases

Parainfluenza virus 5 (PIV5), known as canine parainfluenza virus in the veterinary field, is a negative‐sense, nonsegmented, single‐stranded RNA virus belonging to the Paramyxoviridae family. Parainfluenza virus 5 is an excellent viral vector and has been used as a live vaccine for kennel cough for many years in dogs without any safety concern. It can grow to high titers in many cell types, and its genome is stable even in the presence of foreign gene insertions. So far, PIV5 has been used to develop vaccines against influenza virus, respiratory syncytial virus, rabies virus, and Mycobacterium tuberculosis, demonstrating its ability to elicit robust and protective immune responses in preclinical animal models. Parainfluenza virus 5–based vaccines can be administered intranasally, intramuscularly, or orally. Interestingly, prior exposure of PIV5 does not prevent a PIV5‐vectored vaccine from generating robust immunity, indicating that the vector can be used more than once. Here, these encouraging results are reviewed together along with discussion of the desirable advantages of the PIV5 vaccine vector to aid future vaccine design and to accelerate progression of PIV5‐based vaccines into clinical trials.     

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab

Background: The use of rituximab (RTX) is increasing, even in developing countries. It has become the first-line therapy or adjuvant to chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) for various diseases, including B cell lymphoma and autoimmune diseases.

Aim: We describe the infectious diseases and immunological markers associated with RTX treatment of patients with non-Hodgkin lymphoma (NHL).

Methods: Serum immunoglobulins were determined before and after intravenous immunoglobulin (IVIg) administration. Pneumo-23IgG-specific anti-pneumococcal antibodies were evaluated before and after vaccination. Immunophenotyping and lymphocyte proliferation were determined in the course of the treatment.

Results: Seven patients were followed and median age was 56.0?±?5.0?years (range, 41.9–71.6?years). At baseline, the mean level of IgG was 333.7?±?40.8?and IgM 40.9?±?11.3?mg/dL, respectively; immunoglobulin A and E (IgA and IgE) were under the limit of detection. Two patients had reduced or absent B cells and T cell subsets were at normal levels in five patients. All patients failed to mount an efficient post-vaccination immune response against hepatitis B virus, tetanus, diphtheria and against the 23-valent pneumococcal polysaccharide vaccine. During RTX/CHOP treatment, human-IgG-immunoglobulin (IVIg) therapy was introduced in six patients after recurrent infections, including community-acquired pneumonia (85.7%), chronic sinusitis (85.7%) and gastroenteritis (42.9%).

Conclusion: Poor response against pneumococcal vaccines increases the susceptibility of respiratory diseases in these patients. In patients with NHL treated with RTX, the benefits achieved with IVIg replacement for the control of recurrent infectious diseases is of paramount importance. Clinicians dealing with monoclonal antibodies against cancer therapy, especially RTX, should be aware of the increasing risks for symptomatic induced hypogammaglobulinemia and respiratory infections.     

Emerging role of interleukin‐33 in autoimmune diseases

Interleukin‐33 (IL‐33) is a member of the IL‐1 cytokine family. It predominantly induces type 2 immune responses and thus is protective against atherosclerosis and nematode infections but contributes to allergic airway inflammation. Interleukin‐33 also plays a pivotal role in the development of many autoimmune diseases through mechanisms that are still not fully understood. In this review, we focus on the recent advances in understanding of the expression and function of IL‐33 in some autoimmune disorders, aiming to provide insight into its potential role in disease development.     

2007-2009年江门市医疗机构法定传染病漏报因素分析

目的了解江门市法定传染病的疫情报告和管理情况,为进一步提高各级医疗单位的传染病疫情报告与管理水平提供科学依据。方法回顾性调查分析江门市2007-2009年法定传染病漏报调查工作记录,按照《全国法定传染病漏报调查方案》对不同级别医疗单位传染病漏报资料进行分析。结果江门市2007-2009年各级医疗单位共查出传染病1985例,漏报80例,漏报率为4.03%。不同年份漏报率差异有统计学意义（P=0.0001）,不同级别医疗机构漏报率差异有统计学意义（P=0.0001）,医疗机构内不同科别法定传染病的漏报率差异有统计学意义（P=0.001）。结论市直属医疗机构漏报率最高,乡镇卫生院次之,应加强市直属和乡镇卫生院的传染病漏报管理工作。     

Histopathology of Middle East respiratory syndrome coronovirus (MERS‐CoV) infection – clinicopathological and ultrastructural study

Aims

The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome – coronavirus (MERS‐CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS‐CoV infection and represent a base of MERS‐CoV histopathology.

Methods and results

We analysed the post‐mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33‐year‐old male patient of T cell lymphoma, who acquired MERS‐CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles.

Conclusion

The results highlight the pulmonary and extrapulmonary pathological changes of MERS‐CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS‐CoV in kidney.

     

Prevalence of anti-Fab antibodies in patients with autoimmune and infectious diseases.

Sensitive ELISA were devised to examine the specificity of circulating IgM and IgA autoantibodies for whole human IgG, Fc and Fab fragments of human IgG. Sera from patients with autoimmune and infectious conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), tuberculosis (TB), infectious mononucleosis (IM) and cystic fibrosis (CF) were studied. Results of the ELISA assays using whole human IgG as antigen revealed that a proportion of patients in each of the groups studied had circulating IgM and IgA rheumatoid factors (RF). Fifteen normal individuals studied were negative. In the latex positive RA group, IgM RF and IgA RF had primarily anti-Fc reactivity (100% and 93% respectively), although 3/15 patients also showed IgM anti-Fab reactivity and one patient had high IgA anti-Fab activity. Patients with SLE and TB who had detectable RF levels also revealed predominantly anti-Fc specificity. In contrast, examination of 25 patients with IM showed positivity for IgM RF activity in 8% of patients using whole IgG as antigen, 24% positivity using purified Fc fragments as antigen and 45% positivity when plates were coated with Fab fragments. Similarly, a large number of CF patients (54%) also showed predominantly IgM anti-Fab activity. Of interest, 69% of the CF patients who were all studied at the time of bacterial infection had detectable IgA RF levels, with 46% of these patients showing both IgA anti-Fc and anti-Fab activity. These findings suggest that autoantibody specificities in autoimmune and infectious diseases are different.     

Interleukin‐6 blockade in ocular inflammatory diseases

Interleukin‐6 (IL‐6) is a key cytokine featuring redundancy and pleiotropic activity. It plays a central role in host defence against environmental stress such as infection and injury. Dysregulated, persistent interleukin (IL)‐6 production has been implicated in the development of various autoimmune, chronic inflammatory diseases and even cancers. Significant elevation of IL‐6 has been found in ocular fluids derived from refractory/chronic uveitis patients. In experimental autoimmune uveitis models with IL‐6 knock‐out mice, IL‐6 has shown to be essential for inducing inflammation. IL‐6 blockade can suppress acute T helper type 17 (Th17) responses via its differentiation and, importantly, can ameliorate chronic inflammation. Tocilizumab, a recombinant humanized anti‐IL‐6 receptor antibody, has been shown to be effective in several autoimmune diseases, including uveitis. Herein, we discuss the basic biology of IL‐6 and its role in development of autoimmune conditions, focusing particularly on non‐infectious uveitis. It also provides an overview of efficacy and safety of tocilizumab therapy for ocular inflammatory diseases.     

Significance of COX‐2 and VEGF expression in histopathologic grading and invasiveness of meningiomas

Meningiomas are slow‐growing neoplasms that recur locally. Their morphologic grading does not always correlate with patient outcome. We evaluated the status of several immunohistochemical markers with histopathologic parameters in various grades of meningioma.Eighty‐eight meningioma specimens were examined immunohistochemically to determine the status of Ki‐67, cyclin D1, epidermal growth factor receptor (EGFR), cyclooxygenase‐2 (COX‐2), vascular endothelial growth factor (VEGF), and bcl‐2. Several clinical and pathological parameters were investigated.Forty‐nine Grade I, 33 Grade II, and 6 Grade III meningiomas were observed. VEGF and Ki‐67 expression was correlated with higher tumor grade. The association between grade and other immunohistochemical markers expression was not significant. A correlation was observed between COX‐2 expression and invasiveness to the brain or adjacent soft tissue. Tumor recurrence was correlated with brain or adjacent soft tissue invasion. We also observed a relationship between VEGF level and COX‐2 expression, and they were both correlated with necrosis.Immunohistochemical evaluation of VEGF, COX‐2, and Ki‐67 expression can provide information regarding the behavior of meningiomas, particularly for cases in which histological grading is not straightforward.