Hoff, Paula; Gaber, T; Schmidt-Bleek, K; Sentürk, U; Tran, C L; Blankenstein, K; Lütkecosmann, S; Bredahl, J; Schüler, H J; Simon, P; Wassilew, G; Unterhauser, F; Burmester, G R; Schmidmaier, G; Perka, C; Duda, G N; Buttgereit, F
For patients who are known to have an impaired immune system, bone healing is often impaired. Therefore, it has been suggested that an effectively functioning immune system will have an influence on the quality of bone healing. Here, we demonstrate that cells within the fracture hematoma of immunologically restricted patients (1) exhibit a disturbed osteogenic differentiation (normal SPP1 but diminished RUNX2 expression), (2) show a strong inflammatory reaction (high IL8 and CXCR4), and (3) react on local hypoxia (high expression of HIF1A) but with inadequate target gene responses (diminished LDHA and PGK1 expression). Thus, it is already within the early inflammatory phase of fracture healing that the local gene expression in fracture hematomas of immunologically restricted patients points toward a critical regeneration.
Greiding, L; Mathov, E; Casalá, A; Borda, J M; Slazer, M; Núñez, J; Antonowicz, E
Recently, much has been published on the immunological status of patients affected with various lymphomas. In the particular case of Mycosis fungoide, there was no general agreement on the immunological status of the corresponding patients. In fact, López Borrasca et al, found severe depression of cellular immunity in such patients. On the contrary, Blaylock and Clendenning found very little change in cellular immunity, but a very high serum-IgA. We want to offer our experience on this problem with the immunological survey of four patients with the Alibert-Bazin-form of Mycosis fungoide. The following tests were performed on each patient: a) Intracutaneous test with candidina, PPD and other bacterial antigens. b) Sensitization to a concentrate solution of dinitrochlorobencene (DNCB). c) Lymphocyte Transformation Test (LTT), with phytohemagglutinin as mitogen. d) Quantitative determination of IgG, IgM, IgA and beta1C, with the radial immunodiffusion technique (Mancini et al.). e) Agar immunoelectrophoresis. The following results were obtained: 1) The cellular immunity was markedly depressed in the four patients when any of a, b or c-test was performed. 2) All the patients showed very high levels of serum IgA, 150% higher than control. The reason for this is unknown. On the contrary, IgG in serum was less elevated and IgM and beta1C serum levels were normal. 3) No monoclonal bands were found in any case (immunoelectrophoresis). 4) No definite conclusions could be reached due to the limited number of cases, but the uniformity of results should encourage to carry this work further.
Alavian, Seyed-Moayed; Tabatabaei, Seyed-Vahid
Hepatitis B is an important infection in thalassemia patients and prevention by vaccination is needed. Immunological response to hepatitis B vaccine in polytransfused thalassmia patients needs more attention.
Gusev, E I; Demina, T L; Boĭko, A N; Tatarinova, M Iu
The clinico-immunologic monitoring of 50 patients suffering from genuine multiple sclerosis by means of the clinical, neurophysiological and immunologic methods and NMR tomography attests to the relationship between changes in the clinical and immunologic characteristics. The changes in the immunologic characteristics were found to anticipate the clinical ones. The authors provide evidence for the possibility and necessity of the clinico-immunologic monitoring of the patients' status for predicting the further course of the disease.
Kazeko, N I; Zhmurov, V A; Borovskiĭ, A A; Oskolkov, S A; Mariupol'skiĭ, A A; Dobrovol'skaia, M D; Evlochko, A S
The immunological status was studied in 335 patients with urolithiasis and pyelonephritis. The techniques used for assessment of the immunological status provided a multifactorial control over immune system function in inflammation and urolithiasis: registered a significant rise of the level of proinflammatory and anti-inflammatory mediators of the immune response (IL-1beta, IL-4, IL-6, TNF), of neutrophil metabolic activity with parallel suppression of neutrophil phagocytic and absorbing functions, inhibition of bactericidal activity of the serum, a significant fall in the number of mature T-lymphocytes (CD3+) and T-helpers (CD4+). The immune status indices in urolithiasis patients with secondary pyelonephritis are closely linked with clinico-laboratory manifestations of the inflammatory process and renal function. Thus, the results of the study give grounds for developing indications for use of immunomodulating drugs in patients with secondary pyelonephritis associated with urolithiasis.
Rief, W; Pilger, F; Ihle, D; Bosmans, E; Egyed, B; Maes, M
There is some evidence that major depression is accompanied by activation of the inflammatory response system (IRS). There is also evidence that proinflammatory cytokines and induction of IRS activation are associated with sickness behavior in experimental animals. However, no research has examined the IRS in somatization disorder. The aim of this study was to examine possible immunological differences between major depression, somatization and healthy controls. We measured the following IRS variables in patients with major depression (n=36), somatization syndrome (SSI-8; n=37), major depression and somatization (n=40) and healthy controls (n=37): interleukin-6 (IL-6); interleukin-1-receptor-antagonist (IL-1RA); plasma soluble interleukin-6 receptor (IL-6R); soluble suppressor/cytotoxic antigen (CD8); leukemia inhibitory factor (LIF-R); and Clara cell protein (CC16), an endogenous anticytokine. Serum CD8 concentrations were significantly increased in patients with major depression compared with concentrations in patients with somatization syndrome, whereas concentrations in normal controls were intermediate between those of the two groups of patients. Serum CC16 was significantly lower in major depression than in healthy controls. The highest CC16 scores were found in patients with somatization syndrome. Somatizing patients have significantly lower serum IL-6 values than normal controls and depressed patients. The present results indicate (1) an activation of the IRS in depression with signs of T-cell activation (increased CD8), monocytic activation (IL-1RA) and a lowered anti-inflammatory capacity of the serum (lower CC16) and (2) an immune alteration in somatizing syndrome, such as monocytic activation (increased IL-1RA) and indicators of lowered T-lymphocytic activity (lowered CD8 and IL-6). These results suggest different immune alterations in somatization syndrome and depression.
Aira, Lazaro E.; Hernández, Patricia; Prada, Dinorah; Chico, Araceli; Gómez, Jorge A.; González, Zuyén; Fuentes, Karla; Viada, Carmen; Mazorra, Zaima
Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. PMID:26466969
Aira, Lazaro E; Hernández, Patricia; Prada, Dinorah; Chico, Araceli; Gómez, Jorge A; González, Zuyén; Fuentes, Karla; Viada, Carmen; Mazorra, Zaima
Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.
Leksowski, W; Kawalaski, H; Czuba, Z; Krol, W; Gorczyca, P; Dworniczak, S; Rajca, M; Shani, J
Alcohol abuse is a major cause of abnormal liver development and activity. In addition to enzymatic malfunction, alcohol and its metabolites induce changes in the levels of some liver antigens, resulting in immunological disturbance. The purpose of the present study is to correlate the severity of liver function impairment with the length of alcohol abuse, in order to be able to use such tests as indicative of the severity of Alcohol Dependence Syndrome. Thirty-one alcohol abusers were allocated to three groups on the basis of the levels of their liver enzymes, and were tested for a variety of immunological parameters and skin reactions. The data indicate that even though not all immunological values measured differed significantly from the control values, in those that did (granulocytes, lymphocytes, CD4/CD8 ratio, C3, IgG, IgM and some skin positive reactions), the biggest difference was between the healthy volunteers and the group with the longest abuse period. It is suggested that changes in selected immunological parameters in alcohol abusers may indicate the severity of their liver dysfunction.
Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N; Buttgereit, Frank
Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients.
Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N.; Buttgereit, Frank
Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients. PMID:28282868
García-Carrasco, M; Galarza, C; Gómez-Ponce, M; Cervera, R; Rojas-Rodríguez, J; Espinosa, G; Bucciarelli, S; Gómez-Puerta, J A; Bové, A; Escárcega, R O; Font, J
The objective of this study was to analyse the prevalence and characteristics of the main clinical and immunological manifestations at the onset and during the evolution of the disease in a cohort of patients from Latin America (mainly of mestizo origin) and to compare the Latin American with the European patients. Clinical and serological characteristics of 100 APS patients from Mexico and Ecuador were collected in a protocol form that was identical to that used to study the ;Euro-Phospholipid' cohort. The cohort consisted of 93 female patients (93.0%) and seven (7.0%) male patients. There were 91 mestizos (91.0%), seven whites (7.0%) and two Amerindians (2.0%). The most common manifestations were livedo reticularis (40.0%), migraine (35.0%), inferior extremity deep vein thrombosis (32.0%), thrombocytopenia (28.0%) and hemolytic anemia (20.0%). Several clinical manifestations were more prevalent in Latin American than in European patients and they included mainly neurological (migraine, transient global amnesia, acute ischemic encephalopathy, amaurosis fugax) and cutaneous (livedo reticularis, skin ulcerations, superficial cutaneous necrosis, multiple subungual splinter hemorrhages) manifestations as well as hemolytic anemia. The APS has a wide variety of clinical and immunological manifestations at the onset and during the evolution of the disease and the ethnic origin in addition to environmental and socioeconomic factors can modify the disease expression.
Liu, Ping; Santisteban, Ines; Burroughs, Lauri M; Ochs, Hans D; Torgerson, Troy R; Hershfield, Michael S; Rawlings, David J; Scharenberg, Andrew M
We report detailed genetic and immunologic studies in a patient diagnosed with adenosine deaminase (ADA) deficiency and combined immune deficiency at age 5 years. At the time of diagnosis, although all other lymphocyte subsets were depleted, circulating CD8(+) T cells with a terminally differentiated phenotype were abundant and expressed normal ADA activity due to a reversion mutation in a CD8(+) T cell or precursor. Over the first 9 months of replacement therapy with PEG-ADA, the patient steadily accumulated mature naïve CD4(+) and CD8(+) T cells, as well as CD4(+)/FOXP3(+) regulatory T cells, consistent with restoration of a functional cellular immune system. While CD19(+) naïve B cells also accumulated in response to PEG-ADA therapy, a high proportion of these B cells exhibited an immature surface marker phenotype even after 9 months, and immunization with neoantigen bacteriophage varphiX174 demonstrated a markedly subnormal humoral immune response. Our observations in this single patient have important implications for gene therapy of human ADA deficiency, as they indicate that ADA expression within even a large circulating lymphocyte population may not be sufficient to support adequate immune reconstitution. They also suggest that an immature surface marker phenotype of the peripheral B cell compartment may be a useful surrogate marker for incomplete humoral immune reconstitution during enzyme replacement, and possibly other forms of hematopoietic cell therapies.
Machado, Eleuza R; Teixeira, Eliane M; Gonçalves-Pires, Maria Do Rosario F; Loureiro, Zaira M; Araújo, Rogério A; Costa-Cruz, Julia M
This study examined the frequency of Strongyloides stercoralis infection in patients with gastrointestinal cancer through parasitological and immunological tests. A total of 77 patients were evaluated, 33 with gastrointestinal cancer and 44 controls with other types of cancers. All the patients were undergoing chemotherapy and 14 (18.2%) were receiving concomitant radiotherapy. For a parasitological diagnosis, we applied the Baermann and Lutz methods. The immunological diagnosis involved the indirect fluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA) to detect IgG antibodies using Strongyloides ratti antigens. The frequency of positive S. stercoralis in gastrointestinal cancer diagnosed by parasitological methods was 3 cases (9.1%), by serology it was 8 cases (24.2%). In the control group 1 case (2.3%) of S. stercoralis was diagnosed by parasitological methods and 2 cases (4.5%) by immunological tests (p<0.05). Patients with gastrointestinal cancer had a 6.7-fold greater chance of testing positive for S. stercoralis infection. Our data highlight the importance of parasitological and immunological diagnosis for S. stercoralis in patients with gastrointestinal cancer living in endemic areas of strongyloidiasis, since they have a higher risk of becoming infected with S. stercoralis than patients with other types of cancer.
Moskovskiĭ, A V; Shumskiĭ, A V
Results of complex clinical and immunological study of patients with caries and pulpitis in combination with periodontitis were presented. It was revealed that high intensity of caries and parodontitis combines with significant disturbances in cellular and humoral parts of immune system.
Keven, K; Sengul, S; Celebi, Z K; Tuzuner, A; Yalcin, F; Duman, T; Tutkak, H
An increased number of sensitized patients await kidney transplantation (KTx). Sensitization has a major impact on patient mortality and morbidity due to prolonged waiting time and may preclude live donor transplantation. However, recent reports have shown that KTx can be performed successfully using novel immunosuppressive protocols. This study presents our experience with patients displaying donor-specific antibody (DSA) (+). We enrolled 5 lymphocyte cross-match (LCM) negative (complement-dependent cytotoxicity) and panel-reactive antibody (PRA) plus DSA-positive patients mean fluorescein intensity [MFI] > 1000) who underwent living kidney donor procedures. All subjects were females and their mean age was 36.7 years. In our protocol, we started mycophenolate mofetil (2 g/d), tacrolimus (0.01 mg/kg) and prednisolone (0.5 mg/kg) on day -6. We performed 2 sessions of total plasma exchange (TPE) with albumin replacement and administered 2 doses of IVIG (5 g/d). On day -1, we added rituximab (200 mg). On the operation day and on day +4, the patients received doses of basiliximab. Serum samples were taken on days -6, 0, and 30 as well as at 1 year after transplantation. All patients displayed immediate graft function. Mean basal DSA titer was 5624 MFI. After desensitization, the MFI titers decreased at the time of transplantation to 2753 MFI, and were 2564 MFI at the 1st month and 802 MFI at 1st year. Three patients experienced acute rejection episodes (60%). After treatment for rejection, the average follow-up was 17 months and last creatinine levels were 0.6-0.8 mg/dL (minimum-maximum). In conclusion, KTx can be succesfully performed in sensitized patients displaying DSA. However, there seems to be a greater acute rejection risk. There is no consensus regarding adequate doses of IVIG or plasmapheresis treatments; furthermore, more studies are needed to clarify the safe MFI titer of the DSA.
Background This study aimed to elucidate the phenotypic, immunologic, and clinical characteristics of Korean patients with nontuberculous mycobacterial (NTM) lung disease and compare them with non-NTM bronchiectasis (BE) patients. Methods We prospectively recruited patients between 20 and 80 years of age who had nodular BE type NTM lung disease. Phenotypic, immunologic, and clinical characteristics were evaluated through physical examination, laboratory tests, pulmonary function tests, and radiographic examinations. Questionnaires were also answered. The results of the evaluations were compared with the results of non-NTM BE patients. Results A total of 84 patients with NTM lung disease and 47 non-NTM BE patients participated in the study. Mycobacterium avium complex lung disease and M. abscessus lung disease were most common. Patients with NTM lung disease had lower body mass index than non-NTM BE patients. Scoliosis was observed more frequently in patients with NTM lung disease than in non-NTM BE patients. Conclusions Significant similarities were seen between Korean patients with NTM lung disease and patients from other countries. Differences in phenotypic and clinical characteristics between NTM lung disease and non-NTM BE patients suggest differences in the immunopathogenesis of NTM lung disease and non-NTM BE. Trial registration information ClinicalTrials.gov Registration number; NCT01616745 PMID:24274658
Knopf, H L; Hierholzer, J C
Of 120 individuals suffering from follicular conjunctivitis, with or without keratitis, 56 had epidemic keratoconjunctivitis caused by adenovirus type 8. The remaining 64 patients had keratoconjunctivitis produced by several different viruses, including herpes simplex, adenoviruses types 3, 7, 8, 16, 21, and 29, and others. Positive viral cultures were difficult to obtain after the first week of illness in most viral infections. Serologic tests were far more successful in indetifying causative agents. Hemagglutination-inhibition tests in adenovirus infections proved to be fast, accurate, and more sensitive than other serologic tests. Among the epidemic and nonepidemic adenovirus groups, the degree of corneal involvement in the infections appeared to be correlated with the level antibody against the infectious agent. Patients with low antibody titers had more severe keratitis than those with high titers. This correlation was true for both the epidemic and non epidemic patients.
Bergbrant, I M; Johansson, S; Robbins, D; Scheynius, A; Faergemann, J; Söderström, T
The humoral and cellular immune-status was studied in 30 patients with seborrhoeic dermatitis. Increased frequencies of natural killer cells were found in 46% of patients. Furthermore, subnormal mitogen stimulation responses were demonstrated in 13 patients, whereas two individuals were found to have very high numbers of activated T lymphocytes in peripheral blood. Higher-than-normal total serum IgG and IgA was observed in 14 and 11 patients, respectively. For nine of 12 patients with skin lesions, dermal perivascular cell infiltrates were seen. The majority of the infiltrating cells reacted with anti-CD4 antibodies. HLA-DR-expressing keratinocytes were found in two biopsies. The study suggests that patients with seborrhoeic dermatitis may have depressed T-cell function. This could have a bearing on their susceptibility to the Pityrosporum ovale-associated dermatitis. The very high frequencies of activated T cells observed in the peripheral blood of two otherwise healthy seborrhoeic individuals suggests that intermittent systemic immune activation may occur. Seborrhoeic dermatitis is a common skin disease. It can be diagnosed by its characteristic red to yellow-brown lesions covered with greasy scales distributed in areas with a high number of sebaceous glands, such as the scalp, face and upper trunk. There is an association between seborrhoeic dermatitis and the lipophilic yeast Pityrosporum ovale but its exact aetiological role is not known. The yeast is a member of the normal cutaneous flora but also the aetiological agent of pityriasis versicolor and Pityrosporum folliculitis. P. ovale can activate complement via the direct and alternative pathways. This may play some part in the induction of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)
Suzuki, Mizue; Kanamori, Masao; Nagasawa, Shingo; Saruhara, Takayuki
The purpose of this study was to clarify the efficacy of behavioral, stress and immunological evaluation methods in music therapy (MT) with elderly patients with senile dementia. The MT group consisted of 8 elderly patients with dementia and the control group included 8 similarly matched patients. A total of 25 sessions of music therapy were conducted for one hour, twice each week for three months. The Mini-Mental State Exam (MMSE), Gottfries-Brane-Steen Scale (GBS), and Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) were used to evaluate behavioral changes. Saliva Chromogranin A (Cg A) and Immunoglobulin A (Ig A) were used to assess changes in stress and immunological status, respectively. The results of the study were as follows: 1. In GBS, the mean score of "different symptoms common in dementia" improved significantly after MT. 2. The mean Behave-AD score of "paranoid and delusional ideation" was also significantly improved (p<0.05) after the intervention. 3. In the 25th session, mean saliva Cg A was significantly decreased after MT (p<0.05). IgA was slightly increased prior to intervention. Our results suggest that a combination of behavioral, stress and immunological evaluation methods were valuable for assessing changes that occurred during MT for elderly patients with dementia.
Hsu, S L; Lee, P Y; Chang, C H; Chen, C H
Thyroid orbitopathy (TO) is an autoimmune disease that is complicated by ocular surface disorders, leading to discomfort. Dry eye is very prevalent in patients with TO. Recent studies on the pathogenesis of dry eye have focused on the inflammatory process, and some supporting evidence has been discovered. Because TO is a disorder of autoimmune origin, we assumed that the association between TO and dry eye is related to inflammation. Inflammation of the ocular surface in TO-related dry eye has not been well studied. In this study, we assessed cellular inflammation of the ocular surface and the cytokine profiles in patients with TO-related dry eye. Conjunctival impression cytology (CIC) was assessed with an immunofluorescent assay. TO-related dry eye was diagnosed by using the Schirmer test, tear break-up time, thyroid function, and clinical signs. CIC was combined with immunological staining of interleukin-1a (IL-1a), IL-1b, and IL- 6. The immunological impression cytology (IC) grade was compared to the clinical activity score of TO. All TO patients with dry eye were positive for IL-1a, IL-1b, and IL-6. However, the normal controls were also positive for IL-1a. A trend was observed between the clinical inflammatory score and immunological IC grade. This study was the first to delineate the immunological IC of TO-related dry eye. Our study aimed to investigate the pathogenesis of dry eye in TO. Our findings suggest that the conjunctival cytokines IL-1a, IL-1b, and IL-6 may play a role. The results of this study will be useful for future studies of additional inflammatory cytokines, and the levels of these cytokines could be used as an outcome to assess the efficacy of treatment, such as anti-cytokine or immunosuppression therapy, in patients with TO-related dry eye or other ocular surface inflammatory disorders.
Teplinskaia, L E; Kaliberdina, A F; Zaĭtseva, N S; Bulanova, T D; Katsnel'son, L A
The results of comprehensive clinicoimmunologic examinations of 38 uveitis patients with Behçet's disease indicate that uveitis in the presence of Behçet's disease should be referred to multifactorial diseases to whose pathogenesis immunopathologic reactions in various combinations and genetic predisposition contribute much. Generalization of the process in the eye predominated in the clinical picture with involvement of the anterior and posterior segments, retinal vessels, this being combined with general somatic symptoms (aphthae on the buccal mucosa, genitals, arthritides, urethritis/cystitis symptoms, positive 'pricking' test). Study of the immunity status revealed depressed lymphocyte proliferative response to mitogen in 58.8% of patients, hyperimmunoglobulinemia of the A and M classes in 63.3%, impaired complex formation (increased levels of circulating immune complexes in 78.3% and cryoglobulin presence in 57.1%), and various combinations of these immunologic signs. The results indicated patients' infection with herpes virus, streptococcus, toxoplasma. An associative connection of Behçet's disease with A (II) red cell phenotype in 54.8% of patients (p < 0.05) suggests a relationship between genetic factors and the conditions of a specific geographic region. A variety of immunologic changes necessitated the use of corticosteroids, hemoperfusion, cytostatics, and immunity stimulants in the treatment of uveitis in Behçet's disease patients.
von Boehmer, Lotta; Mattle, Muriel; Bode, Peter; Landshammer, Alexandro; Schäfer, Carolin; Nuber, Natko; Ritter, Gerd; Old, Lloyd; Moch, Holger; Schäfer, Niklaus; Jäger, Elke; Knuth, Alexander; van den Broek, Maries
During cancer progression, malignant cells may evade immunosurveillance. However, evidence for immunological escape in humans is scarce. We report here the clinical course of a melanoma patient whose initial tumor was positive for the antigens NY-ESO-1, MAGE-C1, and Melan-A. Upon immunization with a recombinant vaccinia/fowlpox NY-ESO-1 construct, the patient experienced a mixed clinical response and spreading of the NY-ESO-1 epitopes in the CD4+ T cell compartment. After NY-ESO-1 protein + CpG immunization, the patient's anti-NY-ESO-1 IgG response increased. Over the following years, progressing lesions were resected and found to be NY-ESO-1-negative while being positive for MAGE-C1, Melan-A, and MHC-I. The fatal, inoperable brain metastasis was analyzed after his death and also proved to be NY-ESO-1-negative, while being positive for MAGE-C1 and Melan-A, as well as MHC-I. We propose that cancer control and cancer escape in this patient were governed by NY-ESO-1-specific immunological pressure. Our findings provide evidence for the existence of immunoediting and immunoescape in this cancer patient.
Qiu, Tao; Ding, Ping; Fu, Gengfeng; Huan, Xiping; Xu, Xiaoqin; Zhang, Zhi; Liu, Xiaoyan; Yang, Haitao; Mandel, Jeff; Wei, Chongyi; McFarland, Willi; Yan, Hongjing
The National Free Antiretroviral Treatment Program was implemented in Jiangsu Province, China in 2005. We conducted a retrospective, open cohort study to determine treatment failure rates and associated risk factors. Data were obtained from the national web-based antiretroviral treatment database. WHO criteria were used to define immunologic treatment failure. Kaplan-Meier methods were used to determine treatment failure rates and Cox proportional hazards modeling was used to identify risk factors. A total of 5,083 (87.8%) having at least one CD4 cell count measure were included from 2005 to 2013. Overall, 30.4% had immunologic treatment failure with cumulative treatment failure rates increasing to 50.5% at month 60 and 64.1% at month 90. Factors predicting treatment failure included being treated in the Centers for Disease Control and Prevention system (HR 1.69, 95% CI 1.14–2.50, p = 0.009) or jail hospital (HR 1.20, 95% CI 1.08–1.34, p = 0.001), and having a baseline CD4 count >350 cells/uL (HR 2.37, 95% CI 1.94–2.89. p < 0.001). Immunologic treatment failure was moderate to substantial among treated HIV patients. Providing second-line regimens and shifting treatment providers to professional hospitals should be considered to consolidate gains in averting morbidity and mortality. PMID:28220792
Mekhraliev, A A; Ivanova, L A
A total of 161 male patients, aged 18 to 56, suffering from occupational dermatitis (n = 81) and eczemas (n = 80), have been examined with the use of cytochemical and immunological methods in an outpatient rehabilitation centre in the town of Mingechaur, the Azerbaijan SSR. The patients have been engaged in the manufacture of fiber glass, insulation material, and rubber articles; the dermatoses they have developed have been due to exposure to allergic and irritating components of nonconsolidated synthetic polymers and chemical ingredients of industrial rubber production. The findings evidence a significant increase of the neutrophil metabolic and functional activities in dermatitis patients and a rise of the lymphocyte activities in eczema patients. A complex of methods for the studies of leukocyte function and of changes in the immunity status, both on the cellular and subcellular levels (sensitization, inflammation, toxicity) is recommended for examinations of such patient populations.
Torrentes-Carvalho, Amanda; Hottz, Eugênio Damaceno; Marinho, Cintia Ferreira; da Silva, Jéssica Badolato-Corrêa; Pinto, Luzia Maria de Oliveira; Fialho, Luciana Gomes; Bozza, Fernando Augusto; Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Kubelka, Claire Fernandes; de Azeredo, Elzinandes Leal
The pathogenesis of dengue in subjects coinfected with HIV remains largely unknown. We investigate clinical and immunological parameters in coinfected DENV/HIV patients. According to the new dengue classification, most coinfected DENV/HIV patients presented mild clinical manifestations of dengue infection. Herein, we show that DENV/HIV coinfected patients had higher CD8 T cells percentages reflected as a lower CD4/CD8 ratio. Furthermore, CCR5 expression on CD4 T cells and CD107a expression on both T subsets were significantly higher in coinfected patients when compared with monoinfected DENV and HIV individuals respectively. Increased inflammatory response was observed in treated HAART coinfected patients despite undetectable HIV load. These data indicate that DENV infection may influence the clinical profile and immune response in individuals concomitantly infected with HIV.
Al-Herz, Waleed; Ragupathy, Raj; Massaad, Michel J; Al-Attiyah, Raja'a; Nanda, Arti; Engelhardt, Karin R; Grimbacher, Bodo; Notarangelo, Luigi; Chatila, Talal; Geha, Raif S
Deficiency of dedicator of cytokinesis 8 (DOCK8) is a newly described combined primary immunodeficiency disease. It was found to account for 15% of combined immune deficiency cases in the National Primary Immunodeficiency Disorders Registry in Kuwait, a country with high prevalence of consanguinity. We present the clinical, immunologic and molecular characteristics of 9 Kuwaiti patients with DOCK8 deficiency and discuss differences that distinguish DOCK8 deficiency from atopic dermatitis. Clinical immunologists in areas with high incidence of consanguinity should have a high index of suspicion of DOCK8 deficiency in children with recalcitrant eczema, recurrent non-cutaneous infections and lymphopenia.
Orlova, Iu Iu; Alifirova, V M; Cherdyntseva, N V; Zagrebina, I A; Bychkova, I V
Tipe 1 T-helper cells are of importance in development of multiple sclerosis (MS). Copaxone (TEVA, Israel) is one of the preventive drugs, which modifies T-helpers activity. Thirty-three patients with MS were treated by copaxone for 2 years and 13 patients--for 3 years. Clinical and immunological parameters were examined: amount of CD3+, CD4+, CD8+, CD16+, CD22+, CD95+, CD25+ lymphocytes, HLA-D+ cells, IgG, IgA, IgM and phagocytosis. During the treatment course, mean rate of relapses decreased from the pretreatment value from 1.26 +/- 0.11 to 0.59 +/- 0.11 in the first year and 0.28 +/- 0.07 in the second one. After 3 years no relapses were observed in 13 patients. Relapse rate was the highest in the first 3-6 months. But after 3 months there was an increase of CD22+ cells that persisted for all the period of the study. After a year of the treatment, a level of IgM, IgG, IgA and CD95+ cells has raised significantly, with decreasing of a number of CD4+ and CD8+ cells. The authors suggest that immunological shift is related to mechanism of copaxone action determining its positive effect i.e. reducing of frequency of MS relapses.
Kourkounti, Sofia; Papaizos, Vassilios; Leuow, Kirsten; Kordosis, Theodoros; Antoniou, Christina
Vaccination against hepatitis A is an important intervention to prevent disease in HIV-patients. There are insufficient data on the association of the response to hepatitis A vaccine with immunological parameters, including subpopulations of T-cells. We studied HIV-infected adults with CD4 T-cells>200 cells/mm(3) who received two doses of hepatitis A vaccine (Havrix or Vaqta). The counts of CD3, CD4, CD8, CD4+T-cells, NK, NK CD8+, NK CD8 - cells, and HIV RNA were measured at the time of first dose administration and one month after the end of the vaccination period. The geometric mean titer of antibodies to hepatitis A virus (anti-HAV) and factors affecting response were evaluated. 113 patients (50 antiretroviral treatment-naïve and 63 treatment-experienced) were enrolled in the study. There was no change in the immunological parameters and in the HIV-RNA post-vaccination, except for a decrease in CD8 and in double positive CD4+CD8+t-cell count. The immune response and geometric mean titer of anti-HAV were similar among treated and naïve patients (78% vs. 76% and 237 mIU/mL vs. 158 mIU/mL). Vaccine response was achieved in 71% of patients with CD4=200-499 cells/mm(3) compared with 80% of participants with CD4 ≥500 cells/mm(3) (p>0.05). Logistic regression revealed that immunological cells tested do not affect response differently in treatment-naïve vs. experienced patients. The only factor affecting response is the CD4 T-cell count at vaccination (OR 1.320; 95% CI 1.052-1.656; p=0.016). Patients with CD4 T-cell count ≥500 cells/mm(3) were 4.3 times more likely to respond to the vaccine than patients with CD4 T-cell count 200-499 cells/mm(3) (p=0.005). In conclusion, successful vaccination is associated with CD4 T-cells. The count of other immune cells or the administration of antiretroviral therapy does not predict response to hepatitis A vaccine in HIV patient with baseline CD4 T-cell>200 cells/mm(3).
Grigoriadou, S; Longhurst, H J
Angio-oedema is a common reason for attendance at the accident and emergency department and for referral to immunology/allergy clinics. Causative factors should always be sought, but a large proportion of patients have the idiopathic form of the disease. A minority of patients represent a diagnostic and treatment challenge. Failure to identify the more unusual causes of angio-oedema may result in life-threatening situations. Common and rare causes of angio-oedema will be discussed in this article, as well as the diagnostic and treatment pathways for the management of these patients. A comprehensive history and close monitoring of response to treatment are the most cost-effective diagnostic and treatment tools. PMID:19220828
Kowazaki, Yuka; Osawa, Yosuke; Imamura, Jun; Ohashi, Kazuteru; Sakamaki, Hisashi; Kimura, Kiminori
Patients with resolved hepatitis B virus (HBV) infection undergoing chemo- or immunosuppressive therapy are at potential risk for HBV reactivation. To determine whether the host immune response contributes to liver injury, we performed an immunological analysis of a patient with HBV reactivation. Consistent with the detection of HBV DNA in the sera, the number of polyclonal HBV-specific cytotoxic T lymphocytes (CTLs) gradually increased; however, the number of CD4(+)CD25(+) regulatory T cells (Treg) decreased. The interaction between HBV-specific CTLs and CD4(+)CD25(+) Treg is an important determinant of liver injury during HBV reactivation. Therefore, monitoring the number of these cells might be a useful modality for the diagnosis of acute hepatitis resulting from HBV reactivation.
Hansen, Gaute Lund; Gaudernack, Gustav; Brunsvig, Paal Fredrik; Cvancarova, Milada; Kyte, Jon Amund
We have previously reported two trials in non-small cell lung cancer (NSCLC) evaluating vaccine therapy with the telomerase peptide GV1001. The studies demonstrated considerable differences in survival among immune responders, highlighting that an immune response is not necessarily beneficial. In the present study, we conducted long-term clinical follow-up and investigated immunological factors hypothesized to influence clinical efficacy. Peripheral blood mononuclear cells from 33 NSCLC trial patients and 15 healthy donors were analyzed by flow cytometry for T regulatory cells (Tregs, CD4(+)CD25(+)CD127(low/-)FOXP3(+)) and two types of myeloid-derived suppressor cells (MDSCs, HLA-DR (low) CD14 (+) or Lin (-/lo) HLA-DR (-) CD33 (+) CD11b (+)). T cell cultures were analyzed for 17 cytokines. The results demonstrated that immune responders had increased overall survival (OS, p < 0.001) and progression-free survival (p = 0.003), compared to subjects without immunological response. The mean OS advantage was 54 versus 13 months. Six patients were still alive at the last clinical update, all belonging to the immune responders. No serious toxicity had developed (maximum observation 13 years). Most patients developed a polyfunctional cytokine profile, with high IFNγ/IL-4 and IFNγ/IL-10 ratios. Low Treg levels were associated with improved OS (p = 0.037) and a favorable cytokine profile, including higher IFNγ/IL-10 ratios. High CD33(+) MDSC levels were associated with poorer immune response rate (p = 0.005). The levels of CD14(+) MDSC were significantly higher in patients than in healthy controls (p = 0.012). We conclude that a randomized GV1001 trial in NSCLC is warranted. The findings suggest that Tregs and MDSCs are associated with a tolerogenic cytokine milieu and impaired clinical efficacy of vaccine responses.
Sánchez Caraballo, Jorge Mario; Cardona Villa, Ricardo
Background. Immunotherapy has proven to be an useful tool in the management of allergic respiratory diseases; however, little has been studied in atopic dermatitis. Objective. To evaluate the clinical and immunological impact of immunotherapy with mites allergen extracts in atopic dermatitis. Methods. Patients with atopic dermatitis were assigned with computer-generated randomization to either of the following groups: (a) controls received only topical treatment with steroids and/or tacrolimus and (b) actively treated patients received topical treatment plus immunotherapy. Levels of serum total IgE, mites-specific IgE and IgG4 were assessed at study start and after one year of immunotherapy. Results. 31 patients in the active group and 29 in the control group completed the study. Symptoms and medication scores were significantly reduced in the active group after six months. Three patients in the control group showed new sensitizations to mites, while 3 patients in the active group showed neosensitization to shrimp with negative oral food challenge. We observed significant increase of mites-specific IgG4 levels in active group. Conclusion. Specific allergen immunotherapy induced a tolerogenic IgG4 response to mite allergens associated with favorable clinical effects in atopic dermatitis patients. PMID:23724240
Paitoonpong, Leilani; Suankratay, Chusana
Previous studies showed that an immunological response to hepatitis B virus (HBV) vaccination in patients with AIDS was lower than in the normal population. However, those with virological response to highly active antiretroviral therapy (HAART) may have a normal immunological response to HBV vaccination. In our study, patients with AIDS who had a virological response to HAART and no immunity to HBV received 3 doses of HBV vaccine (20 microg of Engerix-B(R)) on d 0, 30, and 180. Anti-HBs level was measured 1 month after complete vaccination. Of 28 patients, overall response rate to vaccination was 71.4%. The responder group had a significantly higher CD4 count at 1 month after complete vaccination than the non-responder group (466.95+/-146.94 and 335+/-112.62 cells/microl, p =0.035). The patients receiving efavirenz-containing HAART had better response than those without efavirenz-containing HAART (p =0.030). The responder group had received a longer duration of HAART. In conclusion , to our knowledge, ours is the first prospective study to determine the immunological response to HBV vaccination in all patients with AIDS who had maintained the virological response after receiving HAART throughout the study period. Patients with AIDS and virological response to HAART have a good immunological response to HBV vaccination.
Felgentreff, Kerstin; Perez-Becker, Ruy; Speckmann, Carsten; Schwarz, Klaus; Kalwak, Krzysztof; Markelj, Gasper; Avcin, Tadej; Qasim, Waseem; Davies, E G; Niehues, Tim; Ehl, Stephan
Hypomorphic mutations in genes associated with severe combined immunodeficiency (SCID) or Omenn syndrome can also cause milder immunodeficiencies. We report 10 new patients with such "atypical" SCID and summarize 63 patients from the literature. The patient groups with T(low)B(low) (n=28), T(low)B(+) (n=16) and ADA (n=29) SCID variants had similar infection profiles but differed in the frequency of immune dysregulation, which was observed predominantly in patients with recombination defects. Most immunological parameters were remarkably similar in the three groups. Of note, 19/68 patients with "atypical" SCID had normal T cell counts, 48/68 had normal IgG and 23/46 had at least one normal specific antibody titer. Elevated IgE was a characteristic feature of ADA deficiency. This overview characterizes "atypical" SCID as a distinct disease with immune dysregulation in addition to infection susceptibility. Lymphopenia, reduced naïve T cells and elevated IgE are suggestive, but not consistent features of the disease.
Wen, Ying; Ding, Hai bo; Chen, Wei; Zhou, Ying; Wang, Wen; Wang, Yu; Lu, Xu; Liu, Jing; Kang, Jing; Geng, Wenqing; Shang, Hong; Liu, Pei
Abstract To assess the effect that hormonal disturbances have on HIV prognosis in male patients. A prospective follow-up study was conducted among male HIV patients who started antiretroviral therapy (ART) between July 1, 2011 and June 30, 2014. The final follow-up session occurred before December 31, 2014. We examined the correlation between pre-ART hormone levels and disease prognosis. The Kaplan–Meier method and the multivariate Cox proportional hazard model were used to identify hormone-related predictors of immunological failure and mortality. During the follow-up of 163 male HIV patients, mortality rate occurred at a rate of 16.0% (26/163). Of these deaths, 84.6% (22/26) were acquired immunodeficiency syndrome–related. Furthermore, 53 patients were found to have suffered from immunological failure. Both pre-ART CD4+ T cell counts and the clinical stage assigned to the patients correlated strongly with dehydroepiandrosterone sulfate levels. Hyponatremia, high cortisol levels, tuberculosis, and being at World Health Organization (WHO)-defined clinical stage 4 were characteristics that associated significantly with mortality. Being at WHO clinical stage 4 was, itself, a factor that significantly associated with immunological failure. High cortisol levels were found to be an important hormonal disorder that associated with mortality. None of the hormones examined in this study had a strong correlation with immunological failure. PMID:28033281
Sá, Helena; Leal, Rita; Rosa, Manuel Santos
To deride the hope of progress is the ultimate fatuity, the last word in poverty of spirit and meanness of mind. There is no need to be dismayed by the fact that we cannot yet envisage a definitive solution of our problems, a resting-place beyond which we need not try to go. -P.B. Medawar, 1969* [Formula: see text] Thomas E. Starlz, also known as the Father of Clinical Transplantation, once said that organ transplantation was the supreme exception to the rule that most major advances in medicine spring from discoveries in basic science [Starzl T. The mystique of organ transplantation. J Am Coll Surg 2005 Aug;201(2):160-170]. In fact, the first successful identical-twin kidney transplantation performed by Murray's team in December 1954 (Murray J et al. Renal homotransplantations in identical twins. Surg Forum 1955;6:432-436) was the example of an upside down translation medicine: Human clinical transplantation began and researchers tried to understand the underlying immune response and how to control the powerful rejection pathways through experimental models. In the last 20 years, we have witnessed an amazing progress in the knowledge of immunological mechanisms regarding alloimmune response and an outstanding evolution on the identification and characterization of major and minor histocompatibility antigens. This review presents an historical and clinical perspective of those important advances in kidney transplantation immunology in the last 20 years, which contributed to the improvement in patients' quality of life and the survival of end-stage renal patients. In spite of these significant progresses, some areas still need substantial progress, such as the definition of non-invasive biomarkers for acute rejection; the continuous reduction of immunosuppression; the extension of graft survival, and finally the achievement of real graft tolerance extended to HLA mismatch donor: recipient pairs.
Samochocki, Zbigniew; Owczarek, Witold; Rujna, Paweł; Raczka, Alicja
Atopic dermatitis (AD) is a disease with a complex pathomechanism, it is very difficult to establish the exact factors which can either trigger or exacerbate the disease. Knowledge of the mechanisms involved in AD development can be increased by, among others, applying new diagnostic tests and careful assessment of the results obtained. The aim of this study was to determine the allergic mechanisms of hypersensitivity to selected aeroallergens in patients with AD. The study comprised 109 AD patients. In all the patients the total IgE level was measured and atopy patch tests and skin prick tests were performed. We also assessed the presence of specific IgE against house dust mite, birch-tree, mixed grass pollen and cat dander. The highest incidence of positive results was found for house dust mite allergens, irrespective of the test employed. Analysing hypersensitivity to all the examined allergens we revealed the presence of allergic mechanisms in 85.3% of the patients. In 30.2% of the examined individuals we proved a type I immunological response, in 45.9% -- both types I and IV in 9.2% -- only type IV in one patient. In 14.7% of the patients the results of all the tests performed were negative. Analysing hypersensitivity to particular aeroallergens, negative test results to house dust mite were observed in 25.8% of the patients. The percentage of positive results for birch pollen, grass pollen and cat dander were 45.0, 44.1 and 53.2, respectively. Analysis of the results showed that allergic reactions to the same aeroallergens may develop via different mechanisms. We also revealed that the coexistence of various mechanisms involved in the development of hypersensitivity to a particular aeroallergen may occur in individual patients.
Borisov, S B; Shpykov, A S; Terent'eva, N A
The paper analyzes the impact of various millimeter-range electromagnetic radiation schedules on immunological parameters in 152 patients with new-onset respiratory sarcoidosis. It shows that the immunomodulatory effect of millimeter-range therapy depends on the treatment regimen chosen. There is evidence for the advantages of millimeter-range noise electromagnetic radiation.
AlSaleh, J; Jassim, V; ElSayed, M; Saleh, N; Harb, D
To gain better understanding of systemic lupus erythematosus (SLE) in Dubai we studied the clinical and immunological manifestations in a cohort of 151 patients attended Rheumatology Clinic in Dubai Hospital between January 2002 and January 2007. We found that the female to male ratio was 20.5:1, with a mean age of 35.5 years (0.9). The mean age at disease onset was 28.9 years (0.8) and mean disease duration 6.7 years (0.4). Five-year survival rate in our cohort was 94%. The commonest clinical manifestations in this cohort were arthritis (88%), haematological abnormalities (61.6%), and malar rash (60.3%). Leucopenia, fever, hair loss and proteinuria were observed in approximately half of the patients. Anaemia was found in 44.3% but only 9.9% had haemolytic anaemia. Photosensitive rash was seen in 43% of patients. Approximately one-third of the patients had serositis and mouth ulcers, 30.5 and 27.2% respectively. Vasculitis was observed in 19.2% of patients. Neuropsychiatric manifestations (15.9%), discoid lupus lesions (12.6%), and brain infarcts (13.2%) were infrequent. Subacute cutaneous lupus (6%) was also uncommon. Anti-nuclear antibodies were detected in 98%, anti-double stranded DNA antibodies in 88.7%, anti-Sm antibodies in 19.7%, anti-RNP in 40.4%, anti-Ro antibodies in 52.3% and anti-La antibodies in 19.8%. Anti-cardiolipin IgM and IgG were detected in 25.3 and 22.4%, respectively. This study suggests that Arabs with SLE residing in Dubai have comparable clinical features to their counterparts in other Arab countries and Western countries. The high prevalence of positive anti-Ro antibodies among our Arab patients probably reflects a character, that is, commonly seen in SLE patients of Middle East origin.
Cerullo, Vincenzo; Diaconu, Iulia; Kangasniemi, Lotta; Rajecki, Maria; Escutenaire, Sophie; Koski, Anniina; Romano, Valentina; Rouvinen, Noora; Tuuminen, Tamara; Laasonen, Leena; Partanen, Kaarina; Kauppinen, Satu; Joensuu, Timo; Oksanen, Minna; Holm, Sirkka-Liisa; Haavisto, Elina; Karioja-Kallio, Aila; Kanerva, Anna; Pesonen, Sari; Arstila, Petteri T; Hemminki, Akseli
Patients with advanced solid tumors refractory to and progressing after conventional therapies were treated with three different regimens of low-dose cyclophosphamide (CP) in combination with oncolytic adenovirus. CP was given with oral metronomic dosing (50 mg/day, N = 21), intravenously (single 1,000 mg dose, N = 7) or both (N = 7). Virus was injected intratumorally. Controls (N = 8) received virus without CP. Treatments were well tolerated and safe regardless of schedule. Antibody formation and virus replication were not affected by CP. Metronomic CP (oral and oral + intravenous schedules) decreased regulatory T cells (T(regs)) without compromising induction of antitumor or antiviral T-cell responses. Oncolytic adenovirus given together with metronomic CP increased cytotoxic T cells and induced Th1 type immunity on a systemic level in most patients. All CP regimens resulted in higher rates of disease control than virus only (all P < 0.0001) and the best progression-free (PFS) and overall survival (OS) was seen in the oral + intravenous group. One year PFS and OS were 53 and 42% (P = 0.0016 and P < 0.02 versus virus only), respectively, both which are unusually high for chemotherapy refractory patients. We conclude that low-dose CP results in immunological effects appealing for oncolytic virotherapy. While these first-in-human data suggest good safety, intriguing efficacy and extended survival, the results should be confirmed in a randomized trial.
Damuzzo, V; Solito, S; Pinton, L; Carrozzo, E; Valpione, S; Pigozzo, J; Arboretti Giancristofaro, R; Chiarion-Sileni, V; Mandruzzato, S
Ipilimumab, the first immune-checkpoint inhibitor extending overall survival (OS) in metastatic melanoma patients, has a survival benefit only in a proportion of patients and the development of reliable predictive biomarkers is still an unmet need. To meet this request, we used a multivariate statistical approach to test whether myeloid-derived suppressor cells (MDSC) or other tumor-associated and immunological parameters may serve as predictive or prognostic biomarkers in melanoma patients receiving ipilimumab. By using a standardized approach to determine the circulating levels of four MDSC subsets, we observed a significant expansion of three MDSC subsets at baseline, as compared to controls and, upon treatment, that high levels of CD14(+)/IL4Rα(+) MDSCs were an independent prognostic factor of reduced OS. On the contrary, longer OS was associated to low levels of the proinflammatory proteins IL-6 and CRP and tumor-associated factors S100B and LDH both at baseline and after treatment. Increasing number of total T cells and especially of PD-1(+)/CD4(+) T cells were associated with better prognosis, and upregulation of PD-1(+) expression on CD4(+) T cells upon treatment was associated with lower toxicity. As several parameters were associated to OS, we included these factors in a multivariate survival model, and we identified IL-6 and ECOG PS as independent biomarkers associated with improved OS, whereas high levels of LDH and CD14(+)/IL4Rα(+) MDSCs were negative independent markers of reduced OS.
Landay, A; Poon, M C; Abo, T; Stagno, S; Lurie, A; Cooper, M D
Asymptomatic hemophilia patients receiving Factor VIII concentrate were found to have normal natural killer (NK) cells and B cells, and an inverted T helper/suppressor ratio due to an increase in cells of T suppressor phenotype. In contrast, a hemophilia patient with acquired immune deficiency syndrome (AIDS) exhibited nonfunctional NK cells, low B cells, and an inverted T helper/suppressor ratio due to very low numbers of T helper cells. Hemophilia patients on cryoprecipitate therapy exhibited normal immune parameters. A high percentage of hemophilia patients on both treatments had antibody to hepatitis B virus. The isolated finding of elevated levels of T suppressor cells in hemophilia patients receiving Factor VIII concentrate has not been recognized as an early indicator of impending AIDS, and longitudinal studies will be required to determine its clinical significance.
Lara, Humberto H; Turrent, Liliana Ixtepan; Garza-Treviño, Elsa N; Tamez-Guerra, Reyes; Rodriguez-Padilla, Cristina
Dialyzable leukocyte extract (DLE) is one of the immunological agents used as an adjuvant in cancer therapy; it has been associated with improved quality of life during cancer chemotherapy. Based on these previous findings and on the observed clinical benefits attributed to DLE in other types of cancer, we investigated its clinical and immunological effects as a therapy adjuvant on breast cancer patients who received only chemotherapy, as compared to patients administered bovine DLE (bDLE) as an adjuvant. This study included 43 breast cancer patients who were about to begin chemotherapy. This group was divided as follows: 25 received chemotherapy and bDLE as an adjuvant therapy, and 18 received only chemotherapy without the adjuvant. All patient clinical and immunological responses were monitored. Among patients in the group that received bDLE as adjuvant, 60% showed a complete response, 32% showed a partial response and 8% did not respond. By contrast, in the group without the adjuvant, 39% showed a complete response, 50% displayed a partial response and 11% were non-responders. In addition, bDLE treatment in combination with chemotherapy resulted in the enhancement of the Karnofsky performance scale during chemotherapy. Even though patients underwent several cycles of chemotherapy without bDLE, the lymphocyte population dropped to below the reference value. On the other hand, in patients with bDLE as adjuvant, the CD4(+) and CD8(+) lymphocytes and the B lymphocytes were maintained within the median range of the reference value. The number of natural killer cells also increased after chemotherapy treatment with bDLE as an adjuvant. In conclusion, bDLE treatment contributes to significant immunological recovery in patients that have undergone heavy chemotherapy, increasing the clinical response and quality of life during chemotherapy.
Lapolla, A; Betterle, C; Sanzari, M; Zanchetta, R; Pfeifer, E; Businaro, A; Fagiolo, U; Plebani, M; Marini, S; Photiou, E; Fedele, D
The aim of the study was to evaluate the frequency of islet cell (ICA) and insulin (IAA) antibodies and of HLA antigen typing in a group of subjects diagnosed with gestational diabetes mellitus (GDM) in a screening-diagnostic program during pregnancy. ICA, complement-fixing (CF) ICA and other autoantibodies, absolute number and percentage of lymphocyte subpopulations, and HLA antigens were evaluated in 68 women with GDM and compared with those of matched controls. ICA were found in 2 (2.9%) and IAA in 1 (1.5%). Both ICA-positive women had CF-ICA; one of them was receiving insulin therapy. while the other was on a special diet. No correlations were found between ICA and IAA, nor between IAA and insulin treatment. As far as lymphocyte subsets were concerned, we found a significant increase in the absolute number of total and activated (CD3+HLA-DR+) T lymphocytes and a significant increase in the absolute number and percentage of suppressor/cytotoxic T lymphocytes (CD8) and NK lymphocytes (CD57) in GDM patients compared with normal pregnant controls. Concerning frequency for HLA A, B, C, DR antigens in the GDM population, only Cw7 was found to be significantly increased and A10 significantly decreased in comparison with controls. Our study suggests that GDM is a heterogeneous disorder in which few patients present with the immunologic and genetic markers of type 1 diabetes.
Aldırmaz, Sonay; Yücel, Esra; Kıykım, Ayça; Çokuğraş, Haluk; Akçakaya, Necla; Camcıoğlu, Yıldız
Aim: We aimed to determine the rate of primary immune deficiency (PID) among children presenting to our immunology outpatient clinic with a history of frequent infections and with warning signs of primary immune deficiency. Material and Methods: The files of 232 children aged between 1 and 18 years with warning signs of primary immune deficiency who were referred to our pediatric immunology outpatient clinic with a complaint of frequent infections were selected and evaluated retrospectively. Results: Thirty-six percent of the subjects were female (n=84) and 64% were male (n=148). PID was found in 72.4% (n=164). The most common diagnosis was selective IgA deficiency (26.3%, n=61). The most common diseases other than primary immune deficiency included reactive airway disease and/or atopy (34.4%, n=22), adenoid vegetation (12.3%, n=8), chronic disease (6.3%, n=4) and periodic fever, aphtous stomatitis and adenopathy (4.6%, n=3). The majortiy of the subjects (90.5%, n=210) presented with a complaint of recurrent upper respiratory tract infection. PID was found in all subjects who had bronchiectasis. The rates of the diagnoses of variable immune deficiency and Bruton agammaglubulinemia (XLA) were found to be significantly higher in the subjects who had lower respiratory tract infection, who were hospitalized because of infection and who had a history of severe infection compared to the subjects who did not have these properties (p<0.05 and p<0.01, respectively). Growth and developmental failure was found with a significantly higher rate in the patients who had a diagnosis of severe combined immune deficiency or hyper IgM compared to the other subjects (p<0.01). No difference was found in the rates of PID between the age groups, but the diagnosis of XLA increased as the age of presentation increased and this was considered an indicator which showed that patients with XLA were being diagnosed in a late period. Conclusions: It was found that the rate of diagnosis was
Menard, Laurence C.; Habte, Sium; Gonsiorek, Waldemar; Lee, Deborah; Banas, Dana; Holloway, Deborah A.; Cunningham, Mark; Stetsko, Dawn; Casano, Francesca; Kansal, Selena; Davis, Patricia M.; Carman, Julie; Zhang, Clarence K.; Abidi, Ferva; Furie, Richard; Nadler, Steven G.; Suchard, Suzanne J.
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease driven by both innate and adaptive immune cells. African Americans tend to present with more severe disease at an earlier age compared with patients of European ancestry. In order to better understand the immunological differences between African American and European American patients, we analyzed the frequencies of B cell subsets and the expression of B cell activation markers from a total of 68 SLE patients and 69 normal healthy volunteers. We found that B cells expressing the activation markers CD86, CD80, PD1, and CD40L, as well as CD19+CD27–IgD– double-negative B cells, were enriched in African American patients vs. patients of European ancestry. In addition to increased expression of CD40L, surface levels of CD40 on B cells were lower, suggesting the engagement of the CD40 pathway. In vitro experiments confirmed that CD40L expressed by B cells could lead to CD40 activation and internalization on adjacent B cells. To conclude, these results indicate that, compared with European American patients, African American SLE patients present with a particularly active B cell component, possibly via the activation of the CD40/CD40L pathway. These data may help guide the development of novel therapies. PMID:27699274
Mingbunjerdsuk, Pornpimol; Asdamongkol, Nakhon; Sungkanuparph, Somnuek
"Immunological discordance," i.e., immunological failure despite complete viral suppression in human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy (ART), is associated with increased risk of AIDS or death. To evaluate risk factors for immunological discordance in a resource-limited setting in which patients usually present late with low CD4 cell counts, we conducted a case-control study among HIV-infected patients receiving ART and having undetectable HIV RNA. The study included patients with immunological discordance (cases), which was defined as CD4 cell count < 30% above baseline and absolute CD4 cell count < 200 cells/mm(3) at the first 12 months of undetectable HIV RNA (<50 copies/mL). Patients without immunological discordance were included as controls. Of 142 patients (44 cases; 98 controls), the mean age was 38.6 ± 9.4 years and 67.6% were men; 65.5% had history of opportunistic infections. In multivariate analysis, only baseline CD4 cell count < 100 cells/mm(3) (odd ratio [OR], 2.53; 95% confidence interval [CI], 1.04-6.14; P = 0.040) and history of lost to follow-up (OR, 11.04; 95% CI, 2.87-42.46; P < 0.001) were significantly associated with immunological discordance. Early initiation of ART and intervention to improve regular clinic visit compliance and adherence to ART are crucial to prevent immunological discordance among HIV-infected patients.
Environmental microbiology does not deal with all aspects of immunology or the immune responses per se, but instead adapts immunology-based research technologies or immunoassays for the study of microorganisms and chemical contaminants in association with the environment. The primary immunologic-bas...
Štefančič, Martin; Prešern-Štrukelj, Metka; Vidmar, Gaj; Kotnik, Vladimir; Kopitarl, Andreja Nataša; Ihan, Alojz
The immunological status before and after a comprehensive rehabilitation program was studied. Seven persons (4 males, 3 females, mean age 71.4 years) after lower limb amputation due to peripheral arterial disease (PAD) were subject to standard comprehensive rehabilitation program for amputees of four-week duration, which included training in activities of daily living, daily exercise of various types, training of crutch-assisted gait and use of leg prosthesis, and mild transcutaneous electrical stimulation. Before and after rehabilitation, peripherial blood was collected and the number and ratio of white blood cells were determined and analysed for the expression of cell surface antigens (CD3, CD4, CD8, CD19, CD25, CD69), cytokines (IFN-gamma, IL-4) and phagocytosis/oxidative killing functional tests. Due to strict patient selection criteria excluding serious accompanying disease, immunological parameters were within normal limits already before rehabilitation. After rehabilitation, an increase in oxidative burst was observed in monocytes and neutrophil granulocytes, but statistically significant only in monocytes. The expression of CD69 molecules by T cells and monocytes was significantly increased, as well as the expression of IL-4 by T cells. A significant decrease in the ratio of CD4 to CD8 cells was also found, but not a clinically critical one. It can therefore be concluded that the comprehensive rehabilitation treatment in patients with lower limb amputation due to PAD led to some--prevailingly positive--immunological changes, which were consistent with the patients' improved physical condition and clinical status.
Bergström, M; Joly, A-L; Seiron, P; Isringhausen, S; Modig, E; Fellström, B; Andersson, J; Berglund, D
With the increasing interest in clinical trials with regulatory T cells (Tregs), immunological profiling of prospective target groups and standardized procedures for Treg isolation are needed. In this study, flow cytometry was used to assess peripheral blood lymphocyte profiles of young healthy individuals and patients undergoing haemodialysis treatment. Tregs obtained from the former may be used in haematopoietic stem cell transplantation and Tregs from the latter in the prevention of kidney transplant rejection. FOXP3 mRNA expression with accompanying isoform distribution was also assessed by the quantitative reverse transcriptase polymerase chain reaction. Flow-cytometric gating strategies were systematically analysed to optimize the isolation of Tregs. Our findings showed an overall similar immunological profile of both cohorts in spite of great differences in both age and health. Analysis of flow-cytometric gating techniques highlighted the importance of gating for both CD25high and CD127low expression in the isolation of FOXP3-positive cells. This study provides additional insight into the immunological profile of young healthy individuals and uraemic patients as well as in-depth analysis of flow-cytometric gating strategies for Treg isolation, supporting the development of Treg therapy using cells from healthy donors and uraemic patients.
Torres-Landa, Samuel; Coss-Adame, Enrique; Valdovinos, Miguel A.; Alejandro-Medrano, Edgar; Ramos-Ávalos, Bárbara; Martínez-Benítez, Braulio
The aim of the study was to characterize the presence of diverse CD4 and CD8 T cell subsets and regulatory cells in peripheral blood and lower oesophageal sphincter (LES) from a young patient with BE/achalasia without treatment versus achalasia group. In order to characterize the circulating cells in this patient, a cytometric analysis was performed. LES tissue was evaluated by double-immunostaining procedure. Five healthy blood donors, 5 type achalasia patients, and 5 oesophagus tissue samples (gastrooesophageal junction) from transplant donors were included as control groups. A conspicuous systemic inflammation was determined in BE/achalasia patient and achalasia versus healthy volunteer group. Nonetheless, a predominance of Th22, Th2, IFN-α-producing T cells, Tregs, Bregs, and pDCregs was observed in BE/achalasia patient versus achalasia group. A low percentage of Th1 subset in BE/achalasia versus achalasia group was determined. A noticeable increase in tissue of Th22, Th17, Th2, Tregs, Bregs, and pDCregs was observed in BE/achalasia versus achalasia group. Th1 subset was lower in the BE/achalasia patient versus achalasia group. This study suggests that inflammation is a possible factor in the pathogenesis of BE/achalasia. Further research needs to be performed to understand the specific cause of the correlation between BE and achalasia. PMID:27752370
Collazos, Julio; Cartón, José Antonio; Asensi, Víctor
The possible effects on liver fibrosis and HCV viral load of the immunological status of HIV-HCV-coinfected patients are unclear. A cohort of HIV-HCV-coinfected patients was divided according to the current CD4 counts into poor (≤200/μl, n = 117) or good (≥500/μl, n = 441) immunological status. The groups were compared for diverse HCV- and fibrosis-related parameters. Fibrosis was evaluated by transient elastometry and other noninvasive indexes. Many variables were significantly associated with the immunological status in univariate analyses, including fibrosis parameters. However, in multivariate analyses current immunological status or nadir CD4 were not associated with HCV viral load (p = 0.8 and p = 0.3, respectively), liver fibrosis at the time of evaluation (p = 0.9 for both), or fibrosis progression over time (p = 0.98 and p = 0.8, respectively). The factors independently associated with significant fibrosis, advanced fibrosis, and cirrhosis, as compared with minimal or no fibrosis, were alcohol abuse [OR 3.57 (95% CI 1.43-8.85), p = 0.006; OR 10.10 (3.75-27.03), p < 0.0001; and OR 31.25 (10.6-90.90), p < 0.0001, respectively], HBsAg positivity [OR 9.09 (1.47-55.56), p = 0.02; OR 55.56 (9.80-333.33), p < 0.0001; and OR 43.48 (4.76-476.19), p = 0.0008, respectively], and platelet counts [OR 0.994 (0.989-0.998), p = 0.006; OR 0.990 (0.985-0.995), p = 0.0003; and OR 0.985 (0.979-0.991), p < 0.0001, respectively]. Immunological status did not associate with any fibrosis stage (significant fibrosis, p = 0.7; advanced fibrosis, p = 0.4; and cirrhosis p = 0.9). The current or past immunological status of HIV-HCV-coinfected patients does not seem to have any significant influence on HCV viral load or on the development of liver fibrosis when adjusting for important covariates.
Tanigawa, Keishi; Itoh, Yusuke; Kobayashi, Yasunobu
Context • Combined treatment with an extract of Lentinula edodes mycelia (LEM) and chemotherapy has been reported to improve quality of life (QOL) and immunological function in cancer patients. However, those effects have not been elucidated for patients receiving cancer immunotherapy. Objective • The present study intended to investigate the effects of oral LEM on QOL and immunological function in cancer patients receiving immunotherapy. Design • The research team designed an open-label, single-armed pilot study. Setting • The study took place at Bio-Thera Clinic, a facility associated with Tokyo Women's Medical University in Tokyo, Japan. Participants • The participants were 10 cancer patients undergoing cancer immunotherapy at Bio-Thera Clinic. Intervention • The participants received either dendritic cell (DC)-based cancer vaccine therapy or CD3-activated T-lymphocyte (CAT) therapy as immunotherapy. They received the immunotherapy only for the first 4 wk of the study, and then oral LEM (1800 mg/d) was added for the next 4 wk. Outcome Measures • Preintervention and at 4 and 8 wk after the start of the study, participants completed a QOL survey, and immunological parameters were measured. Results • Participants' QOL symptom scores increased (ie, worsened) by 5.1 ± 1.7 during the first 4 wk of treatment when they were receiving immunotherapy only, but it decreased (ie, improved) by -2.5 ± 1.6 during the next 4 wk when the immunotherapy was combined with the LEM, P < .05. The measurement of the immunological parameters during the 4 wk of immunotherapy combined with LEM showed that the amount of interferon-γ (IFN-γ) produced in the peripheral blood tended to increase as compared with that during the first 4 wk of immunotherapy only. The rise in IFN-γ was correlated with changes in several regulatory T cells (Tregs) (ie, forkhead box P3 [FOXP3]+/cluster of differentiation 4 [CD4]+ and transforming growth factor beta [TGF-β]). Conclusions • The
Yeo, Adeline Syin Lian; Rathakrishnan, Anusyah; Wang, Seok Mui; Ponnampalavanar, Sasheela; Manikam, Rishya; Sathar, Jameela; Kumari Natkunam, Santha; Sekaran, Shamala Devi
Dengue virus infection is a common tropical disease which often occurs without being detected. These asymptomatic cases provide information in relation to the manifestation of immunological aspects. In this study, we developed an ELISA method to compare neutralizing effects of dengue prM and E antibodies between dengue patients and their asymptomatic household members. Recombinant D2 premembrane (prM) was constructed, cloned, and tested for antigenicity. The recombinant protein was purified and tested with controls by using an indirect ELISA method. Positive dengue serum samples with their asymptomatic pair were then carried out onto the developed ELISA. In addition, commercially available recombinant envelope (E) protein was used to develop an ELISA which was tested with the same set of serum samples in the prM ELISA. Asymptomatic individuals showed preexisting heterotypic neutralizing antibodies. The recombinant prM was antigenically reactive in the developed ELISA. Dengue patients had higher prM and E antibodies compared to their household members. Our study highlights the neutralizing antibodies levels with respect to dengue prM and E between dengue patients and asymptomatic individuals.
Denue, Ballah Akawu; Kida, Ibrahim Musa; Hammagabdo, Ahmed; Dayar, Ayuba; Sahabi, Mohammed Abubakar
Background There are conflicting reports on the impact of highly active antiretroviral therapy (HAART) in resolving hematological complications. Whereas some studies have reported improvements in hemoglobin and other hematological parameters resulting in reduction in morbidity and mortality of HIV patients, others have reported no improvement in hematocrit values of HAART-treated HIV patients compared with HAART-naïve patients. Objective This current study was designed to assess the impact of HAART in resolving immunological and hematological complications in HIV patients by comparatively analyzing the results (immunological and hematological) of HAART-naive patients and those on HAART in our environment. Methods A total of 500 patients participated, consisting of 315 HAART-naive (119 males and 196 females) patients and 185 HAART-experienced (67 males and 118 females) patients. Hemoglobin (Hb), CD4+ T-cell count, total white blood count (WBC), lymphocyte percentage, plateletes, and plasma HIV RNA were determined. Results HAART-experienced patients were older than their HAART-naive counterparts. In HAART-naive patients, the incidence of anemia (packed cell volume [PCV] <30%) was 57.5%, leukopenia (WBC < 2.5), 6.1%, and thrombocytopenia < 150, 9.6%; it was, significantly higher compared with their counterparts on HAART (24.3%, 1.7%, and 1.2%, respectively). The use of HAART was not associated with severe anemia. Of HAART-naive patients, 57.5% had a CD4 count < 200 cells/μL in comparison with 20.4% of HAART-experienced patients (P < 0.001). The mean viral load log10 was significantly higher in HAART-naive than in HAART-experienced patients (P < 0.001). Total lymphocyte count < 1.0 was a significant predictor of
Santos, Silvane Braga; Oliveira, Paulo; Luna, Tania; Souza, Anselmo; Nascimento, Márcia; Siqueira, Isadora; Tanajura, Davi; Muniz, André Luiz; Glesby, Marshall J; Carvalho, Edgar M.
The majority of patients infected with human T-cell lymphotropic virus-type 1 (HTLV-1) are considered carriers, but a high frequency of urinary symptoms of overactive bladder, common in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) have been documented in these patients. The aim of this study was to determine if immunological and viral factors that are seen in HAM/TSP are also observed in these patients. Participants were classified as HTLV-1 carriers (n=45), HTLV-1 patients suffering from overactive bladder (n=45) and HAM/TSP (n=45). Cells from HTLV-1 overactive bladder patients produced spontaneously more proinflammatory cytokines than carriers. TNF-α and IL-17 levels were similar in HAM/TSP and HTLV-1 overactive bladder patients. High proviral load was found in patients with overactive bladder and HAM/TSP and correlated with proinflammatory cytokines. In contrast with findings in patients with HAM/TSP, serum levels of Th1 chemokines were similar in HTLV-1 overactive bladder and carriers. Exogenous addition of regulatory cytokines decreased spontaneous IFN-γ production in cell cultures from HTLV-1 overactive bladder patients. The results show that HTLV-1 overactive bladder and HAM/TSP patients have in common some immunological features as well as similar proviral load profile. The data show that HTLV-1 overactive bladder patients are still able to down regulate their inflammatory immune response. In addition, these patients express levels of chemokines similar to carriers, which may explain why they have yet to develop the same degree of spinal cord damage as seen in patients with HAM/TSP. These patients present symptoms of overactive bladder, which may be an early sign of HAM/TSP. PMID:22997085
von Boehmer, Lotta; Mattle, Muriel; Bode, Peter; Landshammer, Alexandro; Schäfer, Carolin; Nuber, Natko; Ritter, Gerd; Old, Lloyd; Moch, Holger; Schäfer, Niklaus; Jäger, Elke; Knuth, Alexander; van den Broek, Maries
During cancer progression, malignant cells may evade immunosurveillance. However, evidence for immunological escape in humans is scarce. We report here the clinical course of a melanoma patient whose initial tumor was positive for the antigens NY-ESO-1, MAGE-C1, and Melan-A. Upon immunization with a recombinant vaccinia/fowlpox NY-ESO-1 construct, the patient experienced a mixed clinical response and spreading of the NY-ESO-1 epitopes in the CD4+ T cell compartment. After NY-ESO-1 protein + CpG immunization, the patient’s anti-NY-ESO-1 IgG response increased. Over the following years, progressing lesions were resected and found to be NY-ESO-1-negative while being positive for MAGE-C1, Melan-A, and MHC-I. The fatal, inoperable brain metastasis was analyzed after his death and also proved to be NY-ESO-1-negative, while being positive for MAGE-C1 and Melan-A, as well as MHC-I. We propose that cancer control and cancer escape in this patient were governed by NY-ESO-1-specific immunological pressure. Our findings provide evidence for the existence of immunoediting and immunoescape in this cancer patient. PMID:23882157
Pavoni, Ernesto; Sciandra, Francesca; Tasca, Giorgio; Tittarelli, Roberta; Bozzi, Manuela; Giardina, Bruno; Ricci, Enzo; Brancaccio, Andrea
The dystroglycan (DG) expression pattern can be altered in severe muscular dystrophies. In fact, some congenital muscular dystrophies (CMDs) and limb-girdle muscular dystrophies (LGMDs) are caused by point mutations identified in six glycosyltransferase genes which are likely to target different steps along the posttranslational “O-glycosylation route” leading to a fully decorated and functional α-DG subunit. Indeed, hypoglycosylation of α-DG is thought to represent a major pathological event, in that it could reduce the DG’s ability to bind the basement membrane components, thus leading to sarcolemmal instability and necrosis. In order to set up an efficient standard immunological protocol, taking advantage of a wide panel of antibodies, we have analyzed the two DG subunits in a small cohort of adult dystrophic patients, whom an extensive medical examination had already clinically classified as affected by LGMD (5), Miyoshi (1) or distal (1) myopathy. Immunofluorescence analysis of skeletal muscle tissue sections revealed a proper sarcolemmal localization of the DG subunits in all the patients analyzed. However, Western blot analysis of lectin enriched skeletal muscle samples revealed an abnormal glycosylation of α-DG in two patients. Our work reinforces the notion that a careful immunological and biochemical analysis of the two DG subunits should be always considered as a prerequisite for the identification of new putative cases of dystroglycanopathy. PMID:22046204
de Almeida, C M O; de Lima, T A; Castro, D B; Torres, K L; da Silva Braga, W; Peruhype-Magalhães, V; Teixeira-Carvalho, A; Martins-Filho, O A; Malheiro, A
The rational of this study we intended to investigate whether the peripheral blood immunological/virological biomarkers were associated with distinct patterns of sleeping quality in patients with chronic hepatitis C-(HCV). Distinct well-established indexes/scores were used to categorize the sleeping quality of HCV patients, including the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale and Fatigue Severity Scores. Our findings demonstrated that HCV patients classified as 'good sleeper' displayed an enhanced frequency of circulating CD8(+) T cells, lower frequency of activated (CD69(+)) neutrophils and eosinophils but enhanced frequency of activated lymphocytes besides lower seric levels of IL-4/IL-8/IL-10 but higher levels of IL-12, besides lower HCV virus load and lower anti-HCV IgG levels. In contrast, HCV patients classified as 'poor sleeper' displayed enhanced levels of activated neutrophils and eosinophils but lower frequency of activated lymphocytes, higher seric levels of IL-6/TNF-α/IL-10 but lower levels of IL-12 besides higher HCV virus load and increased anti-HCV IgG levels. Positive correlation was further confirmed by the relationship between the leucocyte activation status, the cytokine levels, the HCV viral load and the anti-HCV IgG reactivity with the PSQI indexes. Analysis of cytokine signature curves demonstrated that lower frequency of IL-10 was observed in HCV patients classified as 'good sleepers', whereas enhanced frequency of IL-6 was found HCV patients classified as 'poor sleepers'. In conclusion, our data suggest that immunological biomarkers (leucocytes activation status and seric cytokines levels) are likely to be associated with sleeping quality patterns in HCV patients, suggesting their putative use for clinical monitoring purposes.
Garg, Abhishek D.; De Ruysscher, Dirk; Agostinis, Patrizia
ABSTRACT The emerging role of the cancer cell-immune cell interface in shaping tumorigenesis/anticancer immunotherapy has increased the need to identify prognostic biomarkers. Henceforth, our primary aim was to identify the immunogenic cell death (ICD)-derived metagene signatures in breast, lung and ovarian cancer that associate with improved patient survival. To this end, we analyzed the prognostic impact of differential gene-expression of 33 pre-clinically-validated ICD-parameters through a large-scale meta-analysis involving 3,983 patients (‘discovery’ dataset) across lung (1,432), breast (1,115) and ovarian (1,436) malignancies. The main results were also substantiated in ‘validation’ datasets consisting of 818 patients of same cancer-types (i.e. 285 breast/274 lung/259 ovarian). The ICD-associated parameters exhibited a highly-clustered and largely cancer type-specific prognostic impact. Interestingly, we delineated ICD-derived consensus-metagene signatures that exhibited a positive prognostic impact that was either cancer type-independent or specific. Importantly, most of these ICD-derived consensus-metagenes (acted as attractor-metagenes and thereby) ‘attracted’ highly co-expressing sets of genes or convergent-metagenes. These convergent-metagenes also exhibited positive prognostic impact in respective cancer types. Remarkably, we found that the cancer type-independent consensus-metagene acted as an ‘attractor’ for cancer-specific convergent-metagenes. This reaffirms that the immunological prognostic landscape of cancer tends to segregate between cancer-independent and cancer-type specific gene signatures. Moreover, this prognostic landscape was largely dominated by the classical T cell activity/infiltration/function-related biomarkers. Interestingly, each cancer type tended to associate with biomarkers representing a specific T cell activity or function rather than pan-T cell biomarkers. Thus, our analysis confirms that ICD can serve as a
Sakamoto, Shijoro; Matsueda, Satoko; Takamori, Shinzou; Toh, Uhi; Noguchi, Masanori; Yutani, Shigeru; Yamada, Akira; Shichijo, Shigeki; Yamada, Teppei; Suekane, Shigetaka; Kawano, Kouichirou; Naitou, Masayasu; Sasada, Tetsuro; Hattori, Noboru; Kohno, Nobuoki; Itoh, Kyogo
The HLA-A11 or -A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA-A11(+) /A11(+) (n=18) or -A33(+) /A33(+) (n=13) allele to personalized peptide vaccine (PPV) regimens. The primary sites of HLA-A11+/A11+ or -A33+/A33+ patients were the colon (n=4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas(2 or 2), and so on. For PPV, a maximum of 4 peptides were selected from 9 different peptides capable of binding to HLA-A11 and -A33 molecules based on the pre-existing peptide-specific IgG responses. There were no severe adverse events related to PPV. At the end of the first cycle, peptide-specific CTL responses were augmented in 4/12 or 2/9 of HLA-A11(+) /A11(+) or -A33(+) /A33(+) patients, while peptide-specific IgG responses were augmented in 6/14 or 4/10 patients, respectively. Clinical responses consisted of 4 stable diseases and 14 progressive diseases in HLA-A11(+) /A11(+) patients, versus 7 and 6 in -A33(+) /A33(+) patients, respectively. Further clinical study of PPV could be recommended because of the safety and positive immunological responses. This article is protected by copyright. All rights reserved.
Medellín-Garibay, S E; Cortez-Espinosa, N; Milán-Segovia, R C; Magaña-Aquino, M; Vargas-Morales, J M; González-Amaro, R; Portales-Pérez, D P; Romano-Moreno, S
Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8(+) T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present.
Medellín-Garibay, S. E.; Cortez-Espinosa, N.; Milán-Segovia, R. C.; Magaña-Aquino, M.; Vargas-Morales, J. M.; González-Amaro, R.; Portales-Pérez, D. P.
Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8+ T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present. PMID:26438503
Kim, Sung Hwa; Kim, Tae Young; Ryu, Vin; Ha, Ra Yeon; Lee, Su Jin; Ha, Kyooseob; Cho, Hyun-Sang
Both emotional and cognitive processes are involved in moral judgments. Ventromedial prefrontal lesions are related to impaired prosocial emotions and emotional dysregulation, and patients with these lesions exhibit increased utilitarian judgments of emotionally salient personal moral dilemmas. Bipolar patients experiencing manic episode also have impaired emotional regulation and behavioral control. We investigated the characteristics of moral judgment in manic and euthymic patients with bipolar disorder using the 50 hypothetical moral dilemma task (17 non-moral, 20 personal, and 13 impersonal). Our study included 27 manic bipolar patients, 26 euthymic bipolar patients, and 42 healthy controls. Subjects were instructed to determine whether or not each dilemma was morally acceptable, and their reaction times were recorded. Manic patients showed significantly greater utilitarian judgment than euthymic patients and normal controls for personal moral dilemmas. However, there were no significant between-group differences for the non-moral and impersonal moral dilemmas. Our results suggest that increased utilitarian judgments of personal moral dilemmas may be a state-related finding observed only in manic patients. This difference in moral judgment assessments may reflect the decision-making characteristics and underlying neurobiological mechanisms of bipolar disorder, especially during the manic state.
Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.
INTRODUCTION: Beta-thalassemias are a cluster of inherited (autosomal recessive) hematological disorders prevalent in the Mediterranean area due to defects in synthesis of β chains of hemoglobin. The aim of present study was to compare the effects of deferasirox and deferoxamine on iron overload and immunological changes in patients with blood transfusion-dependent β-thalassemia major and intermedia. PATIENTS AND METHODS: This study involved 64 patients with known cases of β-thalassemia major or intermedia that has been treated with blood transfusion and iron chelators. Serum ferritin, serum iron, serum total iron binding, unsaturated iron-binding capacity (UIBC), and immunological parameters were assessed in deferoxamine and deferasirox-treated patients. RESULTS: In deferoxamine-treated patients, serum ferritin levels were high (8160.33 ± 233.75 ng/dL) compared to deferasirox-treated patients (3000.62 ± 188.23 ng/dL; P < 0.0001), also there were significant differences in serum iron, total iron-binding capacity and UIBC (P < 0.0001) in deferasirox-treated patients compared to deferoxamine-treated patients. Immunological changes between two treated groups showed insignificant differences in levels of complements (C3 and C4) and immunoglobulin levels (IgM, IgG, and IgA) P > 0.05. CONCLUSION: This study indicated that deferasirox is more effective than deferoxamine regarding the iron overload but not in the immunological profile in patients with blood transfusion-dependent β-thalassemia. PMID:28316434
Shoman, Sahar; Nabil, Mohamed; Tabl, Ashraf; Ghanem, Hussam; Kafrawy, Sherif El
Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3⁺ cells, helper CD4⁺ cells and CD19⁺ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3⁺ and CD4⁺ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.
Background The most common teaching method used in China is lecturing, but recently, efforts have been widely undertaken to promote the transition from teacher-centered to student-centered education. The patient-oriented problem-solving (POPS) system is an innovative teaching-learning method that permits students to work in small groups to solve clinical problems, promotes self-learning, encourages clinical reasoning and develops long-lasting memory. To our best knowledge, however, POPS has never been applied in teaching immunology in China. The aim of this study was to develop POPS in teaching immunology and assess students’ and teachers’ perception to POPS. Methods 321 second-year medical students were divided into two groups: I and II. Group I, comprising 110 students, was taught by POPS, and 16 immunology teachers witnessed the whole teaching process. Group II including the remaining 211 students was taught through traditional lectures. The results of the pre- and post-test of both groups were compared. Group I students and teachers then completed a self-structured feedback questionnaire for analysis before a discussion meeting attended only by the teachers was held. Results Significant improvement in the mean difference between the pre- and post-test scores of those in Groups I and II was seen, demonstrating the effectiveness of POPS teaching. Most students responded that POPS facilitates self-learning, helps them to understand topics and creates interest, and 88.12% of students favored POPS over simple lectures. Moreover, while they responded that POPS facilitated student learning better than lectures, teachers pointed out that limited teaching resources would make it difficult for wide POPS application in China. Conclusions While POPS can break up the monotony of dialectic lectures and serve as a better teaching method, it may not be feasible for the current educational environment in China. The main reason for this is the relative shortage of teaching
Bugni Miotto e Silva, Vanessa; de Freitas Tavares da Silva, Carolina; de Aguiar Vilela Mitraud, Sônia; Nely Vilar Furtado, Rita; Esteves Hilário, Maria Odete; Natour, Jamil; Terreri, Maria Teresa
The aim of the study was to assess the presence and characteristics of subclinical synovitis using power Doppler (PD) ultrasonography on patients with juvenile idiopathic arthritis (JIA) in clinical remission and compare the findings with those of healthy children. A cross-sectional study was carried out involving the clinical (physical exam, functional capacity and laboratory tests) and ultrasonography evaluation of 34 joints (synovial fluid/hypertrophy, PD signal and bone erosion). Subclinical synovitis was defined as the presence of synovial hypertrophy/joint effusion with or without any PD signal. Thirty-six patients (11.5 ± 3.74 years) and 36 controls (sex and age matched) were evaluated (2,448 joints). Twenty-seven patients were in remission on medication (mean duration: 1.8 ± 2.2 years). Subclinical synovitis was detected in 41.7% patients and 11.1% controls (p = 0.003). Erosion was detected in three patients (8.3%). Subclinical synovitis was found in 38/1,224 (3.1%) joints in the patients (most affected: radiocarpal wrist, anterior elbow and tibiotalar ankle) and 8/1,224 (0.6%) joints in the controls (most affected: radiocarpal wrist). Differences in subclinical synovitis between patients and controls were found in the elbows (p = 0.033) and ankles (p = 0.006). A greater frequency of subclinical synovitis was found in patients with the extended oligoarticular or polyarticular subtypes (p = 0.013), those at an older age at disease onset (p = 0.007) and using methotrexate (p = 0.049). Patients with JIA in remission exhibit subclinical synovitis more frequently than controls. Subclinical synovitis was more frequent in patients with the polyarticular involvement and those at an older age at disease onset.
Gazhva, S I; Voronina, A I; Shkarednaia, O V
The article highlights the data about local immunity of the patients having cronic generalized periodontitis. Results of the conservative treatment with adhesive balm Asepta, gel Hyaludent with metronidazole and clorhexidine and Metrogyl Denta have shown the influence upon immunologic status of the patients.
Karbach, Julia; Gnjatic, Sacha; Biskamp, Melina; Atmaca, Akin; Weidmann, Eckhart; Brandt, Kathrin; Wahle, Claudia; Bernhard, Helga; Knuth, Alexander; Jäger, Elke
A melanoma patient with brain metastases was treated by gamma-knife radiosurgery and immunotherapy with autologous tumor-lysate-loaded dendritic cells (DC). Ten years after the combined treatment, the patient remains in complete remission. Remarkable immunologic correlates to the clinical development were the transient induction of NY-ESO-1 antibody and the durable expansion of MAGE-A1p161-169 EADPTGHSY-specific CD8+ T cells. Although the induction of NY-ESO-1 antibody most likely resulted from gamma-knife-mediated "auto-vaccination," the persistence of circulating MAGE-A1-specific T cells, which are still detectable ex vivo in the absence of any tumor manifestation, coincides with DC-based vaccination administered monthly until today.
Background Regulatory T cells (Tregs) play a key role in immune homeostasis in vivo. Tregs have a critical role in preventing the development of autoimmune diseases and defects in Treg function are implicated in various autoimmune disorders. Individuals with posttraumatic stress disorder (PTSD) have higher prevalence of autoimmune disorders than the general population. We hypothesized that war veterans with PTSD would exhibit a decreased number and/or altered phenotype of Tregs. Methods We analyzed peripheral blood mononuclear cells (PBMCs) of patients with PTSD (N = 21) (mean age = 45.9) and age-matched healthy controls (N = 23) (mean age = 45.7) to determine the proportion of Tregs and their phenotype according to the expression of CD127 and HLA-DR markers which describe the differentiation stages of Tregs. In addition, we analyzed the expression of membrane ectoenzyme CD39 on Tregs of the study groups, an important component of the suppressive machinery of Tregs. Results We found no differences in the proportion of Tregs between PTSD patients and controls, but PTSD patients had a higher percentage of CD127-HLA-DR- Tregs and a lower percentage of CD127loHLA-DR+ Tregs compared to controls. There was no difference in expression of CD39 on Tregs of the study groups. Conclusions Although the proportions of Tregs in PTSD patients were unchanged, we found that they exhibit a different phenotype of Tregs that might be less suppressive. Impaired differentiation and function of Tregs is likely involved in disruption of immune homeostasis in PTSD. PMID:25670936
Aira, Lazaro E; López-Requena, Alejandro; Fuentes, Dasha; Sánchez, Liset; Pérez, Teresita; Urquiza, Aleida; Bautista, Heber; Falcón, Leopoldina; Hernández, Patricia; Mazorra, Zaima
Psoriasis is a chronic inflammatory disease with a prevalence of approximately 2–3% in the general population. The majority of diagnosed patients have plaque psoriasis, and about 20% have moderate-to-severe disease. Itolizumab, a new monoclonal antibody specific for the CD6 molecule mainly expressed on T lymphocytes, has demonstrated to inhibit in vitro ligand-induced proliferation and pro-inflammatory cytokine production. We assessed the immunological and histopathological effect of the antibody using clinical samples taken from 26 patients with moderate-to-severe psoriasis included in a clinical trial. The precursor frequency of lymphocytes activated with anti-CD2/CD3/CD28 beads, as well as the number of interferon (IFN)-γ-secreting T cells after stimulation, were measured at different time points of the study. Serum cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. Additionally, lymphocyte infiltration and epidermis hyperplasia were studied in five patients. A significant reduction in T cell proliferation capacity and number of IFN-γ-producing T cells was found in treated patients. Serum levels of interleukin-6, tumor necrosis factor and IFN-γ showed an overall trend toward reduction. No anti-idiotypic antibody response was detected. A significant reduction in the epidermis hyperplasia was observed in analyzed patients. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. PMID:24594862
Aira, Lazaro E; López-Requena, Alejandro; Fuentes, Dasha; Sánchez, Liset; Pérez, Teresita; Urquiza, Aleida; Bautista, Heber; Falcón, Leopoldina; Hernández, Patricia; Mazorra, Zaima
Psoriasis is a chronic inflammatory disease with a prevalence of approximately 2-3% in the general population. The majority of diagnosed patients have plaque psoriasis, and about 20% have moderate-to-severe disease. Itolizumab, a new monoclonal antibody specific for the CD6 molecule mainly expressed on T lymphocytes, has demonstrated to inhibit in vitro ligand-induced proliferation and pro-inflammatory cytokine production. We assessed the immunological and histopathological effect of the antibody using clinical samples taken from 26 patients with moderate-to-severe psoriasis included in a clinical trial. The precursor frequency of lymphocytes activated with anti-CD2/CD3/CD28 beads, as well as the number of interferon (IFN)-γ-secreting T cells after stimulation, were measured at different time points of the study. Serum cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. Additionally, lymphocyte infiltration and epidermis hyperplasia were studied in five patients. A significant reduction in T cell proliferation capacity and number of IFN-γ-producing T cells was found in treated patients. Serum levels of interleukin-6, tumor necrosis factor and IFN-γ showed an overall trend toward reduction. No anti-idiotypic antibody response was detected. A significant reduction in the epidermis hyperplasia was observed in analyzed patients. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.
The need for material standards in the field of clinical immunology, together with the mode of operation of the combined World Health Organization/International Union of Immunological Societies programme for the provision of such standards, are discussed. Attention is drawn to the importance of the use of International Units in reporting concentrations of complex constituents, e.g., immunoglobulins in body fluids, and to the availability of standard materials against which such components can be calibrated. The necessity for the standardization of nomenclature is also emphasized. PMID:1088095
Zeng, Jin-Cheng; Lin, Dong-Zi; Yi, Lai-Long; Liu, Gan-Bin; Zhang, Hui; Wang, Wan-Dang; Zhang, Jun-Ai; Wu, Xian-Jing; Xiang, Wen-Yu; Kong, Bin; Chen, Zheng W; Wang, Cong-Yi; Xu, Jun-Fa
Despite past extensive studies, the role of B and T lymphocyte attenuator (BTLA) in αβ T cells in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here we demonstrate that BTLA expression on αβ T cells is decreased in patients with M. tuberculosis (Mtb) infection. Particularly, BTLA expression levels are likely critical for αβ T cells to manifest and maintain an active central memory phenotype with high capacity for secretion of IFN-γ and perforin, which are important for immune memory against TB infection. BTLAhigh αβ T cells also exhibited higher capacity in response to Mtb peptide stimulation. In contrast to the role of BTLA played for negative regulation of immune responses, our data in the current studies suggest that BTLA expression on αβ T cells is likely associated with protective immune memory against Mtb infection in the setting of patients with active pulmonary tuberculosis. This previous unappreciated role for BTLA may have implications for prevention and treatment of patients with Mtb infection. PMID:25360214
zhevago, N A; Samoĭlova, K A; Davydova, N I; Bychkova, N V; Glazanova, T V; Chubukina, Zh V; Buĭniakova, A I; Zimin, A A
The immunological rehabilitation of the patients with oncological problems after the completion of standard anti-tumour therapy remains a topical problem in modern medicine. The up-to-date phototherapeutic methods find the increasingly wider application for the treatment of such patients including the use of monochromatic visible (VIS) and near infrared (nIR) radiation emitted from lasers and photodiodes. The objective of the present study was to substantiate the expediency of postoperative immune rehabilitation of the patients with breast cancer (BC) by means of irradiation of the body surface with polychromatic visible (pVIS) in combination with polychromatic infrared (pIR) light similar to the natural solar radiation without its minor UV component. The study included 19 patients with stage I--II BC at the mean age of 54.0 +/- 4.28 years having the infiltrative-ductal form of the tumour who had undergone mastectomy. These patients were randomly allocated to two groups, one given the standard course of postoperative rehabilitation (control), the other (study group) additionally treated with pVIS + pIR radiation applied to the lumbar-sacral region from days 1 to 7 after surgery. A Bioptron-2 phototherapeutic device, Switzerland, was used for the purpose (480-3400 nm, 40 mW/cm2, 12 J/cm2, with the light spot diameter of 15 cm). The modern standard immunological methods were employed. It was found that mastectomy induced changes of many characteristics of cellular and humoral immunity; many of them in different patients were oppositely directed. These changes were apparent within the first 7 days postoperatively. The course of phototherapy (PT) was shown to prevent the postoperative decrease in the counts of monocytes and natural killer (NK) cells, the total amount of CD3+ -T-lymphocytes (LPC), CD4+ -T-helpers, activated T-lymphocytes (CD3+ HLA-DR+ cells) and IgA levels as well as intracellular digestion rate of neutrophil-phagocyted bacteria. Moreover PT promoted
Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.
Hartmann, Karin; Escribano, Luis; Grattan, Clive; Brockow, Knut; Carter, Melody C; Alvarez-Twose, Ivan; Matito, Almudena; Broesby-Olsen, Sigurd; Siebenhaar, Frank; Lange, Magdalena; Niedoszytko, Marek; Castells, Mariana; Oude Elberink, Joanna N G; Bonadonna, Patrizia; Zanotti, Roberta; Hornick, Jason L; Torrelo, Antonio; Grabbe, Jürgen; Rabenhorst, Anja; Nedoszytko, Boguslaw; Butterfield, Joseph H; Gotlib, Jason; Reiter, Andreas; Radia, Deepti; Hermine, Olivier; Sotlar, Karl; George, Tracy I; Kristensen, Thomas K; Kluin-Nelemans, Hanneke C; Yavuz, Selim; Hägglund, Hans; Sperr, Wolfgang R; Schwartz, Lawrence B; Triggiani, Massimo; Maurer, Marcus; Nilsson, Gunnar; Horny, Hans-Peter; Arock, Michel; Orfao, Alberto; Metcalfe, Dean D; Akin, Cem; Valent, Peter
Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.
Landy, J; Walker, A W; Li, J V; Al-Hassi, H O; Ronde, E; English, N R; Mann, E R; Bernardo, D; McLaughlin, S D; Parkhill, J; Ciclitira, P J; Clark, S K; Knight, S C; Hart, A L
Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.
Armstrong, W. D.
Since 1950, immunology has developed with such rapidity as an interdisciplinary science that even those within the field have difficulty keeping adequately informed. For this reason it is important that those who are closer to the subject, wherever possible, apply recent advances to the practice of medicine in general and primary care in particular. This paper describes a limited number of recent advances in the field of cellular immunology and immunodeficiency diseases. Above all, it attempts to relate the practical significance of these discoveries to the care of the patient by the primary care physician. PMID:20469161
Balestre, Eric; Ekouevi, Didier Koumavi; Tchounga, Boris; Eholie, Serge Paul; Messou, Eugène; Sawadogo, Adrien; Thiébaut, Rodolphe; May, Margaret T; Sterne, Jonathan Ac; Dabis, François
Introduction Response to antiretroviral therapy (ART) among individuals infected with HIV-2 is poorly described. We compared the immunological response among patients treated with three nucleoside reverse-transcriptase inhibitors (NRTIs) to boosted protease inhibitor (PI) and unboosted PI-based regimens in West Africa. Methods This prospective cohort study enrolled treatment-naïve HIV-2-infected patients within the International Epidemiological Databases to Evaluate AIDS collaboration in West Africa. We used mixed models to compare the CD4 count response to treatment over 12 months between regimens. Results Of 422 HIV-2-infected patients, 285 (67.5%) were treated with a boosted PI-based regimen, 104 (24.6%) with an unboosted PI-based regimen and 33 (7.8%) with three NRTIs. Treatment groups were comparable with regard to gender (54.5% female) and median age at ART initiation (45.3 years; interquartile range 38.3 to 51.8). Treatment groups differed by clinical stage (21.2%, 16.8% and 17.3% at CDC Stage C or World Health Organization Stage IV for the triple NRTI, boosted PI and unboosted PI groups, respectively, p=0.02), median length of follow-up (12.9, 17.7 and 44.0 months for the triple NRTI, the boosted PI and the unboosted PI groups, respectively, p<0.001) and baseline median CD4 count (192, 173 and 129 cells/µl in the triple NRTI, the boosted PI and the unboosted PI-based regimen groups, respectively, p=0.003). CD4 count recovery at 12 months was higher for patients treated with boosted PI-based regimens than those treated with three NRTIs or with unboosted PI-based regimens (191 cells/µl, 95% CI 142 to 241; 110 cells/µl, 95% CI 29 to 192; 133 cells/µl, 95% CI 80 to 186, respectively, p=0.004). Conclusions In this observational study using African data, boosted PI-containing regimens had better immunological response compared to triple NRTI combinations and unboosted PI-based regimens at 12 months. A randomized clinical trial is still required to determine
van Lelyveld, Steven F. L.; Otto, Sigrid A.; Richter, Clemens; Soetekouw, Robin; Prins, Jan M.; Brinkman, Kees; Mulder, Jan Willem; Kroon, Frank; Middel, Ananja; Symons, Jori; Wensing, Annemarie M. J.; Nijhuis, Monique; Borghans, José A. M.; Tesselaar, Kiki; Hoepelman, Andy I. M.
Objective The immunomodulatory effects of the CCR5-antagonist maraviroc might be beneficial in patients with a suboptimal immunological response, but results of different cART (combination antiretroviral therapy) intensification studies are conflicting. Therefore, we performed a 48-week placebo-controlled trial to determine the effect of maraviroc intensification on CD4+ T-cell counts and immune activation in these patients. Design Double-blind, placebo-controlled, randomized trial. Methods Major inclusion criteria were 1. CD4+ T-cell count <350 cells/μL while at least two years on cART or CD4+ T-cell count <200 cells/μL while at least one year on cART, and 2. viral suppression for at least the previous 6 months. HIV-infected patients were randomized to add maraviroc (41 patients) or placebo (44 patients) to their cART regimen for 48 weeks. Changes in CD4+ T-cell counts (primary endpoint) and other immunological parameters were modeled using linear mixed effects models. Results No significant differences for the modelled increase in CD4+ T-cell count (placebo 15.3 CD4+ T cells/μL (95% confidence interval (CI) [1.0, 29.5] versus maraviroc arm 22.9 CD4+ T cells/μL (95% CI [7.4, 38.5] p = 0.51) or alterations in the expression of markers for T-cell activation, proliferation and microbial translocation were found between the arms. However, maraviroc intensification did increase the percentage of CCR5 expressing CD4+ and CD8+ T-cells, and the plasma levels of the CCR5 ligand MIP-1β. In contrast, the percentage of ex-vivo apoptotic CD8+ and CD4+ T-cells decreased in the maraviroc arm. Conclusions Maraviroc intensification of cART did not increase CD4+ T-cell restoration or decrease immune activation as compared to placebo. However, ex-vivo T-cell apoptosis was decreased in the maraviroc arm. Trial Registration ClinicalTrials.gov NCT00875368 PMID:26208341
Hsu, Alan Yi-Hui; Wu, Shang-Rung; Tsai, Jih-Jin; Chen, Po-Lin; Chen, Ya-Ping; Chen, Tsai-Yun; Lo, Yu-Chih; Ho, Tzu-Chuan; Lee, Meed; Chen, Min-Ting; Chiu, Yen-Chi; Perng, Guey Chuen
The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a “sunny-side up egg” appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development. PMID:26657027
Torres, Berta; Rallón, Norma I; Loncá, Montserrat; Díaz, Alba; Alós, Llucia; Martínez, Esteban; Cruceta, Anna; Arnaiz, Joan Albert; Leal, Lorna; Lucero, Constanza; León, Agathe; Sánchez, Marcelo; Negredo, Eugenia; Clotet, Bonaventura; Gatell, José M; Benito, José M; Garcia, Felipe
CD4(+) count increase has been reported to be different with lopinavir/r (LPV/r) and efavirenz (EFV)-containing regimens. The different effect of these two regimens on other immune function parameters and the relationship with the gain of CD4(+) count have not been assessed in a randomized clinical trial. Fifty antiretroviral treatment (cART) naïve HIV-infected individuals were randomized to receive LPV/r or EFV both with tenofovir/emtricitabine for 48 weeks. A substudy of immunological function restoration was performed in 22 patients (LPV/r n=10 and EFV n=12). Activation, thymic function, apoptosis, senescence, exhaustion, Treg cells, interleukin (IL)-7-receptor/IL-7 system, thymic volume, and lymphoid tissue fibrosis were evaluated at baseline and at week 48. Both groups experienced a CD4(+) count increase that was higher in the EFV group (ΔCD4(+) 88 vs. 315 cells/μl LPV/r vs. EFV, respectively, p<0.001). Despite this difference in CD4(+) gain, the change in other immune function parameters was similar in both treatment groups. Most of parameters evaluated tended to normalize after 48 weeks of cART. A significant decrease in levels of activation, senescence, exhaustion, and apoptosis on CD4(+) and CD8(+) T cells (p<0.001 for all) and a significant increase in markers of thymic function, IL-7 receptor, and in the levels of central memory CD4(+) T cells and naive subsets of CD8(+) T cells (p<0.001 for all) with respect to baseline values were observed without any difference between groups. These data indicate that the differences in CD4(+) gain with different cART regimens are not immunologically meaningful and might explain the similar clinical efficacy of these regimens.
Rallón, Norma I.; Loncá, Montserrat; Díaz, Alba; Alós, Llucia; Martínez, Esteban; Cruceta, Anna; Arnaiz, Joan Albert; Leal, Lorna; Lucero, Constanza; León, Agathe; Sánchez, Marcelo; Negredo, Eugenia; Clotet, Bonaventura; Gatell, José M.; Benito, José M.; Garcia, Felipe
Abstract CD4+ count increase has been reported to be different with lopinavir/r (LPV/r) and efavirenz (EFV)-containing regimens. The different effect of these two regimens on other immune function parameters and the relationship with the gain of CD4+ count have not been assessed in a randomized clinical trial. Fifty antiretroviral treatment (cART) naïve HIV-infected individuals were randomized to receive LPV/r or EFV both with tenofovir/emtricitabine for 48 weeks. A substudy of immunological function restoration was performed in 22 patients (LPV/r n=10 and EFV n=12). Activation, thymic function, apoptosis, senescence, exhaustion, Treg cells, interleukin (IL)-7-receptor/IL-7 system, thymic volume, and lymphoid tissue fibrosis were evaluated at baseline and at week 48. Both groups experienced a CD4+ count increase that was higher in the EFV group (ΔCD4+ 88 vs. 315 cells/μl LPV/r vs. EFV, respectively, p<0.001). Despite this difference in CD4+ gain, the change in other immune function parameters was similar in both treatment groups. Most of parameters evaluated tended to normalize after 48 weeks of cART. A significant decrease in levels of activation, senescence, exhaustion, and apoptosis on CD4+ and CD8+ T cells (p<0.001 for all) and a significant increase in markers of thymic function, IL-7 receptor, and in the levels of central memory CD4+ T cells and naive subsets of CD8+ T cells (p<0.001 for all) with respect to baseline values were observed without any difference between groups. These data indicate that the differences in CD4+ gain with different cART regimens are not immunologically meaningful and might explain the similar clinical efficacy of these regimens. PMID:24380397
Kidenya, Benson R.; Kabangila, Rodrick; Mshana, Stephen E.; Kidola, Jeremiah; Kalluvya, Samuel E.; Kongola, Gilbert W.; Klinker, Hartwig
Background Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. Materials and Methods A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. Results Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-value = 0.039), HIV stage (p-value = 0.026) and viral load (p-value = 0.007) within sub-therapeutic, therapeutic and supra-therapeutic ARV plasma drug concentrations. Conclusion There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine
Panis, C.; Matsuo, T.; Reiche, E.M.V.
Antiretroviral therapy advances have proportioned to AIDS patients a survival increase. At the same time, the permanence of the seropositive people in the nosocomial environment becomes common not only by the adverse reactions caused by this therapy, but also by several opportunistic diseases that take them into and out of hospital environment. During the hospital permanence, the patients expose their impaired immune system to the nosocomial virulent microorganisms, and acquire destructive nosocomial infections that sometimes can be lethal. Among several hospital syndromes described, little is known about infections in immunocompromised patients and how their immune system is able to determine the course of the infection. The objective of this study was to describe the major microorganisms involved in the nosocomial infections of HIV-1 seropositive patients associated with their immunological status. The survey was carried out with the Hospital Infection Control Service records, from University Hospital, Londrina, Paraná, Southern of Brazil, during the period from July 2003 to July 2004. From all the cases studied (n=969), 24 patients (2.5%) had AIDS diagnosis and a half of them was women with the mean of CD4+ T cells counts of 158/mm3. The main topography of the infection was pulmonary (50.0%) and the main isolated microorganisms were Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. A major incidence of infection was observed in patients with CD4+ T cells counts lower than 50/mm3. The study of the relationship between the impairment of the immune system and infectious agents could provide a better healthcare of people living with HIV/AIDS and advances into the nosocomial infection control systems. PMID:24031336
Béjot, Yannick; Osseby, Guy-Victor; Caillier, Marie; Moreau, Thibault; Laplanche, Jean-Louis; Giroud, Maurice
Genetic transmissible spongiform encephalopathies (TSEs) account for approximately 10-15% of overall human prion diseases worldwide, but genotype-phenotype correlations remain incomplete. Here we report the case of an 80-year-old man who developed rapidly progressive behavioral abnormalities and myoclonus following a stroke. Repeated electroencephalography (EEG) revealed a general slowing of the basic activity, as well as several episodes of triphasic waves, with neither periodic activity nor recorded seizure. 14.3.3 protein was detected in cerebral cerebrospinal fluid, and direct sequencing of the PRNP gene showed an E196K mutation associated with homozygosity for methionine at codon 129. The patient was diagnosed with probable genetic prion disease with a Creutzfeldt-Jakob disease-like phenotype. The PRNP E196K mutation has only rarely been described in the literature, and generally patients exhibited an atypical initial phenotype, mainly involving abnormal behavioral features. Further observations are needed to confirm this particular clinical pattern associated with the mutation.
Scapellato, Pablo G; Bottaro, Edgardo G; Seoane, María B; Rodriguez Brieschke, María T; Scapellato, Jose L; Dato, Adriana; Vidal, Gabriela I
We studied the prevalence of antibodies against HTLV-1 among every HIV-infected outpatients assisted in our hospital between January 1st 2000 and June 30th 2003. We reviewed the epidemiological data, clinical findings, viral load and CD4 cells-count, comparing coinfected with non HTLV-1 coinfected. We found a prevalence of HTLV-1 infection of 8.1% (23/282); 8.5% (12/141) in men and 7.8% (11/141) in women [[OR=0.91 (0.36
Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system.
Alexander, Tobias; Thiel, Andreas; Rosen, Oliver; Massenkeil, Gero; Sattler, Arne; Kohler, Siegfried; Mei, Henrik; Radtke, Hartmut; Gromnica-Ihle, Erika; Burmester, Gerd-Rüdiger; Arnold, Renate; Radbruch, Andreas; Hiepe, Falk
Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce clinical remission in patients with refractory systemic lupus erythematosus (SLE), but the mechanisms have remained unclear. We now report the results of a single-center prospective study of long-term immune reconstitution after ASCT in 7 patients with SLE. The clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti-double-stranded DNA (dsDNA) antibodies and protective antibodies in serum and a fundamental resetting of the adaptive immune system. The latter comprises recurrence of CD31(+)CD45RA(+)CD4(+) T cells (recent thymic emigrants) with a doubling in absolute numbers compared with age-matched healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic-derived FoxP3(+) regulatory T cells, and normalization of peripheral T-cell receptor (TCR) repertoire usage. Likewise, responders exhibited normalization of the previously disturbed B-cell homeostasis with numeric recovery of the naive B-cell compartment within 1 year after ASCT. These data are the first to demonstrate that both depletion of the autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to reestablish self-tolerance in SLE.
Queiroz, Cleriston Farias; Lemos, Antonio Carlos Moreira; Bastos, Maria de Lourdes Santana; Neves, Margarida Célia Lima Costa; Camelier, Aquiles Assunção; Carvalho, Natália Barbosa; de Carvalho, Edgar Marcelino
ABSTRACT Objective: To determine whether COPD severity correlates with sputum cell counts, atopy, and asthma. Methods: This was a cross-sectional study involving 37 patients with COPD and 22 healthy subjects with normal lung function (controls). Sputum cell counts were determined by microscopy after centrifugation of samples. Skin prick tests were performed, and serum cytokines were determined by ELISA. Results: Patients were stratified by bronchodilator response: a non-reversible airflow limitation (nonRAL) group comprised 24 patients showing no significant post-bronchodilator change in FEV1; and a partially reversible airflow limitation (partialRAL) group comprised 13 patients showing FEV1 reversibility (post-bronchodilator FEV1 increase ≥ 12%). The proportion of eosinophils in sputum was higher in the partialRAL group than in the nonRAL group (p < 0.01), and there was an inverse correlation between the proportion of eosinophils and FEV1 (p < 0.05). However, none of the patients had a history of asthma and skin prick test results did not differ between the two groups. In the patient sputum samples, neutrophils predominated. Serum levels of TNF, IL-6, IL-8, and RANTES (CCL5) were higher in patients than in controls (p < 0.001) but did not differ between the two patient groups. Conclusions: COPD patients with partial FEV1 reversibility appear to have higher sputum eosinophil counts and greater airway hyperresponsiveness than do those with no FEV1 reversibility. However, we found that COPD severity did not correlate with atopy or with the cytokine profile. PMID:27832230
Gorodilova, V V
The importance of immune response indices in tumor patients is discussed on the basis of literature data and the author's findings. Although a correlation between clinical course of malignant disease and the patient's immunocompetence was established, the relationship of immune response indices and clinical TNM staging is not stable. Reasons are given for introducing U-criterion of immune response evaluation into TNM classification. The relationship between immune response in cancer patients and type of therapy as well as the practical importance of this parameter are discussed.
Günaltay, Sezin; Rademacher, Lech; Hultgren Hörnquist, Elisabeth; Bohr, Johan
One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT. The patient remained in remission for 11 mo after the third faecal transplantation. The immunomodulatory effect of the therapy was evaluated using flow cytometry, which showed alterations in the profile of intraepithelial and lamina propria lymphocyte subsets after the second transplantation. Our observations indicate that FMT can have an effect in CC, which support the hypothesis that luminal factors, influencing the intestinal microbiota, are involved in the pathogenesis of CC.
Furyk, E; Ryabokon, E
The article presents information obtained during the survey in 64 patients with acute hepatitis B. We show that acute hepatitis B in patients with concomitant chronic toxic liver characterized by a marked imbalance of cytokine status due to a lower level of interleukin-2 and a higher content of interleukin-8, the highest levels of nitrite content, spontaneous oxidative modifications of blood proteins and the lowest content of L -arginine in the blood serum in the dynamics of disease compared with patients without this concomitant factor. In the period of convalescence these changes in patients with acute hepatitis B with concomitant chronic toxic liver characterized combined with higher cytolysis of liver cells, often circulating in the blood of HBsAg seroconversion and less frequently with the advent of anti-HBeAg.
Günaltay, Sezin; Rademacher, Lech; Hultgren Hörnquist, Elisabeth; Bohr, Johan
One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT. The patient remained in remission for 11 mo after the third faecal transplantation. The immunomodulatory effect of the therapy was evaluated using flow cytometry, which showed alterations in the profile of intraepithelial and lamina propria lymphocyte subsets after the second transplantation. Our observations indicate that FMT can have an effect in CC, which support the hypothesis that luminal factors, influencing the intestinal microbiota, are involved in the pathogenesis of CC. PMID:28275312
El-Khatib, Ziad; Katzenstein, David; Marrone, Gaetano; Laher, Fatima; Mohapi, Lerato; Petzold, Max; Morris, Lynn; Ekström, Anna Mia
Background Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa. Methods In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12–99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO). Results After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2–6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2–3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02). Conclusion One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure. PMID:21408071
Pedersen, S S; Espersen, F; Høiby, N; Shand, G H
Alginates from nine mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis were purified by repeated ethanol precipitation, nuclease digestion, anion-exchange chromatography, dialysis, and lyophilization. Uronic acid constituted 72% of the dry weight when mannuronolactone was used as the internal standard in the carbazole-borate assay for uronic acids. The average degree of acetylation was 16%, and the ratio of mannuronic acid to gluluronic acid was 4.7. No homopolymeric blocks of guluronic acid were found when analyzed by nuclear magnetic resonance spectroscopy. Contaminating proteins were denatured by heating, and during purification the content of protein relative to alginate fell from 566 to 0.9%. The content of lipopolysaccharide was 0.012%. No immunological or biological activity was attributable to the protein or lipopolysaccharide content as estimated by immunoblotting, enzyme-linked immunosorbent assay (ELISA), and a neutrophil chemotaxis assay. Rabbits were hyperimmunized with P. aeruginosa alginates and alginate from the seaweed Laminaria hyperborea, and an ELISA that detected alginate-specific antibodies was developed. Antibodies to P. aeruginosa alginate were detected by ELISA in 1:4,000 dilutions of serum from patients with cystic fibrosis with chronic P. aeruginosa lung infection. The serological cross-reactions between serum from the nine patients with cystic fibrosis and the corresponding P. aeruginosa alginates were investigated and showed considerable heterogeneity. This finding indicates that P. aeruginosa alginate from more than one P. aeruginosa strain should be used in serological tests. There was no serological cross-reactivity between P. aeruginosa and Laminaria hyperborea alginate in either rabbits or patients with cystic fibrosis.
Bacchetta, Rosa; Lucarelli, Barbarella; Sartirana, Claudia; Gregori, Silvia; Lupo Stanghellini, Maria T.; Miqueu, Patrick; Tomiuk, Stefan; Hernandez-Fuentes, Maria; Gianolini, Monica E.; Greco, Raffaella; Bernardi, Massimo; Zappone, Elisabetta; Rossini, Silvano; Janssen, Uwe; Ambrosi, Alessandro; Salomoni, Monica; Peccatori, Jacopo; Ciceri, Fabio; Roncarolo, Maria-Grazia
T-cell therapy after hematopoietic stem cell transplantation (HSCT) has been used alone or in combination with immunosuppression to cure hematologic malignancies and to prevent disease recurrence. Here, we describe the outcome of patients with high-risk/advanced stage hematologic malignancies, who received T-cell depleted (TCD) haploidentical-HSCT (haplo-HSCT) combined with donor T lymphocytes pretreated with IL-10 (ALT-TEN trial). IL-10-anergized donor T cells (IL-10-DLI) contained T regulatory type 1 (Tr1) cells specific for the host alloantigens, limiting donor-vs.-host-reactivity, and memory T cells able to respond to pathogens. IL-10-DLI were infused in 12 patients with the goal of improving immune reconstitution after haplo-HSCT without increasing the risk of graft-versus-host-disease (GvHD). IL-10-DLI led to fast immune reconstitution in five patients. In four out of the five patients, total T-cell counts, TCR-Vβ repertoire and T-cell functions progressively normalized after IL-10-DLI. These four patients are alive, in complete disease remission and immunosuppression-free at 7.2 years (median follow-up) after haplo-HSCT. Transient GvHD was observed in the immune reconstituted (IR) patients, despite persistent host-specific hypo-responsiveness of donor T cells in vitro and enrichment of cells with Tr1-specific biomarkers in vivo. Gene-expression profiles of IR patients showed a common signature of tolerance. This study provides the first indication of the feasibility of Tr1 cell-based therapy and paves way for the use of these Tr1 cells as adjuvant treatment for malignancies and immune-mediated disorders. PMID:24550909
Kumar, Raj; Srivastava, Prakriti; Kumari, Dolly; Fakhr, Hena; Sridhara, S; Arora, Naveen; Gaur, S N; Singh, B P
Sensitization to foods varies in different countries reflecting a possible interaction of genetic factors, cultural and dietary habits. Rice is a major food consumed world wide and needs evaluation for IgE mediated reactions. The present study was carried out to identify rice allergy in patients of rhinitis and asthma and identify the allergenic proteins in raw and cooked rice. Of 1200 patients screened using standard questionnaire, 165 presented with history of rice allergy. Of these, 20 (12.1%) patients demonstrated marked positive skin prick test (SPT) and 13 showed significantly raised specific IgE to rice compared to normal controls. Double blind placebo controlled food challenge (DBPCFC) confirmed rice allergy in 6/10 patients. Immunoblot with hypersensitive individual patients' sera showed 14-16, 33, 56 and 60 kDa proteins as major IgE-binding components in rice. Boiled rice retained four IgE reactive proteins of 16, 23, 33 and 53 kDa. In summary, IgE-mediated rice allergy affects 0.8% [(0.42-1.58) at 95% CI] of asthma and rhinitis cases. The subjects with severe SPT reactions (4 mm or above) and specific IgE, 6.9 ng/ml to rice demonstrated positive blinded food challenge with clinical symptoms.
Dotta, Laura; Scomodon, Omar; Padoan, Rita; Timpano, Silviana; Plebani, Alessandro; Soresina, Annarosa; Lougaris, Vassilios; Concolino, Daniela; Nicoletti, Angela; Giardino, Giuliana; Licari, Amelia; Marseglia, Gianluigi; Pignata, Claudio; Tamassia, Nicola; Facchetti, Fabio; Vairo, Donatella; Badolato, Raffaele
This paper describes the heterogeneous clinical phenotype of a cohort of nine patients diagnosed with heterozygous mutations in STAT1. We report data of extended immunophenotyping over time and we show lung damage in four patients. The increased phosphorylation of STAT1 in response to IFNγ and IFNα stimulation proves the gain-of-function nature of the defects. The data are supplemental to our original article concurrently published “Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease” , where additional results and interpretation of our research can be found. PMID:26981552
Markert, M Louise; Sarzotti, Marcella; Ozaki, Daniel A; Sempowski, Gregory D; Rhein, Maria E; Hale, Laura P; Le Deist, Francoise; Alexieff, Marilyn J; Li, Jie; Hauser, Elizabeth R; Haynes, Barton F; Rice, Henry E; Skinner, Michael A; Mahaffey, Samuel M; Jaggers, James; Stein, Leonard D; Mill, Michael R
Complete DiGeorge syndrome is a fatal condition in which infants have no detectable thymus function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of thymus transplantation were evaluated in 12 infants with complete DiGeorge syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor Vbeta (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge syndrome.
Echeverria, Patricia; Guardiola, Montse; González, Marta; Vallvé, Joan Carles; Bonjoch, Anna; Puig, Jordi; Clotet, Bonaventura; Ribalta, Josep; Negredo, Eugènia
Several studies have reported associations between lipid parameters and clinical progression of HIV infection. We performed a cross-sectional study including 468 antiretroviral-treated HIV-infected patients to investigate the impact of 13 polymorphisms of 9 genes affecting lipid metabolism and CD4 and CD8-T cell levels. Polymorphisms were identified in genes selected for their role in the development of atherogenic dyslipidemia, defined as triglycerides ⩾1.7mmol/L and high-density lipoprotein cholesterol (HDLc) <1.02 in women or 1.28mmol/L in men. Lipid and lipoprotein parameters were determined in all participants, as well as CD4 and CD8 T-cell counts. ANOVA was performed to compare the mean values of lipid and CD4 and CD8 T-cell count data. A Bonferroni correction for multiple comparisons was applied. 468 patients were included, 148 of them had a diagnosis of atherogenic dyslipidemia. The polymorphism rs3135506 in APOA5 was associated with a 9% increase in triglycerides (p=0.002), 10% and 21% decrease in HDLc (p=0.005), and CD4 T-cell count (p=0.024), respectively. APOA5 rs662799, was associated with a 19% increase in CD8 T-cell count (p=0.002). Carriers of LPL rs328 in the dyslipidemic group presented 11% higher levels of HDLc (p=0.015) and 14% higher levels of CD4 cells (p=0.038). In conclusion, polymorphisms in genes associated to the development of atherogenic dyslipidemia, especially variants in APOA5 gene (rs3135506 and rs662799), can influence the circulating CD4 T-cell levels in chronically HIV-infected patients. These data support previous reports on the effect of lipid metabolism on immunologic parameters in HIV+ individuals on antiretroviral therapy.
Mena, Guillermo; Llupià, Anna; García-Basteiro, Alberto L; Díez, Consolación; León, Agathe; García, Felipe; Bayas, José M
Hepatitis B vaccination is recommended in HIV-infected patients. Achieving seroprotection rates (anti-HBs ≥ 10I U/L) comparable to the general population remains a challenge. The aim of this study was to analyze the proportion of responders among patients infected with HIV receiving primary HBV vaccination and identify factors associated with seroprotection rates. We analyzed the response to vaccination (antiHBs titers) in 474 HIV-infected patients receiving ≥ 1 doses of vaccine between 1994 and 2009. Factors associated with response to vaccination were analyzed using a logistic regression model. Considering the first vaccine courses administered, a response rate of 60.3% (286/474) was obtained. Eighty-seven patients began a second course, responding in 58.6% of cases. Regardless of the number of doses, schedules, and whether or not they completed the course, the response rates were 71.1% (337/474). After adjustment for year of reception of the first dose, responders were less likely to have a higher baseline HIV 1-RNA viral load (OR: 0.78 95% CI: 0.68-0.91) and more likely to have a CD4 count ≥ 350 cells/μL (OR: 1.64, 95% CI: 1.03-3.62). Patients receiving less than three doses of vaccine (OR: 0.31 95% CI 0.15-0.61) or three doses of the rapidly accelerated schedule (OR: 0.35 95% CI 0.15-0.81) had a lower probability of response in comparison with those receiving three doses of an accelerated schedule. In patients diagnosed with HIV, HBV vaccination before evolution to greater immunosuppression (CD4 < 350 cells/μL) or delaying vaccination until the CD4 count is higher could provide better seroprotection rates. The rapidly accelerated vaccination schedule should be used with caution, due to its lower effectiveness. If seroprotection is not achieved after the first course, revaccination seems to be effective in increasing the proportion of responders.
Shiratori, Beata; Zhao, Jingge; Okumura, Masao; Chagan-Yasutan, Haorile; Yanai, Hideki; Mizuno, Kazue; Yoshiyama, Takashi; Idei, Tadashi; Ashino, Yugo; Nakajima, Chie; Suzuki, Yasuhiko; Hattori, Toshio
Elevated matricellular proteins (MCPs), including osteopontin (OPN) and galectin-9 (Gal-9), were observed in the plasma of patients with Manila-type tuberculosis (TB) previously. Here, we quantified plasma OPN, Gal-9, and soluble CD44 (sCD44) by enzyme-linked immunosorbent assay (ELISA), and another 29 cytokines by Luminex assay in 36 patients with pulmonary TB, six subjects with latent tuberculosis (LTBI), and 19 healthy controls (HCs) from Japan for a better understanding of the roles of MCPs in TB. All TB subjects showed positive results of enzyme-linked immunospot assays (ELISPOTs). Spoligotyping showed that 20 out of 36 Mycobacterium tuberculosis (MTB) strains belong to the Beijing type. The levels of OPN, Gal-9, and sCD44 were higher in TB (positivity of 61.1%, 66.7%, and 63.9%, respectively) than in the HCs. Positive correlations between OPN and Gal-9, between OPN and sCD44, and negative correlation between OPN and ESAT-6-ELISPOT response, between chest X-ray severity score of cavitary TB and ESAT-6-ELISPOT response were observed. Instead of OPN, Gal-9, and sCD44, cytokines G-CSF, GM-CSF, IFN-α, IFN-γ, IL-12p70, and IL-1RA levels were higher in Beijing MTB-infected patients. These findings suggest immunoregulatory, rather than inflammatory, effect of MCPs and can advance the understanding of the roles of MCPs in the context of TB pathology. PMID:28025511
Ong, S G; Choy, C H
Autoimmune thyroid disease (ATD) has been associated with other systemic autoimmune diseases. To date, there is limited data on thyroid disorders and autoimmune thyroid disease in Malaysia. The frequency of ATD among 189 systemic lupus erythematosus (SLE) patients was 6.3%, with 2.6% in the hyperthyroid group and 3.7% in the hypothyroid group. Hypothyroidism developed at a much younger mean age (24.3 years), suggesting that SLE might be a predisposing factor for the development of Hashimoto's thyroiditis. There was a higher rate of thyroid peroxidase antibody (TPO) positivity compared with anti-thyroglobulin antibody (Tg) in the hyperthyroid subgroup. This study also demonstrated a greater proportion of ATD patients who demonstrated high titres (≥ 1:6400) of TPO compared with high titres of Tg. Although there was an association between ATD and the presence of anti-Ro/SSA and/or anti-La/SSB antibodies, the absence of sicca symptoms and negative Schirmer's tests suggest a lack of association with secondary Sjogren's syndrome. A novel association between ATD and antiphospholipid syndrome (APS) was detected in our cohort. Hence we propose that patients affected by APS be routinely screened for ATD.
Varas-Díaz, Gonzalo; Brunetti, Enzo P.; Rivera-Lillo, Gonzalo; Maldonado, Pedro E.
Spinal cord injury (SCI) is a devastating event for individuals, who frequently develop motor and sensory impairment as well as autonomic dysfunction. Previous studies reported that autonomic activity plays a major role in social cognition and that difficulties in the ability to interpret social information are commonly observed in a variety of mental disorders, which in turn correlate with a poor autonomic nervous system (ANS) regulation. It is well established that subjects with SCI have an alteration in ANS regulation mechanisms. We hypothesized that subjects diagnosed with SCI, who are experiencing a period of adaptation and socio-labor insertion suffer alterations in an emotion recognition task, a component of social cognition, which correlate with poor ANS regulation. We evaluated ANS function by measuring the heart rate variability (HRV) in 18 healthy subjects and 10 subjects with SCI. A 5-min baseline HRV was compared to a task period while performing The reading the mind in the eyes test (RMET). We found that while both groups have similar general performance in the test, healthy subjects responded with greater certainty during the RMET. This level of certainty during the RMET was positively correlated with baseline HRV measures in this group. Also, the group of healthy subjects exhibited higher HRV at baseline than participants with SCI. Finally, the changes in HRV between baseline and task condition were significantly higher in healthy individuals than in SCI participants. Our results show that patients with SCI have low levels of autonomic regulation mechanisms which may promote social cognition problems during their reinsertion to daily life. PMID:28228721
Varas-Díaz, Gonzalo; Brunetti, Enzo P; Rivera-Lillo, Gonzalo; Maldonado, Pedro E
Spinal cord injury (SCI) is a devastating event for individuals, who frequently develop motor and sensory impairment as well as autonomic dysfunction. Previous studies reported that autonomic activity plays a major role in social cognition and that difficulties in the ability to interpret social information are commonly observed in a variety of mental disorders, which in turn correlate with a poor autonomic nervous system (ANS) regulation. It is well established that subjects with SCI have an alteration in ANS regulation mechanisms. We hypothesized that subjects diagnosed with SCI, who are experiencing a period of adaptation and socio-labor insertion suffer alterations in an emotion recognition task, a component of social cognition, which correlate with poor ANS regulation. We evaluated ANS function by measuring the heart rate variability (HRV) in 18 healthy subjects and 10 subjects with SCI. A 5-min baseline HRV was compared to a task period while performing The reading the mind in the eyes test (RMET). We found that while both groups have similar general performance in the test, healthy subjects responded with greater certainty during the RMET. This level of certainty during the RMET was positively correlated with baseline HRV measures in this group. Also, the group of healthy subjects exhibited higher HRV at baseline than participants with SCI. Finally, the changes in HRV between baseline and task condition were significantly higher in healthy individuals than in SCI participants. Our results show that patients with SCI have low levels of autonomic regulation mechanisms which may promote social cognition problems during their reinsertion to daily life.
Nicolás, David; Manzardo, Christian; Agüero, Fernando; Claramonte, Xavier; Plana, Montserrat; Tuset, Montserrat; Pumarola, Tomás; Gallart, Teresa; Gatell, José María; Miró, José María
Background Interventions during primary HIV infection (PHI) can modify the clinical course during the chronic phase. The long-term effect of structured treatment interruptions (STI) followed by low doses of interleukin-2 (IL-2) in treated PHI patients is unknown. Methods Twelve PHI patients with viral load (VL) <20 copies/mL, CD4 cells >500 cells/mm3, and CD4/CD8 ratio >1, on antiretroviral therapy (ART) initiated within the first 90 days of infection and continued for at least 12 months were included. They underwent four STI and were then allocated (week 0 of the study) to ART alone or ART plus low doses of IL-2. ART was stopped once VL <20 copies/mL ('final stop'). Primary endpoints were VL<3000 copies/mL and CD4 cells >500 cells/mm3 at 48 weeks; secondary endpoints were immune activation, inflammatory markers until 48 weeks and the time before resuming ART (CD4 <350 cells/mm3 or AIDS) after ‘final stop’, compared between groups. Results Ten out of 12 patients were males, median age was 35 years and the main risk was men-who-have-sex-with-men. Only one out of 12 patients (in the STI group) maintained VL<3000 copies/mL and CD4 cells >500 cells/mm3 without ART at 48 weeks. All other virological and immunological parameters were comparable between groups at week 0, 'final stop' and week 48. However, the proportion of CD8-CD38+ cells, tumor necrosis factor and srIL-2 were higher in the IL-2 group at 'final stop' and week 24. All these differences vanished during follow-up. At 5 years after the final stop 3 out of 6 patients in the IL-2 group and 6 out of 6 patients in the STI group have resumed ART (P = 0.19). Conclusions STI and IL-2 failed to achieve virological control after ART interruption. STI were not deleterious in long-term follow-up, an important issue for eradication and functional cure trials. Trial Registration ClinicalTrials.gov NCT02300623 PMID:26186440
Christou, N V; Tellado-Rodriguez, J; Chartrand, L; Giannas, B; Kapadia, B; Meakins, J; Rode, H; Gordon, J
We measured the delayed type hypersensitivity (DTH) skin test response, along with additional variables of host immunocompetence in 245 preoperative patients to determine which variables are associated with septic-related deaths following operation. Of the 14 deaths (5.7%), 12 were related to sepsis and in 2 sepsis was contributory. The DTH response (p less than 0.00001), age (p less than 0.0002), serum albumin (p less than 0.003), hemoglobin (p less than 0.02), and total hemolytic complement (p less than 0.03), were significantly different between those who died and those who lived. By logistic regression analysis, only the DTH skin test response (log likelihood = 41.7, improvement X2 = 6.24, p less than 0.012) and the serum albumin (log likelihood = 44.8, improvement X2 = 17.7, p less than 0.001) were significantly and independently associated with the deaths. The resultant probability of mortality calculation equation was tested in a separate validation group of 519 patients (mortality = 5%) and yielded a good predictive capability as assessed by (1) X2 = 0.08 between observed and expected deaths, NS; (2) Goodman-Kruskall G statistic = 0.673) Receiver-Operating-Characteristic (ROC) curve analysis with an area under the ROC curve, Az = 0.79 +/- 0.05. We conclude that a reduced immune response (DTH skin test anergy) plus a nutritional deficit and/or acute-phase response change are both associated with increased septic-related deaths in elective surgical patients. PMID:2472781
Brombin, Chiara; Diomede, Lorenzo; Tudor, Daniela; Drillet, Anne Sophie; Pastori, Claudia; Poli, Elena; Riva, Agostino; Uberti-Foppa, Caterina; Galli, Massimo; Di Serio, Clelia; Bomsel, Morgane; Lopalco, Lucia
This work aims at identifying a set of humoral immunologic parameters that improve prediction of the activation process in HIV patients. Starting from the well-known impact of humoral immunity in HIV infection, there is still a lack of knowledge in defining the role of the modulation of functional activity and titers of serum antibodies from early stage of infection to the development of AIDS. We propose an integrated approach that combines humoral and clinical parameters in defining the host immunity, implementing algorithms associated with virus control. A number of humoral parameters were simultaneously evaluated in a whole range of serum samples from HIV-positive patients. This issue has been afforded accounting for estimation problems typically related to "feasibility" studies where small sample size in each group and large number of parameters are jointly estimated. We used nonparametric statistical procedures to identify biomarkers in our study which included 42 subjects stratified on five different stages of HIV infection, i.e., Elite Controllers (EC), Long Term Non Progressors (LTNP), HAART, AIDS and Acute Infection (AI). The main goal of the paper is to illustrate a novel profiling method for helping to design a further confirmatory study. A set of seventeen different HIV-specific blood humoral factors were analyzed in all subjects, i.e. IgG and IgA to gp120IIIB, to gp120Bal, to whole gp41, to P1 and T20 gp41 epitopes of the MPER-HR2 region, to QARILAV gp41 epitope of the HR1 region and to CCR5; neutralization activity against five different virus strains and ADCC were also evaluated. Patients were selected on the basis of CD4 cell counts, HIV/RNA and clinical status. The Classification and Regression Trees (CART) approach has been used to uncover specific patterns of humoral parameters in different stages of HIV disease. Virus neutralization of primary virus strains and antibodies to gp41 were required to classify patients, suggesting that clinical
Brombin, Chiara; Diomede, Lorenzo; Tudor, Daniela; Drillet, Anne Sophie; Pastori, Claudia; Poli, Elena; Riva, Agostino; Uberti-Foppa, Caterina; Galli, Massimo; Di Serio, Clelia; Bomsel, Morgane; Lopalco, Lucia
This work aims at identifying a set of humoral immunologic parameters that improve prediction of the activation process in HIV patients. Starting from the well-known impact of humoral immunity in HIV infection, there is still a lack of knowledge in defining the role of the modulation of functional activity and titers of serum antibodies from early stage of infection to the development of AIDS. We propose an integrated approach that combines humoral and clinical parameters in defining the host immunity, implementing algorithms associated with virus control. A number of humoral parameters were simultaneously evaluated in a whole range of serum samples from HIV-positive patients. This issue has been afforded accounting for estimation problems typically related to “feasibility” studies where small sample size in each group and large number of parameters are jointly estimated. We used nonparametric statistical procedures to identify biomarkers in our study which included 42 subjects stratified on five different stages of HIV infection, i.e., Elite Controllers (EC), Long Term Non Progressors (LTNP), HAART, AIDS and Acute Infection (AI). The main goal of the paper is to illustrate a novel profiling method for helping to design a further confirmatory study. A set of seventeen different HIV-specific blood humoral factors were analyzed in all subjects, i.e. IgG and IgA to gp120IIIB, to gp120Bal, to whole gp41, to P1 and T20 gp41 epitopes of the MPER-HR2 region, to QARILAV gp41 epitope of the HR1 region and to CCR5; neutralization activity against five different virus strains and ADCC were also evaluated. Patients were selected on the basis of CD4 cell counts, HIV/RNA and clinical status. The Classification and Regression Trees (CART) approach has been used to uncover specific patterns of humoral parameters in different stages of HIV disease. Virus neutralization of primary virus strains and antibodies to gp41 were required to classify patients, suggesting that clinical
Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H.T.; Aarntzen, Erik H.J.G.; Schreibelt, Gerty; Creemers, Jeroen H.A.; Punt, Cornelis J.A.; Figdor, Carl G.; Gerritsen, Winald R.; Bol, Kalijn F.
The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325
Cruz, Adriana R.; Ramirez, Lady G.; Zuluaga, Ana V.; Pillay, Allan; Abreu, Christine; Valencia, Carlos A.; La Vake, Carson; Cervantes, Jorge L.; Dunham-Ems, Star; Cartun, Richard; Mavilio, Domenico; Radolf, Justin D.; Salazar, Juan C.
bring to light the extent of the systemic innate and adaptive immunologic abnormalities that define the secondary stage of the disease, which in the skin of patients trends towards a T-cell cytolytic response. PMID:22816000
Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric
The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323
Belzeaux, R; Bergon, A; Jeanjean, V; Loriod, B; Formisano-Tréziny, C; Verrier, L; Loundou, A; Baumstarck-Barrau, K; Boyer, L; Gall, V; Gabert, J; Nguyen, C; Azorin, J-M; Naudin, J; Ibrahim, E C
To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls. Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we detected transcripts with roles in various biological processes as significantly dysregulated between MDE patients and controls, notably those involved in nucleotide binding and chromatin assembly. We also established putative interactions between dysregulated mRNAs and miRNAs that may contribute to MDE physiopathology. We selected a set of mRNA candidates for quantitative reverse transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures observed in responders is different from nonresponders. Furthermore, we identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could be predictive of treatment response. Altogether, these results highlight the importance of studies investigating the tight relationship between peripheral transcriptional changes and the dynamic clinical progression of MDE patients to provide biomarkers of MDE evolution and prognosis. PMID:23149449
Kim, Jae Hoon; Chun, Yeoun Sook
The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1β in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1β and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders. PMID:21935281
Kim, Jae Hoon; Chun, Yeoun Sook; Kim, Jae Chan
The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1β in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1β and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.
Bovine tuberculosis (TB) is generally considered a slowly progressive disease of extended duration (lasting years) and most cattle do not exhibit readily apparent clinical signs of infection until late in the course of disease. Currently, agent-based strategies for the detection of tuberculous cattl...
Paluy, Yulia; Gilbert, Aubrey L.; Baldo, Juliana V.; Dronkers, Nina F.; Ivry, Richard B.
Patients with left hemisphere (LH) or right hemisphere (RH) brain injury due to stroke were tested on a speeded, color discrimination task in which two factors were manipulated: 1) the categorical relationship between the target and the distracters and 2) the visual field in which the target was presented. Similar to controls, the RH patients were faster in detecting targets in the right visual field when the target and distracters had different color names compared to when their names were the same. This effect was absent in the LH patients, consistent with the hypothesis that injury to the left hemisphere handicaps the automatic activation of lexical codes. Moreover, the LH patients showed a reversed effect, such that the advantage of different target-distracter names was now evident for targets in the left visual field. This reversal may suggest a reorganization of the color lexicon in the right hemisphere following left hemisphere brain injury and/or the unmasking of a heightened right hemisphere sensitivity to color categories. PMID:21216454
Paluy, Yulia; Gilbert, Aubrey L.; Baldo, Juliana V.; Dronkers, Nina F.; Ivry, Richard B.
Patients with left hemisphere (LH) or right hemisphere (RH) brain injury due to stroke were tested on a speeded, color discrimination task in which two factors were manipulated: (1) the categorical relationship between the target and the distracters and (2) the visual field in which the target was presented. Similar to controls, the RH patients…
Haberman, Yael; Tickle, Timothy L; Dexheimer, Phillip J; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N; Noe, Joshua D; Rosh, Joel; Markowitz, James; Heyman, Melvin B; Griffiths, Anne M; Crandall, Wallace V; Mack, David R; Baker, Susan S; Huttenhower, Curtis; Keljo, David J; Hyams, Jeffrey S; Kugathasan, Subra; Walters, Thomas D; Aronow, Bruce; Xavier, Ramnik J; Gevers, Dirk; Denson, Lee A
Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.
Palmer, S S; Hutton, J T
Physiological correlates of postural tremor of the finger seen in Parkinson's disease patients are different from those seen in age-matched control subjects. A significant correlation between the spectral peak of acceleration and the spectral peak of rectified electromyographic activity from the muscle responsible for finger extension was found in Parkinson's disease patients. This correlation was not seen in age-matched control subjects. Any neural drive imposed on the motoneuron pool from supraspinal levels would enhance the electromyographic activity. Likewise, any feedback effects via spinal stretch reflexes or supraspinal stretch responses would be mediated through the motoneuron pool and electromyographic activity. The results of this research support the theory that Parkinson tremor is a centrally driven rhythm that may be influenced by feedback effects, whereas physiological tremor is due to a complex interaction of central, feedback, and mechanical effects.
Inverardi, Luca; Kenyon, Norma S; Ricordi, Camillo
Clinical trials of islet transplantation are showing remarkable success, but they require administration of chronic immunosuppression, and are underscoring the large gap that exists between the number of human donors available and the number of patients that could benefit from the procedure. Recent progress has been made in the definition of key immunological mechanisms that are involved in determining islet transplant outcome. Clinical and preclinical studies, and studies in small animal model systems, will all eventually contribute to the definition of efficient and safe protocols for islet transplantation. If the use of xenografts is successful, it might represent a solution to the shortage of human organs.
Banerjee, Poulomi; Venkatachalam, Sandhyaa; Mamidi, Murali Krishna; Bhonde, Ramesh; Shankar, Krupa; Pal, Rajarshi
Vitiligo is an autoimmune disorder that leads to depigmentation of skin via melanocyte dysfunction. Keratinocyte-induced toxicity is one among the several etiological factors implicated for vitiligo, and hence, autologous keratinocyte grafting is projected as one of the primary mode of treatment for vitiligo. However, reports indicate that perilesional keratinocytes not only display signatures of apoptosis but also could secrete cytokines and mediators which have antagonistic effect on proliferation or survival. Therefore, we investigated how vitiligo patients' derived keratinocytes respond to surplus amounts of inflammatory cytokines and whether they recapitulate events that take place during conventional wound healing. The primary objective of our study was to determine whether keratinocytes isolated from a vitiligo patient would undergo epithelial-mesenchymal transition similar to their normal counterparts upon induction with inflammatory cytokines such as TGF-b1 and EGF. We found that these keratinocytes undergo EMT during wound repair accompanied with increase in the levels of mesenchymal markers and ECM proteins; decrease in the levels of epithelial markers and enhanced migratory ability. Besides, we also demonstrated that EMT induction leads to activation of SMAD and MAPK pathways via Ras, Raf, PAI 1, Snail, Slug and ZO1. To our knowledge, this is the first report on the characterization of primary keratinocytes isolated from vitiligo patients with respect to their wound healing capacity.
Fabrizi, F; Dixit, V; Martin, P; Messa, P
It is well known that the seroconversion rate of patients following hepatitis B virus (HBV) vaccination is lower in uraemic than healthy subjects. A variety of inherited or acquired factors have been implicated in this diminished response, and the high prevalence of hepatitis C virus (HCV) infection among patients on maintenance dialysis has been suggested to play a role. However, the impact of HCV on the immune response to HB vaccine in patients receiving long-term dialysis is not entirely understood. Here, we evaluate the influence of HCV infection on the immunological response to HBV vaccine in dialysis population by performing a systematic review of the literature with a meta-analysis of clinical studies.We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titres at completion of HBV vaccine schedule among HCV-positive versus HCV-negative patients on chronic dialysis. We identified eight studies involving 520 unique patients on long-term dialysis. Aggregation of study results did not show a significant decrease in response rates among HCV-infected versus noninfected patients [pooled odds ratio = 0.621 (95% CI, 0.285; 1.353)]. The P-value was 0.007 for our test of study heterogeneity. Stratified analysis in various subgroups of interest did not meaningfully change our results. Our meta-analysis showed no association between immunological response to hepatitis B vaccine and HCV infection in individuals on long-term dialysis. These results support the use of recombinant vaccine against hepatitis B in patients on regular dialysis with HCV infection.
Donnelly, Ryan F.; Singh, Thakur Raghu Raj; Alkilani, Ahlam Zaid; McCrudden, Maelíosa T.C.; O’Mahony, Conor; Armstrong, Keith; McLoone, Nabla; Kole, Prashant; Woolfson, A. David
We describe, for the first time, the microbial characterisation of hydrogel-forming polymeric microneedle arrays and the potential for passage of microorganisms into skin following microneedle penetration. Uniquely, we also present insights into the storage stability of these hydroscopic formulations, from physical and microbiological viewpoints, and examine clinical performance and safety in human volunteers. Experiments employing excised porcine skin and radiolabelled microorganisms showed that microorganisms can penetrate skin beyond the stratum corneum following microneedle puncture. Indeed, the numbers of microorganisms crossing the stratum corneum following microneedle puncture was greater than 105 cfu in each case. However, no microorganisms crossed the epidermal skin. When using a 21G hypodermic needle, more than 104 microorganisms penetrated into the viable tissue and 106 cfu of C. albicans and S. epidermidis completely crossed the epidermal skin in 24 h. The hydrogel-forming materials contained no microorganisms following de-moulding and exhibited no microbial growth during storage, while also maintaining their mechanical strength, apart from when stored at relative humidities of 86%. No microbial penetration through the swelling microneedles was detectable, while human volunteer studies confirmed that skin or systemic infection is highly unlikely when polymeric microneedles are used for transdermal drug delivery. Since no pharmacopoeial standards currently exist for microneedle-based products, the exact requirements for a proprietary product based on hydrogel-forming microneedles are at present unclear. However, we are currently working towards a comprehensive specification set for this microneedle system that may inform future developments in this regard. PMID:23644043
Donnelly, Ryan F; Singh, Thakur Raghu Raj; Alkilani, Ahlam Zaid; McCrudden, Maelíosa T C; O'Neill, Shannon; O'Mahony, Conor; Armstrong, Keith; McLoone, Nabla; Kole, Prashant; Woolfson, A David
We describe, for the first time, the microbial characterisation of hydrogel-forming polymeric microneedle arrays and the potential for passage of microorganisms into skin following microneedle penetration. Uniquely, we also present insights into the storage stability of these hydroscopic formulations, from physical and microbiological viewpoints, and examine clinical performance and safety in human volunteers. Experiments employing excised porcine skin and radiolabelled microorganisms showed that microorganisms can penetrate skin beyond the stratum corneum following microneedle puncture. Indeed, the numbers of microorganisms crossing the stratum corneum following microneedle puncture were greater than 10⁵ cfu in each case. However, no microorganisms crossed the epidermal skin. When using a 21G hypodermic needle, more than 10⁴ microorganisms penetrated into the viable tissue and 10⁶ cfu of Candida albicans and Staphylococcus epidermidis completely crossed the epidermal skin in 24 h. The hydrogel-forming materials contained no microorganisms following de-moulding and exhibited no microbial growth during storage, while also maintaining their mechanical strength, apart from when stored at relative humidities of 86%. No microbial penetration through the swelling microneedles was detectable, while human volunteer studies confirmed that skin or systemic infection is highly unlikely when polymeric microneedles are used for transdermal drug delivery. Since no pharmacopoeial standards currently exist for microneedle-based products, the exact requirements for a proprietary product based on hydrogel-forming microneedles are at present unclear. However, we are currently working towards a comprehensive specification set for this microneedle system that may inform future developments in this regard.
Pignatelli, Jeanine; Goswami, Sumanta; Jones, Joan G; Rohan, Thomas E; Pieri, Evan; Chen, Xiaoming; Adler, Esther; Cox, Dianne; Maleki, Sara; Bresnick, Anne; Gertler, Frank B; Condeelis, John S; Oktay, Maja H
Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)-responsive cell migration protein] are present with macrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding Mena(INV), an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down Mena(INV) or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that Mena(INV) and TMEM frequency are correlated prognostic markers and CSF-1 and Mena(INV) may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes.
Anticevic, Alan; Hu, Xinyu; Xiao, Yuan; Hu, Junmei; Li, Fei; Bi, Feng; Cole, Michael W.; Savic, Aleksandar; Yang, Genevieve J.; Repovs, Grega; Murray, John D.; Wang, Xiao-Jing; Huang, Xiaoqi; Lui, Su; Krystal, John H.
Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for “hypoconnectivity.” At the whole-brain level, we observed “hyperconnectivity” around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications. PMID:25568120
Rehermann, Barbara; Naoumov, Nikolai V
The need to quantitate and monitor immune responses of large patient cohorts with standardized techniques is increasing due to the growing range of treatment options for hepatitis B and hepatitis C, the development of combination therapies, and candidate experimental vaccines for HCV. In addition, advances in immunological techniques have provided new tools for detailed phenotypic and functional analysis of cellular immune responses. At present, there is substantial variation in laboratory protocols, reagents, controls and analysis and presentation of results. Standardization of immunological assays would therefore allow better comparison of results amongst individual laboratories and patient cohorts. The EASL-sponsored and AASLD-endorsed Monothematic Conference on Clinical Immunology in Viral Hepatitis was held at the University College London, United Kingdom, Oct 7-8, 2006 to bring together investigators with research experience in clinical immunology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections for in-depth discussion, critical evaluation and standardization of immunological assays. This report summarizes the information presented and discussed at the conference, but is not intended to represent a consensus statement. Our aim is to highlight topics and issues that were supported by general agreement and those that were controversial, as well as to provide suggestions for future work.
Winzer, Ralf; Langmann, Peter; Zilly, Michael; Tollmann, Franz; Schubert, Jörg; Klinker, Hartwig; Weissbrich, Benedikt
Background In a retrospective study of HIV-infected patients, we investigated the influence of the MDR1 genotype (G2677T/A and C3435T) on the virological and immunological response of treatment naïve patients. Methods The MDR1 genotype was analysed from 72 patients in whom antiretroviral therapy was initiated between 1998 and 2004. Data were obtained at week 4, 12, 24 and 48 and were analysed by the Kruskal-Wallis test. Results During the first 48 weeks of antiretroviral therapy, there were no significant differences in the virological and immunological response with respect to the MDR1 2677 and 3435 genotypes and the 2677/3435 haplotype. Conclusions In view of different results from several studies concerning the influence of MDR1 polymorphisms on the immunological and virological response to antiretroviral therapy, further studies with larger patient groups and longer follow-up are necessary in order to resolve conflicting issues. PMID:15659247
Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio
As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available…
Eckersten, Dag; Giwercman, Aleksander; Christensson, Anders
Male reproductive function is impaired during end-stage renal disease (ESRD). Disturbance of the hypothalamic-pituitary-gonadal axis, and therefore the regulation of sex hormones, is one of the major causes. Our focus was to include antimüllerian hormone (AMH) and inhibin B concentrations. Twenty male patients on hemodialysis, median age 40 (26-48) years, were analyzed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, sex hormone-binding globulin (SHBG), testosterone, estradiol, AMH and inhibin B levels. We used 144 proven fertile men, median age 32 (19-44) years as a control group and analyzed differences using multiple linear regression. Males with ESRD demonstrated higher mean values for prolactin, 742 versus normal 210 mIE l-1 (95% confidence interval (CI): 60.3, 729), LH, 8.87 versus normal 4.5 IE l-1 (95% CI: 2.75, 6.14), and estradiol 89.7 versus normal 79.0 pmol l-1 (95% CI: -1.31, -0.15). Mean value for AMH was lower, 19.5 versus normal 47.3 pmol l-1 (95% CI: -37.6, -11.6). There were no differences found for FSH, SHBG, inhibin B and testosterone. The most important difference was found for AMH, a marker of Sertoli cell function in the testes, which decreased by close to 60% when compared with controls. Combined with an increase in LH, these findings may indicate a dysfunction of Sertoli cells and an effect on Leydig cells contributing to a potential mechanism of reproductive dysfunction in men with ESRD.
Pediatric patients with inflammatory bowel disease exhibit increased serum levels of proinflammatory cytokines and chemokines, but decreased circulating levels of macrophage inhibitory protein-1β, interleukin-2 and interleukin-17
KLEINER, GIULIO; ZANIN, VALENTINA; MONASTA, LORENZO; CROVELLA, SERGIO; CARUSO, LORENZO; MILANI, DANIELA; MARCUZZI, ANNALISA
Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition of the gastrointestinal tract. Although the causative events that lead to the onset of IBD are yet to be fully elucidated, deregulation of immune and inflammatory mechanisms are hypothesized to significantly contribute to this disorder. Since the onset of IBD is often during infancy, in the present study, the serum values of a large panel of cytokines and chemokines in pediatric patients (<18 years; n=26) were compared with age-matched controls (n=37). While elevations in the serum level of several proinflammatory and immune regulating cytokines were confirmed, such as interleukin (IL)-1β, IL-5, IL-7, interferon (IFN)-γ-inducible protein-10, IL-16, cutaneous T-cell-attracting chemokine, leukemia inhibitory factor, monokine induced by γ-IFN, IFN-α2 and IFN-γ, notably decreased levels of IL-2, IL-17 and macrophage inhibitory protein-1β were also observed. Therefore, while a number of proinflammatory cytokines exhibit increased levels in IBD patients, pediatric IBD patients may also exhibit certain aspects of a reduced immunological response. PMID:26136934
Pediatric patients with inflammatory bowel disease exhibit increased serum levels of proinflammatory cytokines and chemokines, but decreased circulating levels of macrophage inhibitory protein-1β, interleukin-2 and interleukin-17.
Kleiner, Giulio; Zanin, Valentina; Monasta, Lorenzo; Crovella, Sergio; Caruso, Lorenzo; Milani, Daniela; Marcuzzi, Annalisa
Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition of the gastrointestinal tract. Although the causative events that lead to the onset of IBD are yet to be fully elucidated, deregulation of immune and inflammatory mechanisms are hypothesized to significantly contribute to this disorder. Since the onset of IBD is often during infancy, in the present study, the serum values of a large panel of cytokines and chemokines in pediatric patients (<18 years; n=26) were compared with age-matched controls (n=37). While elevations in the serum level of several proinflammatory and immune regulating cytokines were confirmed, such as interleukin (IL)-1β, IL-5, IL-7, interferon (IFN)-γ-inducible protein-10, IL-16, cutaneous T-cell-attracting chemokine, leukemia inhibitory factor, monokine induced by γ-IFN, IFN-α2 and IFN-γ, notably decreased levels of IL-2, IL-17 and macrophage inhibitory protein-1β were also observed. Therefore, while a number of proinflammatory cytokines exhibit increased levels in IBD patients, pediatric IBD patients may also exhibit certain aspects of a reduced immunological response.
Hemminki, Otto; Parviainen, Suvi; Juhila, Juuso; Turkki, Riku; Linder, Nina; Lundin, Johan; Kankainen, Matti; Ristimäki, Ari; Koski, Anniina; Liikanen, Ilkka; Oksanen, Minna; Nettelbeck, Dirk M; Kairemo, Kalevi; Partanen, Kaarina; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli
Oncolytic viruses that selectively replicate in tumor cells can be used for treatment of cancer. Accumulating data suggests that virus induced oncolysis can enhance anti-tumor immunity and break immune tolerance. To capitalize on the immunogenic nature of oncolysis, we generated a quadruple modified oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor (GMCSF). Ad5/3-E2F-Δ24-GMCSF (CGTG-602) was engineered to contain a tumor specific E2F1 promoter driving an E1 gene deleted at the retinoblastoma protein binding site ("Δ24"). The fiber features a knob from serotype 3 for enhanced gene delivery to tumor cells. The virus was tested preclinically in vitro and in vivo and then 13 patients with solid tumors refractory to standard therapies were treated. Treatments were well tolerated and frequent tumor- and adenovirus-specific T-cell immune responses were seen. Overall, with regard to tumor marker or radiological responses, signs of antitumor efficacy were seen in 9/12 evaluable patients (75%). The radiological disease control rate with positron emission tomography was 83% while the response rate (including minor responses) was 50%. Tumor biopsies indicated accumulation of immunological cells, especially T-cells, to tumors after treatment. RNA expression analyses of tumors indicated immunological activation and metabolic changes secondary to virus replication.
Noguchi, Atsutaka; Kaneko, Toru; Naitoh, Keiko; Saito, Masashi; Iwai, Kazuro; Maekawa, Ryuji; Kamigaki, Takashi; Goto, Shigenori
Recent progress has been made in understanding the mechanisms of antitumor immune responses, which may further clarify the immune status of cancer patients. In this study, we performed a detailed evaluation of the immunological status of 47 patients with advanced solid cancer, who had received no immunosuppressive treatment, and compared the results with 32 healthy subjects. Flow-cytometry data for peripheral blood were obtained using 19 monoclonal antibodies against various cell surface and intracellular molecules. Absolute numbers of T cells, several T cell subsets, B cells, and NK cells were significantly decreased in patients compared with healthy subjects. The percentage of CD27(+)CD45RA(+) T cells was lower and that of CD27(-)CD45RA(-) T cells was higher in patients compared with controls. Regulatory and type 2 helper T cells were elevated in patients relative to healthy subjects. The percentage of perforin(+) NK cells was significantly lower in patients than in controls. These results suggest a dysfunctional anti-tumor immune response in cancer patients. Furthermore, peripheral blood from 26 of 47 cancer patients was analyzed after adoptive T cell immunotherapy (ATI). ATI increased the number of T cell subsets, but not B and NK cells. The number and percentage of regulatory T cells decreased significantly. These results suggest that ATI can restore impaired and imbalanced T cell immune status.
Tsiara, C G; Nikolopoulos, G K; Dimou, N L; Bagos, P G; Saroglou, G; Velonakis, E; Hatzakis, A
Co-infection of human immunodeficiency virus (HIV) with hepatitis C virus (HCV) is rather common. In the era of highly active antiretroviral therapy (HAART), viral hepatitis could result in adverse outcomes in HIV+ patients. The current meta-analysis aims to evaluate the impact of HCV on immunological and virological responses after HAART initiation in HIV/HCV co-infected individuals by synthesizing the existing scientific evidence. A comprehensive search of electronic databases was performed. Eligible studies were analysed using univariate and multivariate meta-analytic methods. Totally, 21 studies involving 22533 individuals were eligible. The estimated summary difference in CD4 cell counts increase between HIV and HIV/HCV co-infected subjects after 3-12 months on HAART was 34.86 cells/mm(3) [95% confidence interval (CI): 16.82-52.89]. The difference was more prominent in patients with baseline CD4 counts below 350 cells/mm(3) (38.97, 95% CI: 20.00-57.93) and attenuated 2 years later (13.43, 95% CI: 0.83-26.04). The analysis of ratio measures yielded similar findings. The virological control remained unaffected by the presence of HCV (adjusted Hazard Ratio for co-infected patients vs those with HIV alone: 0.99, 95% CI: 0.91-1.07). The bivariate meta-analytic method confirmed the results of the univariate approaches. This meta-analysis supports the adverse effect of HCV on immune recovery of HIV+ patients initiating HAART, especially of those with initially impaired immunologic status. Although this effect diminishes over time, early administration of HAART in the setting of co-infection seems to be justified.
Valent, Peter; Cerny-Reiterer, Sabine; Hoermann, Gregor; Sperr, Wolfgang R; Müllauer, Leonhard; Mannhalter, Christine; Pehamberger, Hubert
Systemic mastocytosis (SM) is a hematopoietic disorder characterized by abnormal expansion of mast cells (MCs) in visceral organs. The skin is involved in most cases. In adult patients the transforming KIT mutation D816V is usually present and confers resistance against imatinib. Therefore, imatinib is not recommended for patients with KIT D816V+ SM. Nonetheless, imatinib may work in patients with SM lacking KIT D816V. However, little is known about long-term efficacy and safety of this drug in SM. We report on a 62-year-old female patient with indolent SM (ISM) who suffered from severe debilitating skin involvement despite therapy with anti-mediator-type drugs, psoralen and ultraviolet-A-radiation. Although multifocal MC infiltrates were detected in the bone marrow by immunohistochemistry, no KIT mutation was found by sequencing analysis. In 2003, treatment with imatinib (induction, 400 mg/day; maintenance, 200 mg/day) was initiated. During therapy, skin lesions and tryptase levels decreased. Treatment was well tolerated without any side effects. After 10 years, skin lesions have disappeared and the tryptase level is within normal range. This case-study confirms the long-term efficacy and safety of imatinib in patients with SM lacking activating KIT mutations. Imatinib should be considered in select cases of SM in whom MCs exhibit wild-type KIT. PMID:25755909
Adhikari, Prabha M. R.; Chowta, Mukta N.; Ramapuram, John T.; Rao, Satish; Udupa, Karthik; Acharya, Sahana Devdas
Background: Deficiency of micronutrients is prevalent even before the development of symptoms of HIV disease and is associated with accelerated HIV disease progression. Aims: This study evaluates the prevalence of folate and Vitamin B12 deficiency in HIV-positive patients with or without tuberculosis (TB) and its association with neuropsychiatric symptoms and immunological response. Settings and Design: Cross-sectional, observational study in an outpatient setting. Patients and Methods: Four groups of HIV-positive patients with TB (Group I), HIV-positive patients with neuropsychiatric symptoms (Group II), HIV-positive patients without neuropsychiatric symptoms or TB (Group III), and HIV-negative controls with neuropsychiatric symptoms (Group IV). Vitamin B12 and folate estimation was done using carbonyl metallo-immunoassay method. Statistical Analysis Used: ANOVA, Kruskal–Wallis and Mann–Whitney, Pearson's correlation. Results: The prevalence of folic acid deficiency was 27.1% in the Group I, 31.9% in the Group II, 23.4% in the Group III, and 32% in the Group IV being higher in patients with neuropsychiatric symptoms in both HIV and non-HIV patients. The prevalence of Vitamin B12 deficiency was 18.8% in Group I, 9.1% in Group II, 4.8% in Group III, and 16.7% in Group IV. The patients with folate deficiency had more severe depression and anxiety. Conclusion: Nearly, 30% of the HIV patients had a folic acid deficiency, and about 10% of the HIV patients had Vitamin B12 deficiency. The folate deficiency was highest among neuropsychiatric patients with or without HIV infection and Vitamin B12 deficiency was higher among HIV patients with TB. PMID:27890954
Link, Brian K; Ballas, Zuhair K; Weisdorf, Daniel; Wooldridge, James E; Bossler, Aaron D; Shannon, Mary; Rasmussen, Wendy L; Krieg, Arthur M; Weiner, George J
Oligodeoxynucleotides containing CpG motifs (CpG ODN) can alter various immune cell subsets important in antibody therapy of malignancy. We undertook a phase I trial of CPG 7909 (also known as PF-3512676) in patients with previously treated lymphoma with the primary objective of evaluating safety across a range of doses, and secondary objectives of evaluating immunomodulatory effects and clinical effects. Twenty-three patients with previously treated non-Hodgkin lymphoma received up to 3 weekly 2-hour intravenous (IV) infusions of CPG ODN 7909 at dose levels 0.01 to 0.64 mg/kg. Evaluation of immunologic parameters and clinical endpoints occurred for 6 weeks. Infusion-related toxicity included grade 1 nausea, hypotension, and IV catheter discomfort. Serious adverse hematologic events observed more than once included anemia (2=Gr3, 2=Gr4), thrombocytopenia (4=Gr3), and neutropenia (2=Gr3), and were largely judged owing to progressive disease. Immunologic observations included: (1) The mean ratio of NK-cell concentrations compared with pretreatment at day 2 was 1.44 (95% CI=0.94-1.94) and at day 42 was 1.53 (95% CI=1.14-1.91); (2) NK activity generally increased in subjects; and (3) Antibody-dependent cellular cytotoxicity activity increased in select cohorts. No clinical responses were documented radiographically at day 42. Two subjects demonstrated late response. We conclude CpG 7909 can be safely given as a 2-hour IV infusion to patients with previously treated non-Hodgkin lymphoma at doses that have immunomodulatory effects.
Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio
As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available free of charge in Portuguese and English, which can be used by teachers and students in physiology, immunology, and cellular biology classes. We discuss the development of the initial two modules: "Organs and Lymphoid Tissues" and "Inflammation" and the use of interactive activities to provide microscopic and macroscopic understanding in immunology. Students, both graduate and undergraduate, were questioned along with university level professors about the quality of the software and intuitiveness of use, facility of navigation, and aesthetic organization using a Likert scale. An overwhelmingly satisfactory result was obtained with both students and immunology teachers. Programs such as "Virtual Immunology" are offering more interactive, multimedia approaches to complex scientific principles that increase student motivation, interest, and comprehension.
Albinsson, Sebastian; Della Corte, Alessandro; Alajbegovic, Azra; Krawczyk, Katarzyna K; Bancone, Ciro; Galderisi, Umberto; Cipollaro, Marilena; De Feo, Marisa; Forte, Amalia
MicroRNAs are able to modulate gene expression in a range of diseases. We focused on microRNAs as potential contributors to the pathogenesis of ascending aorta (AA) dilatation in patients with stenotic tricuspid (TAV) or bicuspid aortic valve (BAV). Aortic specimens were collected from the 'concavity' and the 'convexity' of mildly dilated AAs and of normal AAs from heart transplant donors. Aortic RNA was analyzed through PCR arrays, profiling the expression of 84 microRNAs involved in cardiovascular disease. An in silico analysis identified the potential microRNA-mRNA interactions and the enriched KEGG pathways potentially affected by microRNA changes in dilated AAs. Distinct signatures of differentially expressed microRNAs are evident in TAV and BAV patients vs. donors, as well as differences between aortic concavity and convexity in patients only. MicroRNA changes suggest a switch of SMC phenotype, with particular reference to TAV concavity. MicroRNA changes potentially affecting mechanotransduction pathways exhibit a higher prevalence in BAV convexity and in TAV concavity, with particular reference to TGF-β1, Hippo, and PI3K/Akt/FoxO pathways. Actin cytoskeleton emerges as potentially affected by microRNA changes in BAV convexity only. MicroRNAs could play distinct roles in BAV and TAV aortopathy, with possible implications in diagnosis and therapy.
Piloto Valdés, L J; Valdés Sánchez, A F; Gómez Echevarría, A H
Thirty-two adult patients with atopic dermatitis were studied at the Allergology Service of the "Hnos. Ameijeiras" Clinical Surgical Hospital. The diagnosis was established following the criteria of Hanifin and Lobitz. A detailed medical history was written for the patients; the study of some immunological parameters, such as the serum immunoglobulin quantification, delayed skin tests with a battery of antigens, and the spontaneous rosette-test, was also carried out. Almost all the patients showed serum IgE values above 150 UI, by means of the ELISA test modified by C.E.N.I.C. The mean values of the spontaneous rosette-test were low; this was more noticeable during the exacerbation period of the lesions. Candida sp, Mantoux and Streptokinase-Streptodornase antigens showed negative results in a high proportion of patients with atopic dermatitis, in relation with the control group. In atopic dermatitis, there are humoral disorders of immunity; this was demonstrated in our group by increased values of IgE and cellular disorders due to skin anergy, and to a low percentage of rosette forming cells; this does not allow to state that these phenomena have an active participation in the etiopathogenesis of this entity.
Comin-Anduix, Begoña; Lee, Yohan; Jalil, Jason; Algazi, Alain; de la Rocha, Pilar; Camacho, Luis H; Bozon, Viviana A; Bulanhagui, Cecile A; Seja, Elisabeth; Villanueva, Arturo; Straatsma, Bradley R; Gualberto, Antonio; Economou, James S; Glaspy, John A; Gomez-Navarro, Jesus; Ribas, Antoni
Background CTLA4-blocking antibodies induce tumor regression in a subset of patients with melanoma. Analysis of immune parameters in peripheral blood may help define how responses are mediated. Methods Peripheral blood from HLA-A*0201-positive patients with advanced melanoma receiving tremelimumab (formerly CP-675,206) at 10 mg/kg monthly was repeatedly sampled during the first 4 cycles. Samples were analyzed by 1) tetramer and ELISPOT assays for reactivity to CMV, EBV, MART1, gp100, and tyrosinase; 2) activation HLA-DR and memory CD45RO markers on CD4+/CD8+ cells; and 3) real-time quantitative PCR of mRNA for FoxP3 transcription factor, preferentially expressed by T regulatory cells. The primary endpoint was difference in MART1-specific T cells by tetramer assay. Immunological data were explored for significant trends using clustering analysis. Results Three of 12 patients eligible for immune monitoring had tumor regression lasting > 2 years without relapse. There was no significant change in percent of MART1-specific T cells by tetramer assay. Additionally, there was no generalized trend toward postdosing changes in other antigen-specific CD8+ cell populations, FoxP3 transcripts, or overall changes in surface expression of T-cell activation or memory markers. Unsupervised hierarchical clustering based on immune monitoring data segregated patients randomly. However, clustering according to T-cell activation or memory markers separated patients with clinical response and most patients with inflammatory toxicity into a common subgroup. Conclusion Administration of CTLA4-blocking antibody tremelimumab to patients with advanced melanoma results in a subset of patients with long-lived tumor responses. T-cell activation and memory markers served as the only readout of the pharmacodynamic effects of this antibody in peripheral blood. Clinical trial registration number NCT00086489 PMID:18452610
Fox, G J; Menzies, D
Immunological impairment plays a major role in the epidemiology of TB. Globally, the most common causes of immunological impairment are malnutrition, diabetes, HIV/AIDS, aging, and smoking. With the notable exception of HIV, each factor leads to relatively mild immunological impairment in individuals. However, as these conditions affect a significant proportion of the population, they contribute substantially to the incidence of TB at a global scale. Understanding immunological impairment is central to understanding the global TB pandemic, and vital to the development of effective disease control strategies.
Veerman, Christiaan C.; Mengarelli, Isabella; Guan, Kaomei; Stauske, Michael; Barc, Julien; Tan, Hanno L.; Wilde, Arthur A. M.; Verkerk, Arie O.; Bezzina, Connie R.
Brugada syndrome (BrS) is a rare cardiac rhythm disorder associated with sudden cardiac death. Mutations in the sodium channel gene SCN5A are found in ~20% of cases while mutations in other genes collectively account for <5%. In the remaining patients the genetic defect and the underlying pathogenic mechanism remain obscure. To provide insight into the mechanism of BrS in individuals without identified mutations, we here studied electrophysiological properties of cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) from 3 BrS patients who tested negative for mutations in the known BrS-associated genes. Patch clamp studies revealed no differences in sodium current (INa) in hiPSC-CMs from the 3 BrS patients compared to 2 unrelated controls. Moreover, action potential upstroke velocity (Vmax), reflecting INa, was not different between hiPSC-CMs from the BrS patients and the controls. hiPSC-CMs harboring the BrS-associated SCN5A-1795insD mutation exhibited a reduction in both INa and Vmax, demonstrating our ability to detect reduced sodium channel function. hiPSC-CMs from one of the BrS lines demonstrated a mildly reduced action potential duration, however, the transient outward potassium current (Ito) and the L-type calcium current (ICa,L), both implicated in BrS, were not different compared to the controls. Our findings indicate that ion channel dysfunction, in particular in the cardiac sodium channel, may not be a prerequisite for BrS. PMID:27485484
Frøsig, Thomas Mørch
This review is focused on research within three different areas of tumor immunology: discovery of new T-cell epitopes and a new immunological antigen (reported in Paper I and II), elucidation of the immunological effects of treatment with a hypomethylating drug (reported in Paper III) and discovery of new conditional ligands (reported in Paper IV). Many melanoma-associated T-cell epitopes have been described, but 45% of these are restricted to human leukocyte antigen (HLA)-A2, leaving the remaining 36 different HLA molecules with only a few described T-cell epitopes each. Therefore we wanted to expand the number of T-cell epitopes restricted to HLA-A1, -A3, -A11 and -B7, all HLA molecules frequently expressed in Caucasians in Western Europe and Northern America. In Paper I we focused on the proteins gp100, Mart1, MAGE-A3, NY-ESO-1, tyrosinase and TRP-2, all melanoma-associated antigens frequently recognized by T cells from HLA-A2 patients. On contrary, in Paper II we wanted to investigate the protein Nodal as a novel immunological target. We took advantage of a T-cell epitope mapping platform in which HLA ligands are predicted by computer-based algorithms, further tested in the laboratory by an ELISA-based method and used for flow cytometry-based detection of specific T-cell responses by use of combinatorial encoded major histocompatibility (MHC) class I multimers. This procedure resulted in 127 (Paper I) and 32 (Paper II) confirmed HLA ligands, respectively, which we used for screening of the T-cell recognition within peripheral blood mononuclear cell samples from melanoma patients. As spontaneous tumor-specific T-cell responses tend to be of very low frequency and probably below the detection threshold of the method, we incorporated a T-cell enrichment step prior to the detection of these responses. Our screening of 39 melanoma patients resulted in 26 (17 different) T-cell responses against the common melanoma-associated antigens and 10 (8 different) T
Golden, Deborah; Elbaz-Luwisch, Freema
This paper examines some of the dilemmas that accompany the emergence of the personal voice in scholarly work, by taking a close, grounded look at the way in which these unfolded in a specific academic course. As part of the course, entitled "A cultural approach to the life cycle", students were asked to participate in a group exhibition in which…
Peces, R; Laurés, A S
Hepatitis B (HB) vaccine is effective in producing protection against HB virus infection, but the persistence of immunity remains largely unknown. Seventy-six hemodialysis (HD) patients (60 after primary HB vaccination and 16 with natural immunity) and 46 healthcare workers (32 after primary HB vaccination and 14 with natural immunity) were followed up for 10 years to evaluate the persistence of immunity. Ten years after vaccination, the analysis showed a lower seroconversion rate (38 vs. 75%, p < 0.001) in HD patients as compared with healthcare workers. In the follow-up period, the protective immunity developed through HB virus infection also showed a lower seroconversion rate (44 vs. 86%, p < 0.025) in HD patients as compared with healthcare workers. To assess the status of immunologic memory, we administered a booster dose of HB vaccine 3-12 years (mean 6.7 +/- 0.6 years) after primary vaccination in a selected group of 37 HD patients who presented a decline of their antibodies or were nonresponders. In another group of 12 healthcare workers who had a decline of their antibodies, we also administered a booster dose of HB vaccine 5-8 years (mean 5.8 +/- 0.3 years) after primary vaccination. Nineteen of the 37 HD patients (51%) presented an anamnestic response to the booster dose, and 15 of these (40%) were high responders. All of the healthcare workers responded to the booster dose with a high antibody response. We conclude that patients undergoing HD not only have lower rates of immunization to HB than healthy adults, but also that these are frequently transient. Booster doses after a primary course of vaccine are effective in about the half of HD patients who presented a decline of their antibodies or were nonresponders but whether they are necessary is unclear. The majority of healthcare workers continue to have high levels of protective HBs antibody for at least 10 years and routine boosters are not required.
Sprung, Carl N; Forrester, Helen B; Siva, Shankar; Martin, Olga A
Radiotherapy is a major modality of cancer treatment responsible for a large proportion of cancer that is cured. Radiation exposure induces an inflammatory response which can be influenced by genetic, epigenetic, tumour, health and other factors which can lead to very different treatment outcomes between individuals. Molecules involved in the immunological response provide excellent potential biomarkers for the prediction of radiation-induced toxicity. The known molecular and cellular immunological responses in relation to radiation and the potential to improve cancer treatment are presented in this review. In particular, immunological biomarkers of radiation-induced fibrosis and pneumonitis in cancer radiotherapy patients are discussed.
Cortesina, G; De Stefani, A; Galeazzi, E; Bussi, M; Giordano, C; Cavallo, G P; Jemma, C; Vai, S; Forni, G; Valente, G
Clinical, immunological, immunophenotypical, pathological and molecular biological studies were performed on tumor infiltrating lymphocytes (TIL) and lymph node lymphocytes (LN-ly) of 8 patients with squamous cell carcinoma of the oral cavity and oropharynx treated with 10 daily locoregional injections of low doses of IL-2 before surgery. No complications were seen during or after surgery. In 3 cases the LN-ly showed a moderate LAK activity, higher in the LN-ly omolateral to the tumor and near the IL-2 injection site; in 2 of these 3 patients a good LAK activity was induced after 6-day culture with IL-2. The LN-ly derived from nodes next to the tumor showed a decreased NK activity and proliferative ability both in basal conditions and after in vitro lymphokine challenging. LN-ly of 2 IL-2 treated patients showed high levels of mRNA encoding for IL-2-R, while it was absent in 2 untreated cases. Immunophenotypical studies on TIL showed statistically improved levels of CD25+ and LAK1+ cells in treated cases. Clusters of CD11c+ (macrophages) cells were seen close to the neoplastic sheets.
Chimenti, Ruth L; Flemister, A Samuel; Tome, Joshua; McMahon, James M; Houck, Jeff R
Study Design Controlled laboratory study; cross-sectional. Background Little is known about ankle range of motion (ROM) and strength among patients with insertional Achilles tendinopathy (IAT) and whether limited ankle ROM and plantar flexor weakness impact IAT symptom severity. Objectives The purposes of the study were (1) to examine whether participants with IAT exhibit limited non-weight-bearing dorsiflexion ROM, reduced plantar flexor strength, and/or altered ankle biomechanics during stair ascent; and (2) to determine which impairments are associated with symptom severity. Methods Participants included 20 patients with unilateral IAT (mean ± SD age, 59 ± 8 years; 55% female) and 20 individuals without tendinopathy (age, 58.2 ± 8.5 years; 55% female). A dynamometer was used to measure non-weight-bearing ROM and isometric plantar flexor strength. Three-dimensional motion analysis was used to quantify ankle biomechanics during stair ascent. End-range dorsiflexion was quantified as the percentage of non-weight-bearing dorsiflexion used during stair ascent. Group differences were compared using 2-way and 1-way analyses of variance. Pearson correlations were used to test for associations among dependent variables and symptom severity. Results Groups differed in ankle biomechanics, but not non-weight-bearing ROM or strength. During stair ascent, the IAT group used greater end-range dorsiflexion (P = .03), less plantar flexion (P = .02), and lower peak ankle plantar flexor power (P = .01) than the control group. Higher end-range dorsiflexion and lower ankle power during stair ascent were associated with greater symptom severity (P<.05). Conclusion Patients with IAT do not experience restrictions in non-weight-bearing dorsiflexion ROM or isometric plantar flexor strength. However, altered ankle biomechanics during stair ascent were linked with greater symptom severity and likely contribute to decreased function. J Orthop Sports Phys Ther 2016;46(12):1051-1060. Epub
A TSP from NASA Tech Briefs provided the solution to an electrical problem at a Florida museum. When a model train would not start without a jerk, a Marshall Space Flight Center development called pulse width control was adapted. The new circuit enables the train to start smoothly and reduces construction and maintenance costs. The same technology is also used in another hands-on exhibit. Applications of other TSPs are anticipated.
Celik, Gülfem; Bakirtas, Arzu; Sackesen, Cansin; Reisli, Ismail; Tuncer, Ayfer
Allergic diseases constitute a significant health problem in Turkey. According to a recent multicenter study, which used the ISAAC questionnaire, the mean prevalence of wheezing, rhinoconjunctivitis, and eczema in 10-yr-old school children during the past year was 15.8%, 23.5%, and 8.1%, respectively. A healthcare level system, regulated by Ministry of Health, is available in Turkey. Pediatric allergists and pediatric immunologists provide patient care at the tertiary level. Currently, 48 centers deliver care for allergic and immunologic diseases in children. There are 136 pediatric and 61 adult allergists/immunologists. Although the number of allergy/clinical immunology specialists is limited, these centers are capable of delivering many of the procedures required for the proper management and diagnosis of allergy/immunology. Pediatric allergy and/or immunology is a subspecialty lasting 3 yr and follows a 4-yr pediatric specialist training. Fellow training involves gaining knowledge in basic and clinical allergy and immunology as well as the performance and interpretation of laboratory procedures in the field of allergy and clinical immunology. The Turkish National Society of Allergy and Clinical Immunology (TNSACI) was officially established in 1989 and currently has 356 members. The society organizes a national congress annually and winter schools for fellowship training as well as training courses for patients and their relatives. TNSACI also has a strong representation in European Academy of Allergy and Clinical Immunology (EAACI) and European Society for Immunodeficiencies (ESID) through its participation in the executive committee, consensus reports, and initiatives in the diagnosis of allergic and immunologic diseases of children. The 30th Congress of the EAACI is also due to be held in Istanbul, Turkey, between June 11 and 15, 2011.
Claman, Henry N.
Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)
Sologuren, Ithaisa; Boisson-Dupuis, Stéphanie; Pestano, Jose; Vincent, Quentin Benoit; Fernández-Pérez, Leandro; Chapgier, Ariane; Cárdenes, María; Feinberg, Jacqueline; García-Laorden, M. Isabel; Picard, Capucine; Santiago, Esther; Kong, Xiaofei; Jannière, Lucile; Colino, Elena; Herrera-Ramos, Estefanía; Francés, Adela; Navarrete, Carmen; Blanche, Stéphane; Faria, Emilia; Remiszewski, Paweł; Cordeiro, Ana; Freeman, Alexandra; Holland, Steven; Abarca, Katia; Valerón-Lemaur, Mónica; Gonçalo-Marques, José; Silveira, Luisa; García-Castellano, José Manuel; Caminero, José; Pérez-Arellano, José Luis; Bustamante, Jacinta; Abel, Laurent; Casanova, Jean-Laurent; Rodríguez-Gallego, Carlos
We report a series of 14 patients from 11 kindreds with recessive partial (RP)-interferon (IFN)-γR1 deficiency. The I87T mutation was found in nine homozygous patients from Chile, Portugal and Poland, and the V63G mutation was found in five homozygous patients from the Canary Islands. Founder effects accounted for the recurrence of both mutations. The most recent common ancestors of the patients with the I87T and V63G mutations probably lived 1600 (875–2950) and 500 (200–1275) years ago, respectively. The two alleles confer phenotypes that are similar but differ in terms of IFN-γR1 levels and residual response to IFN-γ. The patients suffered from bacillus Calmette-Guérin-osis (n= 6), environmental mycobacteriosis (n= 6) or tuberculosis (n= 1). One patient did not suffer from mycobacterial infections but had disseminated salmonellosis, which was also present in two other patients. Age at onset of the first environmental mycobacterial disease differed widely between patients, with a mean value of 11.25 ± 9.13 years. Thirteen patients survived until the age of 14.82 ± 11.2 years, and one patient died at the age of 7 years, 9 days after the diagnosis of long-term Mycobacterium avium infection and the initiation of antimycobacterial treatment. Up to 10 patients are currently free of infection with no prophylaxis. The clinical heterogeneity of the 14 patients was not clearly related to either IFNGR1 genotype or the resulting cellular phenotype. RP-IFN-γR1 deficiency is, thus, more common than initially thought and should be considered in both children and adults with mild or severe mycobacterial diseases. PMID:21266457
Martin, S F
Contact allergy is a skin disease that is caused by the reaction of the immune system to low molecular weight chemicals. A hallmark of contact allergens is their chemical reactivity, which is not exhibited by toxic irritants. Covalent binding of contact allergens to or complex formation with proteins is essential for the activation of the immune system. As a consequence antigenic epitopes are formed, which are recognized by contact allergen-specific T cells. The generation of effector and memory T cells causes the high antigen specificity and the repeated antigen-specific skin reaction of contact allergy. New findings reveal that the less specific reaction of the innate immune system to contact allergens closely resembles the reaction to an infection. Therefore, contact allergy can be viewed as an immunologic misunderstanding since the skin contact with chemical allergens is interpreted as an infection. The growing understanding of the molecular and cellular pathologic mechanisms of contact allergy can aid the development of specific therapies and of in vitro alternatives to animal testing for the identification of contact allergens.
Sung, Cynthia; Wei, Yuan; Watanabe, Satoru; Lee, How Sung; Khoo, Yok Moi; Fan, Lu; Rathore, Abhay P. S.; Chan, Kitti Wing-Ki; Choy, Milly M.; Kamaraj, Uma S.; Sessions, October M.; Aw, Pauline; de Sessions, Paola F.; Lee, Bernett; Connolly, John E.; Hibberd, Martin L.; Vijaykrishna, Dhanasekaran; Wijaya, Limin; Ooi, Eng Eong; Low, Jenny Guek-Hong
CELADEN was a randomized placebo-controlled trial of 50 patients with confirmed dengue fever to evaluate the efficacy and safety of celgosivir (A study registered at ClinicalTrials.gov, number NCT01619969). Celgosivir was given as a 400 mg loading dose and 200 mg bid (twice a day) over 5 days. Replication competent virus was measured by plaque assay and compared to reverse transcription quantitative PCR (qPCR) of viral RNA. Pharmacokinetics (PK) correlations with viremia, immunological profiling, next generation sequence (NGS) analysis and hematological data were evaluated as exploratory endpoints here to identify possible signals of pharmacological activity. Viremia by plaque assay strongly correlated with qPCR during the first four days. Immunological profiling demonstrated a qualitative shift in T helper cell profile during the course of infection. NGS analysis did not reveal any prominent signature that could be associated with drug treatment; however the phylogenetic spread of patients’ isolates underlines the importance of strain variability that may potentially confound interpretation of dengue drug trials conducted during different outbreaks and in different countries. Celgosivir rapidly converted to castanospermine (Cast) with mean peak and trough concentrations of 5727 ng/mL (30.2 μM) and 430 ng/mL (2.3 μM), respectively and cleared with a half-life of 2.5 (± 0.6) hr. Mean viral log reduction between day 2 and 4 (VLR2-4) was significantly greater in secondary dengue than primary dengue (p = 0.002). VLR2-4 did not correlate with drug AUC but showed a trend of greater response with increasing Cmin. PK modeling identified dosing regimens predicted to achieve 2.4 to 4.5 times higher Cmin. than in the CELADEN trial for only 13% to 33% increase in overall dose. A small, non-statistical trend towards better outcome on platelet nadir and difference between maximum and minimum hematocrit was observed in celgosivir-treated patients with secondary dengue
The National Data Buoy Center (NDBC) at the John C. Stennis Space Center has exhibits located in front of the Visitors Center. These boat-shaped buoys are moored in areas of the ocean that experience hostile environmental conditions. The instruments installed gather information and relay it to the National Weather Service by satellite. Nomad buoys are 20 feet long and weigh 13,900 pounds. They provide information on wind speed and direction, humidity levels, air and sea surface temperature and air pressure. U.S. Coast Guard ships transport buoys to their mooring sites.
Fabiani, J E; Avigliano, A; Dupont, J C; Fabiana, J E
Since the detection of the first patient with hereditary angioedema (HA) in 1978, 88 new patients belonging to 16 families have been referred to our clinic. Eighty patients had Type I disease, 5 Type II, and 3 Type III (secondary). We describe the clinical onset, frequent complications, diagnostic tests of the complement system, and abnormalities of the coagulation pathway linked to complement activation. Particular attention was paid to family members who could present succedaneum symptoms. The results of danazole and other therapies and protective and preventive treatment for surgery also are discussed.
Immunologic laboratory tests serve critical roles in the care of patients with various rheumatic diseases. These tests can provide relevant information of rheumatic diseases based on their immunopathophysiological condition. Although immunologic laboratory tests are quite useful for the determination of diagnosis and the estimation of disease activity, organ involvement and prognosis, they are frequently misused and resulted in an inappropriate diagnosis and treatment. Appropriate use of immunologic laboratory tests and accurate clinical interpretation of the test results can prevent false diagnosis and unnecessary treatment. In order to improve clinical care of patients with rheumatic diseases, clinicians caring patients with rheumatic disease should recognize meanings, characteristics and limitations of each result of immunologic laboratory testing. This article reviewed recent advances in immunologic laboratory testing such as antinuclear antibody, anti-DNA antibody and anti-neutrophil cytoplasmic antibody, and introduced guidelines for these testing. These guidelines based on evidences of EBM may contribute to the appropriate use of immunologic laboratory tests for rheumatic diseases.
Smit, M J; Beelen, R H; Eijsbouts, Q A; Meijer, S; Cuesta, M A
Immunological response to surgical trauma may be protected during laparoscopic surgery. A less surgical trauma, in comparison with conventional surgery, may explained these important advantages. Plasma and macrophages studies have demonstrated that laparoscopic cholecystectomy causes less depression of cell mediated immunity than open cholecystectomy. What will be the impact of this immunological protection in laparoscopic advanced and oncological surgery? Experimental studies have showed that laparoscopic techniques in advanced and oncological surgery may have important advantages concerning the "preservation of the immune status" of the patient. That will imply in the future a lower percentage of infections, local recurrence and even a lower percentage of distant metastases. On the other hand, the appearance of tumor implants in the port sites after laparoscopic resection for cancer is a significant drawback of this procedure. Proper investigations have to be carried out in order to find the cause and the solution of this dilemma.
Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il; Yoo, Young-Choon; Byun, Myung-Woo; Hwang, Young-Jeong; Lee, Ju-Woon
Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-α and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX ( P<0.05). In vivo study on the tumor mass inhibition, gamma-irradiated DOX showed a considerable inhibition of tumor mass and this effect was statistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.
Dustin, Michael L.
The molecular interactions underlying regulation of the immune response take place in a nano-scale gap between T cells and antigen presenting cells, termed the immunological synapse. If these interactions are regulated appropriately, the host is defended against a wide range of pathogens and deranged host cells. If these interactions are dis-regulated, the host is susceptible to pathogens or tumor escape at one extreme and autoimmunity at the other. Treatments targeting the synapse have helped to establish immunotherapy as a mainstream element in cancer treatment. This Masters primer will cover the basics of the immunological synapse and some of the applications to tumor immunology. PMID:25367977
Song, Jing; Huang, Yi-Fei; Zhang, Wen-Jing; Chen, Xiao-Fei; Guo, Yu-Mian
Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation. PMID:27275439
Lévy, Romain; Okada, Satoshi; Béziat, Vivien; Moriya, Kunihiko; Liu, Caini; Chai, Louis Yi Ann; Migaud, Mélanie; Hauck, Fabian; Al Ali, Amein; Cyrus, Cyril; Vatte, Chittibabu; Patiroglu, Turkan; Unal, Ekrem; Ferneiny, Marie; Hyakuna, Nobuyuki; Nepesov, Serdar; Oleastro, Matias; Ikinciogullari, Aydan; Dogu, Figen; Asano, Takaki; Ohara, Osamu; Yun, Ling; Della Mina, Erika; Bronnimann, Didier; Itan, Yuval; Gothe, Florian; Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Tahuil, Natalia; Aytekin, Caner; Salhi, Aicha; Al Muhsen, Saleh; Kobayashi, Masao; Toubiana, Julie; Abel, Laurent; Li, Xiaoxia; Camcioglu, Yildiz; Celmeli, Fatih; Klein, Christoph; AlKhater, Suzan A; Casanova, Jean-Laurent; Puel, Anne
Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface.
Sabado, Rachel Lubong; Pavlick, Anna; Gnjatic, Sacha; Cruz, Crystal M; Vengco, Isabelita; Hasan, Farah; Spadaccia, Meredith; Darvishian, Farbod; Chiriboga, Luis; Holman, Rose Marie; Escalon, Juliet; Muren, Caroline; Escano, Crystal; Yepes, Ethel; Sharpe, Dunbar; Vasilakos, John P; Rolnitzsky, Linda; Goldberg, Judith D; Mandeli, John; Adams, Sylvia; Jungbluth, Achim; Pan, Linda; Venhaus, Ralph; Ott, Patrick A; Bhardwaj, Nina
The Toll-like receptor (TLR) 7/8 agonist resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide (Seppic) with or without resiquimod in patients with high-risk melanoma. In part I of the study, patients received 100 μg of full-length NY-ESO-1 protein emulsified in 1.25 mL of Montanide (day 1) followed by topical application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle. In part II, patients were randomized to receive 100-μg NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel [(arm A; n = 8) or 1,000 mg of 0.2% resiquimod gel (arm B; n = 12)] using the dosing regimen established in part I. The vaccine regimens were generally well tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4⁺ T-cell responses. CD8⁺ T-cell responses were only seen in 3 of 12 patients in arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8⁺ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical resiquimod is safe and induces both antibody and CD4⁺ T-cell responses in the majority of patients; the small proportion of CD8⁺ T-cell responses suggests that the addition of topical resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8⁺ T-cell responses.
Zandvoort, A; van der Geld, Y M; Jonker, M R; Noordhoek, J A; Vos, J T W M; Wesseling, J; Kauffman, H F; Timens, W; Postma, D S
Chronic obstructive pulmonary disease (COPD) is characterised by destruction of extracellular matrix (ECM) in parenchymal areas, whereas the bronchial walls can show fibrosis. In addition, an extensive inflammatory process is observed. CD8+ T-cells, located throughout the lung, and epithelial cells in centrally located airways, produce cytokines involved in the inflammatory process. These cytokines may influence the present fibroblasts, the key effectors in the defective ECM repair and maintenance in COPD. The current authors explored the effects of the cytokine microenvironment on cell-cell interaction gene expression in pulmonary fibroblasts of controls (n = 6), and Global Initiative for Chronic Obstructive Lung Disease stage II (n = 7) and stage IV (n = 7) COPD patients. The current authors simulated the in vivo microenvironment using supernatants of CD3/CD28 stimulated CD8+ T-cells isolated from peripheral blood of COPD patients, supernatant of a bronchial-epithelial cell line, or a combination of both. The present data show that fibroblasts of chronic obstructive pulmonary disease patients display an altered response to the cytokine microenvironment, depending on both the disease stage and the central or peripheral location in the lung. Especially adhesion-related genes are upregulated in fibroblasts of chronic obstructive pulmonary disease patients, which can indicate a more pronounced role of fibroblasts in the inflammatory process in chronic obstructive pulmonary disease, possibly resulting in reduced function as effectors of extracellular matrix repair.
Godon, O; Fontaine, H; Kahi, S; Meritet, Jf; Scott-Algara, D; Pol, S; Michel, Ml; Bourgine, M
A substudy of a phase I/II, prospective, multicenter clinical trial was carried out to investigate the potential benefit of therapeutic vaccination on hepatitis B e antigen-negative patients with chronic hepatitis B (CHB), treated efficiently with analogues. Patients were randomized in 2 arms, one receiving a hepatitis B virus (HBV) envelope DNA vaccine, and one without vaccination. At baseline, HBV-specific interferon (IFN)-γ-producing T cells were detected in both groups after in vitro expansion of peripheral blood mononuclear cells. Vaccine-specific responses remained stable in the vaccine group, whereas in the control group the percentage of patients with HBV-specific IFN-γ-producing T cells decreased over time. The vaccine-specific cytokine-producing T cells were mostly polyfunctional CD4(+) T cells, and the proportion of triple cytokine-producer T cells was boosted after DNA injections. However, these T-cell responses did not impact on HBV reactivation after stopping analogue treatment. Importantly, before cessation of treatment serum hepatitis B surface antigen (HBsAg) titers were significantly associated with DNA or HBsAg clearance. Therapeutic vaccination in CHB patients with persistent suppression of HBV replication led to the persistence of T-cell responses, but further improvements should be searched for to control infection after treatment discontinuation.
Serhat Inaloz, H; Ozturk, Savas; Akcali, Cenk; Kirtak, Necmettin; Tarakcioglu, Mehmet
The present study aimed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin (CsA) treatment in patients with severe chronic idiopathic urticaria (CIU) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU. Twenty-seven CIU patients and 24 healthy control subjects were included in the study. The autologous serum skin test (ASST) for autoantibodies and urticaria activity scoring (UAS) were measured for the evaluation of the clinical severity and the response to therapy, and the serum levels of interleukin (IL)-6, IL-8, IL-2 receptor, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-5 were measured. The mean UAS score was 32.07 +/- 7.05 and 6.22 +/- 3.84 before and after CsA treatment, respectively. The serum IL-2 receptor, TNF-alpha and IL-5 levels of patients before CsA treatment were statistically higher than those of the control group (P = 0.001), and after 4 weeks of CsA therapy the mean IL-2R, TNF-alpha and IL-5 levels were significantly decreased. The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients. Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting.
Significant prospects in research on the pathology of schizophrenia are revealed in connection with the use of autoimmune reactions in clinical...practice. Important to this problem is the question concerning the presence of autoantibodies in the blood of patients with schizophrenia . It is necessary
Turnock, Amy; Calder, Philip C.; West, Annette L.; Izzard, Mark; Morton, Randall P.; Plank, Lindsay D.
Limited work is available on the benefits of nutritional support enriched with arginine and n-3 fatty acids in surgical patients with head and neck cancer, particularly if well-nourished. We conducted a pilot study in these patients to examine effects on inflammatory markers and clinical outcome. Patients scheduled for radical resection of the oral cavity were randomised to 5 day preoperative and 5 day postoperative Impact® (IMN, n = 4), or no preoperative supplementary nutrition and Isosource® postoperatively (STD, n = 4). Plasma fatty acids, C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were measured at baseline, day of surgery and on postoperative days (POD) 2, 4 and 10. Postoperative complications were recorded. The (eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid ratio was significantly higher in IMN patients on POD 2, 4 and 10 (P < 0.01). While not statistically significant, CRP, TNF-α, and IL-6 concentrations were higher in the STD group on POD2 while IL-10 was lower. Median length of stay was 10 (range 10–43) days in the IMN group and 21.5 (7–24) days in the STD group. Five complications were seen in the STD group and two in the IMN group. The results support the need for a larger trial focusing on clinical outcome. PMID:23571650
Picat, Marie-Quitterie; Pellegrin, Isabelle; Bitard, Juliette; Wittkop, Linda; Proust-Lima, Cécile; Liquet, Benoît; Moreau, Jean-François; Bonnet, Fabrice; Blanco, Patrick; Thiébaut, Rodolphe
Objectives To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes. Design Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France. Methods Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years. CIA was defined by the percentage of HLA-DR+/CD38+ among CD8+T-cells. Integrative analyses were performed using structural equation modelling (SEM). Results The main analysis was performed in 57 HLA-A*0201 positive patients, due to availability of percentages of actin-, vimentin-, lamin-specific CD8+T-cells (HLA-A2-restricted tests) to further characterize autoimmune response. Cytomegalovirus-induced response was assessed by Quantiferon and pp-65 ELISPOT. SEM revealed a direct effect of cytomegalovirus-induced response on CIA (standardized estimate βstd = 0.56, p-value = 0.0004). The effect of autoimmune-induced response on CIA was indirect through alpha-interferon pathway, assessed by expression levels of 5 alpha-interferon-stimulated genes ADAR, ISG15, IFIT1, Mx1 and OAS1 (effect of autoimmune response on alpha-interferon: βstd = 0.36, p-value = 0.0401; effect of alpha-interferon on CIA: βstd = 0.39, p-value = 0.0044). There was no direct effect of autoimmune-induced response on CIA (p-value = 0.3169). Microbial translocation as measured by 16SrDNA and sCD14 in plasma was not associated with CIA. Results were consistent in 142 patients in whom cytomegalovirus and auto-immunity responses were measured by Quantiferon and anti-nuclear antibodies, respectively. All analyses performed in HLA-A*0201 positive patients and in the overall population revealed a significant effect
Pertovaara, M; Pukkala, E; Laippala, P; Miettinen, A; Pasternack, A
OBJECTIVE—To evaluate outcome in a cohort of Finnish patients with primary Sjögren's syndrome (pSS). METHODS—Clinical and laboratory data from the time of diagnosis and follow up were collected from 110 patients with pSS (107 women, three men) diagnosed in 1977-1992 in central Finland. The standardised incidence ratio for cancers was determined as the ratio of the observed number of cases to the expected number based on regional population rates. Eighty one of the 93 patients still alive were interviewed, and clinical and laboratory examinations performed in 1994-1997. RESULTS—The mean (SD) erythrocyte sedimentation rate (33 (22) v 45 (28) mm/1st h), serum IgG (18.8 (7.4) v 22.5 (8.5) g/l), and serum IgM (1.6 (1.1) v 2.0 (1.2) g/l) at the control visit were significantly (p<0.0001) lower than those at baseline. A similar change was observed in a subgroup of patients never treated with glucocorticosteroids or disease modifying antirheumatic drugs. Three non-Hodgkin's lymphomas were diagnosed (standardised incidence ratio 13; 95% confidence interval 2.7 to 38). In a logistic regression model, the patients with pSS with subsequent lymphoma were found to have higher baseline levels of serum β2 microglobulin than the others (odds ratio 1.9; 95% confidence interval 1.1 to 3.4). CONCLUSION—The results suggest that mean concentrations of serum IgG and IgM in patients with pSS decline with time, possibly reflecting diminishing inflammatory activity. As in previous studies, the incidence of non-Hodgkin's lymphomas in this cohort of patients with pSS was significantly higher than in the reference population. PMID:11302868
Abate, E; Elias, D; Getachew, A; Alemu, S; Diro, E; Britton, S; Aseffa, A; Stendahl, O; Schön, T
Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6±2.9 for albendazole versus 5.9±2.5 for placebo, P=0.59). The albendazole-treated group showed a decline in eosinophil cells (P=0.001) and IL-10 (P=0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2±8.5 kg versus 8.2±8.7 kg, P=0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation.
Smith, Benjamin; Sigal, Ian R; Grande, Daniel A
The intrinsic regenerative capacity of avascular cartilage is limited. Cartilage injuries result in chronic, non-healing lesions requiring surgical management. Frequently, these surgical techniques make use of allogeneic cells and tissues. This review discusses the immune status of these materials. Cartilage allografts, often used in orthopedic and plastic surgeries, have rarely provoked a significant immune response. In whole cartilage transplants, the dense matrix produced by chondrocytes inhibits lymphocyte migration, preventing immune detection rendering them "antigen sequestered." It is unclear whether isolated chondrocytes are immune-privileged; chondrocytes express immune inhibitory B7 molecules, indicating that they have some ability to modulate immune reactions. Allogeneic cartilage grafts often involve a bony portion often retaining immunogenic cells and proteins-to facilitate good surgical attachment and concern that this may enhance inflammation and immune rejection. However, studies of failed cartilage grafts have not found immune responses to be a contributing factor. Meniscus allografts, which also retain a bony portion, raise similar concerns as cartilage allografts. Despite this, the plugs improved patient outcomes, indicating that the immunological effects were not clinically significant. Finally, allogeneic mesenchymal stromal cells (MSCs) also are being investigated as a treatment for cartilage damage. MSCs have been demonstrated to have unique immunomodulatory properties including their ability to reduce immune cell infiltration and to modulate inflammation. In summary, the immunogenic properties of cartilage vary with the type of allograft used: Cartilage allografts demonstrate active immune-suppressive mechanisms as evidenced by lack of allograft rejection, while MSC allografts appear to be safe for transplantation.
Bajor, David L.; Xu, Xiaowei; Torigian, Drew A.; Mick, Rosemarie; Garcia, Laura R.; Richman, Lee P.; Desmarais, Cindy; Nathanson, Katherine L.; Schuchter, Lynn M.; Kalos, Michael; Vonderheide, Robert H.
Direct immune activation via agonistic monoclonal antibodies (mAb) is a potentially complementary approach to therapeutic blockade of inhibitory immune receptors in cancer. Here, we provide genetic analysis of the immunological consequences associated with the use of an agonistic CD40 mAb in a patient with metastatic melanoma who responded, underwent a single metastasectomy, and then achieved a complete remission ongoing for more than 9 years after starting therapy. Tumor microenvironment after immunotherapy was associated with pro-inflammatory modulations and emergence of a de novo T-cell repertoire as detected by next-generation sequencing of T-cell receptors (TCR) in the tumor and blood. The de-novo T-cell repertoire identified in the post-treatment metastasectomy sample was also present – and in some cases expanded – in the circulation years after completion of therapy. Comprehensive study of this “exceptional responder” highlights the emerging potential of direct immune agonists in the next wave of cancer immunotherapies and a potential role for TCR deep sequencing in cancer immune assessment. PMID:25252722
Zhang, Lian-Bin; Wang, Bo; Wang, Xu-Yi; Zhang, Liang
In this study, we compared the effects of video-assisted thoracic surgery (VATS) and traditional open surgery (TOS) on immune system functioning in non-small cell lung cancer (NSCLC) patients. We enrolled 122 NSCLC patients in this study. The patients were randomly divided into VATS group (n = 61) and TOS group (n = 61). Plasma DNA concentration was analyzed by fluorescence quantitative PCR. Automatic blood analyzer was used to measure WBC-C, and immune nephelometry was employed to assess hs-CRP concentrations. The number of CD3+T, CD4+T and CD8+T lymphocytes in peripheral blood was estimated by flow cytometry. ELISA was used to quantify the levels of IGFBP-3, VEGF and IL-6. Compared to the TOS group, surgery-related blood loss and pain score on day 1 after surgery were lower in VATS group. After surgery, the out-of-bed activity occurred earlier and in-hospital stays were shorter in the VATS group compared to the TOS group. Plasma free DNA concentration of VATS group patients at first, third and fifth days after surgery was lower than that of the TOS group. WBC-C and hs-CRP levels were lower in the VATS group at each time point after surgery. The number of CD3+T, CD4+T, CD8+T lymphocytes and CD4+/CD8+ was lower in the TOS group compared to VATS group. Plasma IGFBP-3, VEGF and IL-6 levels were significantly lower in VATS group compared to the TOS group. Finally, incidence of complications in the VATS group was dramatically lower than the TOS group (all P < 0.05). Based on our findings, compared to TOS, VATS significantly decreased the incidence of acute-phase reaction and lowered the inhibition of immune functions after surgery.
Burastero, S E; Mistrello, G; Paolucci, C; Breda, D; Roncarolo, D; Zanotta, S; Falagiani, P
Sublingual immunotherapy is safe and efficacious in the treatment of patients with allergic rhinitis. The clinical and biological efficacy of modified allergens (allergoids) has not been fully clarified. We investigated in birch allergic patients the effect of a pre-co-seasonal sublingual immunotherapy regimen with a modified allergen extract on clinical parameters and on T cell proliferation and regulatory cytokine production (IL-10, TGF-beta). We found that during the birch pollen season symptoms and drug usage scores were 30 and 40 percent improved, respectively, in treated versus control subjects (p<0.0001 for both comparisons) whereas well days were 23.5 (33 percent) versus 16.9 (23 percent) (p=0.0024), respectively. Bet v 1 allergen specific proliferation decreased (p = 0.0010), whereas IL-10 transcription increased (p=0.0010) in treated, but not in control patients. Moreover, TGF-beta transcription was increased, although not significantly (p=0.066), following immunotherapy. Thus, sublingual immunotherapy with modified allergen in birch-allergic subjects was safe, clinically efficacious and associated with the reduction of allergen-specific proliferation and with the increased production of the IL-10 regulatory cytokine.
Keogan, M T
Patients presenting with recurrent orogenital ulcers may have complex aphthosis, Behçet's disease, secondary complex aphthosis (e.g. Reiter's syndrome, Crohn's disease, cyclical neutropenia) or non-aphthous disease (including bullous disorders, erythema multiforme, erosive lichen planus). Behçet's syndrome is a multi-system vasculitis of unknown aetiology for which there is no diagnostic test. Diagnosis is based on agreed clinical criteria that require recurrent oral ulcers and two of the following: recurrent genital ulcers, ocular inflammation, defined skin lesions and pathergy. The condition can present with a variety of symptoms, hence a high index of suspicion is necessary. The most common presentation is with recurrent mouth ulcers, often with genital ulcers; however, it may take some years before diagnostic criteria are met. All patients with idiopathic orogenital ulcers should be kept under review, with periodic focused assessment to detect evolution into Behçet's disease. There is often a delay of several years between patients fulfilling diagnostic criteria and a diagnosis being made, which may contribute to the morbidity of this condition. Despite considerable research effort, the aetiology and pathogenesis of this condition remains enigmatic. PMID:19210521
Wong, Monica TY; Schölvinck, Elisabeth H; Lambeck, Annechien JA; van Ravenswaaij-Arts, Conny MA
CHARGE syndrome is caused by a dominant variant in the CHD7 gene. Multiple organ systems can be affected because of haploinsufficiency of CHD7 during embryonic development. CHARGE syndrome shares many clinical features with the 22q11.2 deletion syndrome. Immunological abnormalities have been described, but are generally given little attention in studies on CHARGE syndrome. However, structured information on immunological abnormalities in CHARGE patients is necessary to develop optimal guidelines for diagnosis, treatment and follow-up in these patients. Here, we provide an overview of the current literature on immunological abnormalities in CHARGE syndrome. We also explore immunological abnormalities in comparable multiple congenital anomaly syndromes to identify common immunological phenotypes and genetic pathways that might regulate the immune system. Finally, we aim to identify gaps in our knowledge on the immunological aspects in CHARGE syndrome that need further study. PMID:25689927
Davidson, J K; DeBra, D W
The efficacy of sulfated beef insulin for plasma glucose control in 35 patients with immunologic insulin resistance was studied. Patients were on a mean dose of 550 U./day (range 200--2,000) of U-500 regular beef insulin. Mean maximum 125I-insulin-binding capacity was 191 mU./ml. serum (range 13--1,080). Mean in vivo half-life (T 1/2) of 125I-regular beef insulin was 614 minutes (range 114--1,300), as against a mean T 1/2 of 13.9 minutes (range 11.8--16.5) in normal controls. Treatment was successful in 34 patients and unsuccessful in one with lipoatrophic diabetes. The mean initial dose of sulfated insulin was 89 U./day (range 15--400) and at three months was 66 U./day (range 20--400). Twenty-eight patients who responded and survived have been on sulfated insulin for a mean of 39 months (range 2-66) and are on a mean dose of 25 U./day (range 0--100). The mean maximum binding capacity fell to 9 mU./ml. (range 0--34) during therapy (p less than 0.01). Mean 125I-insulin T 1/2 fell from 614 to 249 minutes after sulfated insulin therapy (p less than 0.001). A comparative study of 15 patients on consecutive days showed a 35 sulfated insulin T 1/2 of 60 minutes (range 15--94) and a mean 125I-regular insulin T 1/2 of 246 minutes (range 62--560, p less than 0.001). These results indicate that sulfated insulin is less antigenic than regular beef insulin and combines less avidly with human antibodies to regular beef insulin. The response to sulfated insulin therapy was significantly better than the response reported by other investigators to pork insulin or to steroid therapy in similar patients.
Background HIV-infection results in damage and dysfunction of the gastrointestinal system. HIV enteropathy includes pronounced CD4+ T-cell loss, increased intestinal permeability, and microbial translocation that promotes systemic immune activation, which is implicated in disease progression. A synbiotic is the combination of probiotics and prebiotics that could improve gut barrier function. Our study goal was to determine whether the use of a synbiotic, probiotics or a prebiotic can recover immunological parameters in HIV-infected subjects through of a reduction of microbial translocation and pro-inflammatory cytokine production. Methods A randomized, double-blind controlled study was performed; twenty Antiretroviral treatment-naïve HIV-infected subjects were subgrouped and assigned to receive a synbiotic, probiotics, a prebiotic, or a placebo throughout 16 weeks. Results We had no reports of serious adverse-events. From baseline to week 16, the synbiotic group showed a reduction in bacterial DNA concentrations in plasma (p = 0.048). Moreover, the probiotic and synbiotic groups demonstrated a decrease in total bacterial load in feces (p = 0.05). The probiotic group exhibited a significant increment of beneficial bacteria load (such as Bifidobacterium; p = 0.05) and a decrease in harmful bacteria load (such as Clostridium; p = 0.063). In the synbiotic group, the CD4+ T-cells count increased (median: +102 cells/μL; p = 0.05) and the level of Interleukin 6 cytokine decreased significantly (p = 0.016). Conclusions Our study showed a significant increase in CD4+ T lymphocyte levels in the synbiotic group, which could delay the initiation of antiretroviral therapy and decrease costs in countries with limited resources. PMID:23101545
Ashman, R.F.; Kemp, J.D.; Yokoyama, W.M. ); Zhu, Z.B.; Cooper, M.D.; Volanakis, J.E. )
A family with 13 members included 2 subjects with selective IgA deficiency (IgA-D) and 3 subjects with common-variable immune deficiency (CVID), diseases which usually occur sporadically. Reciprocal combinations of B and T cells in vitro between one normal and two immune-deficient family members and normal subjects revealed that defective Ig synthesis was determined by the B cells, while the patient T cells functioned normally. Normal T helper and suppressor function was demonstrated even in one patient with CVID who developed a T-cell lymphoproliferative disorder associated with elevated IgM; this patient's B cells made only IgM in vitro. Immune deficiencies were inherited in this family in a pattern consistent with an autosomal dominant trait with incomplete penetrance. All the immune-deficient patients in this family possessed at least one copy of an MHC haplotype previously shown to be abnormally frequent in IgA-D and CVID: HLA-DQB1*0201, HLA-DR3, C4B-Sf, C4A-deleted, G11-15, Bf-0.4, C2-a, HSP70-7.5, TNF[alpha]-5, HLA-B8, and HLA-A1. The patient who developed the lymphoproliferative disorder was homozygous for this haplotype. Four immunologically normal members, one of whom was 80 years old, also possessed this MHC haplotype, indicating that its presence is not sufficient for disease expression. A small segment of another MHC haplotype associated with Ig deficiency in the population also occurred in this family, but it was not associated with immune deficiency. The presence of neutral amino acids at position 57 of DQ[beta], previously correlated with IgA-D, was associated with disease in this family approximately to the same degree reported previously in unrelated patients. Thus the expression of immunodeficiency in individuals bearing a disease-associated MHC haplotype appears to require either additional genes or an environmental trigger.
Solomon, Sunil Suhas; Ganesh, Aylur K.; Mehta, Shruti H.; Yepthomi, Tokugha; Balaji, Kavitha; Anand, Santhanam; Gallant, Joel E.; Solomon, Suniti
Background & objectives: Sustainability of free antiretroviral therapy (ART) roll out programmes in resource-limited settings is challenging given the need for lifelong therapy and lack of effective vaccine. This study was undertaken to compare treatment outcomes among HIV-infected patients enrolled in a graduated cost-recovery programme of ART delivery in Chennai, India. Methods: Financial status of patients accessing care at a tertiary care centre, YRGCARE, Chennai, was assessed using an economic survey; patients were distributed into tiers 1- 4 requiring them to pay 0, 50, 75 or 100 per cent of their medication costs, respectively. A total of 1754 participants (ART naïve = 244) were enrolled from February 2005-January 2008 with the following distribution: tier 1=371; tier 2=338; tier 3=693; tier 4=352. Linear regression models with generalized estimating equations were used to examine immunological response among patients across the four tiers. Results: Median age was 34; 73 per cent were male, and the majority were on nevirapine-based regimens. Median follow up was 11.1 months. The mean increase in CD4 cell count within the 1st three months of HAART was 50.3 cells/μl per month in tier 1. Compared to those in tier 1, persons in tiers 2, 3 and 4 had comparable increases (49.7, 57.0, and 50.9 cells/μl per month, respectively). Increases in subsequent periods (3-18 and >18 months) were also comparable across tiers. No differential CD4 gains across tiers were observed when the analysis was restricted to patients initiating ART under the GCR programme. Interpretation & conclusions: This ART delivery model was associated with significant CD4 gains with no observable difference by how much patients paid. Importantly, gains were comparable to those in other free rollout programmes. Additional cost-effectiveness analyses and mathematical modelling would be needed to determine whether such a delivery programme is a sustainable alternative to free ART programmes. PMID
Bartos, Ales; Pitha, Jirí
A peculiar clinical presentation characterized by the triad of opsoclonus,myoclonus and ataxia, mainly in a form of dysequilibrium, is usually associated with infectious or paraneoplastic processes. Serial cerebrospinal fluid (CSF) analysis in two patients with opsoclonus-myoclonus-dysequilibrium syndrome suggestive of viral encephalitis were performed from disease onset for up to 8 months. A cell count, cytology, total protein and glucose concentrations in CSF, the blood-CSF barrier function, intrathecal synthesis of immunoglobulins (Ig) in class M, G and A expressed as IgM, IgG and IgA indices and oligoclonal IgG bands were monitored. Cellular and humoral alterations in both patients were slight at the onset becoming more pronounced a month later. The kinetics of the CSF changes mirrored the subacute clinical deterioration and subsequent recovery. The delayed response in the CSF measures and the gradual clinical deterioration suggest the development of subacute brain inflammation. A mononuclear pleocytosis, including macrophages and plasma cells, increased within the first month and then normalized during the following weeks. Intrathecally synthesized IgM occurred only transiently after one month of illness, whereas intrathecal IgG production increased during the first month and persisted for at least eight months. An increasing number of oligoclonal IgG bands during the course, indicative of expanding local intrathecal synthesis, was noted. The dynamics of these CSF changes supports the hypothesis that opsoclonus-myoclonus syndrome is a post-infectious immune- mediated condition.
Schiffner, Rebecca; Kostev, Karel; Gothe, Holger
Background The increase in food intolerances poses a burgeoning problem in our society. Food intolerances not only lead to physical impairment of the individual patient but also result in a high socio-economic burden due to factors such as the treatment required as well as absenteeism. The present study aimed to explore whether lactose intolerant (LI) patients exhibit more frequent comorbidities than non-LI patients. Methods The study was conducted on a case-control basis and the results were determined using routine data analysis. Routine data from the IMS Disease Analyzer database were used for this purpose. A total of 6,758 data records were processed and analyzed. Results There were significant correlations between LI and the incidence of osteoporosis, changes in mental status, and the presence of additional food intolerances. Comparing 3,379 LI vs. 3,379 non-LI patients, 34.5% vs. 17.7% (P<0.0001) suffered from abdominal pain; 30.6% vs. 17.2% (P<0.0001) from gastrointestinal infections; and 20.9% vs. 16.0% (P=0.0053) from depression. Adjusted odds ratios (OR) were the highest for fructose intolerance (n=229 LI vs. n=7 non-LI; OR 31.06; P<0.0001), irritable bowel syndrome (n=247 LI vs. n=44 non-LI; OR 5.23; P<0.0001), and bloating (n=351 LI vs. n=68 non-LI; OR 4.94; P<0.0001). Conclusion The study confirms that LI should not be regarded as an isolated illness but considered a possible trigger for further diseases. Additional research is necessary to assert more precise statements. PMID:27065730
Orekhova, L Iu; Neĭzberg, D M; Stiuf, I Iu
Clinical, immunological and DNA diagnostic examinations of 101 patients with chronic generalized parodontitis and peptic ulcer have revealed similar features of immunological disorders of gastric and oral mucosa and the role of Helicobacter pylori.
Casanova, Jean-Laurent; Abel, Laurent; Quintana-Murci, Lluis
Human genetic studies are rarely conducted for immunological purposes. Instead, they are typically driven by medical and evolutionary goals, such as understanding the predisposition or resistance to infectious or inflammatory diseases, the pathogenesis of such diseases, and human evolution in the context of the long-standing relationships between humans and their commensal and environmental microbes. However, the dissection of these experiments of Nature has also led to major immunological advances. In this review, we draw on some of the immunological lessons learned in the three branches of human molecular genetics most relevant to immunology: clinical genetics, epidemiological genetics, and evolutionary genetics. We argue that human genetics has become a new frontier not only for timely studies of specific features of human immunity, but also for defining general principles of immunity. These studies teach us about immunity as it occurs under "natural" conditions, through the transition from the almost complete wilderness that existed worldwide until about a century ago to the current unevenly distributed medically shaped environment. Hygiene, vaccines, antibiotics, and surgery have considerably decreased the burden of infection, but these interventions have been available only recently, so have yet to have a major impact on patterns of genomic diversity, making it possible to carry out unbiased evolutionary studies at the population level. Clinical genetic studies of childhood phenotypes have not been blurred by modern medicine either. Instead, medical advances have actually facilitated such studies, by making it possible for children with life-threatening infections to survive. In addition, the prevention and treatment of infectious diseases have increased life expectancy at birth from ∼20 yr to ∼80 yr, providing unique opportunities to study the genetic basis of immunological phenomena against which there is no natural counterselection, such as
Smith, D.J.; Forrest, S.; Perelson, A.S.
The purpose of this paper is to show that immunological memory is an associative and robust memory that belongs to the class of sparse distributed memories. This class of memories derives its associative and robust nature by sparsely sampling the input space and distributing the data among many independent agents. Other members of this class include a model of the cerebellar cortex and Sparse Distributed Memory (SDM). First we present a simplified account of the immune response and immunological memory. Next we present SDM, and then we show the correlations between immunological memory and SDM. Finally, we show how associative recall in the immune response can be both beneficial and detrimental to the fitness of an individual.
Sakakibara, Mitsuru; Kanto, Tatsuya; Hayakawa, Michiyo; Kuroda, Shoko; Miyatake, Hideki; Itose, Ichiyo; Miyazaki, Masanori; Kakita, Naruyasu; Higashitani, Koyo; Matsubara, Tokuhiro; Hiramatsu, Naoki; Kasahara, Akinori; Takehara, Tetsuo; Hayashi, Norio
Dendritic cell (DC) vaccine has been used to treat patients with advanced colorectal cancer (CRC). The results of vaccine-induced clinical responses have not always been satisfactory partially because of DC incompetence. In order to evaluate the feasibility of novel mature DCs for therapeutic adjuvants against CRC, we conducted clinical trials with carcinoembryonic antigen (CEA) peptide-loaded DC quickly generated with a combination of OK432 (Streptococcuspyogenes preparation), prostanoid, and interferon-α (OPA-DC). In the ten patients enrolled in this study, the OPA-DC vaccine was well tolerated and administered four times every 2 weeks except for two patients, who were switched to other treatments due to disease progression. Among the eight evaluable patients, one displayed stable disease (SD), while the remaining seven showed progressive disease (PD). In the SD patient, natural killer (NK) cell frequency and cytolytic activity were increased. In the same patient, the frequency of CEA-specific cytotoxic T cells (CTLs) increased stepwise with repetitive vaccinations; however, most of the CTLs exhibited central memory phenotype. In those with PD, NK cells proliferated well regardless of failure of response, whereas CTLs failed to do so. We concluded that the OPA-DC vaccine is well tolerated and has immune-stimulatory capacity in patients with CRC. Additional modulation is needed to attain significant clinical impact.
Geller-Bernstein, Carmi; Etzioni, Amos
After the geographic and sociodemographic settings as well as the health care in Israel are briefly described, the scope of pediatric allergy and immunology in Israel is presented. This includes specific disorders commonly encountered, the environment that induces symptoms, the specialists who treat them, and the common challenges of patients, parents, doctors, and allied health personnel who collaborate to manage the maladies and patient care. Allergies usually affect some overall 15-20% of the pediatric population. The main allergens are inhaled, ingested, or injected (insects stings). Generally, the incidence of the various allergens affecting children in Israel, is similar to other parts of the Western world. Owing to the high consanguinity rate in the Israeli population, the prevalence of the various immunodeficiency conditions (in the adaptive as well as the innate system) is higher than that reported worldwide. Pediatric allergists/immunologists also treat autoimmune disorders affecting the pediatric group. Pediatric allergy and clinical immunology are not separate specialties. The 25 specialists who treat children with allergic/immunologic diseases have undergone a basic training in Pediatrics. They also received an additional 2-yr training in allergy and clinical immunology and then have to pass the board examinations. They work mainly in pediatric allergy units, in several hospitals that are affiliated to the five medical schools in the country. Aside from clinical work, most of the centers are also heavily involved in clinical and basic research in allergy and immunology.
Rijkers, Ger T; Damoiseaux, Jan G M C; Hooijkaas, Herbert
Medical immunology in The Netherlands is a laboratory specialism dealing with immunological analyses as well as pre- and post-analytical consultation to clinicians (clinical immunologists and other specialists) involved in patients with immune mediated diseases. The scope of medical immunology includes immunodeficiencies, autoimmune diseases, allergy, transfusion and transplantation immunology, and lymphoproliferative disorders plus the monitoring of these patients. The training, professional criteria, quality control of procedures and laboratories is well organized. As examples of the bridge function of medical immunology between laboratory (bench) and patient (bedside) the contribution of medical immunologists to diagnosis and treatment of primary immunodeficiency diseases (in particular: humoral immunodeficiencies) as well as autoantibodies (anti-citrullinated proteins in rheumatoid arthritis) are given.
Cohly, Hari Har Parshad; Panja, Asit
elevated in autistic brains. In measles virus infection, it has been postulated that there is immune suppression by inhibiting T-cell proliferation and maturation and downregulation MHC class II expression. Cytokine alteration of TNF-alpha is increased in autistic populations. Toll-like-receptors are also involved in autistic development. High NO levels are associated with autism. Maternal antibodies may trigger autism as a mechanism of autoimmunity. MMR vaccination may increase risk for autism via an autoimmune mechanism in autism. MMR antibodies are significantly higher in autistic children as compared to normal children, supporting a role of MMR in autism. Autoantibodies (IgG isotype) to neuron-axon filament protein (NAFP) and glial fibrillary acidic protein (GFAP) are significantly increased in autistic patients (Singh et al., 1997). Increase in Th2 may explain the increased autoimmunity, such as the findings of antibodies to MBP and neuronal axonal filaments in the brain. There is further evidence that there are other participants in the autoimmune phenomenon. (Kozlovskaia et al., 2000). The possibility of its involvement in autism cannot be ruled out. Further investigations at immunological, cellular, molecular, and genetic levels will allow researchers to continue to unravel the immunopathogenic mechanisms' associated with autistic processes in the developing brain. This may open up new avenues for prevention and/or cure of this devastating neurodevelopmental disorder.
Chinen, Javier; Shearer, William T.
Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.
Dawson, Jeffrey R.; And Others
This monograph was designed for the high school biology curriculum. The first section reviews the major areas of importance in immunology. Section three contains six instructional activities for the high school classroom and the second section contains teacher's materials for those activities. The activities address for students some of the major…
This article discusses research findings that indicate immunological abnormalities in children with autism, including the dysregulation of the immune system, and concludes that there are sufficient data to suggest a role of the immune system in the pathogenesis of autism. Various biological therapies are analyzed, including intravenous…
Sukari, Ammar; Nagasaka, Misako; Al-Hadidi, Ameer; Lum, Lawrence G
Hanahan and Weinberg described six distinct biological properties of cancer cells that enable tumor growth and metastasis. These properties were referred to as the traditional hallmarks of cancer. Recent discoveries further elucidated hallmarks including evasion of immune destruction by tumor cells that disrupt anticancer response pathways. This review discusses cancer immunology and new treatment strategies aimed at restoration of antitumor immune responses.
Ullrich, Stephen E; Byrne, Scott N
UV radiation targets the skin and is a primary cause of skin cancer (both melanoma and nonmelanoma skin cancer). Exposure to UV radiation also suppresses the immune response, and UV-induced immune suppression is a major risk factor for skin cancer induction. The efforts of dermatologists and cancer biologists to understand how UV radiation exposure suppresses the immune response and contributes to skin cancer induction led to the development of the subdiscipline we call photoimmunology. Advances in photoimmunology have generally paralleled advances in immunology. However, there are a number of examples in which investigations into the mechanisms underlying UV-induced immune suppression reshaped our understanding of basic immunological concepts. Unconventional immune regulatory roles for Langerhans cells, mast cells, and natural killer T (NKT) cells, as well as the immune-suppressive function of lipid mediators of inflammation and alarmins, are just some examples of how advances in immunodermatology have altered our understanding of basic immunology. In this anniversary issue celebrating 75 years of cutaneous science, we provide examples of how concepts that grew out of efforts by immunologists and dermatologists to understand immune regulation by UV radiation affected immunology in general.
Yusim, Karina; Korber, Bette Tina; Brander, Christian; Barouch, Dan; de Boer, Rob; Haynes, Barton F.; Koup, Richard; Moore, John P.; Walker, Bruce D.; Watkins, David
The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins
The recurrence of a cancer - local or distant (metastasis) - is manifested by the persistence of cancer cells in the organism after the ablation of the primary lesion, an ineffective anticancer immune response, and by the activity of biological/immunological factors that can stimulate and sustain its development. This review focuses on colorectal carcinoma and discusses some aspects of cancer immunology regarding cancer development and its recurrence. It is addressed also to the clinician to provide new insights helpful for designing better therapeutic strategies and patient's follow up. Therapeutic approaches used during and after surgical treatments, found capable of modulating immunity (differently affecting disease outcome), will also be described.
Gobert, Alain P.; Sagrestani, Giulia; Delmas, Eve; Wilson, Keith T.; Verriere, Thomas G.; Dapoigny, Michel; Del’homme, Christophe; Bernalier-Donadille, Annick
The intestinal microbiota of patients with constipated-predominant irritable bowel syndrome (C-IBS) displays chronic dysbiosis. Our aim was to determine whether this microbial imbalance instigates perturbation of the host intestinal mucosal immune response, using a model of human microbiota-associated rats (HMAR) and dextran sulfate sodium (DSS)-induced experimental colitis. The analysis of the microbiota composition revealed a decrease of the relative abundance of Bacteroides, Roseburia-Eubacterium rectale and Bifidobacterium and an increase of Enterobacteriaceae, Desulfovibrio sp., and mainly Akkermansia muciniphila in C-IBS patients compared to healthy individuals. The bacterial diversity of the gut microbiota of healthy individuals or C-IBS patients was maintained in corresponding HMAR. Animals harboring a C-IBS microbiota had reduced DSS colitis with a decreased expression of pro-inflammatory cytokines from innate, Th1, and Th17 responses. The pre-treatment of conventional C57BL/6 mice or HMAR with A. muciniphila, but not with Escherichia coli, prior exposure to DSS also resulted in a reduction of colitis severity, highlighting that the anti-inflammatory effect of the gut microbiota of C-IBS patients is mediated, in part, by A. muciniphila. This work highlights a novel aspect of the crosstalk between the gut microbiota of C-IBS patients and host intestinal homeostasis. PMID:27982124
Yusim, Karina; Korber, Bette Tina Marie; Barouch, Dan; Koup, Richard; de Boer, Rob; Moore, John P.; Brander, Christian; Haynes, Barton F.; Walker, Bruce D.
HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.
Calvaruso, Vincenza; Craxì, Antonio
A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus (HCV) infection, focusing the attention of physicians and researchers on the close association between HCV and immune disorders. HCV lymphotropism represents the most important step in the pathogenesis of virus-related immunological diseases and experimental, virologic, and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases, such as rheumatoid arthritis, Sjögren syndrome, hemolytic anemia and severe thrombocytopenia, and in organ-specific autoimmune diseases, such as autoimmune hepatitis, thyroid disorders and diabetes. This review will outline the principal aspects of such HCV-induced immunological alterations, focusing on the prevalence of these less characterized HCV extrahepatic manifestations.
Illingworth, Kenneth David; Mihalko, William M; Parvizi, Javad; Sculco, Thomas; McArthur, Benjamin; el Bitar, Youssef; Saleh, Khaled J
Total joint arthroplasty is one of the most common and most successful orthopaedic procedures. Infection after total joint arthroplasty is a devastating problem that expends patient, surgeon, and hospital resources, and it substantially decreases the chances of a successful patient outcome. Postoperative infection affects approximately 1% to 7% of all total joint arthroplasties, at a cost of approximately $50,000 per infection. Decreasing postoperative periprosthetic joint infection is of the utmost importance for the total joint arthroplasty surgeon. Preoperative, perioperative, intraoperative, and postoperative measures to minimize infection and optimize patient outcomes in total joint arthroplasty are discussed. Preoperative measures include management of patients colonized by Staphylococcus aureus, nutritional optimization, and management of medical comorbidities. Perioperative measures include skin preparation and prophylactic antibiotics. Intraoperative measures include body exhaust suits, laminar flow, ultraviolet light, operating-room traffic control, surgical suite enclosures, anesthesia-related considerations, and antibiotic-loaded bone cement. Postoperative measures include continued antibiotic prophylaxis, blood transfusions, hematoma formation and wound drainage, duration of hospital stay, and antibiotic prophylaxis for future invasive procedures.
Liu, Aijun; Li, Anmin; Zhang, Haitao; Zhang, Zhiwen
The authors examined brain neurochemistry in four patients with mental retardation with self-injurious behaviors after ablative surgeries. The authors found that surgeries in the human limbic system can alter dopamine levels in the frontal cortex over a 36-hour period.
Dee, T H; Schiffman, G; Sottile, M I; Rytel, M W
Many patients die from pneumococcal disease despite the availability of effective antimicrobial agents. Immunologic studies including detection, typing, and quantitation of serum pneumococcal capsular polysaccharide (PCP) antigen by counterimmunoelectrophoresis (CIE), quantitation of PCP antibody by radioimmunoassay (RIA), and quantitation of serum complement components C3, C4, and C3PA and serum immunoglobulins IgG, IgM, and IgA by the radial immunodiffusion technique of Mancini were performed with the sera of 18 patients. Five patients died (group I), and 13 survived (group II) pneumococcal infection. Both groups were comparable in age, underlying disease, and leukopenia on admission. All patients of group I and 10 of 13 (77%) of group II patients were bacteremic. Two patients in each group had an extrapulmonary focus infection. PCP antigen was detected in the sera of all group I and nine of 13 group II patients. PCP antigen levels were larger than or equal to 15 microng/ml in four of five group I and two of 13 group II patients (p = 0.022). Levels of antibody to PCP exceeded 100 ng/ml of antibody nitrogen (AbN) in 10 of 12 group II and one of five group I patients (p = 0.027) during the course of illness. All group I patients and three of 12 group II patients had decreased levels of one or more complement components on admission (p less than 0.01). One or more complement components remained decreased until death in four group I patients but returned to normal or elevated levels in all group II patients. No difference in serum immunoglobulin concentrations were found.
Skendzel, Jack G; Weber, Alexander E; Ross, James R; Larson, Christopher M; Leunig, Michael; Kelly, Bryan T; Bedi, Asheesh
The mechanical causes of hip pain in a young athlete often reflect a complex combination of static and dynamic factors. A comprehensive diagnostic approach is paramount to the development of a rational treatment strategy that will address all underlying pathologic factors. The goals of this paper are to highlight the pertinent biomechanical factors of the hip joint in femoroacetabular impingement and to discuss the clinical history, physical examination, and radiographic findings that are essential to formulating a proper diagnosis and an effective treatment plan. In addition, the current literature and reported outcomes of femoroacetabular impingement surgery in athletic patients are reviewed.
Ozawa, Yoko; Yamamoto, Hiroshi; Yasuo, Masanori; Takahashi, Hidekazu; Tateishi, Kazunari; Ushiki, Atsuhito; Kawakami, Satoshi; Fujinaga, Yasunari; Asaka, Shiho; Sano, Kenji; Takayama, Hiroshi; Imamura, Hiroshi; Hanaoka, Masayuki
We herein report on two middle-aged men with TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis or renal failure, and organomegaly) syndrome, a unique clinicopathological variant of multicentric Castleman׳s disease recently proposed in Japan. Strikingly similar anterior mediastinal fat swellings with soft tissue density were observed in the patients on chest computed tomography. In TAFRO syndrome, bilateral pleural effusion and slight lymph node swelling are common in the thoracic region; however, anterior mediastinal lesions have not been previously observed. Although the mechanisms of anterior mediastinal lesions have not been defined, these lesions seem to have a close relationship with TAFRO syndrome.
Kimzey, S. L.; Fischer, C. L.; Johnson, P. C.; Ritzmann, S. E.; Mengel, C. E.
The hematology and immunology program conducted in support of the Apollo missions was designed to acquire specific laboratory data relative to the assessment of the health status of the astronauts prior to their commitment to space flight. A second objective was to detect and identify any alterations in the normal functions of the immunohematologic systems which could be attributed to space flight exposure, and to evaluate the significance of these changes relative to man's continuing participation in space flight missions. Specific changes observed during the Gemini Program formed the basis for the major portion of the hematology-immunology test schedule. Additional measurements were included when their contribution to the overall interpretation of the flight data base became apparent.
Shibata, Masahiko; Gonda, Kenji; Kumamoto, Kensuke; Takenoshita, Seiichi
Recently there is a great advance in anti-colorectal cancer treatment. Several molecular targeting agents, mostly are antibody drugs, are playing an important role. It has recently been proven that new approaches using antibody to immunological checkpoints are effective against certain types of cancer. This is one of the reasons why cancer immunotherapy is now focused in the clinics. In this chapter, several effective immunotherapy against cancer are shown and discussed. Among several types of cancer immunotherapy, immunological cell therapy including lymphokine activated killer (LAK) cell, cytotoxic T lymphocytes (CTL), gamma delta T cell and dendritic cell therapies are reviewed. Major mechanisms that disturb cancer immunotherapy such as escape mechanisms are also discussed.
The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14lowCD16+ monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14highCD16+ and CD14lowCD16+ monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP controls. These data suggest that PE monocytes are hyper-responsive to TLR ligands and this may contribute to exacerbation of the disease. PMID:22848746
Al-ofi, Ebtisam; Coffelt, Seth B; Anumba, Dilly O
The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14(low)CD16(+) monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14(high)CD16(+) and CD14(low)CD16(+) monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP controls. These data suggest that PE monocytes are hyper-responsive to TLR ligands and this may contribute to exacerbation of the disease.
Watson, J. N.; Addison, P. S.; Clegg, G. R.; Steen, P. A.; Robertson, C. E.
We report on an improved method for the prediction of the outcome from electric shock therapy for patients in ventricular fibrillation: the primary arrhythmia associated with sudden cardiac death. Our wavelet transform-based marker, COP (cardioversion outcome prediction), is compared to three other well-documented shock outcome predictors: median frequency (MF) of fibrillation, spectral energy (SE) and AMSA (amplitude spectrum analysis). Optimum specificities for sensitivities around 95% for the four reported methods are 63 ± 4% at 97 ± 2% (COP), 42 ± 15% at 90 ± 7% (MF), 12 ± 3% at 94 ± 5% (SE) and 56 ± 5% at 94 ± 5% (AMSA), with successful defibrillation defined as the rapid (<60 s) return of sustained (>30 s) spontaneous circulation. This marked increase in performance by COP at specificity values around 95%, required for implementation of the technique in practice, is achieved by its enhanced ability to partition pertinent information in the time-frequency plane. COP therefore provides an optimal index for the identification of patients for whom shocking would be futile and for whom an alternative therapy should be considered.
experimental autoimmune I. Pecht (Department of Chemical myasthenia gravis (EAMG). These anti- " Immunology, Weizmann Institute) and his bodies block...of histocompatability tributlons that played a major role in antigens and was the first to show the the complete eradication of malaria from theta...were compared to School, Jerusalem) and J. Haimovich (De- conventional antibodies. The role of partment of Human Microbiology, Tel-Aviv monoclonal
Finn, Olivera J; Salter, Russell D
The University of Pittsburgh School of Medicine has a long tradition of excellence in immunology research and training. Faculty, students, and postdoctoral fellows walk through hallways that are pictorial reminders of the days when Dr. Jonas Salk worked here to develop the polio vaccine, or when Dr. Niels Jerne chaired the Microbiology Department and worked on perfecting the Jerne Plaque Assay for antibody-producing cells. Colleagues and postdoctoral fellows of Professor Salk are still on the faculty of the University of Pittsburgh Medical School as are graduate students of Professor Jerne. A modern research building, the 17 story high Biomedical Science Tower, is a vivid reminder of the day when Dr. Thomas Starzl arrived in Pittsburgh and started building the most prominent solid-organ-transplant program in the world. The immunology research that developed around the problem of graft rejection and tolerance induction trained numerous outstanding students and fellows. Almost 20 yr ago, the University of Pittsburgh founded the University of Pittsburgh Cancer Institute (UPCI) with the renowned immunologist Dr. Ronald Herberman at its helm. This started a number of new research initiatives in cancer immunology and immunotherapy. A large number of outstanding young investigators, as well as several well-established tumor immunologists, were recruited to Pittsburgh at that time.
Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. The number of flight experiments has been small, and the full breadth of immunological alterations occurring after space flight remains to be established. Among the major effects on immune responses after space flight that have been reported are: alterations in lymphocyte blastogenesis and natural killer cell activity, alterations in production of cytokines, changes in leukocyte sub-population distribution, and decreases in the ability in the ability of bone marrow cells to respond to colony stimulating factors. Changes have been reported in immunological parameters of both humans and rodents. The significance of these alterations in relation to resistance to infection remains to be established. The current study involved a determination of the effects of flight on Cosmos mission 2044 on leukocyte subset distribution and the sensitivity of bone marrow cells to colony stimulating factor-GM. A parallel study with antiorthostatic suspension was also carried out. The study involved repetition and expansion of studies carried out on Cosmos 1887.
Kovacs, K L; Seefeldt, L C; Tigyi, G; Doyle, C M; Mortenson, L E; Arp, D J
We examined the immunological cross-reactions of 11 different hydrogenase antigens with 9 different hydrogenase antibodies. Included were antibodies and antigens of both subunits of the hydrogenases of Bradyrhizobium japonicum and Thiocapsa roseopersicina. The results showed a strong relationship among the Ni-Fe dimeric hydrogenases. The two subunits of Ni-Fe dimeric hydrogenases appeared immunologically distinct: specific interactions occurred only when antibodies to the 60- and 30-kilodalton subunits reacted with the 60- and 30-kilodalton-subunit antigens. The interspecies cross-reactions suggested that at least one conserved protein region exists among the large subunits of these enzymes, whereas the small subunits are less conserved. Antibodies to the Fe-only bidirectional hydrogenase of Clostridium pasteurianum reacted with the Desulfovibrio vulgaris bidirectional hydrogenase. Surprisingly, antibodies to the clostridial uptake hydrogenase did not react with any of the Fe-only bidirectional hydrogenases but did react with several of the Ni-Fe dimeric hydrogenases. The two hydrogenases from C. pasteurianum were found to be quite different immunologically. The possible relationship of these findings to the structure and catalytic functions of hydrogenase are discussed. Images PMID:2464579
Ratio of Circulating IFNγ (+) "Th17 Cells" in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project.
Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi
Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17(+)Th17 cells, and IFNγ (+)Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ (+)Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.
Chinen, Javier; Finkelman, Fred; Shearer, William T
This review comments on basic and clinical immunology articles that were published in 2005, with a focus on those that appeared in the Journal of Allergy and Clinical Immunology. In the area of basic immunology, mechanisms of the innate immune system and its interaction with the adaptive immune system were described, with special consideration to applications in biodefense strategies. T regulatory cells were further characterized in their role for the control of allergic, autoimmune, and neoplastic disorders. The function of the thymus Hassall's corpuscles was reported to be the generation of T regulatory cells. Flavonoid molecules obtained from medicinal herbs, including astilbin and epigallocatechin gallate, were discovered to have immunomodulatory properties. Advances in clinical immunology resulted from efforts to develop a newborn screening test for severe combined immunodeficiency and the elucidation of the crystal structure of the IL-2 receptor gamma chain. Mutations in the membrane receptor transmembrane activator and calcium modulator and cyclophilin ligand interactor were found in patients with common variable immunodeficiency. New therapeutic options are described, such as the use of infliximab for granulomas and GM-CSF for chronic ulcers in patients with common variable immunodeficiency. The importance of mucosal immunity in acute HIV infection is cited, as is the role of CD8+ T-cell activation in HIV disease progression in children.
Chen, Shuo; Lei, Jie; Fu, Kai-Yuan; Wang, Xing; Yi, Biao
Purpose This study evaluated the differences in the facial morphological characteristics of female patients exhibiting skeletal class II deformity with and without temporomandibular joint osteoarthrosis. Methods Eighty-three female patients with skeletal class II deformity were included in this study; these patients were classified into three groups on the basis of the condylar features shown in cone-beam computed tomography scans: normal group, indeterminate for osteoarthrosis group, and osteoarthrosis group. The cephalometric differences among the three groups were evaluated through one-way ANOVA. Results Of the 83 patients, 52.4% were diagnosed with osteoarthrosis, as indicated by the changes in the condylar osseous component. The cephalometric measurements that represented skeletal characteristics, including mandibular position relative to the cranial base, mandibular plane angle (MP-SN), posterior facial height (S-Go), and facial height ratio, were significantly different among the three groups (p < 0.05). The patients in the osteoarthrosis group yielded the smallest S-Go, the highest MP-SN, and the most retruded mandible. Conclusions Temporomandibular joint osteoarthrosis is commonly observed in female patients with skeletal class II deformity. The morphological characteristics of the facial skeleton in patients with bilateral condylar osteoarthrosis may be altered. PMID:26474490
The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has high temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.
The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has high temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.
Spencer, A; Granter, N
Improvement in diagnostic cytogenetic techniques has led to the recognition of an increasing number of leukemia-associated chromosomal translocations and inversions. These genetic lesions frequently are associated with the disruption of putative transcription factors and the production of hybrid transcripts that are implicated in leukemogenesis. Epidemiologic evidence suggests that some, but not all, individuals with a history of gamma-irradiation exposure are at increased risk of developing chronic myeloid leukemia (CML). CML is characterized by the Philadelphia chromosome and transcription of the resulting hybrid BCR-ABL gene. Utilizing the leukemia-associated BCR-ABL p210 transcript as a marker, we sought differences in the induction of illegitimate genetic recombination following high-dose gamma-irradiation of karyotypically normal lymphoblastoid cell lines (LCL) derived from individuals with and without a history of myeloid leukemias. Six LCL [4 leukemia patient derived [2 acute myeloid leukemia and 2 CML] and 2 from normal individuals were analyzed with reverse transcriptase polymerase chain reaction for BCR-ABL under stringent conditions following exposure to 0, 50, or 100 Gy of LET gamma-irradiation delivered via a Varian linear accelerator at 4 MV. Transcripts identical to disease-associated b2a2 and b3a2 transcripts were detected both spontaneously (background illegitimate genetic recombination) and following gamma-irradiation. Background BCR-ABL positivity was demonstrable in 4 of the 6 LCL, with no significant difference in detection between leukemic- and nonleukemic-derived LCL. Overall, increasing gamma-irradiation dose resulted in an increased frequency of BCR-ABL transcript detection (0 Gy vs 50 Gy vs 100 Gy,p = 0.0023, Chi-square test). Within the leukemic- but not the nonleukemic-derived LCL there was significantly greater BCR-ABL positivity after gamma-irradiation compared to unirradiated equivalents. Furthermore, the BCR-ABL positivity of both
CANCER IMMUNOLOGY -1 DTICS ELECTED SEP 9 8 UNITED STATES NAVAL ACADEMY ANNAPOLIS, MARYLAND V ,1986 %,e docment ha le approved for public A." I and sale...1986 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED KINETICS MODELING OF CANCER IMMUNOLOGY Final: 1985/1986 6. PERFORMING ORG. REPORT...137 (1986) "Kinetics Modeling of Cancer Immunology " A Trident Scholar Project Report by Midn I/C Scott Helmers, Class of 1986 United States Naval
Castro, Mario; Lythe, Grant; Molina-París, Carmen; Ribeiro, Ruy M.
Mathematical and statistical methods enable multidisciplinary approaches that catalyse discovery. Together with experimental methods, they identify key hypotheses, define measurable observables and reconcile disparate results. We collect a representative sample of studies in T-cell biology that illustrate the benefits of modelling–experimental collaborations and that have proven valuable or even groundbreaking. We conclude that it is possible to find excellent examples of synergy between mathematical modelling and experiment in immunology, which have brought significant insight that would not be available without these collaborations, but that much remains to be discovered. PMID:27051512
Kimzey, S. L.
A coordinated series of experiments were conducted to evaluate immunologic and hemotologic system responses of Skylab crewmen to prolonged space flights. A reduced PHA responsiveness was observed on recovery, together with a reduced number of T-cells, with both values returning to normal 3 to 5 days postflight. Subnormal red cell count, hemoglobin concentration, and hematocrit values also returned gradually to preflight limits. Most pronounced changes were found in the shape of red blood cells during extended space missions with a rapid reversal of these changes upon reentry into a normal gravitational environment.
Castro, Mario; Lythe, Grant; Molina-París, Carmen; ...
Mathematical and statistical methods enable multidisciplinary approaches that catalyse discovery. Together with experimental methods, they identify key hypotheses, define measurable observables and reconcile disparate results. Here, we collect a representative sample of studies in T-cell biology that illustrate the benefits of modelling–experimental collaborations and that have proven valuable or even groundbreaking. Furthermore, we conclude that it is possible to find excellent examples of synergy between mathematical modelling and experiment in immunology, which have brought significant insight that would not be available without these collaborations, but that much remains to be discovered.
Cossarizza, Andrea; Nolan, John; Radbruch, Andreas; Tárnok, Attila
Cytometry is a key technology for immunology. It allows researchers to scrutinize the cells of the immune system in molecular detail, and to assess phenotype and function at the level of individual cells, no matter how rare these cells may be. The International Society for the Advancement of Cytometry, ISAC, by way of its meetings, online resources and publications (e.g. Cytometry Part A and Current Protocols in Cytometry, which are all published by Wiley) track the ever advancing developments regarding cytometry instrumentation and reagents, and the analysis of complex data sets. In June this year in Leipzig, Germany, ISAC held its annual conference "CYTO 2012", a marketplace of innovation in cytometry.
Roth, Patrick; Eisele, Günter; Weller, Michael
Brain tumors of different origin, but notably malignant gliomas, are characterized by their immunosuppressive properties which allow them to escape the host's immune surveillance. The activating immune cell ligands that are expressed by tumor cells, together with potentially immunogenic antigens, are overridden by numerous immune inhibitory signals, with TGF-3 as the master immunosuppressive molecule (Figure 4.1).The ongoing investigation of mechanisms of tumor-derived immunosuppression allows for an increasing understanding of brain tumor immunology. Targeting different mechanisms of tumor-derived immunosuppression, such as inhibition of TGF-[, may represent a promising strategy for future immunotherapeutic approaches.
Kawamura, N; Ariga, T; Ohtsu, M; Kobayashi, I; Yamada, M; Tame, A; Furuta, H; Okano, M; Egashira, M; Niikawa, N; Kobayashi, K; Sakiyama, Y
We previously reported successful peripheral T cell-directed gene therapy in a boy with adenosine deaminase (ADA)-SCID. In the present study, to better understand the reconstitutive effect of this gene therapy on his immunological system, we investigated the in vivo kinetics and functional subsets of T cells in PBL. Apparent immunological improvements were obtained after infusion of transduced cells at more than 4 x 108 cells/kg/therapy/3 mo. Frequency of ADAcDNA-integrated cells in PBL, ADA activity in PBL and clinical improvement showed good correlation, even though CD8+ cells gradually became predominant in PBL. On the basis that polyethylene glycol (PEG)-ADA was maintained at the same dosage as before gene therapy, we consider that his immunological improvement resulted from the gene therapy itself. Most CD3+ cells in PBL after gene therapy expressed TCRalphabeta. Analysis of TCR repertoire based on TCR V region usage revealed no expansion of limited clones in his PBL. The T cell subset cells CD8+CDw60+ and CD8+CD27+CD45RA-, which are reported to provide substantial help to B cells, were maintained throughout the gene therapy. Furthermore, his reconstituted peripheral T cells helped normal B cells to produce substantial IgG in vitro. Expression of both Th1- and Th2-type cytokine genes was induced in his reconstituted T cells at the same comparably high level as in normal subjects. Collectively, these results provide evidence of persistent and distinct functions of transduced cells in this patient's PBL after gene therapy.
Colley, D G; Secor, W E
There is a wealth of immunologic studies that have been carried out in experimental and human schistosomiasis that can be classified into three main areas: immunopathogenesis, resistance to reinfection and diagnostics. It is clear that the bulk of, if not all, morbidity due to human schistosomiasis results from immune-response-based inflammation against eggs lodged in the body, either as regulated chronic inflammation or resulting in fibrotic lesions. However, the exact nature of these responses, the antigens to which they are mounted and the mechanisms of the critical regulatory responses are still being sorted out. It is also becoming apparent that protective immunity against schistosomula as they develop into adult worms develops slowly and is hastened by the dying of adult worms, either naturally or when they are killed by praziquantel. However, as with anti-egg responses, the responsible immune mechanisms and inducing antigens are not clearly established, nor are any potential regulatory responses known. Finally, a wide variety of immune markers, both cellular and humoral, can be used to demonstrate exposure to schistosomes, and immunologic measurement of schistosome antigens can be used to detect, and thus diagnose, active infections. All three areas contribute to the public health response to human schistosome infections. PMID:25142505
Knowledge of the immunological basis of the leishmaniases and of the host's response is fragmentary and largely pragmatic. This paper reviews certain conceptual and clinical aspects of the immunology of these diseases. Consideration is given to man's natural resistance and his ability to acquire resistance from natural infections and from vaccination. The age-distribution of infection in different populations is discussed in relation to the effects that interaction between the parasite and its intermediate host may have on its infection characteristics and virulence. Studies in the USSR of differences in virulence among 30 human strains and 39 rodent strains are reported. The rodent strains showed a broader range of virulence than did the human isolates. Serological tests for determining species relationships among the leishmaniae are generally nonspecific, but work concerned with the development of the antiserum—culture test is reviewed. Species identification and the recognition of new forms, perhaps with different infection characteristics, is, nevertheless, of the utmost importance in the prevention and treatment of the disease. The review concludes with a discussion of functional immunity and hypotheses of the immune process in leishmaniasis. PMID:5316252
Serrallach, N; Jimenez, J F; Aguiló, F; Anguera, A; Clavo, M; Orejas, V; Torner, V; Serrate, R
In this study, 32 cases of cancer of the genito-urinary tract are discussed from the viewpoint of immunology. In eight cases treated surgically, there has been no evidence of recurrence over a period of 1-4 years. Those with a good immunological response have a satisfactory course. Patients with a good response have been treated by radical surgery depending on the stage of the tumour, whilst those with a poor response have been treated less radically by reduction of the tumour mass in the hope that a better response may develop. The authors of this report feel that the 'inhibition of the lymphocyte migration test' is a very important factor to evaluate in the study and immunological evolution of the patient. Also, and concerning cases with good immunological response, the poor results after surgery makes us consider the importance and value of blocking factors of the serum closely related to the B type lymphocytes.
Yasukochi, Atsushi; Teye, Kwesi; Ishii, Norito; Hashimoto, Takashi
Diagnosis of anti-BP180-type mucous membrane pemphigoid (BP180-MMP) is frustrated by the difficulty of detecting BP180 reactivity. A total of 721 patients with suspected MMP, selected from a cohort of 4,698 patients with autoimmune bullous disease (AIBD), were included in this study. Of these, 332 patients were tentatively diagnosed as BP180-MMP if they showed IgG/IgA reactivity with the epidermal side of 1M NaCl-split-skin and/or positive reactivity with BP180 in at least one of our antigen detection methods. Clinically, a predominance of female patients was found. Oral mucosal and cutaneous lesions were found in 85.5% and 41.0% of patients, respectively, and frequent treatments were systemic steroids, tetracycline/minocycline and diaminodiphenyl sulfone. Various immunological methods, including a newly developed BP180 C-terminal domain enzyme-linked immunosorbent assay (ELISA), revealed frequent reactivity with BP180 C-terminal and NC16a domains. Some patients reacted with BP180 and other antigens, indicating that BP180-MMP tends to concur with other AIBDs. This large study of patients with suspected BP180-MMP indicates the difficulty of diagnosis of BP180-MMP and the diagnostic usefulness of BP180 C-terminal domain ELISA.
Darmoise, Alexandre; Maschmeyer, Patrick; Winau, Florian
Saposins or sphingolipid activator proteins (SAPs) are small, nonenzymatic glycoproteins that are ubiquitously present in lysosomes. SAPs comprise the five molecules saposins A–D and the GM2 activator protein. Saposins are essential for sphingolipid degradation and membrane digestion. On the one hand, they bind the respective hydrolases required to catabolize sphingolipid molecules; on the other hand, saposins can interact with intralysosomal membrane structures to render lipids accessible to their degrading enzymes. Thus, saposins bridge the physicochemical gap between lipid substrate and hydrophilic hydrolases. Accordingly, defects in saposin function can lead to lysosomal lipid accumulation. In addition to their specific functions in sphingolipid metabolism, saposins have membrane-perturbing properties. At the low pH of lysosomes, saposins get protonated and exhibit a high binding affinity for anionic phospholipids. Based on their universal principle to interact with membrane bilayers, we present the immunological functions of saposins with regard to lipid antigen presentation to CD1-restricted T cells, processing of apoptotic bodies for antigen delivery and cross-priming, as well as their potential antimicrobial impact. PMID:20510729
Chao, Chia-Ter; Huang, Jenq-Wen
Background. Patients with end-stage renal disease (ESRD) have a high symptom burden, among which fatigue is highly prevalent. Many fatigue-assessing instruments exist, but comparisons among instruments in this patient population have yet to be investigated. Methods. ESRD patients under chronic hemodialysis were prospectively enrolled and seven types of fatigue instruments were administered: Brief Fatigue Inventory (BFI), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Fatigue Severity Scale (FSS), Lee Fatigue Scale (LFS), Fatigue Questionnaire (FQ), Fatigue Symptom Inventory (FSI), and Short-Form 36-Vitality (SF36-V). Using these instruments, we investigated the correlation between fatigue severity and clinical/biochemical parameters, including demographic/comorbidity profile, dialysis-related complications, and frailty severity. We used regression analysis with serum albumin and frailty severity as the dependent variables to investigate the independent correlations. Results. A total of 46 ESRD patients were enrolled (average age of 67 ± 11.6 years), and 50% of them had type 2 diabetes mellitus. Results from the seven tested instruments showed high correlation with each other. We found that the fatigue severity by FACIT-F was significantly associated with age (p = 0.03), serum albumin (p = 0.003) and creatinine (p = 0.02) levels, while SF36-V scores were also significantly associated with age (p = 0.02) and serum creatinine levels (p = 0.04). However, the fatigue severity measured by the FSS, FSI, FQ, BFI, and LFS did not exhibit these associations. Moreover, regression analysis showed that only FACIT-F scores were independently associated with serum albumin levels and frailty severity in ESRD patients. Conclusion. Among the seven fatigue-assessing instruments, only the FACIT-F yielded results that demonstrated significant and independent associations with important outcome-related features in ESRD patients. PMID:26998414
Barnaba, Vincenzo; Paroli, Marino; Piconese, Silvia
In the present article, we discuss the various ambiguous aspects of the immune system that render this complex biological network so highly flexible and able to defend the host from different external invaders. This ambiguity stems mainly from the property of the immune system to be both protective and harmful. Immunity cannot be fully protective without producing a certain degree of damage (immunopathology) to the host. The balance between protection and tissue damage is, therefore, critical for the establishment of immune homeostasis and protection. In this review, we will consider as ambiguous, various immunological tactics including: (a) the opposing functions driving immune responses, immune-regulation, and contra-regulation, as well as (b) the phenomenon of chronic immune activation as a result of a continuous cross-presentation of apoptotic T cells by dendritic cells. All these plans participate principally to maintain a state of chronic low-level inflammation during persisting infections, and ultimately to favor the species survival. PMID:22566903
Intensification of Antiretroviral Therapy through Addition of Enfuvirtide in Naive HIV-1-Infected Patients with Severe Immunosuppression Does Not Improve Immunological Response: Results of a Randomized Multicenter Trial (ANRS 130 Apollo)
Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick
We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm3 or stage B/C disease with CD4 counts of <200/mm3. Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥200/mm3 at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm3, and the median HIV-1 RNA load was 5.4 log10 copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥200/mm3 at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression. PMID:23165467
Intensification of antiretroviral therapy through addition of enfuvirtide in naive HIV-1-infected patients with severe immunosuppression does not improve immunological response: results of a randomized multicenter trial (ANRS 130 Apollo).
Joly, Véronique; Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick
We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm(3) or stage B/C disease with CD4 counts of <200/mm(3). Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥ 200/mm(3) at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm(3), and the median HIV-1 RNA load was 5.4 log(10) copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥ 200/mm(3) at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression.
Elhelu, Mohamed A.
Macrophages play a significant part in immunity and immune responses. They assume a defensive role exhibited by their ability to carry on phagocytosis of parasites and microbes. They regulate lymphocyte activation and proliferation and they are essential in the activation process of T- and B-lymphocytes by antigens and allogenic cells. Enhanced bactericidal activity of “activated macrophages” is based on immunologically linked mechanisms involving lymphocytes. Macrophages kill ingested microbes but the mechanism by which this is accomplished is not completely understood. This paper discusses the role of macrophages in relation to immunity. PMID:6343621
Stark, J H; Smit, J A; Neethling, F A; Nortman, P J; Myburgh, J A
Predictions of an increasing shortage of donor organs for the future has led to a resurgence of interest in xenotransplantation. We have methodically assessed the immunological compatibility of humans against the chacma baboon with a view to narrowing the gap of concordance by careful immunological screening. The necessity of major blood group compatibility in xenotransplantation is now established. While no group O universal donor exists in the baboon, groups A (45%), B (15%), and AB (40%) are well represented. Baboon histocompatibility antigens could not be precisely defined using human antisera. This does not necessarily imply lack of homology between the species, as we have shown specific crossreactivity of numerous antihuman monoclonal antibodies with baboon leukocytes. Normal humans do not exhibit preformed agglutinins to erythrocytes of the chacma baboon (Papio ursinus orientalis)) but cytotoxic antibodies are occasionally found. Sera from allosensitized patients may contain crossreacting hemagglutinins, leukoagglutinins and complement-dependent cytotoxic antibodies. Binding of human immunoglobulin-G and -M to baboon targets was demonstrated by flow cytometry. Negative crossmatch combinations for antibodies of the IgG subclass were easily found, but IgM antibodies from allosensitized patients were polyspecific in their action. In vitro assessment of lymphocyte mediated cytotoxicity showed that preformed cellular immunity between the species was rare. The response of human lymphocytes to xenoantigen stimulation in mixed lymphocyte cultures showed a normal distribution, permitting the selection of low-responding combinations. Screening for viruses, especially HTLV-1 and Coxsackie-BL34, is important. These findings demonstrate a closer degree of concordance than has previously been suspected.
Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.
Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema
African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity.
Bhardwaj, Arun; Singh, Ajay P.; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L.; Zotto, Valeria Dal; Carter, James E.; Singh, Seema
African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978
The biopsychosocial paradigm is now the main model when dealing with most human health disorders. One of the strengths of this model is that it encourages broader thinking when assessing and managing patients. It also encourages broader reading into areas not traditionally associated with manual therapy. Immunology and neuroscience are amongst the fastest growing medical sciences. These fields come together in the relatively new area of psychoneuroimmunolgy. This article examines some findings from these fields that are not widely discussed in the physical therapy professions. These findings are of relevance to many of the disciplines within the physical therapies. It is the authors aim to stimulate further interest in the relevant, yet often under explored areas of immunology and psychoneuroimmunology.
Li, Qian; Liu, Qiang
Cancer immunology is the study of interaction between cancer cells and immune system by the application of immunology principle and theory. With the recent approval of several new drugs targeting immune checkpoints in cancer, cancer immunology has become a very attractive field of research and is thought to be the new hope to conquer cancer. This chapter introduces the aberrant expression and function of noncoding RNAs, mainly microRNAs and long noncoding RNAs, in tumor-infiltrating immune cells, and their significance in tumor immunity. It also illustrates how noncoding RNAs are shuttled between tumor cells and immune cells in tumor microenvironments via exosomes or other microvesicles to modulate tumor immunity.
Belden, Orrin S.; Baker, Sarah Catherine; Baker, Brian M.
Crowdsourcing by recruiting volunteers who can provide computational time, programming expertise, or puzzle-solving talent has emerged as a powerful tool for biomedical research. Recent projects demonstrate the potential for crowdsourcing in immunology. Tools for developing applications, new funding, and an eager public make crowdsourcing a serious option for creative solutions for computationally-challenging immunological problems. Expanded uses of crowdsourcing in immunology will allow for more efficient large-scale data collection and analysis. It will also involve, inspire, educate, and engage the public in a variety of meaningful ways. The benefits are real – it’s time to jump in! PMID:26139599
Circulating complexes in leprosy studied by the platelet aggregation test. The platelet aggregation test and its relation to the rubino test and other sero-immunological parameters in 135 patients with leprosy
Wager, O.; Penttinen, K.; Almeida, J. D.; Opromolla, D. V. A.; Godal, T.; Kronvall, G.
Sera from 135 patients with leprosy were tested by the platelet aggregation test (PAT), by the Rubino test and by other sero-immunological assays. PAT positivity (titre≥10) was 53% in the lepromatous subgroups and 5% in the tuberculoid subgroups (P<0·005). The higher PAT titres and Rubino titres clustered significantly (P<0·0005) toward the lepromatous end of the disease spectrum. A statistically significant correlation was found between the PAT and the Rubino titres (0·05>P>0·025). Removal of the effect of the disease spectrum, however, resulted in a partial correlation between the PAT and the Rubino titres that was not significant (P>0·1), suggesting different basic mechanisms for the platelet aggregation (PA) and the Rubino activity of the lepromatous sera. The correlation between the PAT titres and twenty-nine other sero-immunological parameters was calculated, and a highly significant correlation was found between the PAT and the IgG level (P<0·005) and between the PAT and the antistaphylolysin-α titre (P<0·005). The PA activity in most lepromatous sera studied sedimented in the heavy (>19S) fractions and was inhibitable by IgM rheumatoid factor. It thus fulfilled the criteria for IgG complexes as defined in previous studies with known model Ag/Ab complexes and with sera from patients with immune complex states. The addition of an excess of soluble mycobacterial antigens affected the PA activity of some lepromatous sera, which suggests that the putative complexes were composed of mycobacterial antigens complexed with corresponding IgG antibody. It was concluded that the PAT is a sensitive detector of IgG complexes peculiar to the lepromatous leprosy. In leprosy the discriminatory power of the PAT seems to be superior to that of other immune complex tests recently applied for the analysis of leprosy series. ImagesFIG. 1 PMID:369750
Tozzi, Alberto E; Armenio, Lucio; Bernardini, Roberto; Boner, Attilio; Calvani, Mauro; Cardinale, Fabio; Cavagni, Giovanni; Dondi, Arianna; Duse, Marzia; Fiocchi, Alessandro; Marseglia, Gian L; del Giudice, Michele Miraglia; Muraro, Antonella; Pajno, Giovanni B; Paravati, Francesco; Peroni, Diego; Tripodi, Salvatore; Ugazio, Alberto G; Indinnimeo, Luciana
In Italy, according to the International Study on Asthma and Allergies in Childhood study, the prevalence of current asthma, allergic rhinoconjunctivitis, and atopic eczema in 2006 was 7.9%, 6.5%, and 10.1% among children aged 6-7 and 8.4%, 15.5%, and 7.75% among children aged 13-14 yr. University education in this field is provided by the Postgraduate Schools of Pediatrics and those of Allergology and Clinical Immunology, as well as several annual Master courses. The Italian Society of Pediatric Allergology and Immunology (SIAIP) was founded in 1996 and counts about 1000 members. SIAIP promotes evidence-based management of allergic children and disseminates information to patients and their families through a quite innovative website and the National Journal 'Rivista Italiana di Allergologia Pediatrica'. In the last decade, four major regional, inter-regional, and national web-based networks have been created to link pediatric allergy centers and to share their clinical protocols and epidemiologic data. In addition, National Registers of Primary Immune-deficiencies and on Pediatric HIV link all clinical excellence centers. Research projects in the field of pediatric allergy and immunology are founded by the Italian Ministry of Education, University and Research (MIUR) and by the National Research Council (CNR), but the overall investments in this research area are quite low. Only a handful Italian excellence centers participate in European Projects on Pediatric Allergy and Immunology within the 7th Framework Program. The European Academy of Allergy and Clinical Immunology currently hosts two Italians in its Executive Committee (EC) and one in the EC of the Pediatric Section; moreover, major European Academy of Allergy and Clinical Immunology meetings and courses in the area of pediatrics (e.g., PAAM, Venice, 2009) have been held in Italy in the last 3 yr. Italian hallmarks in the management of allergic diseases in childhood are a quite alive and spread interest in
Woollard, Kevin J
Cardiovascular disease is the leading cause of death in several countries. The underlying process is atherosclerosis, a slowly progressing chronic disorder that can lead to intravascular thrombosis. There is overwhelming evidence for the underlying importance of our immune system in atherosclerosis. Monocytes, which comprise part of the innate immune system, can be recruited to inflamed endothelium and this recruitment has been shown to be proportional to the extent of atherosclerotic disease. Monocytes undergo migration into the vasculature, they differentiate into macrophage phenotypes, which are highly phagocytic and can scavenge modified lipids, leading to foam cell formation and development of the lipid-rich atheroma core. This increased influx leads to a highly inflammatory environment and along with other immune cells can increase the risk in the development of the unstable atherosclerotic plaque phenotype. The present review provides an overview and description of the immunological aspect of innate and adaptive immune cell subsets in atherosclerosis, by defining their interaction with the vascular environment, modified lipids and other cellular exchanges. There is a particular focus on monocytes and macrophages, but shorter descriptions of dendritic cells, lymphocyte populations, neutrophils, mast cells and platelets are also included.
Schulenburg, Hinrich; Kurtz, Joachim; Moret, Yannick; Siva-Jothy, Michael T.
An organism's fitness is critically reliant on its immune system to provide protection against parasites and pathogens. The structure of even simple immune systems is surprisingly complex and clearly will have been moulded by the organism's ecology. The aim of this review and the theme issue is to examine the role of different ecological factors on the evolution of immunity. Here, we will provide a general framework of the field by contextualizing the main ecological factors, including interactions with parasites, other types of biotic as well as abiotic interactions, intraspecific selective constraints (life-history trade-offs, sexual selection) and population genetic processes. We then elaborate the resulting immunological consequences such as the diversity of defence mechanisms (e.g. avoidance behaviour, resistance, tolerance), redundancy and protection against immunopathology, life-history integration of the immune response and shared immunity within a community (e.g. social immunity and microbiota-mediated protection). Our review summarizes the concepts of current importance and directs the reader to promising future research avenues that will deepen our understanding of the defence against parasites and pathogens. PMID:18926970
This Memorandum, after summarizing the life cycle of the different species of human schistosome, reviews the present knowledge of the immunology of schistosomiasis. Each stage of the parasite contains antigen that may stimulate an immune response. However, at the moment there are no accepted serological in vitro tests that correlate with protection; this develops only after the host has experienced a living infection, which suggests that the stimulation of immunity is due to some metabolic process involving the release of protective antigen. The adult worm, however, seems to be able to escape the immune mechanism of the host. Specific antigens are also released by the eggs, and the immune response against these antigens seems to cause granuloma formation around the egg itself. The granuloma is the main lesion found in schistosomiasis. Evidence for protective immunity in experimental animals and man is reviewed, together with the possible mechanism by which the adult worm escapes the immune response of the host. A review of methods used for the diagnosis of schistosomiasis and a list of recommendations for further research are also included. PMID:4219757
Vadori, M; Cozzi, E
The availability of cells, tissues and organs from a non-human species such as the pig could, at least in theory, meet the demand of organs necessary for clinical transplantation. At this stage, the important goal of getting over the first year of survival has been reported for both cellular and solid organ xenotransplantation in relevant preclinical primate models. In addition, xenotransplantation is already in the clinic as shown by the broad use of animal-derived medical devices, such as bioprosthetic heart valves and biological materials used for surgical tissue repair. At this stage, however, prior to starting a wide-scale clinical application of xenotransplantation of viable cells and organs, the important obstacle represented by the humoral immune response will need to be overcome. Likewise, the barriers posed by the activation of the innate immune system and coagulative pathway will have to be controlled. As far as xenogeneic nonviable xenografts, increasing evidence suggests that considerable immune reactions, mediated by both innate and adaptive immunity, take place and influence the long-term outcome of xenogeneic materials in patients, possibly precluding the use of bioprosthetic heart valves in young individuals. In this context, the present article provides an overview of current knowledge on the immune processes following xenotransplantation and on the possible therapeutic interventions to overcome the immunological drawbacks involved in xenotransplantation.
Nizri, Eran; Greenman-Maaravi, Nofar; Bar-David, Shoshi; Ben-Yehuda, Amir; Weiner, Gilad; Lahat, Guy; Klausner, Joseph
Abstract Lymph node (LN) involvement in colonic carcinoma (CC) is a grave prognostic sign and mandates the addition of adjuvant treatment. However, in light of the histological variability and outcomes observed, we hypothesized that patients with LN metastases (LNM) comprise different subgroups. We retrospectively analyzed the histological sections of 82 patients with CC and LNM. We studied various histological parameters (such as tumor grade, desmoplasia, and preservation of LN architecture) as well as the prevalence of specific peritumoral immune cells (CD8+, CD20+, T-bet+, and GATA-3+). We correlated the histological and immunological data to patient outcome. Tumor grade was a significant prognostic factor even in patients with LNM. So was the number of LN involved (N1/N2 stage). From the morphological parameters tested (LN extracapsular invasion, desmoplasia in LN, LN architecture preservation, and mode of metastases distribution), none was found to be significantly associated with overall survival (OS). The mean OS of CD8+ low patients was 66.6 ± 6.25 versus 71.4 ± 5.1 months for CD8+ high patients (P = 0.79). However, T-helper (Th) 1 immune response skewing (measured by Th1/Th2 ratio >1) was significantly associated with improved OS. For patients with low ratio, the median OS was 35.5 ± 5 versus 83.5 months for patients with high Th1/Th2 ratio (P = 0.001). The histological presentation of LNM does not entail specific prognostic information. However, the finding of Th1 immune response in LN signifies a protective immune response. Future studies should be carried to verify this marker and develop a strategy that augments this immune response during subsequent adjuvant treatment. PMID:27828856
Several papers described different immunological properties of thyroglobulin (Tg) after iodination. The influence of iodine-iodide solution on the immunological properties of hTg and its immunological complexes with autoantibodies (aAbs) were studied. Human Tg coated to polystyrene plates, incubated for 30 min with iodine-iodide solution at concentration from 1 to 200 microM at pH 9.0 lost its ability to bind aAbs. Preincubation with iodine (2 microM), decreased aAbs binding by 50%. Tg epitope inactivation induced by iodine depended on the buffer pH and the presence of carbonate ions. The binding of rabbit Tg-antibodies to iodine pretreated Tg was only slightly changed. Thyroglobulin preincubation with iodine solutions decreased aAbs binding from all tested sera (67) of patients with autoimmune thyroid disease (AITD). Excess of iodide (0.2 M KJ) or equimolar concentration of diiodotyrosine protects the Tg molecule from iodine induced inactivation. Immunological complexes of Tg with aAbs dissociate at low iodine concentrations. The results suggest that a product of iodine disproportionation reaction induces changes in the Tg molecule and Tg-aAb's complexes leading to complex dissociation or epitope inactivation.
Markert, Udo R; Fitzgerald, Justine S; Seyfarth, Lydia; Heinzelmann, Joana; Varosi, Frauke; Voigt, Sandra; Schleussner, Ekkehard; Seewald, Hans-Joachim
Reproduction is indispensable to evolution and, thus, life. Nonetheless, it overcomes common rules known to established life. Immunology of reproduction, and especially the tolerance of two genetically distinct organisms and their fruitful symbiosis, is one of the most imposing paradox of life. Mechanisms, which are physiologically used for induction of said tolerance, are frequently abused by pathogens or tumors intending to escape the host's immune response. Understanding the regulation of immune responses in pregnancy and the invasion of allogeneic fetus-derived trophoblast cells into the decidua may lead to new therapeutic concepts. In transplantation, knowledge concerning local physiological immunotolerance may be useful for the development of new therapies, which do not require a general immune suppression of the patient. In immunological disorders, such as autoimmune diseases or allergies, immune deviations occur which are either prevented during pregnancy or have parallels to pregnancy. Vice versa, lessons from other fields of immunology may also offer new notions for the comprehension of reproductive immunology and may lead to new therapies for the treatment of pregnancy-related problems.
Marbou, Wiliane J T; Kuete, Victor
This study investigated the variations in some cells of the immune system, as well as the antibiotic resistance of the bacteria responsible for enteric infections among HIV+ patients compared to HIV- patients in Mbouda AD LUCEM Hospital, Cameroon. A cross-sectional study was performed from September 2014 to February 2015 in 67 human immunodeficiency virus (HIV)-seropositive (HIV+) and 37 HIV-seronegative (HIV-) patients. Blood collected from these patients was used to perform cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) lymphocyte blood counts and a white blood cell count, as well as to measure C-reactive protein (CRP) blood by flow cytometry and perform optical and immuno-turbidimetric detection. Enteric bacteria were isolated from the stool of patients, and their antibiotic susceptibility profiles were determined using agar diffusion methods. The results showed that Escherichia coli was the main pathogenic bacteria in the digestive tracts of HIV+ (85.3%) and HIV- (81.1%) patients, and infections with Klebsiella sp. were also predominant among HIV- patients (29.4%). Resistance of Klebsiella sp. to ceftriaxone (CRO; P=0.001), gentamicin (GEN; P=0.005), chloramphenicol (CHL; P=0.0004), ciprofloxacin (CIP; P=0.005) and doxycycline (DOX; P<0.0001) was significantly higher in HIV+ patients than in HIV- patients. Enterobacter sp. showed high resistance to GEN (P=0.009) and CIP (P=0.001) in HIV+ patients compared to HIV- patients. Citrobacter sp. was resistant to GEN (P=0.009) in HIV+ patients compared to HIV- patients. Salmonella sp. showed high resistance to CHL (P<0.0001) and DOX (P<0.0001) in HIV+ patients compared to HIV- patients. Resistance of Serratia sp. to AMO (P=0.005), AMC (P=0.005) and CHL (P=0.005) was significantly higher in HIV+ patients than in HIV- patients. Lymphopenia was higher in HIV+ patients (36.8%) than in HIV- patients (2.7%). In 45.9% of the HIV- patients, the CRP rate was higher than 6mg/L compared to 16.2% in HIV
Chen, Wei R.; Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Liu, Hong
Combination therapy using laser photothermal interaction and immunological stimulation has demonstrated its ability to induce immunological responses. Glycated chitosan (GC), an immunological stimulant, and imiquimod, a new type of immune response modifier (IRM), when used in conjunction with laser phototherapy, have shown to have a great immunological stimulation function. Specifically, imiquimod can help release cytokines from immunocompetent cells, stimulate TH1 lymphocyte responses (CD8+ T-cells), and recruit additional dendritic cells. To study the effects of immunoadjuvnats in combination of laser photo-irradiation, we treated animal tumors with laser-ICG-GC combination and late-stage melanoma patients with laser-ICG-imiquimod combination. At designated times, tumors, blood, and spleens in both treated and untreated animals were colleted for analysis. The major immunological indicators, such as IL-6, IL-12, IFN-gamma, CD4, and CD8 were analyzed. The same immunological analysis was also performed for melanoma patients treated by the laser-imiquimod combination.
Voena, Claudia; Chiarle, Roberto
After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models.
Rosario-Filho, Nelson A; Jacob, Cristina M; Sole, Dirceu; Condino-Neto, Antonio; Arruda, Luisa K; Costa-Carvalho, Beatriz; Cocco, Renata R; Camelo-Nunes, Inês; Chong-Neto, Herberto J; Wandalsen, Gustavo F; Castro, Ana P M; Yang, Ariana C; Pastorino, Antonio C; Sarinho, Emanuel S
The subspecialty of pediatric allergy and immunology in Brazil is in its early years and progressing steadily. This review highlights the research developed in the past years aiming to show the characteristics of allergic and immunologic diseases in this vast country. Epidemiologic studies demonstrated the high prevalence of asthma in infants, children, and adolescents. Mortality rates and average annual variation of asthma hospitalization have reduced in all pediatric age groups. Indoor aeroallergen exposure is excessively high and contributes to the high rates of allergy sensitization. Prevalence of food allergy has increased to epidemic levels. Foods (35%), insect stings (30%), and drugs (23%) are the main etiological agents of anaphylaxis in children and adolescents. Molecular diagnosis of primary immunodeficiencies (PID) showed a high incidence of fungal infections including paracoccidioidomycosis in X-linked hyper-IgM syndrome, and the occurrence of BCG adverse reactions or other mycobacterial infections in patients with chronic granulomatous disease. Education in pediatric allergy and immunology is deficient for medical students, but residency programs are effective in training internists and pediatricians for the practice of allergy. The field of PID requires further training. Last, this review is a tribute to Prof. Dr. Charles Naspitz, one of the pioneers of our specialty in Brazil.
Sepúlveda, Sofía E; Beltrán, Caroll J; Peralta, Alexis; Rivas, Paola; Rojas, Néstor; Figueroa, Carolina; Quera, Rodrigo; Hermoso, Marcela A
Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies.
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a...
Most adverse blood transfusion (BT) events are immune-mediated and in the majority of severe reactions antibodies can be identified as causal factors. Alloimmunization not only causes symptomatic reactions, transfused cells can also be (silently) destroyed. Immunization by BT can contribute to hemolytic disease of the newborn as well as to allograft rejection after transplantation. Reversely, pregnancy and transplantation may evoke immunity hampering transfusion therapy. Besides causing mortality and morbidity, alloimmunization has a huge economic impact. Transfusion reactions prolong hospital stay, require diagnostic tests and complex donor selection procedures and create the need for typed donor registries. In the 1970s, Opeltz and colleagues described that pre-transplantation BT impaired rejection of renal transplants. Leukocytes were essential for this immunosuppressive BT effect that raised concern about negative effects on cancer growth and resistance against infections. Studies on the mechanism were however preliminary abandoned when calcineurin inhibitors for prevention of graft rejection became available and since all blood products underwent leukoreduction in most countries as precautionary measure against transmission of variant Creutzfeldt-Jacob disease. Whether current leukoreduced BT are immunosuppressive and for which patients or circumstances this may contribute to worse outcome, is unknown. The last decades of the previous century, leukoreduction of cellular blood products for leukemia patients significantly reduced the incidence of immunological platelet transfusion refractoriness. The first decade of this century the avoidance of plasma- and platelet-products from females, that may contain donor-derived leukocyte antibodies, decreased transfusion related acute lung injury (TRALI) by more than 30%. These were major achievements. Challenge for the near future is to further reduce alloimmunization in particular against red blood cells (RBC) as a
Huang, Steven K.; Scruggs, Anne M.; McEachin, Richard C.; White, Eric S.; Peters-Golden, Marc
Excessive fibroproliferation is a central hallmark of idiopathic pulmonary fibrosis (IPF), a chronic, progressive disorder that results in impaired gas exchange and respiratory failure. Fibroblasts are the key effector cells in IPF, and aberrant expression of multiple genes contributes to their excessive fibroproliferative phenotype. DNA methylation changes are critical to the development of many diseases, but the DNA methylome of IPF fibroblasts has never been characterized. Here, we utilized the HumanMethylation 27 array, which assays the DNA methylation level of 27,568 CpG sites across the genome, to compare the DNA methylation patterns of IPF fibroblasts (n = 6) with those of nonfibrotic patient controls (n = 3) and commercially available normal lung fibroblast cell lines (n = 3). We found that multiple CpG sites across the genome are differentially methylated (as defined by P value less than 0.05 and fold change greater than 2) in IPF fibroblasts compared to fibroblasts from nonfibrotic controls. These methylation differences occurred both in genes recognized to be important in fibroproliferation and extracellular matrix generation, as well as in genes not previously recognized to participate in those processes (including organ morphogenesis and potassium ion channels). We used bisulfite sequencing to independently verify DNA methylation differences in 3 genes (CDKN2B, CARD10, and MGMT); these methylation changes corresponded with differences in gene expression at the mRNA and protein level. These differences in DNA methylation were stable throughout multiple cell passages. DNA methylation differences may thus help to explain a proportion of the differences in gene expression previously observed in studies of IPF fibroblasts. Moreover, significant variability in DNA methylation was observed among individual IPF cell lines, suggesting that differences in DNA methylation may contribute to fibroblast heterogeneity among patients with IPF. These
Snyder, Alexandra; Makarov, Vladimir; Hellmann, Matthew; Rizvi, Naiyer; Merghoub, Taha; Wolchok, Jedd D; Chan, Timothy A
Immune checkpoint blockade therapy is changing oncology by improving the outcome of patients with advanced malignancies. Our research has revealed the genetic features of tumors present in patients who initiate a successful antitumor immune response and derive clinical benefit from immune checkpoint blockade therapy versus non-responders. PMID:26451299
Srinivasan, T.N.; Suresh, T.R.; Devar, J.V.; Jayaram, Vasantha
SUMMARY Studies on association of psychiatric diseases and immunopathology has been an area of recent research activities. Alcohol has been implicated in some immune mediated disorders. Observation of occurrence of psoriasis, an immune mediated skin disorder in alcoholic patients has not been reported anywhere in literature. We report here 4 cases of alcoholism related psoriasis and discuss the possible immunological relationship between these two disorders. The need for study of effect of alcoholism on cell-medicated immunity associated conditions like auto-immune disorders and malignancy is presented. PMID:21897472
Weiner, Louis M
Cancer immunotherapy is coming of age. It has become abundantly clear that immunotherapy-which has been described as treating the body's immune system so the immune system can treat the cancer-can be routinely effective, and may indeed cure advanced cancers. Accordingly, it is important to understand the basic, clinically relevant principles of cancer immunology to better prepare for an increasingly exciting future. The host immune system is the only active enemy faced by a malignant cell population as it develops. So it is helpful to think of the battle between the cancer cell population and the developing cancer as a Darwinian crucible in which only the malignant cells most fit to thrive in the face of active immune system attack are able to survive in the reluctant host. All successful cancers thus have overcome the defenses mounted by host immune systems by actively thwarting the evolution of anticancer immunity. A malignant cell population that has "solved" the riddle of the host immune system need not employ all of these mechanisms in order to survive in a particular host. Hence, it may be that the dominant mechanism or mechanisms of immune evasion in fact represent potential Achilles' heels that can be therapeutically attacked to restore immune control of a cancer. To better understand where opportunities exist for immunotherapy, it is important to first consider how developing cancers overcome host immunity: by overwhelming, hiding from, subverting, shielding from, defending against, and outlasting the host immune response. Clearly, more than one of these mechanisms may be present in any particular patient, but it is likely that many cancer types employ dominant immune defense mechanisms. There can be no doubt that mobilizing the immune system to attack a cancer, remember the enemy, and continually target emerging clones represents an extremely promising path to cancer prevention and cure.
Vick, Randy M.
This article discusses ethical questions raised by an exhibition of work by an artist with a history of mental illness and the exhibition's relevance to art therapy and “outsider art” discourse on the subject. Considerations for how such an exhibit could be handled had the circumstances included an art therapist and art therapy client are…
Loke, Wei Sheng Joshua; Herbert, Cristan; Thomas, Paul S.
Sarcoidosis is a multisystem granulomatous disorder invariably affecting the lungs. It is a disease with noteworthy variations in clinical manifestation and disease outcome and has been described as an “immune paradox” with peripheral anergy despite exaggerated inflammation at disease sites. Despite extensive research, sarcoidosis remains a disease with undetermined aetiology. Current evidence supports the notion that the immune response in sarcoidosis is driven by a putative antigen in a genetically susceptible individual. Unfortunately, there currently exists no reliable biomarker to delineate the disease severity and prognosis. As such, the diagnosis of sarcoidosis remains a vexing clinical challenge. In this review, we outline the immunological features of sarcoidosis, discuss the evidence for and against various candidate etiological agents (infective and noninfective), describe the exhaled breath condensate, a novel method of identifying immunological biomarkers, and suggest other possible immunological biomarkers to better characterise the immunopathogenesis of sarcoidosis. PMID:26464848
Belden, Orrin S; Baker, Sarah Catherine; Baker, Brian M
Recruiting volunteers who can provide computational time, programming expertise, or puzzle-solving talent has emerged as a powerful tool for biomedical research. Recent projects demonstrate the potential for such 'crowdsourcing' efforts in immunology. Tools for developing applications, new funding opportunities, and an eager public make crowdsourcing a serious option for creative solutions for computationally-challenging problems. Expanded uses of crowdsourcing in immunology will allow for more efficient large-scale data collection and analysis. It will also involve, inspire, educate, and engage the public in a variety of meaningful ways. The benefits are real - it is time to jump in!
Smith, Douglas M; Simon, Jakub K; Baker, James R
Nanotechnology uses the unique properties of objects that function as a unit within the overall size range of 1-1,000 nanometres. The engineering of nanostructure materials, including nanoparticles, nanoemulsions or nanotubules, holds great promise for the development of new immunomodulatory agents, as such nanostructures can be used to more effectively manipulate or deliver immunologically active components to target sites. Successful applications of nanotechnology in the field of immunology will enable new generations of vaccines, adjuvants and immunomodulatory drugs that aim to improve clinical outcomes in response to a range of infectious and non-infectious diseases.
Li, Hongqiang; Xu, Shumin; Cheng, Tingting; Tang, Lunxian; Bai, Jianwen; Lin, Minjia
Pneumonia is one of the most serious infectious diseases for elderly people who have impaired organ functions and are more susceptible to infection. Elderly patients having pneumonia often need long-term hospitalization, leading to declined quality of life, and increase of financial burden to the society and their family. Therefore, studies on novel therapeutic strategies and the clinical prognosis of the pneumonia patients are imperative. In the present study, we found that the Chinese herbal medicine Fu Zheng decoction had great immunomodulatory effects during the recovery period of elderly pneumonia patients. Patients treated with combined treatment of Fu Zheng decoction and antibiotic had a faster decline of temperature and a more significant decrease of C reactive protein and inflammatory factors level, and it is easier for them to cough off phlegm, compared with the antibiotic only treatment. Furthermore, the inflammation absorption and the reduction of NK-cell proportion as well as the inflammatory factors were more remarkable in the patients taken Fu Zheng decoction. Especially, the Fu Zheng decoction treatment could decrease the duration of antibiotic treatment, which may help reduce the side effects of antibiotics. Our study also found that MyD88 might play a role in the immunomodulatory effect of Fu Zheng decoction. Our study provides novel insight for the further development of intravenous injection of Chinese materia medica preparation on the regulation of immune function.
Kohn, D B
Gene therapy using autologous hematopoietic stem cells (HSC) that are corrected with the normal gene may have a beneficial effect on blood cell production or function, without the immunologic complications of allogeneic HSC transplantation. Childhood immunological diseases are highly favorable candidates for responses to gene therapy using HSC. Hemoglobinopathies, lysosomal and metabolic disorders and defects of hematopoietic stem and progenitor cells should also be ameliorated by gene therapy using autologous HSC. At present, gene therapy has been beneficial for patients with XSCID, ADA-deficient SCID and chronic granulomatous disease. The principle that partial marrow conditioning increases engraftment of gene-corrected HSC has been demonstrated. Clinical trials are being developed in Europe and the United States to treat several other genetic blood cell disorders. This progress is tempered by the serious complication observed in XSCID patients developing T lymphoproliferative disease. New methods for gene transfer (lentiviral and foamy viral vectors, semi-viral systems and gene correction) may retain or further increase the efficacy and decrease the risks from gene therapy using HSC. Ultimately, the relative benefits and risks of autologous gene therapy will be weighed against other available options (for example, allogeneic HSCT) to determine the treatment of choice.
Bobocea, A C; Trandafir, B; Bolca, C; Cordoş, I
Minimally invasive surgery produced major changes in treating abdominal malignancies and early stage lung cancer. Laparoscopy and thoracoscopy are less traumatic than open surgery: allow faster recovery, shorter hospital stay, better cosmesis. Although these clinical benefits are important, prolonged disease-free interval, long-term survival with improved quality of life are most important endpoints for oncologic surgery. Major surgery causes significant alteration of immunological response, of particular importance in oncologic patients, as postoperative immunosuppression has been related to septic complications, lower survival rate, tumor spread and metastases. Clinical studies have shown laparoscopic surgery preserves better the patient's immunological function. Postoperative plasma peak concentrations of IL-6, IL-10, C-reactive protein (CRP) and TNF-alpha were lower after laparoscopic colonic resection. Prospective thoracoscopic VATS lobectomy trials found better preservation of lymphocyte T-cell function and quicker return of proliferative responses to normal, lower levels of CRP, thromboxane and prostacyclin. Immune function is influenced by the extent of surgical trauma. Minimally invasive surgery show reduced acute-phase responses compared with open procedures and better preservation of cellular immune mechanisms.
An exhibit designed for visually handicapped persons presented by the Kalamazoo (Michigan) Institute of Art included bronze sculptures and oil paintings from the institute's permanent collection. (CL)
Nossal, Gustav J. V.
The immune system can recognize and produce antibodies to virtually any molecule in the Universe. This enormous diversity arises from the ingenious reshuffling of DNA sequences encoding components of the immune system. Immunology is an example of a field completely transformed during the past 50 years by the discovery of the structure of DNA and the emergence of DNA technologies that followed.
Lee, Y W; Shin, K W; Paik, I-Y; Jung, W M; Cho, S-Y; Choi, S T; Kim, H D; Kim, J Y
Immunological changes in elite adolescent female athletes during Taekwondo competitions were investigated on-field. 6 female athletes (16.7 ± 0.8 year-old) volunteered and performed 5 bouts of demonstration Taekwondo competitions simulating real tournaments in intensity, duration, and break-time intervals on the same day. Blood samples were taken before, after the competitions and during the recovery, respectively. Immunological changes and oxidative stress in peripheral blood mononuclear cells were evaluated by flow-cytometry. During the competitions, exercise intensity was 92.2 ± 3.8% (86.1~95.7) of the maximal heart rate. Blood lactate increased immediately after the competitions (p=0.0165) and decreased to baseline during recovery. Intracellular reactive oxygen species (ROS) in the peripheral blood increased continuously during recovery (p<0.05, respectively). Natural killer cells increased immediately after the competitions (p=0.0006), and decreased during recovery. B and T cells increased immediately after the competitions and remained elevated throughout recovery (p<0.05, respectively). CD4/CD8 ratio after the competitions was decreased (p=0.0091) and returned to baseline during recovery. These results suggest that the immunological function of the elite female adolescent athletes could be attenuated after Taekwondo competitions. Further large-scaled Taekwondo studies on immunologic and apoptotic changes related to oxidative stress should be performed for improving and protecting the health of adolescent athletes.
Chez, Michael G; Chin, Kathleen; Hung, Paul C
Public fears of rising rates of children being diagnosed with autistic spectrum disorders has led to a fear that immunizations, specifically the measles-mumps-varicella vaccine (MMR), may trigger autism. This article reviews theories of immunization as a risk factor for autism, including thimerosal exposure. We also review theories of autoimmunity as a predisposing genetic risk in autistic patients. We summarize from multiple population-based studies and extensive review committee reports that neither immunization nor thimerosal exposure has been conclusively linked to autism. Current treatments for autoimmunity in autism are reviewed and summarized as being only anecdotally effective, with no controlled studies to conclusively determine effectiveness. The goal of this article is to allow child neurologists to effectively counsel parents of autistic patients about vaccination risks and treatment options in presumed cases of autoimmune dysfunction.
Dietrich, K; Theobald, M
Tumor cells could fundamentally be recognized and eliminated by the immune system but malignant cells are able to escape the immune surveillance system. The idea of immunotherapy of cancer is to activate, modulate and amplify the host immune response or to genetically equip the immune repertoire of patients with anti-tumor specificities and effectors. In recent years, a variety of promising immunotherapy strategies have been developed, such as bispecific, multispecific and immunoregulatory antibodies, gene-modified T lymphocytes and tumor vaccines. Some drugs have already been approved and others are available for patients in clinical trials. This article presents the current anti-tumor immune strategies and their molecular basis. Even though further research is needed in some areas, such as the establishment of biomarkers for targeted therapy, duration of therapeutic activity and compatibility of combined strategies, cancer immunotherapy is likely to be a key component in oncological treatment concepts in the very near future.
Bade, Geetanjali; Khan, Meraj Alam; Srivastava, Akhilesh Kumar; Khare, Parul; Solaiappan, Krishna Kumar; Guleria, Randeep; Palaniyar, Nades; Talwar, Anjana
Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process.
Steinman, Ralph M
This volume provides a small sampling of the rapidly growing science of cancer immunology. Growth in the field includes advances on the requirements for immunization or vaccination and the ways in which immunity can be suppressed or blocked, including active tumor-based mechanisms. I would like to introduce the papers in this volume and then deal with a subject that pervaded many discussions among symposium participants. The subject is the need for a much better supported and organized effort to design optimal studies of immunology in cancer patients so that cancer vaccines can become a major means to prevent and treat this disease.
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Beta-globulin immunolog-ical test system. 866.5160 Section 866.5160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5160...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Beta-globulin immunolog-ical test system. 866.5160 Section 866.5160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5160...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
Describes an exhibition for the benefit of teachers of English in Arab Primary Schools, which was prepared by third-year students at the Teachers College for Arab Teachers. The exhibition included games, songs, audiovisual aids, crossword puzzles, vocabulary, spelling booklets, preposition aids, and worksheet and lesson planning aids. (SED)
... 42 Public Health 5 2010-10-01 2010-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...
... 42 Public Health 5 2012-10-01 2012-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...
... 42 Public Health 5 2013-10-01 2013-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...
... 42 Public Health 5 2011-10-01 2011-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...
... 42 Public Health 5 2014-10-01 2014-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...
Chinen, Javier; Shearer, William T
This review highlights some of the most significant advances in basic and clinical immunology that were published from August 2002 to December 2003, focusing on manuscripts that appeared in the Journal. Articles selected were those considered most relevant to Journal readers. With regard to basic immunology, this report includes articles describing FcepsilonRI expression in mucosal Langerhans cells and type II dendritic cells, mechanisms of TH1 and TH2 regulation, the role of Foxp3 in the development of CD4+CD25+ regulatory T cells, and the increasing importance of Toll receptors in immunity. Articles related to clinical immunology that were selected include the first report of lymphocyte subsets values from a large cohort of normal children; the description of new genetic defects in primary immunodeficiencies; a description of the complications of gene therapy for X-linked severe combined immunodeficiency; a report of 79 patients with hyper-IgM syndrome; a report of the mechanism of action and complications of intravenous immunoglobulin; a report of new approaches for immunotherapy; and an article on advances in HIV infection and management, including a report of defensins, small molecules with anti-HIV properties. Also summarized is an article that studied the immune system during a prolonged stay in the Antarctic, a model for human studies on the effect of environmental conditions similar to space expeditions.
Seignalet, J; Hedon, B
Spontaneous repeated miscarriages are often explained by an immunological mechanism. Whereas in normal pregnancy the mother develops a tolerance immune response induced by paternal antigens of fetus, she is unable to react in this variety of miscarriage. The immunological theory is supported by some solid experimental arguments, which are detailed. Antigens generating the tolerance response are probably TLX antigens, expressed on syncitiotrophoblast and cross reacting with class I HLA antigens. Diagnosis of immunological miscarriage is based on elimination of other causes and on absence in woman of antibodies directed against husband class I antigens. Tolerance immune response can be induced by injections to wife of great quantity of conjunct lymphocytes. An anti HLA, and later on anti TLX, immunization is often obtained. Several teams have applied this treatment, with frequent good results: about 80% of fecundated patients conduct a normal pregnancy until its time.
After reviewing present knowledge of the morphology, multiplication, and transmission of Trypanosoma cruzi, this Memorandum discusses the animal models that may be of value in understanding the immune mechanisms operating in Chagas' disease. The role of both circulating antibody and cell-mediated immunity in protection against the parasite is discussed, together with the possibility that immunopathological mechanisms may be responsible for some of the lesions found in patients with Chagas' disease. The immunodiagnostic methods at present available are also reviewed, and the possibility of producing a vaccine for human use is considered in the light of recent findings in experimental animals. A series of recommendations for further research is included. PMID:4218137
Štajner, Tijana; Vasiljević, Zorica; Vujić, Dragana; Marković, Marija; Ristić, Goran; Mićić, Dragan; Pašić, Srdjan; Ivović, Vladimir; Ajzenberg, Daniel
In immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient's HLA-identical brother. Prophylaxis with cotrimoxazole was discontinued a day before the HSCT procedure. Signs of lung infection appeared as early as day 14 post-HSCT. The presence of tachyzoite-like structures on Giemsa-stained bronchoalveolar lavage (BAL) fluid smears suggested toxoplasmosis. Real-time PCR targeted at the T. gondii AF146527 gene revealed extremely high parasite burdens in both blood and BAL fluid. Although immediate introduction of specific treatment resulted in a marked reduction of the parasite load and transient clinical improvement, the patient deteriorated and died of multiple organ failure on day 39 post-HSCT. Direct genotyping of T. gondii DNA from blood and BAL fluid with the PCR-restriction fragment length polymorphism method revealed type II alleles with SAG1, SAG2, and GRA6 markers but alleles of both type I and type II with GRA7. Additional analysis with 15 microsatellite markers showed that the T. gondii DNA was atypical and genetically divergent from that of the clonal type I, II, and III strains. This is the first report of increased clinical severity of toxoplasmosis associated with an atypical strain in the setting of immunosuppression, which emphasizes the need to diagnose and monitor toxoplasmosis by quantitative molecular methods in cases of reactivation risk. PMID:23761151
This case reports an immunocompetent 29-year-old woman with suspected pneumonia, suggestive of fungal infection. Immunoblotting analysis reactivity against Histoplasma capsulatum and Paracoccidioides brasiliensis were observed. Nested-PCR in blood employing species-specific primers was positive for H. capsulatum and Cryptococcus neoformans. The evaluation of paucisymptomatic patients with positive results for H. capsulatum and C. neoformans could be relevant for the prevention as well as the possible evaluation of the reactivated quiescent foci. In conclusion, the associated methodology may have contributed to the monitoring endogenous reactivation of these diseases. PMID:25180029
Dusenbery, P.; Harold, J.; Morrow, C.
It is critically important for the public to better understand the scientific process. Museum exhibitions are an important part of informal science education that can effectively reach public audiences as well as school groups. They provide an important gateway for the public to learn about compelling scientific endeavors. There are many ways for scientists to help develop science exhibitions. The Space Science Institute (SSI) is a national leader in producing traveling science exhibitions and their associated educational programming (i.e. interactive websites, educator workshops, public talks, instructional materials). Two of its exhibitions, Space Weather Center and MarsQuest, are currently on tour. Another exhibition, Alien Earths, is in development. The Space Weather Center was developed in partnership with various research missions at NASA's Goddard Space Flight Center. MarsQuest is a 5000 square-foot traveling exhibition. The exhibit's second 3-year tour began this January at the Detroit Science Center. It is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and to learn more about their own planet in the process. The 3,000 square-foot traveling exhibition, called Alien Earths, will bring origins-related research and discoveries to students and the American public. Alien Earths has four interrelated exhibit areas: Our Place in Space, Star Birth, PlanetQuest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in ``habitable zones'' around other stars; and finally they will be able to learn about how scientists are looking for signs of life beyond Earth. Besides the exhibits, SSI is also developing interactive web sites based on exhibit themes. New technologies are transforming the Web from a static medium to an interactive environment with tremendous
Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.
Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient. PMID:26015713
Fan, Wen-Chien; Liu, Chih-Wei; Ou, Shuo-Ming; Huang, Chia-Chang; Li, Tzu-Hao; Lee, Kuei-Chuan; Huang, Shiang-Fen; Yang, Ying-Ying; Hsieh, Yun-Cheng; Hsieh, Shie-Liang; Hou, Ming-Chih; Lin, Han-Chieh
Genetic variants and dysfunctional monocyte had been reported to be associated with infection susceptibility in advanced cirrhotic patients. This study aims to explore genetic predictive markers and relevant immune dysfunction that contributed to severe sepsis in febrile acute de-compensated cirrhotic patents. Polymorphism analysis of candidate genes was undergone in 108 febrile acute de-compensated cirrhotic patients and 121 healthy volunteers. Various plasma inflammatory/regulatory cytokines, proportion of classical (CD 16-, phagocytic) and non-classical (CD16+, inflammatory) monocytes, lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) and intracellular/extracellular cytokines on cultured non-classical monocytes, mCD14/HLA-DR expression and phagocytosis of classical monocytes were measured. For TLR4+896A/G variant allele carriers with severe sepsis, high plasma endotoxin/IL-10 inhibits HLA-DR expression and impaired phagocytosis were noted in their classical monocyte. In the same group, increased non-classical monocyte subset, enhanced LPS-stimulated TLR4 expression and TNFα/nitrite production, and systemic inflammation [high plasma soluble CD14 (sCD14) and total nitric oxide (NOx) levels] were noted. For CD14-159C/T variant allele carriers with severe sepsis, persist endotoxemia inhibited mCD14/HLA-DR expression and impaired phagocytosis of their classical monocyte. In the same group, increased non-classical monocyte subset up-regulated TLR4-NFκB-iNOS and p38MAPK pathway, stimulated TNFα/nitrite production and elicited systemic inflammation. In febrile acute de-compensated cirrhotic patients, TLR4+896A/G and CD14-159C/T polymorphisms-related non-classical and classical monocytes dysfunction resulted in increased severe sepsis risk. Malnutrition, high plasma endotoxin and sCD14 levels, single TLR4+896A/G or CD14-159C/T variant allele carriers and double variant allele carriers are significant predictive factors for the development of severe
A new exhibit in StenniSphere depicting NASA's role in hurricane prediction and research and SSC's role in helping the region recover from Hurricane Katrina. The cyclone-shaped exhibit focuses on the effects of the Aug. 29, 2005 storm and outlines how NASA is working to improve weather forecasting. Through photos, 3-D models and digital animations, the exhibit tells the story of what happened inside the storm and how NASA's scientific research can increase the accuracy of hurricane tracking and modeling.
Cardona-Castro, Nora; Beltrán-Alzate, Juan Camilo; Romero-Montoya, Marcela
Follow-up of the household contacts (HHC) of leprosy patients is still the best strategy for early detection of leprosy. HHC from a post-elimination region of Colombia studied in 2001-2002 were re-contacted in 2007. They were tested at both times by clinical examination, bacillary index (BI), PCR from a slit skin smear (SSS) and anti PGL-1 IgM titres. Thirty-two of 61 HHC (52%) were re-contacted. Nine HHC (28%) showed sero-conversion and one had a skin lesion (BI negative, nested PCR positive). Periodic evaluation of HHC can contribute to the detection of infected HHC as well as new and early leprosy cases.
Walochnik, J; Obwaller, A; Aspöck, H
Various species of the genus Acanthamoeba have been described as potential pathogens; however, differentiation of acanthamoebae remains problematic. The genus has been divided into 12 18S rDNA sequence types, most keratitis causing strains exhibiting sequence type T4. We recently isolated a keratitis causing Acanthamoeba strain showing sequence type T6, but being morphologically identical to a T4 strain. The aim of our study was to find out, whether the 18S rDNA sequence based identification correlates to immunological differentiation. The protein and antigen profiles of the T6 isolate and three reference Acanthamoeba strains were investigated using two sera from Acanthamoeba keratitis patients and one serum from an asymptomatic individual. It was shown, that the T6 strain produces a distinctly different immunological pattern, while patterns within T4 were identical. Affinity purified antibodies were used to further explore immunological cross-reactivity between sequence types. Altogether, the results of our study support the Acanthamoeba 18S rDNA sequence type classification in the investigated strains.
Gaudillière, Brice; Ganio, Edward A; Tingle, Martha; Lancero, Hope L; Fragiadakis, Gabriela K; Baca, Quentin J; Aghaeepour, Nima; Wong, Ronald J; Quaintance, Cele; El-Sayed, Yasser Y; Shaw, Gary M; Lewis, David B; Stevenson, David K; Nolan, Garry P; Angst, Martin S
Single-cell technologies have immense potential to shed light on molecular and biological processes that drive human diseases. Mass cytometry (or Cytometry by Time Of Flight mass spectrometry, CyTOF) has already been employed in clinical studies to comprehensively survey patients' circulating immune system. As interest in the "bedside" application of mass cytometry is growing, the delineation of relevant methodological issues is called for. This report uses a newly generated dataset to discuss important methodological considerations when mass cytometry is implemented in a clinical study. Specifically, the use of whole blood samples versus peripheral blood mononuclear cells (PBMCs), design of mass-tagged antibody panels, technical and analytical implications of sample barcoding, and application of traditional and unsupervised approaches to analyze high-dimensional mass cytometry datasets are discussed. A mass cytometry assay was implemented in a cross-sectional study of 19 women with a history of term or preterm birth to determine whether immune traits in peripheral blood differentiate the two groups in the absence of pregnancy. Twenty-seven phenotypic and 11 intracellular markers were simultaneously analyzed in whole blood samples stimulated with lipopolysaccharide (LPS at 0, 0.1, 1, 10, and 100 ng mL(-1)) to examine dose-dependent signaling responses within the toll-like receptor 4 (TLR4) pathway. Complementary analyses, grounded in traditional or unsupervised gating strategies of immune cell subsets, indicated that the prpS6 and pMAPKAPK2 responses in classical monocytes are accentuated in women with a history of preterm birth (FDR<1%). The results suggest that women predisposed to preterm birth may be prone to mount an exacerbated TLR4 response during the course of pregnancy. This important hypothesis-generating finding points to the power of single-cell mass cytometry to detect biologically important differences in a relatively small patient cohort.
Immunological effects of nilotinib prophylaxis after allogeneic stem cell transplantation in patients with advanced chronic myeloid leukemia or philadelphia chromosome-positive acute lymphoblastic leukemia
Shouval, Roni; Eldror, Shiran; Lev, Atar; Davidson, Jacqueline; Rosenthal, Esther; Volchek, Yulia; Shem-Tov, Noga; Yerushalmi, Ronit; Shimoni, Avichai; Somech, Raz; Nagler, Arnon
Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib. Lymphocyte subpopulations and their functional activities including T-cell response to mitogens, NK cytotoxic activity and thymic function, determined by quantification of the T cell receptor (TCR) excision circles (TREC) and TCR repertoire, were evaluated at several time points, including pre-nilotib-post-allo-SCT, and up to 365 days on nilotinib treatment. NK cells were the first to recover post allo-SCT. Concomitant to nilotinib administration, total lymphocyte counts and subpopulations gradually increased. CD8 T cells were rapidly reconstituted and continued to increase until day 180 post SCT, while CD4 T cells counts were low until 180−270 days post nilotinib treatment. T-cell response to mitogenic stimulation was not inhibited by nilotinib administration. Thymic activity, measured by TREC copies and surface membrane expression of 24 different TCR Vβ families, was evident in all patients at the end of follow-up after allo-SCT and nilotinib treatment. Finally, nilotinib did not inhibit NK cytotoxic activity. In conclusion, administration of nilotinib post allo-SCT, in attempt to reduce relapse rates or progression of Ph+ ALL and CML, did not jeopardize immune reconstitution or function following transplantation. PMID:27880933
Beck, Sarah C; Lock, Robert J
'Measurement uncertainty of measured quantity values' (ISO15189) requires that the laboratory shall determine the measurement uncertainty for procedures used to report measured quantity values on patients' samples. Where we have numeric data measurement uncertainty can be expressed as the standard deviation or as the co-efficient of variation. However, in immunology many of the assays are reported either as semi-quantitative (i.e. an antibody titre) or qualitative (positive or negative) results. In the latter context, measuring uncertainty is considerably more difficult. There are, however, strategies which can allow us to minimise uncertainty. A number of parameters can contribute to making measurements uncertain. These include bias, precision, standard uncertainty (expressed as standard deviation or coefficient of variation), sensitivity, specificity, repeatability, reproducibility and verification. Closely linked to these are traceability and standardisation. In this article we explore the challenges presented to immunology with regard to measurement uncertainty. Many of these challenges apply equally to other disciplines working with qualitative or semi-quantitative data.
Wing, S S; Fantus, I G
Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299
Have you ever wondered how the engineers at John C. Stennis Space Center in Hancock County, Miss., test fire a Space Shuttle Main Engine? The Test Control Center exhibit at StenniSphere can answer your questions by simulating the test firing of a Space Shuttle Main Engine. A recreation of one of NASA's test control centers, the exhibit explains and portrays the 'shake, rattle and roar' that happens during a real test firing.
It is critically important for the public to better understand the scientific process. Museum exhibitions are an important part of informal science education that can effectively reach public audiences as well as school groups. They provide an important gateway for the public to learn about compelling scientific endeavors. Science exhibitions also provide a marvelous opportunity for scientists to become engaged in the exhibit development process. The Space Science Institute (SSI) is a national leader in producing traveling science exhibitions and their associated educational programming (i.e. interactive websites, educator workshops, public talks, instructional materials). The focus of this presentation will be on two of its exhibit projects: MarsQuest (on tour for four years) and Alien Earths (its tour began early in 2005). MarsQuest is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and to learn more about their own planet in the process. Alien Earths will bring origins-related research and discoveries to students and the American public. It has four interrelated exhibit areas: Our Place in Space, Star Birth, Planet Quest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in ``habitable zones'' around other stars; and finally they will be able to learn about how scientists are looking for signs of life beyond Earth. SSI is also developing interactive web sites based on exhibit themes. New technologies are transforming the Web from a static medium to an interactive environment with tremendous potential for informal education and inquiry-based investigations. This talk will focus on the role informal science projects play in effectively communicating science to a broad, public audience.
Ivanov, A A; Shvets, V N
Immunological reactivity of rats flown aboard the biosatellites Cosmos-605 and Cosmos-690 was compared with respect to the complementary activity of serum and frequency antibodies to sheep red blood cells. Cosmos-605 rats showed changes that rapidly returned to the normal whereas Cosmos-690 rats irradiated inflight with a dose of 800 rad exhibited significant and stable changes in immunological reactivity. Those latter seemed to be associated with the combined effect of ionizing radiation and other space flight factors.
Snyder, Paul W
The immune system functions primarily as a defense mechanism to provide protective immunity against microbial pathogens and cancer. The resulting protective responses occur through the complex interaction of tissues, cells, proteins, and molecular pathways that act in concert with other systems (e.g., nervous and endocrine) to provide the host with immunologic responses that cause pathologic processes seen primarily as inflammatory reactions. The pathologic responses can be attributed to either normal responses to infectious organisms and cancer cells, misdirected responses as in the case of hypersensitivity or autoimmune diseases, or deficient responses attributable to deficiencies or defects in components of the immune system. Pathologists need to have a basic understanding of the immune system to not only interpret findings as to their likely pathogenesis, but also to predict when the immune system may be a potential target. This review will be limited to a general overview of the basic immunologic responses and primary components involved.
Schwartz, Ronald H
A fundamental property of the immune system is its ability to mediate self-defense with a minimal amount of collateral damage to the host. The system uses several different mechanisms to achieve this goal, which is collectively referred to as the "process of immunological tolerance." This article provides an introductory historical overview to these various mechanisms, which are discussed in greater detail throughout this collection, and then briefly describes what happens when this process fails, a state referred to as "autoimmunity."
Stejskalová, S; Dolezal, Z; Nekvasil, R
The authors demonstrate two cases of non-immunological foetal hydrops. In the first case the initial cause of foetal hydrops was hypoalbuminaemia (hypoproteinaemia), in the second case intrauterine cardiac failure resulting from supraventricular tachycardia of unknown aetiology. The authors explain the pathogenesis of the condition, its early diagnosis and therapy. They draw attention to possible intoxication of the neonate by digoxin administered to the mother during pregnancy.
Sakai, Kazuyoshi; Senda, Takao; Hata, Ryuji; Kuroda, Makoto; Hasegawa, Midori; Kato, Masao; Abe, Masato; Kawaguchi, Kazunori; Nakai, Shigeru; Hiki, Yoshiyuki; Yuzawa, Yukio; Kitaguchi, Nobuya
As a proof of concept that removal of blood amyloid-β (Aβ) can reduce Aβ deposition in the brains of patients with Alzheimer's disease, cortices of patients who had undergone hemodialysis (HD), which removes Aβ from the blood, were histochemically analyzed; postmortem brain sections were stained with anti-Aβ antibodies. Brains from patients who had undergone HD had significantly fewer senile plaques than those of patient who had not undergone HD. This significant difference was also confirmed by silver staining. Our findings suggest that removal of blood Aβ by hemodialysis results in lower accumulation of Aβ in the brain.
Shahi, Shipra; Katiyar, Raj Kishore; Gaur, Shailendra; Jain, Vikram
Background Rapeseed-mustard is the second most important source of edible oil in India. Several species of Brassica are grown in different parts of country for its oilseeds. Objective The objective was to investigate allergenicity to antigenic extracts of pollen of 4 species of Brassica. Methods Brassica campestris, Brassica juncea, Brassica nigra, and Brassica napus were selected for the detailed investigation. Pollen samples from each of the four species were collected from the polliniferous materials. The antigenic and allergenic profiles of these extracts were evaluated by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Skin prick test, enzyme linked immuno sorbent assay and Western blot on atopic individuals. Results Out of the 159 atopic subjects tested, 21.38% were positive to at least one or other species of Brassica pollen, with highest skin positivity (13.20%) to B. campestris extract. Raised IgE with significant linear correlation with intensity of skin reactions was obtained. Protein fractions of 20, 25, 32, 37, 56, and 90 kDa were recognized by B. campestris and B. juncea whereas 56, 76, 87, and 90 kDa were recognized by B. nigra and B. napus as major IgE binding protein fractions. The patients also showed positivity to other inhalant pollen allergens tested. Conclusion IgE mediated hypersensitivity varied from 4.40% to 13.20% in Indian atopic subjects to pollen of one or the other species of Brassica. Protein fractions of 47, 56, 76, 87, and 90 kDa were identified as IgE binding by all the four species, however individual heterogeneity exists. Thus a local species may be more pertinent for immunotherapy. The major allergen needs to be further characterized. PMID:25379479
De Mercanti, Stefania; Rolla, Simona; Cucci, Angele; Bardina, Valentina; Cocco, Eleonora; Vladic, Anton; Soldo-Butkovic, Silva; Habek, Mario; Adamec, Ivan; Horakova, Dana; Annovazzi, Pietro; Novelli, Francesco; Clerico, Marinella
Objective: To analyze changes in T-helper (Th) subsets, T-regulatory (Treg) cell percentages and function, and mRNA levels of immunologically relevant molecules during a 24-month follow-up after alemtuzumab treatment in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Multicenter follow-up of 29 alemtuzumab-treated patients with RRMS in the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I and CARE-MS II trials. Peripheral blood (PB) samples were obtained at months 0, 6, 12, 18, and 24. We evaluated (1) mRNA levels of 26 immunologic molecules (cytokines, chemokines, chemokine receptors, and transcriptional factors); (2) Th1, Th17, and Treg cell percentages; and (3) myelin basic protein (MBP)–specific Treg suppressor activity. Results: We observed 12 relapses in 9 patients. mRNA levels of the anti-inflammatory cytokines interleukin (IL)–10, IL-27, and transforming growth factor–β persistently increased whereas those of proinflammatory molecules related to the Th1 or Th17 subsets persistently decreased after alemtuzumab administration throughout the follow-up period. PB CD4+ cell percentage remained significantly lower than baseline while that of Th1 and Th17 cells did not significantly change. A significant increase in Treg cell percentage was observed at month 24 and was accompanied by an increase in Treg cell suppressive activity against MBP-specific Th1 and Th17 cells. Conclusions: The long-lasting therapeutic benefit of alemtuzumab in RRMS may involve a shift in the cytokine balance towards inhibition of inflammation associated with a reconstitution of the PB CD4+ T-cell subsets that includes expansion of Treg cells with increased suppressive function. PMID:26819963
There are several factors involved in studying cancer immunology. For convenience, those factors can be consolidated into two. Firstly, no definite tumor-specific or -associated antigen has been ascertained as yet, except for certain types of tumor. Secondly, there is no definite pattern of immune response of the host against weak antigenic tumor cells. Nobody knows as to what is the nature of the tumor-specific antigen even if it exists, and nobody knows the escape mechanism of tumor cells from the immune defence of the host. There have been a number of approaches for cancer immunotherapy, but so far there has been no definite answer as to whether immunotherapy is a promising approach for cancer treatment. In this review, cancer immunology is divided into three separate subjects. The first of these is tumor antigen; the second, the immune response against tumor antigen; and the third, methods of attacking tumor cells by immunological means including how to increase the antigenicity of tumor cells (xenogenization), and how to increase the immune response of the host (immunotherapy).
The menacing-looking alligator is really harmless. It is one of the realistic props to help convince visitors that the feel of the swamp is real in StenniSphere's Swamp to Space exhibit at John C. Stennis Space Center in Hancock County, Miss. The historical section of the Swamp to Space exhibit tells the story of why and how Stennis Space Center came to be. It also pays tribute to the families who moved their homes to make way for the space age in Mississippi.
das Chagas Medeiros, M M; Bezerra, M Campos; Braga, F N Holanda Ferreira; da Justa Feijão, M R Melo; Gois, A C Rodrigues; Rebouças, V C do Rosário; de Carvalho, T M Amorim Zaranza; Carvalho, L N Solon; Ribeiro, Át Mendes
The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality.
Godwin, James W; Rosenthal, Nadia
Salamanders and frogs are distinct orders of Amphibians with very different immune systems during adult life, exhibiting varying potential for scar free repair and regeneration. While salamanders can regenerate a range of body parts throughout all stages of life, regeneration is restricted to early stages of frog development. Comparison of these two closely related amphibian orders provides insights into the immunological influences on wound repair, and the different strategies that have evolved either to limit infection or to facilitate efficient regeneration. After injury, cells of the immune system are responsible for the removal of damaged cells and providing a cohort of important growth factors and signaling molecules. Immune cells not only regulate new vessel growth important for supplying essential nutrients to damaged tissue but, modulate the extracellular matrix environment by regulating fibroblasts and the scarring response. The profile of immune cell infiltration and their interaction with local tissue immune cells directly influences many aspects of the wound healing outcomes and can facilitate or prevent regeneration. Evidence is emerging that the transition from wound healing to regeneration is reliant on immune cell engagement and that the success of regeneration in amphibians may depend on complex interactions between stem cell progenitors and immune cell subsets. The potential immunological barriers to mammalian regeneration are discussed with implications for the successful delivery of stem cell therapeutic strategies in patients.
Silva, Francesca A. R.; Rodrigues, Bruno L.; Ayrizono, Maria de Lourdes S.
Inflammatory bowel diseases (IBDs) are chronic ailments, Crohn's disease and ulcerative colitis being the most important. These diseases present an inflammatory profile and they differ according to pathophysiology, the affected area in the gastrointestinal tract, and the depth of the inflammation in the intestinal wall. The immune characteristics of IBD arise from abnormal responses of the innate and adaptive immune system. The number of Th17 cells increases in the peripheral blood of IBD patients, while Treg cells decrease, suggesting that the Th17/Treg proportion plays an important role in the development and maintenance of inflammation. The purpose of this review was to determine the current state of knowledge on the immunological basis of IBD. Many studies have shown the need for further explanation of the development and maintenance of the inflammatory process. PMID:28070181
Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.
HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571
Binks, Sophie; Vincent, Angela; Palace, Jacqueline
Myasthenia gravis (MG) is the archetypic disorder of both the neuromuscular junction and autoantibody-mediated disease. In most patients, IgG1-dominant antibodies to acetylcholine receptors cause fatigable weakness of skeletal muscles. In the rest, a variable proportion possesses antibodies to muscle-specific tyrosine kinase while the remainder of seronegative MG is being explained through cell-based assays using a receptor-clustering technique and, to a lesser extent, proposed new antigenic targets. The incidence and prevalence of MG are increasing, particularly in the elderly. New treatments are being developed, and results from the randomised controlled trial of thymectomy in non-thymomatous MG, due for release in early 2016, will be of particular clinical value. To help navigate an evidence base of varying quality, practising clinicians may consult new MG guidelines in the fields of pregnancy, ocular and generalised MG (GMG). This review focuses on updates in epidemiology, immunology, therapeutic and clinical aspects of GMG in adults.
Convente, Michael R.; Wang, Haitao; Pignolo, Robert J.; Kaplan, Frederick S.; Shore, Eileen M.
The formation of bone outside the endogenous skeleton is a significant clinical event, rendering affected individuals with immobility and a diminished quality of life. This bone, termed heterotopic ossification (HO), can appear in patients following invasive surgeries and traumatic injuries, as well as progressively manifest in several congenital disorders. A unifying feature of both genetic and non-genetic episodes of HO is immune system involvement at the early stages of disease. Activation of the immune system sets the stage for the downstream anabolic events that eventually result in ectopic bone formation, rendering the immune system a particularly appealing site of early therapeutic intervention for optimal management of disease. In this review we will discuss the immunological contributions to HO disorders, with specific focus on contributing cell types, signaling pathways, relevant in vivo animal models, and potential therapeutic targets. PMID:25687936
Kunz, Walter S., Jr.
Describes the Youth Art Month exhibit in Howard County (Maryland) where students submitted their art focusing on school buildings and their interiors. Their art reveals concerns and desires about overcrowding, space utilization, school building height, outside lighting, solitude needs, and visual stimulation. The artwork is discussed in terms of…
Early in the eighteenth century, Pompeii was discovered, a city that had been hidden for sixteen centuries by volcanic lava. There is a traveling exhibition of the sculptures, friezes, mosaics, and paintings being shown around the United States. Described is the history and contents of "Pompeii--A.D. 79." (RK)
School Business Affairs, 1990
Winners of the 1989 Architectural Exhibition sponsored annually by the ASBO International's School Facilities Research Committee include the Brevard Performing Arts Center (Melbourne, Florida), the Capital High School (Santa Fe, New Mexico), Gage Elementary School (Rochester, Minnesota), the Lakewood (Ohio) High School Natatorium, and three other…
Ludwig Mies van der Rohe is known primarily as an architect. However, he also designed chairs and tables. Discusses an exhibit held in New York City a few months ago which showed how well the famous architect achieved his goals in the area of furniture design. (Author/RK)
Nieto, Antonio; Mazon, Angel; Martin-Mateos, Maria Anunciacion; Plaza, Ana-Maria; Garde, Jesus; Alonso, Elena; Martorell, Antonio; Boquete, Manuel; Lorente, Felix; Ibero, Marcel; Bone, Javier; Pamies, Rafael; Garcia, Juan Miguel; Echeverria, Luis; Nevot, Santiago; Martinez-Cañavate, Ana; Fernandez-Benitez, Margarita; Garcia-Marcos, Luis
The data of the ISAAC project in Spain show a prevalence of childhood asthma ranging from 7.1% to 15.3%, with regional differences; a higher prevalence, 22.6% to 35.8%, is described for rhinitis, and atopic dermatitis is found in 4.1% to 7.6% of children. The prevalence of food allergy is 3%. All children in Spain have the right to be visited in the National Health System. The medical care at the primary level is provided by pediatricians, who have obtained their titles through a 4-yr medical residency training program. The education on pediatric allergy during that period is not compulsory and thus very variable. There are currently 112 certified European pediatric allergists in Spain, who have obtained the accreditation of the European Union of Medical Specialist for proven skills and experience in pediatric allergy. Future specialists in pediatric allergy should obtain their titles through a specific education program to be developed in one of the four accredited training units on pediatric allergy, after obtaining the title on pediatrics. The Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) gathers over 350 pediatric allergists and pediatricians working in this field. SEICAP has a growing activity including yearly congresses, continued education courses, elaboration of technical clinical documents and protocols, education of patients, and collaboration with other scientific societies and associations of patients. The official journal of SEICAP is Allergologia et Immunophatologia, published every 2 months since 1972. The web site of SEICAP, http://www.seicap.es, open since 2004, offers information for professionals and extensive information on pediatric allergic and immunologic disorders for the lay public; the web site is receiving 750 daily visits during 2011. The pediatric allergy units are very active in clinical work, procedures as immunotherapy or induction of oral tolerance in food allergy, contribution to scientific literature, and
Hänggi, Pascal; Makhro, Asya; Gassmann, Max; Schmugge, Markus; Goede, Jeroen S; Speer, Oliver; Bogdanova, Anna
Recently we showed that N-methyl D-aspartate receptors (NMDARs) are expressed in erythroid precursors (EPCs) and present in the circulating red blood cells (RBCs) of healthy humans, regulating intracellular Ca(2+) in these cells. This study focuses on investigating the possible role of NMDARs in abnormally high Ca(2+) permeability in the RBCs of patients with sickle cell disease (SCD). Protein levels of the NMDAR subunits in the EPCs of SCD patients did not differ from those in EPCs of healthy humans. However, the number and activity of the NMDARs in circulating SCD-RBCs was substantially up-regulated, being particularly high during haemolytic crises. The number of active NMDARs correlated negatively with haematocrit and haemoglobin levels in the blood of SCD patients. Calcium uptake via these non-selective cation channels was induced by RBC treatment with glycine, glutamate and homocysteine and was facilitated by de-oxygenation of SCD-RBCs. Oxidative stress and RBC dehydration followed receptor stimulation and Ca(2+) uptake. Inhibition of the NMDARs with an antagonist memantine caused re-hydration and largely prevented hypoxia-induced sickling. The EPCs of SCD patients showed higher tolerance to memantine than those of healthy subjects. Consequently, NMDARs in the RBCs of SCD patients appear to be an attractive target for pharmacological intervention.
Said, Heba S; Suda, Wataru; Nakagome, Shigeki; Chinen, Hiroshi; Oshima, Kenshiro; Kim, Sangwan; Kimura, Ryosuke; Iraha, Atsushi; Ishida, Hajime; Fujita, Jiro; Mano, Shuhei; Morita, Hidetoshi; Dohi, Taeko; Oota, Hiroki; Hattori, Masahira
Analysis of microbiota in various biological and environmental samples under a variety of conditions has recently become more practical due to remarkable advances in next-generation sequencing. Changes leading to specific biological states including some of the more complex diseases can now be characterized with relative ease. It is known that gut microbiota is involved in the pathogenesis of inflammatory bowel disease (IBD), mainly Crohn's disease and ulcerative colitis, exhibiting symptoms in the gastrointestinal tract. Recent studies also showed increased frequency of oral manifestations among IBD patients, indicating aberrations in the oral microbiota. Based on these observations, we analyzed the composition of salivary microbiota of 35 IBD patients by 454 pyrosequencing of the bacterial 16S rRNA gene and compared it with that of 24 healthy controls (HCs). The results showed that Bacteroidetes was significantly increased with a concurrent decrease in Proteobacteria in the salivary microbiota of IBD patients. The dominant genera, Streptococcus, Prevotella, Neisseria, Haemophilus, Veillonella, and Gemella, were found to largely contribute to dysbiosis (dysbacteriosis) observed in the salivary microbiota of IBD patients. Analysis of immunological biomarkers in the saliva of IBD patients showed elevated levels of many inflammatory cytokines and immunoglobulin A, and a lower lysozyme level. A strong correlation was shown between lysozyme and IL-1β levels and the relative abundance of Streptococcus, Prevotella, Haemophilus and Veillonella. Our data demonstrate that dysbiosis of salivary microbiota is associated with inflammatory responses in IBD patients, suggesting that it is possibly linked to dysbiosis of their gut microbiota.
Forty-five patients with Takayasu's disease were studied between 1972 and the end of 1979. Operative treatment was less frequently needed for aortic arch disease than for descending aorta disease. Correct evaluation may be difficult in the latter till the time of operative exploration. Children with significant stenosis need early operation and a "plasty' type of repair is favoured over bypass grafts. Contrary to some descriptions, the disease process can affect the region of the aortoiliac bifurcation, needing surgical management based on established principles. Correct evaluation can make operative treatment safe and rewarding for those patients who need intervention as the recurrence rate of the disease process has been low in surgically treated patients. Immunologically the patients show defective T-lymphocyte function, increase in ther serum level of IgG, and a reduction in serum complement constituents C3 and C4, indicating the possibility of formation of a complement-binding immune complex. Histochemical studies show deposition of IgG and PAS-positive material in the intima and probable deposition of IgM and IgA in the junctional area of media and intima, with total destruction of the elastic lamina. A hypothesis for the pathogenesis of the disease is presented. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:6115612
Michalski, Christina; Kan, Bernard; Lavoie, Pascal M.
Newborns are prone to fungal infections, largely due to Candida species. The immunological basis for this vulnerability is not yet fully understood. However, useful insights can be gained from the knowledge of the maturation of immune pathways during ontogeny, particularly when placed in context with how rare genetic mutations in humans predispose to fungal diseases. In this article, we review these most current data on immune functions in human newborns, highlighting pathways most relevant to the response to Candida. While discussing these data, we propose a framework of why deficiencies in these pathways make newborns particularly vulnerable to this opportunistic pathogen. PMID:28360910
Zitvogel, Laurence; Apetoh, Lionel; Ghiringhelli, François; Kroemer, Guido
Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies.
This photograph shows the Starship 2040 leaving the Marshall Space Flight Center (MSFC) for the exhibit site. Developed by the Space Transportation Directorate at MSFC, the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit, automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids and emergency and safety systems, are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.
This photograph shows onlookers viewing displays within the Starship 2040 exhibit on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.
This photograph shows Justin Varnadore, son of a Marshall TV employee, at the controls of one of the many displays within the Starship 2040 exhibit on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.
Presenting the complexity of geosciences to the public via the Internet poses a number of challenges. For example, utilizing various - and sometimes redundant - Web 2.0 tools can quickly devour limited time. Do you tweet? Do you write press releases? Do you create an exhibit or concept map? The presentation will provide participants with a context for utilizing Web 2.0 tools by briefly highlighting methods of online scientific communication across several dimensions. It will address issues of: * breadth and depth (e.g. from narrow topics to well-rounded views), * presentation methods (e.g. from text to multimedia, from momentary to enduring), * sources and audiences (e.g. for experts or for the public, content developed by producers to that developed by users), * content display (e.g. from linear to non-linear, from instructive to entertaining), * barriers to entry (e.g. from an incumbent advantage to neophyte accessible, from amateur to professional), * cost and reach (e.g. from cheap to expensive), and * impact (e.g. the amount learned, from anonymity to brand awareness). Against this backdrop, the presentation will provide an overview of two methods of online information dissemination, exhibits and concept maps, using the WebExhibits online museum (www.webexhibits.org) and SpicyNodes information visualization tool (www.spicynodes.org) as examples, with tips on how geoscientists can use either to communicate their science. Richly interactive online exhibits can serve to engage a large audience, appeal to visitors with multiple learning styles, prompt exploration and discovery, and present a topic’s breadth and depth. WebExhibits, which was among the first online museums, delivers interactive information, virtual experiments, and hands-on activities to the public. While large, multidisciplinary exhibits on topics like “Color Vision and Art” or “Calendars Through the Ages” require teams of scholars, user interface experts, professional writers and editors
Emmi, Giacomo; Silvestri, Elena; Bella, Chiara Della; Grassi, Alessia; Benagiano, Marisa; Cianchi, Fabio; Squatrito, Danilo; Cantarini, Luca; Emmi, Lorenzo; Selmi, Carlo; Prisco, Domenico; D’Elios, Mario Milco
Abstract Background: Gastrointestinal involvement is one of the most serious in Behçet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behçet patients with early intestinal involvement. Methods: We isolated T cells from intestinal mucosa of 8 patients with intestinal symptoms started within 6 months. T lymphocytes were cloned and analyzed for surface phenotype and cytokines production. Results: We obtained 382 T-cell clones: 324 were CD4+ and 58 were CD8+. Within the 324 CD4+ clones, 195 were able to secrete IFN-γ and TNF-α, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-γ and IL-17 (Th1/Th17 profile) were 79. Likewise, the number of CD8 clones producing type 1 cytokines was higher than those of CD8 clones producing both type 1 and 2 cytokines. Almost all intestinal-derived T-cell clones expressed perforin-mediated cytotoxicity and Fas–Fas Ligand-mediated pro-apoptotic activity. Conclusions: Our results indicate that in the early stages of the disease, both Th1 and Th17 cells drive inflammation leading to mucosal damage via abnormal and long-lasting cytokines production as well as via both perforin- and Fas–Fas ligand-mediated cytotoxicity. Finally, all the T cells at mucosal level were able to produce large amount of TNF-α, suggesting that its production is a property of intestinal T cells of patients with early active intestinal disease. These results support the therapy with anti-TNF-α agents and suggest the use of anti-IL-17 monoclonal antibodies in Behçet patients with early intestinal involvement. PMID:27930541
Taylor, G. R.
The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.
Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A
In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization.
Want to sit in the cockpit of the Space Shuttle and watch astronauts work in outer space? At StenniSphere, you can do that and much more. StenniSphere, the visitor center at John C. Stennis Space Center in Hancock County, Miss., presents 14,000-square-feet of interactive exhibits that depict America's race for space as well as a glimpse of the future. StenniSphere is open free of charge from 9 a.m. to 5 p.m. daily.
Ruiz-Núñez, B; van den Hurk, G H A M; de Vries, J H M; Mariani, M A; de Jongste, M J L; Dijck-Brouwer, D A J; Muskiet, F A J
CHD may ensue from chronic systemic low-grade inflammation. Diet is a modifiable risk factor for both, and its optimisation may reduce post-operative mortality, atrial fibrillation and cognitive decline. In the present study, we investigated the usual dietary intakes of patients undergoing elective coronary artery bypass grafting (CABG), emphasising on food groups and nutrients with putative roles in the inflammatory/anti-inflammatory balance. From November 2012 to April 2013, we approached ninety-three consecutive patients (80% men) undergoing elective CABG. Of these, fifty-five were finally included (84% men, median age 69 years; range 46-84 years). The median BMI was 27 (range 18-36) kg/m(2). The dietary intake items were fruits (median 181 g/d; range 0-433 g/d), vegetables (median 115 g/d; range 0-303 g/d), dietary fibre (median 22 g/d; range 9-45 g/d), EPA+DHA (median 0.14 g/d; range 0.01-1.06 g/d), vitamin D (median 4.9 μg/d; range 1.9-11.2 μg/d), saturated fat (median 13.1% of energy (E%); range 9-23 E%) and linoleic acid (LA; median 6.3 E%; range 1.9-11.3 E%). The percentages of patients with dietary intakes below recommendations were 62% (fruits; recommendation 200 g/d), 87 % (vegetables; recommendation 150-200 g/d), 73% (dietary fibre; recommendation 30-45 g/d), 91% (EPA+DHA; recommendation 0.45 g/d), 98% (vitamin D; recommendation 10-20 μg/d) and 13% (LA; recommendation 5-10 E%). The percentages of patients with dietary intakes above recommendations were 95% (saturated fat; recommendation < 10 E%) and 7% (LA). The dietary intakes of patients proved comparable with the average nutritional intake of the age- and sex-matched healthy Dutch population. These unbalanced pre-operative diets may put them at risk of unfavourable surgical outcomes, since they promote a pro-inflammatory state. We conclude that there is an urgent need for intervention trials aiming at rapid improvement of their diets to reduce peri-operative risks.
The clinical, human and economic burden associated with sepsis is huge. Initiatives such as the Surviving Sepsis Campaign aim to effectively reduce risk of death from severe sepsis and septic shock. Nonetheless, although substantial benefits raised from the implementation of this campaign have been obtained, much work remains if we are to realise the full potential promised by this strategy. A deeper understanding of the processes leading to sepsis is necessary before we can design an effective suite of interventions. Dysregulation of the immune response to infection is acknowledged to contribute to the pathogenesis of the disease. Production of both proinflammatory and immunosuppressive cytokines is observed from the very first hours following diagnosis. In addition, hypogammaglobulinemia is often present in patients with septic shock. Moreover, levels of IgG, IgM and IgA at diagnosis correlate directly with survival. In turn, nonsurvivors have lower levels of C4 (a protein of the complement system) than the survivors. Natural killer cell counts and function also seem to have an important role in this disease. HLA-DR in the surface of monocytes and counts of CD4+CD25+ T-regulatory cells in blood could also be useful biomarkers for sepsis. At the genomic level, repression of networks corresponding to major histocompatibility complex antigen presentation is observed in septic shock. In consequence, cumulative evidence supports the potential role of immunological monitoring to guide measures to prevent or treat sepsis in a personalised and timely manner (early antibiotic administration, immunoglobulin replacement, immunomodulation). In conclusion, although diffuse and limited, current available information supports the development of large comprehensive studies aimed to urgently evaluate immunological monitoring as a tool to prevent sepsis, guide its treatment and, as a consequence, diminish the morbidity and mortality associated with this severe condition. PMID
This photograph shows the Starship 2040 on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.
Blastocystis Isolates from Patients with Irritable Bowel Syndrome and from Asymptomatic Carriers Exhibit Similar Parasitological Loads, but Significantly Different Generation Times and Genetic Variability across Multiple Subtypes.
Vargas-Sanchez, Gie-Bele; Romero-Valdovinos, Mirza; Ramirez-Guerrero, Celedonio; Vargas-Hernandez, Ines; Ramirez-Miranda, Maria Elena; Martinez-Ocaña, Joel; Valadez, Alicia; Ximenez, Cecilia; Lopez-Escamilla, Eduardo; Hernandez-Campos, Maria Elena; Villalobos, Guiehdani; Martinez-Hernandez, Fernando; Maravilla, Pablo
Blastocystis spp is a common intestinal parasite of humans and animals that has been associated to the etiology of irritable bowel syndrome (IBS); however, some studies have not found this association. Furthermore, many biological features of Blastocystis are little known. The objective of present study was to assess the generation times of Blastocystis cultures, from IBS patients and from asymptomatic carriers. A total of 100 isolates were obtained from 50 IBS patients and from 50 asymptomatic carriers. Up to 50 mg of feces from each participant were cultured in Barret's and in Pavlova's media during 48 h. Initial and final parasitological load were measured by microscopy and by quantitative PCR. Amplicons were purified, sequenced and submitted to GenBank; sequences were analysed for genetic diversity and a Bayesian inference allowed identifying genetic subtypes (ST). Generation times for Blastocystis isolates in both media, based on microscopic measures and molecular assays, were calculated. The clinical symptoms of IBS patients and distribution of Blastocystis ST 1, 2 and 3 in both groups was comparable to previous reports. Interestingly, the group of cases showed scarce mean nucleotide diversity (π) as compared to the control group (0.011±0.016 and 0.118±0.177, respectively), whilst high gene flow and small genetic differentiation indexes between different ST were found. Besides, Tajima's D test showed negative values for ST1-ST3. No statistical differences regarding parasitological load between cases and controls in both media, as searched by microscopy and by qPCR, were detected except that parasites grew faster in Barret's than in Pavlova's medium. Interestingly, slow growth of isolates recovered from cases in comparison to those of controls was observed (p<0.05). We propose that generation times of Blastocystis might be easily affected by intestinal environmental changes due to IBS probably because virulent strains with slow growth may be selected
Blastocystis Isolates from Patients with Irritable Bowel Syndrome and from Asymptomatic Carriers Exhibit Similar Parasitological Loads, but Significantly Different Generation Times and Genetic Variability across Multiple Subtypes
Ramirez-Guerrero, Celedonio; Vargas-Hernandez, Ines; Ramirez-Miranda, Maria Elena; Martinez-Ocaña, Joel; Valadez, Alicia; Ximenez, Cecilia; Lopez-Escamilla, Eduardo; Hernandez-Campos, Maria Elena; Villalobos, Guiehdani; Martinez-Hernandez, Fernando; Maravilla, Pablo
Blastocystis spp is a common intestinal parasite of humans and animals that has been associated to the etiology of irritable bowel syndrome (IBS); however, some studies have not found this association. Furthermore, many biological features of Blastocystis are little known. The objective of present study was to assess the generation times of Blastocystis cultures, from IBS patients and from asymptomatic carriers. A total of 100 isolates were obtained from 50 IBS patients and from 50 asymptomatic carriers. Up to 50 mg of feces from each participant were cultured in Barret’s and in Pavlova’s media during 48 h. Initial and final parasitological load were measured by microscopy and by quantitative PCR. Amplicons were purified, sequenced and submitted to GenBank; sequences were analysed for genetic diversity and a Bayesian inference allowed identifying genetic subtypes (ST). Generation times for Blastocystis isolates in both media, based on microscopic measures and molecular assays, were calculated. The clinical symptoms of IBS patients and distribution of Blastocystis ST 1, 2 and 3 in both groups was comparable to previous reports. Interestingly, the group of cases showed scarce mean nucleotide diversity (π) as compared to the control group (0.011±0.016 and 0.118±0.177, respectively), whilst high gene flow and small genetic differentiation indexes between different ST were found. Besides, Tajima’s D test showed negative values for ST1-ST3. No statistical differences regarding parasitological load between cases and controls in both media, as searched by microscopy and by qPCR, were detected except that parasites grew faster in Barret’s than in Pavlova’s medium. Interestingly, slow growth of isolates recovered from cases in comparison to those of controls was observed (p<0.05). We propose that generation times of Blastocystis might be easily affected by intestinal environmental changes due to IBS probably because virulent strains with slow growth may be
dexamethasone and cortisol whereas F. nucleatum and B. intermedius do not. Biopsies of the diseased tissues from two of the ptients were obtained and the... intermedius in the sera of ANUG patients when compared to sera of healthy > J -10- individuals and those with gingivitis (57). Immunologic studies of... intermedius was shown to be a prominent microorganism in ANUG by Slots and Zambon (61). Other black-pigmented Bacteroides, including B. ginqivalis and B
This Introduction to the special issue of Veterinary Immunology and Immunopathology summarizes the Proceedings of the 9th International Veterinary Immunology Symposium (9th IVIS) held August, 2010, in Tokyo, Japan. Over 340 delegates from 30 countries discussed research progress analyzing the immune...
Vaz, N M
Paraphrasing what Gregory Bateson says on evolution, we might say that: "Immunology has long been badly taught. In particular, students--and even professional immunologists--acquire theories of immunological activity without any deep understanding of what problems these theories attempt to solve."
Slocum, R. D.; Williamson, C. L.; Poggenburg, C. A.; Lynes, M. A.
Pea (Pisum sativum L.) ornithine transcarbamylase (OTC) antisera were used to investigate the immunological relatedness of several plant and animal OTC enzymes. The antisera immunoprecipitated OTC activity in all monocot and dicot species tested, and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of immunoprecipitated protein revealed monomeric proteins ranging from 35,200 to 36,800 daltons in size. Pea OTC antisera did not recognize mammalian OTC protein. OTC activity and protein levels detected on sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblots from homogenates of green leaf, etiolated epicotyl and cotyledon, and root tissues of pea were poorly correlated. This might result from differences in amounts of enzymatically active OTC protein in the homogenates. Alternatively, the antisera may fail to recognize different isozyme forms of OTC, which have been reported for some plant species. A putative cytosolic precursor OTC (pOTC) polypeptide exhibiting and Mr = 39,500 to 40,000 daltons was immunoprecipitated from in vitro translation mixtures of total pea leaf poly(A)+ RNA. The size of the pOTC polypeptide, as compared with mature OTC monomer (36,000 daltons), suggests that a 4 kilodalton N-terminal leader sequence, like that responsible for mitochondrial targeting of the mammalian enzyme, may be involved in organellar import of the plant enzyme.
Hildebrandt, Isabel Junie; Gambhir, Sanjiv Sam
The use of multimodality molecular imaging has recently facilitated the study of molecular and cellular events in living subjects in a noninvasive and repetitive manner to improve the diagnostic capability of traditional assays. The noninvasive imaging modalities utilized for both small animal and human imaging include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT). Techniques specific to small-animal imaging include bioluminescent imaging (BIm) and fluorescent imaging (FIm). Molecular imaging permits the study of events within cells, the examination of cell trafficking patterns that relate to inflammatory diseases and metastases, and the ability to rapidly screen new drug treatments for distribution and effectiveness. In this paper, we will review the current field of molecular imaging assays (especially those utilizing PET and BIm modalities) and examine how they might impact animal models and human disease in the field of clinical immunology.
Andersson, Ulf; Tracey, Kevin J.
The reasoning that neural reflexes maintain homeostasis in other body organs, and that the immune system is innervated, prompted a search for neural circuits that regulate innate and adaptive immunity. This elucidated the inflammatory reflex, a prototypical reflex circuit that maintains immunological homeostasis. Molecular products of infection or injury activate sensory neurons traveling to the brainstem in the vagus nerve. The arrival of these incoming signals generates action potentials that travel from the brainstem to the spleen and other organs. This culminates in T cell release of acetylcholine, which interacts with α7 nicotinic acetylcholine receptors (α7 nAChR) on immunocompetent cells to inhibit cytokine release in macrophages. Herein is reviewed the neurophysiological basis of reflexes that provide stability to the immune system, the neural- and receptor-dependent mechanisms, and the potential opportunities for developing novel therapeutic devices and drugs that target neural pathways to treat inflammatory diseases. PMID:22224768
Meng, Xiaoli; Ariza, Adriana; Waddington, James; Park, Kevin; Naisbitt, Dean
Drug hypersensitivity reactions (DHRs) are adverse drug reactions that may be divided into several categories; namely pharmacologic intolerance, idiosyncratic reactions, pseudo-allergic reactions and allergic reactions. Drug allergic reactions are those DHRs that are mediated by either antibodies or drug-specific T cells. They vary in terms of severity, time-to-onset of clinical manifestations and target organ. Skin is most commonly implicated in drug hypersensitivity reactions; however, it is now apparent that reactions targeting internal organs fall under the definition of drug hypersensitivity. Multiple hypotheses have been proposed to explain the diverse immune mechanisms involved and the heterogeneous clinical presentation. The discovery of human leukocyte antigen (HLA) risk alleles for some DHRs has provided insights in the pathogenesis of these reactions. In this review we summarize immune cells involved in DHRs, discuss the possible immunological mechanisms of DHRs, with an emphasis on the IgE-mediated immediate reactions and T cell-dependent delayed type reactions.
McMurray, D N; Rey, H
Compared to normal children, pre-natally infected infants had significantly elevated IgM concentrations throughout the first year of life and elevated IgA levels for the first 6 months. In contrast, IgG levels dropped significantly below normal at 3 months post-partum. Infants born without overt disease but with elevated IgM were found to have precocious development of serum IgA when compared to control children. Levels of IgA and IgG in tears were markedly reduced in symptomatic children at 3 months of age. Lymphocyte response in vitro to phytohaemagglutinin and pokeweed mitogen was low in symptomatic infants. These results suggest that intratuerine infection may result in multiple immunological abnormalities. PMID:7198020
The Chicago Museum of Science and Industry recently opened its 4,000-square-foot permanent exhibit on the science of AIDS. The exhibit is designed to educate visitors about immunology and virology by presenting AIDS as an example of an immune system breakdown and showing advances made in research and prevention of diseases caused by viruses. The exhibit also seeks to engage preteens with compelling graphics and interactive displays in the hope of motivating them to pursue careers in science. One exhibit, called Frontline, allows visitors to question several physicians and researchers specializing in HIV/AIDS through a touch-screen video program. The exhibit allows these professionals to reveal their commitment and explain their views on the future of the pandemic.
Beineke, Andreas; Siebert, Ursula; Wohlsein, Peter; Baumgärtner, Wolfgang
The increasing disease susceptibility in different whale and dolphin populations has led to speculation about a possible negative influence of environmental contaminants on the immune system and therefore on the health status of marine mammals. Despite current efforts in the immunology of marine mammals several aspects of immune functions in aquatic mammals remain unknown. However, assays for evaluating cellular immune responses, such as lymphocyte proliferation, respiratory burst as well as phagocytic and cytotoxic activity of leukocytes and humoral immune responses have been established for different cetacean species. Additionally, immunological and molecular techniques enable the detection and quantification of pro- and anti-inflammatory cytokines in lymphoid cells during inflammation or immune responses, respectively. Different T and B cell subsets as well as antigen-presenting cells can be detected by flow cytometry and immunohistochemistry. Despite great homologies between marine and terrestrial mammal lymphoid organs, some unique anatomical structures, particularly the complex lymphoepithelial laryngeal glands in cetaceans represent an adaptation to the marine environment. Additionally, physiological changes, such as age-related thymic atrophy and cystic degeneration of the "anal tonsil" of whales have to be taken into account when investigating these lymphoid structures. Systemic morbillivirus infections lead to fatalities in cetaceans associated with generalized lymphoid depletion. Similarly, chronic diseases and starvation are associated with a loss of functional lymphoid cells and decreased resistance against opportunistic infections. There is growing evidence for an immunotoxic effect of different environmental contaminants in whales and dolphins, as demonstrated in field studies. Furthermore, immunomodulatory properties of different persistent xenobiotics have been confirmed in cetacean lymphoid cells in vitro as well as in animal models in vivo
Singh, P. P.; Kumar, Ashok; Chauhan, R. S.; Pankaj, P. K.
Aim: The present study was aimed to investigate the immunological competence of endosulfan insecticide after limited oral administration in White Leghorn layer chickens. Materials and Methods: A total of 20 White Leghorn birds were given endosulfan in drinking water at 30 ppm/bird/day (no observable effect level dose) for a period of 3-months. Immune competence status of layer birds and chicks hatched from endosulfan offered birds were estimated at 15-day interval in layer birds and at monthly interval in chicks using immunological, biochemical parameters, and teratological estimates. Results: There was a significant decrease in levels of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds fed with endosulfan as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with endosulfan as compared to control. Subsequently, chicks produced from endosulfan-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. Conclusion: The exposure to endosulfan in limited oral dosage was able to exhibit hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting cautious usage of endosulfan insecticide in poultry sheds. PMID:27536042
Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.
Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.
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Zammarchi, Lorenzo; Stella, Giulia; Mantella, Antonia; Bartolozzi, Dario; Tappe, Dennis; Günther, Stephan; Oestereich, Lisa; Cadar, Daniel; Muñoz-Fontela, César; Bartoloni, Alessandro; Schmidt-Chanasit, Jonas
We report the first two cases of laboratory confirmed Zika virus (ZIKV) infections imported into Italy from French Polynesia. Both patients presented with low grade fever, malaise, conjunctivitis, myalgia, arthralgia, ankle oedema, and axillary and inguinal lymphadenopathy. One patient showed leukopenia with relative monocytosis and thrombocytopenia. The diagnosis was based on ZIKV seroconversion in both cases and on ZIKV RNA detection in one patient from acute serum sample. Sera from both patients exhibited cross-reactivity with dengue virus antigens. Our immunological analysis demonstrated that recovery from ZIKV infection is associated with restoration of normal numbers of immune cells in the periphery as well as with normal function of antigen-presenting cells. ZIKV is an emerging arbovirus, which has recently spread extensively in tourist destinations on several West Pacific islands. Returning viremic travelers may ignite autochthonous infections in countries like Italy, which are infested by Aedes albopictus, a suitable vector for ZIKV. The role of clinicians is crucial and includes early diagnosis and timely notification of public health authorities in order to quickly implement adequate focal vector control measurements.
Ratio of Circulating IFNγ+ “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project
Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi
Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ+Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ+Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. PMID:27294146
Torres-Rasgado, Enrique; Porchia, Leonardo M.; Ruiz-Vivanco, Guadalupe; Gonzalez-Mejia, M. Elba; Báez-Duarte, Blanca G.; Pulido-Pérez, Patricia; Rivera, Alicia; Romero, Jose R.
Abstract Background: Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and β-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT). Methods: We studied 372 FDR-T2DM subjects (ages,18–65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob−) or obese (Ob+)] and TGs levels (TG−, <150 mg/dL, or TG+, ≥150 mg/dL). β-cell function, IR, and IS were determined by the homeostasis model assessment of β-cell function (HOMA2-β), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively. Results: The obese subjects with elevated TGs levels had 21%–60% increased β-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with β-cell function (ρ=0.502, P<0.001). Conclusion: We characterized FDR-T2DM subjects from central Mexico with NGT and revealed a class of obese subjects with elevated TGs and β-cell function, which may precede PT2DM. PMID:25423015
M. Milush, Jeffrey; Cunha-Neto, Edecio; G. Kallas, Esper; Kalil, Jorge; D. Passero, Luiz Felipe; W. Hunt, Peter; G. Deeks, Steven; F. Nixon, Douglas; SenGupta, Devi
Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16 INK4a (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls. Results showed that untreated HIV-infected subjects exhibited increased per-cell p16 protein expression that was discordant with chronological aging. ART restored p16 protein expression to levels comparable with HIV-negative subjects in the CD4 compartment, but not in CD8 T cells, which can be an indicative of an irreversible activation/exhaustion status on these cells. Additionally, the frequency of activated CD4+ and CD8+ T cells was positively correlated with p16 expression in CD4+ and CD8+ T cells in untreated subjects. In contrast to healthy controls, untreated HIV-infected individuals had increased p16 levels within the effector memory (TEM) subset, indicating a possible role for this marker in impaired clonal expansion during antiviral effector function. Taken together, these data demonstrate that chronic HIV infection is associated with elevated expression of the cellular aging marker p16 in T cells. ART restored normal p16 levels in the CD4+ T cell compartment, indicating that use of therapy can be of fundamental importance to normal cell cycling and maintaining immune homeostasis. PMID:27861555
Ebisawa, Motohiro; Nishima, Sankei; Ohnishi, Hidenori; Kondo, Naomi
The Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) was started in 1966 and currently has 3613 members as of August 1, 2012. The number of pediatricians specializing in allergies who have been certified by the Japanese Society of Allergology is 817. Among these, there are 125 training directors and training facilities for allergy and clinical immunology. The JSPACI first published an asthma guideline specific for children in 2000, and this has been revised every 3 yrs, contributing to better control of pediatric asthma. Food allergy management guidelines were first developed in 2005, which have helped to improve the care of food allergy patients. Among 514 pediatric training programs by the Japanese Society of Pediatrics, there are 312 facilities routinely performing oral food challenges. Among these, there were already 53 facilities performing oral immunotherapy at the end of 2011, treating 1400 cases of food allergy. The prevalence of pediatric allergic diseases has increased in Japan over the past 50 yrs. A number of International Study of Asthma and Allergies in Childhood surveys have been conducted in the past at specific times. The prevalence of wheezing among children aged 13-14 yrs in 2002 was 13.0%. Multi-year surveys found a 1.5- to 2-fold increase every 10 yrs until 2002. However, according to the latest data in 2012, asthma prevalence seems to have slightly decreased in Japan. Food allergy mainly associated with infantile atopic eczema among infants younger than 1 yr of age is the most common form as with other developed countries. The estimated food allergy prevalence based on data from several surveys is 5-10% among infants (0-6 yrs) and 1-2% among schoolchildren (6-15 yrs). A variety of patients suffering from primary deficiency syndrome have been actively analyzed. Previously, antibody defects and well-defined syndromes with immunodeficiency were analyzed, but recent research is focusing on not only acquired immune
Chinen, Javier; Shearer, William T
Reports in basic and clinical immunology in 2010 reflected the use of state-of-the-art genetic and immunologic tools to characterize the pathogenesis of immunologic diseases and the development of novel therapies directed to these conditions. B-cell biology has been explained in greater detail, significantly with lessons from the genetic defects found in the humoral immunodeficiencies. Therapeutic mAbs are given for an increasing number of indications, such as anti-CD20 antibodies or rituximab, which was initially developed for non-Hodgkin lymphomas and is currently used in diverse autoimmune and inflammatory disorders. The report of an infant with severe combined immunodeficiency (SCID) in Massachusetts detected by means of newborn screening and successfully treated with hematopoietic stem cell transplantation validated recent efforts toward newborn screening for SCID. Improvement of survival outcomes for patients with primary immunodeficiencies treated with hematopoietic stem cell transplantation was demonstrated in a large European cohort, with significant appreciation of the type of donor graft, particularly the use of HLA-matched unrelated donors for patients with non-SCID. Progress in cellular mechanisms of drug hypersensitivity included the characterization of nitroso-modified drug metabolites as potent T-cell activators and the identification of the relocation of plasmacytoid dendritic cells from blood to skin as a potential risk factor for reactivation of viral disease.
Flisser, A.; Pérez-Montfort, R.; Larralde, C.
In this review of the literature concerning the immunology of animal and human cysticercosis, emphasis is placed on whether previous exposure to the antigen confers protection to the host. Statistical analysis of the published data indicates that immunized animals have a lower risk than non-immunized animals of contracting cysticercosis, there being large variations within and between different host—cysticercus relationships. There is no indication as to which antigen is best for immunization but, although live parasites in all stages of development, or extracts, appear to give protection, embryos, eggs, and excretions are most frequently used. Antibodies appear to be the principal mediators of resistance, but the action seems to be only upon very young larvae, while fully grown cysticerci are unharmed. Several immunological methods are valuable in the diagnosis of cysticercosis, the choice depending more on the purpose of the study than on differences in their ability to discriminate between healthy and sick. The presence of anticysticercus antibodies in the serum of up to 50% of human patients indicates that human vaccination may be possible in high-risk areas; the remaining patients pose an interesting problem open to speculation and research on immunological evasion, immunodepression, and the existence of serotypes. ImagesFig. 3Fig. 4Fig. 4(Contd.) PMID:396058
Serio, B; Risitano, AM; Giudice, V; Montuori, N; Selleri, C
Hypocellular or hypoplastic myelodysplastic syndromes (HMDS) are a distinct subgroup accounting for 10–15% of all MDS patients, that are characterized by the presence of bone marrow (BM) hypocellularity, various degree of dysmyelopoiesis and sometimes abnormal karyotype. Laboratory and clinical evidence suggest that HMDS share several immune-mediated pathogenic mechanisms with acquired idiopathic aplastic anemia (AA). Different immune-mediated mechanisms have been documented in the damage of marrow hematopoietic progenitors occurring in HMDS; they include oligoclonal expansion of cytotoxic T lymphocytes (CTLs), polyclonal expansion of various subtypes of T helper lymphocytes, overexpression of FAS-L and of the TNF–related apoptosis-inducing ligand (TRAIL), underexpression of Flice-like inhibitory protein long isoform (FLIPL) in marrow cells as well as higher release of Th1 cytokines, such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). It has also been documented that some HMDS patients have higher frequency of polymorphisms linked both to high production of proinflammatory cytokines such as TNF-α and transforming growth factor-β and to the inhibition of T-cell mediated immune responses such as interleukin-10, further suggesting that immune-mediated mechanisms similar to those seen in AA patients may also operate in HMDS. Clinically, the strongest evidence for immune–mediated hematopoietic suppression in some HMDS is the response to immunosuppression including mainly cyclosporine, anti-thymocyte globulin and/or cyclosporine, or alemtuzumab. Here we review all these immune mechanisms as well as the influence of this deranged cellular and humoral immunologic mileau on the initiation and possible progression of MDS. All these observations are pivotal not only for a better understanding of MDS pathophysiology, but also for their immediate clinical implications, eventually leading to the identification of MDS patients who may benefit from
Clark, David A
Whether maternal immune effector mechanisms with the exception of anti-phospholipid antibodies cause pregnancy loss, and whether effective treatment is possible are subjects of controversy. Hence, in this study the current literature was searched and critically reviewed. In both animals and humans, similar immune effector mechanisms are linked to pregnancy failure. Several levels of evidence indicate that treatments such as aspirin + heparin, intravenous immunoglobulins, corticosteroids, and transfer of allogeneic blood cells bearing paternal antigens may improve the live birth rate. Combination therapy appears promising, but better diagnosis of subgroups responsive to specific therapies is critical. There are fallacies and flaws in the logic of previous arguments against immunological mechanisms and therapeutic interventions. In order to select patients most likely to benefit from known treatments, more extensive immunological testing is required. It is also important to determine the karyotype of all failing embryos.
Volozhin, A I; Poriadin, G V; Kazimiski, T I; Barer, G M; Askerova, S Sh; Salmasi, Zh M
Systemic immunity was studied in patients with chronic generalized parodontitis. This group of patients had distinct changes in immunologic system: depression of T- and stimulation of B-cellular immunity without accumulation of plasma cells and initiation of effective humoral response. Increased peripheral blood number of lymphocytes expressing induction of apoptosis CD95 receptors and ligand for this receptor CD95L (Fas-L) can lead to intensification of lymphocyte apoptosis and may be the reason for T-cell deficit development. The results of the study confirm the important role of immune system disturbances in pathogenesis of chronic generalized parodontitis.
Fernandez-Botran, Rafael; Sonnenfeld, Gerald
The purpose of the work carried under this interchanges was to support the development of space flight biotechnology experiments in the areas of immunology and hematopoiesis to facilitate the commercial development of space. The studies involved the interaction and development of experiments with biotechnology companies for necessary ground-based studies to allow the development of flight studies. The thrust of the work was to develop experiments with the Chiron Corporation and Bioserve involving the use of interleukin-2 to modulate the effects of spaceflight on immune responses. Spaceflight has been shown to have multiple effects on immune responses (1). lnterleukin-2 is an immuno-regulator that could have potential to counter some of the alterations induced in immune responses by spaceflight (1). To test this possibility before flight, rats were suspended antiorthostatically (2) and treated with interleukin-2. Antiorthostatic suspension is a model for some of the effects of spaceflight on immune responses (2). The interleukin-2 was given to see if it could alter some of the effects of suspension. This was achieved. As a result of these studies, two flight experiments were developed and flown with the Chiron Corp. And Bioserve to determine if use of interleukin-2 could prevent or attenuate the effects of space flight on immune responses.
Kumar, Vijay; Kumar, Asha
Corneal transplant is the most common solid tissue transplant in humans. Advances in microsurgical techniques, eye banking and the use of corticosteroids have improved the success of corneal transplants. Over 65,000 corneal transplants are being performed worldwide annually. Most of these transplants are performed in developed countries. Cornea is considered an immune privileged site. Despite this, immune mediated graft rejection is the most single cause of cornea graft failure and is one of the major postoperative complications. Incidences from as low as 2% to as high as 50% have been reported depending upon the degree of vascularization. Rejection involves donor tissue recognition and various factors may influence this rejection. Major factors include the antigenic load of the donor tissue; other factors include death to enucleation time, methods and temperature of preserving the tissue. Host factors that may impact the graft include ocular surface diseases such as dry eye, chemical burns and autoimmune diseases such as mucous membrane pemphigoid. Following infection, surgery or trauma, cells of the innate immune system invade the cornea as a result of up-regulation of cytokines, cellular adhesion molecules and growth and angiogenic factors. These factors results in neoangiogenesis and lymphoangiogenesis, leading to immune activation and graft rejection. The various immunological mechanisms that may play a role in the corneal transplant are discussed.
The turning point of modern immunological theory was the advent of the clonal selection theory (Burnet, Talmage - 1957). A useful heuristic in the classification of theoretical models was the contrast of 'instructive' with 'selective' models of the acquisition of information by biological systems. The neo-Darwinian synthesis of the 1940s had consolidated biologists' model of evolution based on prior random variation and natural selection, viz. differential fecundity. While evolution in the large was by then pretty well settled, controversy remained about examples of cellular adaptation to chemical challenges, like induced drug-resistance, enzyme formation and the antibody response. While instructive theories have been on the decline, some clear cut examples can be found of molecular imprinting in the abiotic world, leading, e.g. to the production of specific sorbents. Template-driven assembly, as in DNA synthesis, has remained a paradigm of instructive specification. Nevertheless, the classification may break down with more microscopic scrutiny of the processes of molecular fit of substrates with enzymes, of monomers to an elongating polymer chain, as the reactants often traverse a state space from with activated components are appropriately selected. The same process may be 'instructive' from a holistic, 'selective' from an atomic perspective.
Pichler, Karin; Fischerauer, Stefan; Ferlic, Peter; Martinelli, Elisabeth; Brezinsek, Hans-Peter; Uggowitzer, Peter J.; Löffler, Jörg F.; Weinberg, Annelie-Martina
The use of biodegradable magnesium implants in pediatric trauma surgery would render surgical interventions for implant removal after tissue healing unnecessary, thereby preventing stress to the children and reducing therapy costs. In this study, we report on the immunological response to biodegradable magnesium implants—as an important aspect in evaluating biocompatibility—tested in a growing rat model. The focus of this study was to investigate the response of the innate immune system to either fast or slow degrading magnesium pins, which were implanted into the femoral bones of 5-week-old rats. The main alloying element of the fast-degrading alloy (ZX50) was Zn, while it was Y in the slow-degrading implant (WZ21). Our results demonstrate that degrading magnesium implants beneficially influence the immune system, especially in the first postoperative weeks but also during tissue healing and early bone remodeling. However, rodents with WZ21 pins showed a slightly decreased phagocytic ability during bone remodeling when the degradation rate reached its maximum. This may be due to the high release rate of the rare earth-element yttrium, which is potentially toxic. From our results we conclude that magnesium implants have a beneficial effect on the innate immune system but that there are some concerns regarding the use of yttrium-alloyed magnesium implants, especially in pediatric patients.
Lotze, Michael T; Papamichail, Michael
The role of immunity in cancer has been abundantly demonstrated in murine tumor models as well as in man. Induction of clinically effective antitumor immune responses, based on this information, in patients with cancer however, remains elusive. This is not because tumors lack recognizable antigens [in fact there is evidence that there are thousands of potential novel targets in each tumor cell] but rather due to the fact that the induction of responses is not adequate nor particularly well understood. Tumors seem to be rather effective at limiting immune responses. Many of the molecularly defined antigens that have been detected on tumor cells are derived from self-proteins and as such are subject to tolerizing mechanisms. Such tumors have also developed escape mechanisms capable of evading or suppressing immune responses. Understanding the role of dendritic cells during the effector phase of the immune response and the complex interactions of stromal, immune, and tumor cells in the tumor microenvironment represent the next challenges to be understood for tumor immunology.
Asbestos is a generic name for a group of silicate minerals. The most common are chrysotile, crocidolite, amosite, tremolite and anthophyllite. Exposure to asbestos may cause asbestos-related non-malignant diseases of the lung and pleura, including asbestosis, pleural plaques, diffuse pleural fibrosis, small airway disease, and malignant diseases such as lung cancer and malignant mesothelioma. Inhaled asbestos fibres deposit in the distal regions of the respiratory system where they interact with epithelial cells and alveolar macrophages, and trigger active immunological response which leads to a slowly progressing lung fibrosis. Asbestos may affect immunocompetent cells and induce malignant transformation of mesothelial cells. It is still not clear whether asbestos causes mesothelioma directly or indirectly. There is a general opinion that malignant mesothelioma is a complex tumour that results from the accumulation of multiple genetic alterations over many years. There is no specific antibody for malignant mesothelioma as yet which could act as a single diagnostic tool. Recent studies have demonstrated that asbestos acts on peripheral T cells as superantigen and that in malignant mesothelioma patients there is an overexpression of the Bcl-2 gene on peripheral CD4+ T cells. These findings contribute to better understanding of biological effects of asbestos in respect to the duration and intensity of exposure.
Maecker, Holden T; McCoy, J Philip; Nussenblatt, Robert
The heterogeneity in the healthy human immune system, and the immunological changes that portend various diseases, have been only partially described. Their comprehensive elucidation has been termed the 'Human Immunology Project'. The accurate measurement of variations in the human immune system requires precise and standardized assays to distinguish true biological changes from technical artefacts. Thus, to be successful, the Human Immunology Project will require standardized assays for immunophenotyping humans in health and disease. A major tool in this effort is flow cytometry, which remains highly variable with regard to sample handling, reagents, instrument setup and data analysis. In this Review, we outline the current state of standardization of flow cytometry assays and summarize the steps that are required to enable the Human Immunology Project.
Verma, Meghna; Hontecillas, Raquel; Abedi, Vida; Leber, Andrew; Tubau-Juni, Nuria; Philipson, Casandra; Carbo, Adria; Bassaganya-Riera, Josep
This review highlights the fundamental role of nutrition in the maintenance of health, the immune response, and disease prevention. Emerging global mechanistic insights in the field of nutritional immunology cannot be gained through reductionist methods alone or by analyzing a single nutrient at a time. We propose to investigate nutritional immunology as a massively interacting system of interconnected multistage and multiscale networks that encompass hidden mechanisms by which nutrition, microbiome, metabolism, genetic predisposition, and the immune system interact to delineate health and disease. The review sets an unconventional path to apply complex science methodologies to nutritional immunology research, discovery, and development through “use cases” centered around the impact of nutrition on the gut microbiome and immune responses. Our systems nutritional immunology analyses, which include modeling and informatics methodologies in combination with pre-clinical and clinical studies, have the potential to discover emerging systems-wide properties at the interface of the immune system, nutrition, microbiome, and metabolism. PMID:26909350
Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible-infected-recovered (SIR) model. However, there is growing evidence that the complexity of many host-pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity.
van Rood, Jon J; Claas, Frans H J; Brand, Anneke; Tilanus, Marcel G J; van Kooten, Cees
The sixties have not only witnessed the start of the Dutch Society for Immunology (NvvI), but were also the flourishing beginning of the discipline of transplant immunology. The interest in immunology in the Netherlands had its start in the context of blood transfusions and not for instance in the field of infectious disease, as in many other countries. It began in the 1950-ties thanks to Joghem van Loghem at that time director of the Central Laboratory of Blood Transfusion in Amsterdam. The discoveries of these times have had major impact for transfusion medicine, hematopoietic stem cell transplantation and organ transplantation. In this review we will look back at some early highlights of Dutch transplant immunology and put them in the perspective of some recent developments.
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lactic dehydrogenase immunological test system... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5560 Lactic dehydrogenase immunological test system. (a) Identification. A lactic...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lactic dehydrogenase immunological test system... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5560 Lactic dehydrogenase immunological test system. (a) Identification. A lactic...
Stirling, R G; Chung, K F
The aims of current asthma treatment are to suppress airway inflammation and control symptoms, and corticosteroids maintain a commanding position in this role. Steroids effectively suppress inflammation in the majority of patients but have little impact on the natural history of this disease. In severe asthmatics, corticosteroids may have relatively less beneficial effects. Recent advances in understanding the inflammatory and immunological mechanisms of asthma have indicated many potential therapeutic avenues that may prevent or reverse abnormalities that underlie asthma. As the roles of effector cells, and of signalling and adhesion molecules are better understood, the opportunities to inhibit or prevent the inflammatory cascade have increased. In addition, there have been advances in the synthesis of proteins, monoclonal antibodies and new small molecule chemical entities, which may provide valuable flexibility in the therapeutic approach to asthma. The novel immunological approaches include the prevention of T-cell activation, attempts to influence the balance of T-helper cell (Th) populations to inhibit or prevent Th2-derived cytokine expression, and the inhibition or blockade of the downstream actions of these cytokines such as effects on immunoglobulin-E and eosinophils. These approaches provide broad as well as highly specific targeting, and also prospects for prevention and reversal of immunological and inflammatory abnormalities associated with asthma. Hopefully, the development of effective antiasthma agents with effects beyond those provided by current therapies coupled with lesser side-effects will further address the unmet needs of asthma.
Naito, Munekazu; Terayama, Hayato; Hirai, Shuichi; Qu, Ning; Lustig, Livia; Itoh, Masahiro
Clinically, 60-75% of male infertility cases are categorized as idiopathic spermatogenic disturbance. In previous studies of this condition, lymphocytic infiltration and immune deposits were present in several testis biopsy specimens, indicating that inflammatory or immunological factors contribute to the occurrence of the lesions. However, there is currently little evidence regarding immunological infertility in men. Previously, we established an immunological infertility model, experimental autoimmune orchitis (EAO), that can be induced in mice by two subcutaneous injections of viable syngeneic testicular germ cells without the use of any adjuvant. In this EAO model, lymphocytes surround the tubuli recti and then induce spermatogenic disturbance. In addition, after the active inflammation stage of this model, the seminiferous epithelium is damaged irreversibly, resembling the histopathology of human male idiopathic spermatogenic disturbance. In the majority of patients with testicular autoimmunity, there is a chronic and asymptomatic development of the inflammatory reaction. Therefore, this disease is very difficult to diagnose at the ongoing stage, and it is possible that the histopathology of idiopathic spermatogenic disturbance in the clinic is reported at the post-active inflammation stage of autoimmune orchitis. In this review, the histopathology of EAO before and after inflammation is discussed, comparing it with human orchitis.
Contreras-Rodriguez, Araceli; Quiroz-Limon, Jose; Martins, Ana M; Peralta, Humberto; Avila-Calderon, Eric; Sriranganathan, Nammalwar; Boyle, Stephen M; Lopez-Merino, Ahide
Background The sequenced genomes of the Brucella spp. have two urease operons, ure-1 and ure-2, but there is evidence that only one is responsible for encoding an active urease. The present work describes the purification and the enzymatic and phylogenomic characterization of urease from Brucella suis strain 1330. Additionally, the urease reactivity of sera from patients diagnosed with brucellosis was examined. Results Urease encoded by the ure-1 operon of Brucella suis strain 1330 was purified to homogeneity using ion exchange and hydrophobic interaction chromatographies. The urease was purified 51-fold with a recovery of 12% of the enzyme activity and 0.24% of the total protein. The enzyme had an isoelectric point of 5, and showed optimal activity at pH 7.0 and 28–35°C. The purified enzyme exhibited a Michaelis-Menten saturation kinetics with a Km of 5.60 ± 0.69 mM. Hydroxyurea and thiourea are competitive inhibitors of the enzyme with Ki of 1.04 ± 0.31 mM and 26.12 ± 2.30 mM, respectively. Acetohydroxamic acid also inhibits the enzyme in a competitive way. The molecular weight estimated for the native enzyme was between 130–135 kDa by gel filtration chromatography and 157 ± 7 kDa using 5–10% polyacrylamide gradient non-denaturing gel. Only three subunits in SDS-PAGE were identified: two small subunits of 14,000 Da and 15,500 Da, and a major subunit of 66,000 Da. The amino terminal sequence of the purified large subunit corresponded to the predicted amino acid sequence encoded by ureC1. The UreC1 subunit was recognized by sera from patients with acute and chronic brucellosis. By phylogenetic and cluster structure analyses, ureC1 was related to the ureC typically present in the Rhizobiales; in contrast, the ureC2 encoded in the ure-2 operon is more related to distant species. Conclusion We have for the first time purified and characterized an active urease from B. suis. The enzyme was characterized at the kinetic, immunological and phylogenetic levels
Salvaggio, J E
Some believe that an abnormal immunoregulatory response based on environmental damage to T cells is fundamental to the production of symptoms in patients with alleged "multiple chemical sensitivity" and/or "environmental illness." According to this theory stimulation of T cells or T cell phenotypic subsets by environmental chemicals results in release of cytokines that can effect appropriate target cells of multiple organ systems, resulting in a wide range of symptoms. This concept is reinforced by frequent media reporting of pollution incidents and environmental disasters plus continued isolated reports of immunologic abnormalities in patients with various forms of alleged environmental illness, multiple chemical sensitivities, or other related syndromes. These include reports of slight perturbations in quantity and function of immunoglobulins, complement and its components, B cells, natural killer cells, T cells, phenotypic T cell subsets, and helper suppressor T cell ratios. There are also reports of increased or decreased interleukin levels including IL-1 and IL-2 or their receptors (IL-2R) in these patients. Such assays are not infrequently performed even though there is no evidence for their diagnostic efficacy in these alleged conditions. It is reasonable, however, to anticipate that with the wide development of assays for many of the interleukins and their receptors, these assays may become important in the future diagnosis of many autoimmune, allergic, neoplastic, and infectious diseases. At this time, however, the induction of environmental illness or multiple chemical sensitivity by exposure to trace levels of environmental "immunotoxins" is unproven and remains a matter of speculation. The reproducibility of immunologic test abnormalities reported under these conditions has not been documented, and the data have often not been analyzed statistically. Appropriate controls also have not usually been employed, nor have control values been provided in many
Gorelik, M.; Narisety, S.D.; Guerrerio, A.L.; Chichester, K.; Keet, C.A.; Bieneman, A.P.; Hamilton, R. G.; Wood, R.A; Schroeder, J.T.; Frischmeyer-Guerrerio, P.A.
Background Studies suggest that oral (OIT) and sublingual (SLIT) immunotherapy for food allergy hold promise; however, the immunologic mechanisms underlying these therapies are not well understood. Objective To generate insights into the mechanisms and duration of immunologic suppression to peanut during immunotherapy (IT). Methods Blood was obtained from subjects at baseline and at multiple timepoints during a placebo-controlled trial of peanut OIT and SLIT. Immunologic outcomes included spontaneous and stimulated basophil activity by automated fluorometry (histamine) and flow cytometry (activation markers, IL-4), allergen-induced cytokine expression in dendritic cell (DC)-T cell co-cultures by multiplexing technology, and expression of MHC II and costimulatory molecules on DCs by flow cytometry. Results Spontaneous and allergen-induced basophil reactivity (histamine release, CD63 expression, and IL-4 production) were suppressed during dose escalation and after 6 months of maintenance dosing. Peanut- and dust mite-induced expression of TH2 cytokines was reduced in DC-T cell co-cultures during IT. This was associated with decreased levels of CD40, HLA-DR, and CD86 expression on DCs, and increased expression of CD80. These effects were most striking in myeloid DC-T cell co-cultures from subjects receiving OIT. Many markers of immunologic suppression reversed following withdrawal from IT, and in some cases during ongoing maintenance therapy. Conclusion OIT and SLIT for peanut allergy induce rapid suppression of basophil effector functions, dendritic cell activation, and Th2 cytokine responses during the initial phases of IT in an antigen non-specific manner. While there was some inter-individual variation, in many patients, suppression appeared to be temporary. PMID:25542883
Dimov, Ves; Eidelman, Frank
Online social networks are used to connect with friends and family members, and increasingly, to stay up-to-date with the latest news and developments in allergy and immunology. As communication is a central part of healthcare delivery, the utilization of such networking channels in allergy and immunology will continue to grow. There are inherent risks to online social networks related to breaches of patient confidentiality, professionalism and privacy. Malpractice and liability risks should also be considered. There is a paucity of information in the literature on how social network interventions affect patient outcomes. The allergy and immunology community should direct future studies towards investigating how the use of social networks and other technology tools and services can improve patient care.
Heeger, Peter S; Dinavahi, Rajani
Transplantation is the treatment of choice for end-stage kidney, heart, lung, and liver disease. Short-term outcomes in solid-organ transplantation are excellent, but long-term outcomes remain suboptimal. Advances in immune suppression and human leukocyte antigen matching techniques have reduced the acute rejection rate to <10%. Chronic allograft injury remains problematic and is in part immune-mediated. This injury is orchestrated by a complex adaptive and innate immune system that has evolved to protect the organism from infection, but, in the context of transplantation, could result in allograft rejection. Such chronic injury is partially mediated by anti-human leukocyte antigen antibodies. Severe rejections have largely been avoided by the development of tissue-typing techniques and crossmatch testing, which are discussed in detail. Further advances in the understanding of T- and B-cell immunology have led to the development of new immunomodulatory therapies directed at prolonging allograft survival, including those that decrease antibody production as well as those that remove antibodies from circulation. Further application of these immunomodulatory therapies has allowed expansion of the donor pool in some cases by permitting ABO-incompatible transplantation and transplantation in patients with preformed antibodies. Although vast improvements have been made in allograft survival, patients must remain on lifetime immunosuppression. Withdrawal of immunosuppression almost always ultimately leads to allograft rejection. The ultimate dream of transplant biologists is the induction of tolerance, where immune function remains intact but the allograft is not rejected in the face of withdrawn immunosuppression. This, however, has remained a significant challenge in human studies.
Dykewicz, M S; Fineman, S; Skoner, D P; Nicklas, R; Lee, R; Blessing-Moore, J; Li, J T; Bernstein, I L; Berger, W; Spector, S; Schuller, D
This document contains complete guidelines for diagnosis and management of rhinitis developed by the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology and the Joint Council on Allergy, Asthma and Immunology. The guidelines are comprehensive and begin with statements on clinical characteristics and diagnosis of different forms of rhinitis (allergic, non-allergic, occupational rhinitis, hormonal rhinitis [pregnancy and hypothyroidism], drug-induced rhinitis, rhinitis from food ingestion), and other conditions that may be confused with rhinitis. Recommendations on patient evaluation discuss appropriate use of history, physical examination, and diagnostic testing, as well as unproven or inappropriate techniques that should not be used. Parameters on management include use of environmental control measures, pharmacologic therapy including recently introduced therapies and allergen immunotherapy. Because of the risks to patients and society from sedation and performance impairment caused by first generation antihistamines, second generation antihistamines that reduce or eliminate these side effects should usually be considered before first generation antihistamines for the treatment of allergic rhinitis. The document emphasizes the importance of rhinitis management for comorbid conditions (asthma, sinusitis, otitis media). Guidelines are also presented on special considerations in patients subsets (children, the elderly, pregnancy, athletes and patients with rhinitis medicamentosa); and when consultation with an allergist-immunologist should be considered.
This is the Special Issue of Vet. Immunol. Immunopathol. that summarizes the 8th International Veterinary Immunology Symposium (8 th IVIS) held August 15th-19th, 2007, in Ouro Preto, Brazil. The 8 th IVIS highlighted the importance of veterinary immunology for animal health, vaccinology, reproducti...
12 and interferon alfa - 2b : phase I trial of patients with metastatic renal cell carcinoma or malignant melanoma. J Clin Oncol. 22: 2891-2900. 6...Alatrash G., et al. (2004). Clinical and immunologic effects of subcutaneously administered interleukin-12 and interferon alfa - 2b : phase I trial of...tumor growth monitored. As illustrated in Fig 2B , NV1023 was significantly more effective than G207, G47A or mock (pɘ.05, student’s t test; days
Nicod, Isabelle; Girard, J. P.; Cruchaud, A.
Membrane-associated immunoglobulins of peripheral blood lymphocytes were studied by indirect immunofluorescence for γ, α, μ, κ and λ chains in healthy subjects and patients with immunologic disease. In healthy subjects, heavy chains were found on 30·7% of lymphocytes (γ 15·3%, α 7·2% and μ 8·2%) and light chains on 32·8% of cells (κ 20·4% and λ 12·4%). Patients with humoral immune deficiencies had fewer immunoglobulin-bearing cells; sarcoidosis or thymectomy patients had normal or decreased immunoglobulin-bearing lymphocytes; cells with light chains were fewer than those with heavy chains on their lymphocytes. In some cases, normal levels of serum immunoglobulins were found in the absence of the corresponding immunoglobulin-bearing cells, and in others normal immunoglobulin-bearing lymphocytes were present in the absence of the corresponding serum immunoglobulins. These data suggest that (1) immunoglobulin-bearing lymphocytes in blood do not reflect the condition of immunoglobulin-synthesizing cells in peripheral lymphoid tissues, and (2) in certain immunologic disorders, either some B-lymphocytes do not synthesize immunoglobulins, or immunoglobulins are in such a situation that the whole molecule or part of the molecule is not visualized by current methods. PMID:4587505
Dukor, P.; Dietrich, F. M.; Rosenthal, M.
After a limited period of immunological unresponsiveness, neonatally thymectomized colony-bred Swiss mice were found to recover their ability to form haemagglutinins and haemolysins as well as their antibody-plaque-forming capacity following injection of sheep erythrocytes. No such spontaneous reconstitution was observed in F1-hybrids of highly inbred CBA and CBA-T6T6 mice. Adult thymectomized and irradiated Swiss mice similarly regained their ability to form haemolysins and haemagglutinins, but no regeneration of antibody-plaque production occurred in these mice during the period of observation. No regular correlation was found between the degree of immunological deficiency on the one hand and the level of circulating lymphocytes or the histological appearance of the spleens on the other, following neonatal thymectomy or adult thymectomy and irradiation. The possible mechanism of recovery from immunological impairment after thymectomy and the apparent discrepancies between overall haemolysin production and haemolytic plaque production in the spleen are discussed. PMID:5969684
Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai
An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description.
Cryptococcus neoformans isolates from Yaoundé human immunodeficiency virus-infected patients exhibited intra-individual genetic diversity and variation in antifungal susceptibility profiles between isolates from the same patient.
Kammalac Ngouana, Thierry; Drakulovski, Pascal; Krasteva, Donika; Kouanfack, Charles; Reynes, Jacques; Delaporte, Eric; Boyom, Fabrice Fekam; Mallié, Michèle; Bertout, Sebastien
Cryptococcal meningitis is a dreadful opportunistic fungal infection amongst human immunodeficiency virus (HIV)-infected patients. One complication in the management of the disease is the possible infection of a patient by two or more different strains of Cryptococcus neoformans. This study investigated the intra-individual genetic diversity and antifungal susceptibility of C. neoformans isolates from Yaoundé (Cameroon) HIV-infected patients with cryptococcal meningitis. Twenty-five clinical isolates were obtained during a prospective study. Five colonies were randomly collected from each initial sample. The 150 isolates obtained (125 colonies and 25 initial samples) were submitted to serotyping by multiplex PCR. Genotyping analyses were achieved using RFLP, and minisatellite- and microsatellite-length polymorphism. The antifungal susceptibility testing was carried out using a Sensititre YeastOne kit. Seven antifungals were tested: itraconazole, fluconazole, amphotericin B, ketoconazole, 5-fluorocytosine, posaconazole and voriconazole. The 150 isolates were identified as C. neoformans serotype A and genotype VNI. The microsatellite and minisatellite sequence analyses generated 15 genotypes. Six out of 25 (24 %) patients were found to be infected by two different genotypes. Antifungal susceptibility showed several profiles: posaconazole (0.015-0.25 µg ml-1), amphotericin B (0.06-1 µg ml-1), fluconazole (0.5-16 µg ml-1), itraconazole (0.008-0.12 µg ml-1), ketoconazole (0.008-0.12 µg ml-1), 5-fluorocytosine (0.25-16 µg ml-1) and voriconazole (0.008-0.12 µg ml-1). It was noted that isolates from the same patient might present different susceptibility profiles to an antifungal drug with differences of more than four dilutions. The results achieved highlighted the possible presence of isolates with different genotypes in a patient with dissimilar antifungal susceptibility profiles during a single episode of cryptococcal meningitis.
Zielinski, Christina E; Corti, Davide; Mele, Federico; Pinto, Dora; Lanzavecchia, Antonio; Sallusto, Federica
Studies on immunologic memory in animal models and especially in the human system are instrumental to identify mechanisms and correlates of protection necessary for vaccine development. In this article, we provide an overview of the cellular basis of immunologic memory. We also describe experimental approaches based on high throughput cell cultures, which we have developed to interrogate human memory T cells, B cells, and plasma cells. We discuss how these approaches can provide new tools and information for vaccine design, in a process that we define as 'analytic vaccinology'.
Schneider, David S
Speculative fiction examines the leading edge of science and can be used to introduce ideas into the classroom. For example, most students are already familiar with the fictional infectious diseases responsible for vampire and zombie outbreaks. The disease dynamics of these imaginary ailments follow the same rules we see for real diseases and can be used to remind students that they already understand the basic rules of disease ecology and immunology. By engaging writers of this sort of fiction in an effort to solve problems in immunology we may be able to perform a directed evolution experiment where we follow the evolution of plots rather than genetic traits.
Lagercrantz, R.; Hammarström, S.; Perlmann, P.; Gustafsson, B. E.
The incidence and height of antibody titers to colon, assayed by indirect hemagglutination with a heat stable colon extract from germ free rats, is significantly higher in sera from patients with ulcerative colitis than in those from healthy controls or from patients with amebic liver abscess or dysentery. While sera from ulcerative colitis patients and controls are indistinguishable in regard to incidence and height of antibody titers to Forsman antigen, Staphylococcus aureus S 209, Clostridium difficile, and several common strains of E. coli, they have elevated titers and increased incidence of antibodies to a heat stable antigen of E. coli O14. Patients with amebic dysentery have normal titers of such antibodies. Absorption of patients' sera with E. coli O14 antigen inhibits the colon directed hemagglutination reaction in approximately 30% of the cases tested. Likewise, the anti-E. coli O14 reaction can sometimes be inhibited with the colon extract. Other E. coli strains and other bacteria are inactive or have only weak inhibitory activity. Hemagglutination inhibition experiments show that germ free rat colon and E. coli O14 contain common structures, depicted by antibodies in the patients' sera. This pattern of reactivity closely resembles that seen in rats made autoimmune to colon by injection of newborn rabbit colon. E. coli O14 is known to carry a heterogenetic antigen present in lower concentration (or activity) in most Enterobacteriaceae. Hemagglutination inhibition experiments with rabbit antisera to E. coli O14 suggest that the antigen common for E. coli O14 and colon is related to this heterogenetic antigen. The findings imply that this antigen, which is constantly present in low concentrations in the human colon, may give rise to anticolon antibody formation in ulcerative colitis through breakage of tolerance. Since this antigen is present in healthy individuals as well, additional factors are required to explain the induction of anti
Dusenbery, P.; Morrow, C.; Harold, J.
The Space Science Institute (SSI) of Boulder, Colorado has recently developed two museum exhibits called the Space Weather Center and MarsQuest. It is currently planning to develop two other exhibitions called Cosmic Origins and InterActive Earth. Museum exhibitions provide research scientists the opportunity to engage in a number of activities that are vital to the success of earth and space outreach programs. The Space Weather Center was developed in partnership with various research missions at NASA's Goddard Space Flight Center. The focus of the presentation will be on the Institute's MarsQuest exhibition. This project is a 5000 square-foot, 2.5M, traveling exhibition that is now touring the country. The exhibit's 3-year tour is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and learn more about their own planet in the process. The associated planetarium show and education program will also be described, with particular emphasis on workshops to orient host museum staff (e.g. museum educators and docents). The workshops make innovative connections between the exhibitions interactive experiences and lesson plans aligned with the National Science Education Standards. SSI is also developing an interactive web site called MarsQuest On-line. The linkage between the web site, education program and exhibit will be discussed. MarsQuest and SSI's other exhibitions are good models for actively involving scientists and their discoveries to help improve informal science education in the museum community and for forging a stronger connection between formal and informal education.
Maccalli, Cristina; Volontè, Andrea; Cimminiello, Carolina; Parmiani, Giorgio
Cancer stem cells (CSCs) represent a minor subpopulation of tumour cells that share some features with the normal stem cells of the tissue from which tumour derives and have the properties of self-renewal, multiple differentiation and tumour initiation (tumour-initiating cells, TICs). Thus CSCs/TICs need to survive cancer therapies in order to provide new, more differentiated, metastatic-prone tumour cells. This occurs through different signals delivered within the tumour microenvironment. The immune system of cancer patients may recognise CSCs/TICs and kill them though it is unclear whether this may occur in vivo during spontaneous tumour growth. This review summarises findings on the immunological profile of CSCs/TICs as compared with neoplastic non-stem cells and discusses the possible antigens recognised by the patients' immune system, the in vitro and the potential in vivo immunogenicity of such antigens and the ability of human CSCs/TICs to down-regulate the immune response by the release of a variety of suppressive factors. We conclude that available data on immunological characterisation of CSCs/TICs may be useful in the perspective of designing new translational immunotherapy protocols targeting CSCs/TICs.
Nikolopoulos, Symeon; Peteinaki, Efthymia; Castanas, Elias
Tissue regeneration after therapeutic manipulations is essential in periodontology, oral surgery, and trauma of the periodontal tissues. Local inflammation because of poor oral hygiene also plays a crucial role in the above situations. Local inflammatory reaction, accompanied by the local production of cytokines, profoundly influences bone turnover and regeneration. Several products of low immunogenicity for augmenting tissue regeneration have been recently proposed as boosters of soft and mineralized tissue regeneration. Among them, Emdogain, an amelogenin derivative of porcine origin, has recently been introduced. Clinical results indicate that this product might be a good additive, producing fast tissue regeneration with no apparent clinical side effects. In contrast, very little is known about its in vivo immunologic effects. A previous study showed that Emdogain does not modify the cellular or humoral immune response in vitro. In the present work, performed in 10 patients, only a slight, nonsignificant activation of the immune system occurred during the first year following Emdogain application. Neither cellular immunity nor humoral immune response was significantly modified. In addition, the in vitro response of the patients' lymphocytes to Emdogain was assayed 2 and 12 months postoperative. We did not find any significant specific lymphocyte transformation in the presence of Emdogain, although lymphocytes could be stimulated by nonselective mitogens. These results indicate the immunologic safety of the agent in vivo, at least after 1 year.
Lock, R J; Virgo, P F; Unsworth, D J
A broad overview, with examples, of the potential pitfalls encountered in the clinical immunology laboratory is presented. Illustrative examples and case scenarios are provided from autoimmunity, immunochemistry and cellular immunology, looking at both technical and interpretative pitfalls.
What’s so special about chickens? Firstly, chickens are not only an invaluable model for studying immunology, they also provide the world’s main source of meat and will be a key protein source needed to feed the growing human population into the future. Poultry meat production is highly efficient ...
The International regulatory agencies Codex Alimentarius, European Commission Regulation and the U.S. Food and Drug Administration have set 20 mg/kg (ppm) as the maximum limit of gluten allowed in foods labeled as “gluten-free”. Immunological approaches appear to be, so far, the most suitable method...
Higgins, P J; Rand, C S
The antigenic properties of the major hemoglobin component of the Galapgaos iguanas were studied using second-approximation qualitative and quantitative immunochemical techniques. Phylogenetic distances, relative to the Galapagos marine iguana. Amblyrhynchus cristatus, were established on the basis of immunological cross-reactions.
The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Improved tools for the measurement of immunologic responses in ruminant species, par...
Elder, Robert W; George, Roshan P; McCabe, Nancy M; Rodriguez, Fred H; Book, Wendy M; Mahle, William T; Kirk, Allan D
Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change.
Fell, Lisa H.; Zawada, Adam M.; Rogacev, Kyrill S.; Seiler, Sarah; Fliser, Danilo; Heine, Gunnar H.
Background Iron deficiency contributes to anaemia in patients with chronic kidney disease. I.v. iron is therefore widely used for anaemia treatment, although it may induce oxidative stress and activate monocytes. Different i.v. iron preparations are available, but interestingly their substance-specific immunologic effects are poorly studied. Methods We analysed the effect of iron sucrose, ferric carboxymaltose, iron isomaltoside 1000, low-molecular-weight iron dextran and ferumoxytol on classical, intermediate and nonclassical monocyte biology. We therefore stimulated in vitro mature monocytes and haematopoietic CD34+ stem cells during their differentiation into monocytes with different concentrations (0.133, 0.266, 0.533 mg/mL) of i.v. iron preparations. Alterations of monocyte subset distribution, expression of surface markers (CD86, CCR5, CX3CR1), as well as production of pro-inflammatory cytokines (TNF-α, IL-1β) and reactive oxygen species were measured using flow cytometry. Additionally, we analysed phagocytosis and antigen presentation capacity. Results We found specific immunologic effects after stimulation with iron sucrose which were not induced by the other iron preparations. Iron sucrose activated monocyte subsets leading to significantly increased CD86 expression. Simultaneously CD16 and CX3CR1 expression and monocytic phagocytosis capacity were decreased. Additionally, differentiation of monocytes from haematopoietic CD34+ stem cells was almost completely abolished after stimulation with iron sucrose. Conclusions Our findings demonstrate that specific immunologic effects of distinct i.v. iron preparations exist. The clinical relevance of these findings requires further investigation. PMID:24523357
Hardy, Mark A; Furr, Allen; Barret, Juan P; Barker, John H
The idea of head transplantation appears at first as unrealistic, unethical, and futile. Here we discuss immunological considerations in human head transplantation. In a separate accompanying article we discuss surgical, ethical, and psychosocial issues concerned in body-to-head transplantation (BHT) . The success of such an unusual allograft, where the donor and the recipient can reject each other, depends on prevention of complex immunologic reactions, especially rejection of the head by the body (graft-vs-host) or probably less likely, the possibility of the head rejecting the total body allograft (host-vs-graft). The technical and immunologic difficulties are enormous, especially since rapid nerve and cord connections and regeneration have not yet been possible to achieve. In this article we begin by briefly reviewing neuro-immunologic issues that may favor BHT such as the blood brain barrier (BBB) and point out its shortcomings. And we touch on the cellular and humoral elements in the brain proper that differ in some respects from those in other organs and in the periphery. Based on recent successes in vascular composite allografts (VCAs), we will elaborate on potential specific advantages and difficulties in BHT of various available immunosuppressive medications already utilized in VCAs. The risk/benefit ratio of these drugs will be emphasized in relation to direct brain toxicity such as seizure disorders, interference, or promotion of nerve regeneration, and potentiation of cerebral viral infections. The final portion of this article will focus on pre-transplant immunologic manipulation of the deceased donor body along with pretreatment of the recipient.
... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...
... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...
... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...
... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...
... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...
... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...
... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...
... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...
... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...
... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Antimitochondrial antibody immunological test... Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification. An antimitochondrial antibody immunological test system is a device that consists of the reagents used to measure...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Albumin immunological test system. 866.5040 Section 866.5040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5040...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Prealbumin immunological test system. 866.5060 Section 866.5060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer PRINCIPAL INVESTIGATOR: Brad H. Nelson, Ph.D...From - To) 1 MAR 2008 - 28 FEB 2009 4. TITLE AND SUBTITLE Exploiting the immunological effects of standard treatments in 5a. CONTRACT NUMBER...treatment of prostate cancer. 15. SUBJECT TERMS Tumor immunology , immunotherapy, prostate cancer, antibody, T cell, tumor antigen, hormone therapy
... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breast milk immunological test system....
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Multiple autoantibodies immunological test system. 866.5660 Section 866.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Thyroid autoantibody immunological test system. 866.5870 Section 866.5870 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Myoglobin immunological test system. 866.5680 Section 866.5680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... system. 866.5090 Section 866.5090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification....
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Multiple autoantibodies immunological test system. 866.5660 Section 866.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Complement components immunological test system. 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Transferrin immunological test system. 866.5880 Section 866.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Myoglobin immunological test system. 866.5680 Section 866.5680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Antinuclear antibody immunological test system. 866.5100 Section 866.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lactoferrin immunological test system. 866.5570 Section 866.5570 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ferritin immunological test system. 866.5340 Section 866.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Plasminogen immunological test system. 866.5715 Section 866.5715 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Plasminogen immunological test system. 866.5715 Section 866.5715 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... system. 866.5090 Section 866.5090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification....
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ferritin immunological test system. 866.5340 Section 866.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Thyroid autoantibody immunological test system. 866.5870 Section 866.5870 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Prealbumin immunological test system. 866.5060 Section 866.5060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Multiple autoantibodies immunological test system. 866.5660 Section 866.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ferritin immunological test system. 866.5340 Section 866.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Albumin immunological test system. 866.5040 Section 866.5040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5040...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Complement components immunological test system. 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Infectious mononucleosis immunological test system. 866.5640 Section 866.5640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Myoglobin immunological test system. 866.5680 Section 866.5680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Albumin immunological test system. 866.5040 Section 866.5040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5040...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Antinuclear antibody immunological test system. 866.5100 Section 866.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ferritin immunological test system. 866.5340 Section 866.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Infectious mononucleosis immunological test system. 866.5640 Section 866.5640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lactoferrin immunological test system. 866.5570 Section 866.5570 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Transferrin immunological test system. 866.5880 Section 866.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Prealbumin immunological test system. 866.5060 Section 866.5060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... system. 866.5090 Section 866.5090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification....
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infectious mononucleosis immunological test system. 866.5640 Section 866.5640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Infectious mononucleosis immunological test system. 866.5640 Section 866.5640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...
... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Breast milk immunological test system....
... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Breast milk immunological test system....
... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Breast milk immunological test system....
... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Breast milk immunological test system....
Kaplan, Melvin H.; Dallenbach, Frederick D.
Using fluorescent antibody methods, deposits of bound gamma globulin, as determined in unfixed washed sections of auricular appendages from rheumatic hearts, were noted in a significant number (18 per cent) of 100 specimens studied. Such deposits were observed in myofibers, sarcolemma, interstitial connective tissue, and vessel walls. Albumin and fibrin were generally found absent from these sites. Control hearts from normal and pathologic material, including postmortem and biopsied specimens, in general, did not reveal such deposits. These various tissue sites which contained bound gamma globulin frequently exhibited evidence of alteration as indicated both by enhanced affinity for eosin and by strongly positive reaction with the periodic acid-Schiff reagent, and appeared comparable in some cases to "fibrinoid." Bound gamma globulin was not observed in cellular or stromal components of Aschoff lesions, nor was the occurrence of Aschoff lesions correlated with presence of bound gamma globulin. It is suggested that deposition of gamma globulin and the eosinophilic alteration associated with such deposition are related to certain of the pathologic changes of rheumatic heart disease. The nature of such deposits of gamma globulin was considered from immune and non-immune points of view. PMID:13751306
Tuo, Jingsheng; Grob, Seanna; Zhang, Kang; Chan, Chi-Chao
Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch's membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflammatory effects of chronic inflammation and oxidative stress can result in abnormal retinal pigment epithelium, photoreceptor atrophy and choroidal neovascularization. The associations of immunological and inflammatory genes, in particular the genes related to innate immunity with AMD support the involvement of various immunological pathways in the AMD pathogenesis. We review the literature on the involvements of inflammatory genes in AMD, highlight recent genetic discoveries, and discuss the potential application of such knowledge in the management of patients with AMD.
Larson, Spencer P; Kovilam, Oormila; Agrawal, Devendra K
Summary Intrahepatic cholestasis of pregnancy poses a great risk to both maternal and fetal health. Despite extensive research, much of the pathogenesis of this disorder is unknown. The increase in bile acids observed in patients with intrahepatic cholestasis of pregnancy has been noted to cause a change in the immune system from the normally mediated TH2 response to one that is more oriented towards TH1. In this literature review, we have critically reviewed the current literature regarding the changes in the immune system and the potential effects of immunological changes in the management of the patient. The current treatment, ursodeoxycholic acid, is also discussed along with potential combination therapies and future directions for research. PMID:26469633
Kirkpatrick, C. H.; Rich, R. R.; Graw, R. G.; Smith, T. K.; Mickenberg, Irad; Rogentine, G. N.
The immunological defect in a patient with chronic mucocutaneous moniliasis was characterized. While his Candida skin test was negative. exposure of his lymphocytes to candida extracts in vitro produced an increase in thymidine incorporation. Supernatants from cultures of antigen-stimulated lymphocytes did not contain macrophage migration-inhibition factor (MIF) activity. Restoration of the immune system with transfusions of immuno-competent allogeneic lymphocytes was accompanied by conversion of the Candida skin test to positive, and MIF production by his lymphocytes. During the period that his immune system remained intact, there was marked clearing of the moniliasis. Eight months following the transfusions, the moniliasis recurred and when restudied, the patient again had negative skin tests and insignificant MIF production. These observations demonstrate the importance of mediators in the expression of delayed hypersensitivity and provide evidence of a role of cellular immunity in resistance to certain chronic fungal infections. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:4945734
Prolonged bouts of exercise and heavy training regimens are associated with depression of immune system functions that can increase the risk of picking up opportunistic infections such as the common cold and influenza. Some common sport nutrition practices including high-carbohydrate diets and carbohydrate ingestion during exercise, training with low-glycogen stores, intentional dieting for weight loss, ingestion of high-dose antioxidant supplements and protein ingestion post exercise may influence immune system status in athletes. In order to maintain robust immunity, athletes need to consume a well-balanced diet that is sufficient to meet their requirements for energy, carbohydrate, protein and micronutrients. Dietary deficiencies of protein and specific micronutrients are well known to be potential causes of immune dysfunction and an adequate intake of some essential minerals including iron and zinc and the vitamins A, D, E, B6 and B12 are important to maintain a healthy immune function. Vitamin D may be a particular concern as recent studies have emphasised its importance in limiting infection episode incidence and duration in both the general population and in athletes and many individuals exhibit inadequate vitamin D status during the winter months. There is only limited evidence that individual amino acids, β-glucans, herbal extracts and zinc are capable of boosting immunity or reducing infection risk in athletes. The ingestion of carbohydrate during exercise and daily consumption of probiotics, vitamin D3, bovine colostrum and plant polyphenol containing supplements or foodstuffs currently offer the best chance of success, particularly for those individuals who are prone to illness.
Kelly, Michelle N; Shellito, Judd E
Pneumocystis jirovecii is the opportunistic fungal organism that causes Pneumocystis pneumonia (PCP) in humans. Similar to other opportunistic pathogens, Pneumocystis causes disease in individuals who are immunocompromised, particularly those infected with HIV. PCP remains the most common opportunistic infection in patients with AIDS. Incidence has decreased greatly with the advent of HAART. However, an increase in the non-HIV immunocompromised population, noncompliance with current treatments, emergence of drug-resistant strains and rise in HIV+ cases in developing countries makes Pneumocystis a pathogen of continued interest and a public health threat. A great deal of research interest has addressed therapeutic interventions to boost waning immunity in the host to prevent or treat PCP. This article focuses on research conducted during the previous 5 years regarding the host immune response to Pneumocystis, including innate, cell-mediated and humoral immunity, and associated immunotherapies tested against PCP. PMID:20020829
Igarashi, Toru; Mori, Katsuya; Inoue, Kei; Suzuki, Takeshi; Morisaki, Hiroshi
Regional anesthesia has been widely applied as an excellent method for perioperative analgesia. Recent studies suggested that regional anesthesia is a promising approach to minimize the risk of surgical site infection and postoperative cancer recurrence, subsequently providing the benefits to the long-term outcome. In particular, it is of great interest that regional anesthesia might be able to reduce cancer recurrence. In cancer patients, innate immunity against cancer could be depressed, resulting in the predisposition to evoke metastasis. Besides, during the perioperative periods, tumor immunity is significantly depressed due to surgical pain, activation of sympathetic nervous system, inflammatory responses, and others. In this review article, we discuss the tumor immunity during the perioperative period, with focus on the alterations of tumor immunity and regional anesthesia.
Tubby, Carolyn; Harrison, Tim; Todd, Ian; Fairclough, Lucy
Asthma is characterized by airflow obstruction that is usually completely reversible either spontaneously or in response to treatment. However, a small subset of patients with asthma display FAO (fixed airflow obstruction) despite optimal treatment, a feature more commonly associated with smoking-induced COPD (chronic obstructive pulmonary disease). Why some asthma patients develop FAO is not understood, and it is not clear whether (i) they represent a subset of patients with more severe disease, (ii) they share some characteristics of patients who develop COPD, or (iii) they represent a different disease entity altogether. The present review compares the pulmonary inflammatory profile of asthma patients with FAO with those without FAO, as well as COPD sufferers. The inflammation in asthma patients with FAO can vary from neutrophilic with CD8 T-cell involvement, similar to that of COPD, to eosinophilic with CD4 Th2 cell involvement, akin to that of asthma patients without FAO. Although studies of FAO in asthma sufferers would benefit hugely from consistent inclusion criteria, further research work is also required to shed more light on the immunological processes involved.
Marshall, Gailen D
The American Academy of Allergy, Asthma & Immunology has tracked the US allergy/immunology physician workforce (AIPW) over the past 3 decades by funding 2 workforce surveys (1999, 2004). Results have demonstrated both accomplishments of and challenges for the US AIPW. Accomplishments include increases in diversity (25% women in 2004, 20% in 1999, 10% in 1989; 6% underrepresented minorities in 2004, 5% in 1999), 95% of AIPW has completed an allergy/immunology (A/I) training program, and 91% are American Board of Allergy and Immunology (a conjoint board of the American Board of Internal Medicine and the American Board of Pediatrics)-certified (90% in 1999). Training positions and program numbers are slowly increasing, and numbers of new graduates from accredited A/I programs have also increased. We are seeing patients with more complex allergic and immune diseases and giving less allergen immunotherapy. Personal, professional, and economic satisfaction is increasing. Challenges relate primarily to diminishing practitioner supply (4245 in 2004 vs 4356 in 1999) amid growing US population demand. The AIPW is gradually aging (the average age is 53 years in 2004, compared with 51 years in 1999) and working longer before retiring. The combination of job satisfaction, the high demand for A/I services, and the large number of fellowship applicants all support expanding the supply of trained allergists/immunologists.
Tsung, Kangla; Norton, Jeffrey A
As surgery is able to remove primary tumors and limit metastases, the major challenge in cancer management is the prevention of post-resection recurrence and metastases. From the immune point of view, tumor resection removes the supply of tumor antigens that maintain an active concomitant antitumor immunity elicited by the primary tumor, and may also signal for deposition of immunological memory against future metastases. However, the natural course of this antitumor immunity in many cancer patients following complete tumor resection may not be favorable because protection is often lost after 1-3 years. Recent studies suggest that chemotherapy is able to activate this pre-existing antitumor immunity, and tumor resection following immune activation may lead to higher levels of immunological memory against future tumor antigens (in the form of metastases). Interleukin-12 added to chemotherapy mimics the function of a vaccine adjuvant in that it helps to enhance the antitumor immunity activated by chemotherapy and leaves a much stronger antitumor immune memory. This finding, when applied to cancer management, may help to maintain a strong and long lasting antitumor immunity following complete tumor resection, thus eliminating post-surgery recurrence and metastases.
Woelke, Anna Lena; Murgueitio, Manuela S; Preissner, Robert
Currently, cancer is one of the leading causes of death in industrial nations. While conventional cancer treatment usually results in the patient suffering from severe side effects, immunotherapy is a promising alternative. Nevertheless, some questions remain unanswered with regard to using immunotherapy to treat cancer hindering it from being widely established. To help rectify this deficit in knowledge, experimental data, accumulated from a huge number of different studies, can be integrated into theoretical models of the tumor-immune system interaction. Many complex mechanisms in immunology and oncology cannot be measured in experiments, but can be analyzed by mathematical simulations. Using theoretical modeling techniques, general principles of tumor-immune system interactions can be explored and clinical treatment schedules optimized to lower both tumor burden and side effects. In this paper, we aim to explain the main mathematical and computational modeling techniques used in tumor immunology to experimental researchers and clinicians. In addition, we review relevant published work and provide an overview of its impact to the field.
Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration. In this review, the immune reaction main components and neurodegeneration present in multiple sclerosis are analyzed, as well as the inflammatory cascade associated with demyelination. Available treatments' main purpose is to modulate aspects related to the adaptive immune response (B and T cells). The therapeutic challenge will be antigen-specific immune-tolerance induction, for example, with the use of tolerance protocols with peptides or DNA or nanoparticles vaccines. Future therapies should aim to control innate components (microglia, macrophages, astrocytes) and to promote remyelination. To optimize the treatment, a combined therapeutic approach targeting the control of inflammatory and neurodegenerative components of the disease and monitoring of biomarkers will be necessary.
Embleton, M. J.; Ransom, J. H.; McIllmurray, M. B.; Reeves, W. G.
Fifteen patients undergoing surgery for Stage IIb malignant melanoma were randomly allocated either to a group who received a vaccine of BCG mixed with irradiated autologous melanoma cells, or a control group who received no further treatment. All patients were monitored sequentially for immunological competence and tumour-directed immunity, using a wide range of techniques, and the results were compared retrospectively with their clinical course. Three months after surgery, there was a trend towards inhibition of PHA-induced lymphocyte transformation by autologous serum in patients who developed recurrent tumour within 12 months after treatment. Serum from patients who remained tumour-free for 12 months did not inhibit stimulation of autologous lymphocytes by PHA. Apart from this test, no other immunological parameters correlated either with clinical course or with the type of treatment received. PMID:565645
Marques, Pedro Elias; Oliveira, André Gustavo; Chang, Lynne; Paula-Neto, Heitor Affonso; Menezes, Gustavo Batista
The liver has come a long way since it was considered only a metabolic organ attached to the gastrointestinal tract. The simultaneous ascension of immunology and intravital microscopy evidenced the liver as a central axis in the immune system, controlling immune responses to local and systemic agents as well as disease tolerance. The multiple hepatic cell populations are organized in a vascular environment that promotes intimate cellular interactions, including initiation of innate and adaptive immune responses, rapid leukocyte recruitment, pathogen clearance and production of a variety of immune mediators. In this review, we focus on the advances in liver immunology supported by intravital microscopy in diseases such as isquemia/reperfusion, acute liver injury and infections.
Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.
Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.
Schülke, Stefan; Scheurer, Stephan
Recent advances in immunology have greatly improved our understanding of the pathomechanisms of food allergies. Food allergies are caused and maintained by complex interactions of the innate and adaptive immune system involving antigen-presenting cells (APC), T cells, group 2 innate lymphoid cells (ILC2), epithelial cells (EC) and effectors cells. Additionally, epigenetic factors, the intestinal microbiome and nutritional factors modulating the gastrointestinal lymphatic tissue probably have a significant impact on allergy development. However, why certain individuals develop tolerance while others mount allergic responses, the factors defining the allergenicity of food proteins, as well as the immunological mechanisms triggering allergy development have yet to be analyzed in detail.
dos Santos, Rafael Guimarães
Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans.
Husztik, E; Lázár, G; Szabó, E
Peliosis hepatis has been induced immunologically with anti-rat glomerular basal membrane rabbit serum in rats pre-sensitized with a rare earth metal complex, neodymium pyrocatechin disulphonate (NPD). This is the first experimental evidence that peliosis hepatis may develop as a result of an immunological process. It is noteworthy that in this experimental form of peliosis hepatis and in that observed earlier in rats treated with basic polyglutamic acid derivatives, severe defibrination was detected and, as in most human cases, not only the liver but other organs were also involved in the peliotic lesions. Since the rare earth metal compounds, among them the pyrocatechin disulphonate complex of neodymium, depress the reticulo-endothelial activity, a role of the reticulo-endothelial system in the pathogenesis of this experimental form of peliosis hepatis is suggested.
Messaoudi, Ilhem; Basler, Christopher F.
Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. PMID:26163194
as opposed to celular immune suppression, we decided to use anti-rubella antibody in test sera to control for this alterantive interpretation. An...Chambers Dr. Terry C. Johnson Health Sciences Center Division of Biology University of Illinois at Chicago Ackert Hall P.O. Box 6998 Kansas State...Program Manager Scientific Officer, Immunology Program Biological/Human Factors Division Office of Naval Research Office of Naval Research, Code 125
Baxevanis, Constantin N; Papamichail, Michael; Perez, Sonia A
One major achievement in cancer therapy is to select patients who will most likely benefit from a specific treatment. Predictive biomarkers play an important role in this respect being already useful in management of breast cancer and melanoma. For example, HER-2/neu (HER-2) overexpression selects for breast cancer patients to be treated with trastuzumab, and BRAFV600E mutations select for melanoma patients to be treated with vemurafenib. Identification of factors associated with T cell responsiveness to vaccination remains critical. Pre-existent immunity and circulating suppressor cells may regulate the levels of vaccine-specific T cell immunity after vaccination. The identification of immunologic endpoints to immunotherapy would thus considerably help guide the development of immunotherapy-based clinical trials. This commentary is based on a retrospective analysis we performed of data from prostate cancer patients vaccinated and boosted with the AE37 vaccine. The aim of these exploratory analyses was to identify factors useful in predicting which patients are more likely to respond to the treatment under study. The issue we are addressing here is to which extent common variables used pre- and/or following vaccinations with AE37 to assess the immune response status of the prostate cancer patients, may predict overall survival.
Della-Torre, E; Lanzillotta, M; Doglioni, C
Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4+ plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed. PMID:25865251
Della-Torre, E; Lanzillotta, M; Doglioni, C
Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4(+) plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed.
Kroemer, Guido; Fridman, Wolf Hervé; Sautès-Fridman, Catherine; Zitvogel, Laurence
The European Academy of Tumor Immunology (EATI, official website: http://eati.landesbioscience.com/index.html) has been founded in 2011 with the idea of creating a novel organization that responds to the need of structuring the European research space in this expanding, clinically ever more important area of research. Rapidly, this initiative, which regroups (part of) the elite of tumor immunologists, has been joined by 110 scientists, who accepted to join EATI as founding members. Obviously, EATI will not enter in competition with existing prestigious organizations, be they supranational (such as the Cancer Research Institute, CRI; the European Society for Cancer Immunology and Immunotherapy, ESCII; and the Society for the Immunotherapy of Cancer, SITC), or national [such as the Cancer Immunology Working Group, CIMM, of the American Association for Cancer Reserch; the (German) Association for Cancer Immunotherapy, CIMT; the (US) Cancer Immunotherapy Consortium, CIC; the (US) Cancer Vaccine Consortium, CVC; and the Italian Network for Cancer Biotherapy, NIBIT]. The choice of cooperation (rather than competition) with these organizations is clearly documented by the fact that many prominent members of CIMM, CIC, CIMT, CRI, CVC, ESCII, NIBIT and SITC are also EATI Academicians. PMID:22720233
Murphy, Timothy F.; Chonmaitree, Tasnee; Barenkamp, Stephen; Kyd, Jennelle; Nokso-Koivisto, Johanna; Patel, Janak A.; Heikkinen, Terho; Yamanaka, Noboru; Ogra, Pearay; Swords, W. Edward; Sih, Tania; Pettigrew, Melinda M.
Objective The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. Data Sources PubMed database of the National Library of Medicine. Review Methods Three subpanels with co-chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. Conclusion Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory-based basic studies, cell-based assays, work in animal models, and clinical studies. Implications for Practice The advances of the past 4 years formed the basis of a series of short-term and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media. PMID:23536533
Griswold, Ryan T.; Henderson, Brock; Goddard, Jessica; Tan, Yongqiang; Hode, Tomas; Liu, Hong; Nordquist, Robert E.; Chen, Wei R.
Carbon nanotubes have a great potential in the biomedical applications. To use carbon nanotubes in the treatment of cancer, we synthesized an immunologically modified single-walled carbon nanotube (SWNT) using a novel immunomodifier, glycated chitosan (GC), as an effective surfactant for SWNT. This new composition SWNT-GC was stable due to the strong non-covalent binding between SWNT and GC. The structure of SWNT-GC is presented in this report. The photothermal effect of SWNT-GC was investigated under irradiation of a near-infrared laser. SWNT-GC retained the optical properties of SWNT and the immunological properties of GC. Specifically, the SWNT-GC could selectively absorb a 980-nm light and induce desirable thermal effects in tissue culture and in animals. It could also induce tumor cell destruction, controlled by the laser settings and the doses of SWNT and GC. Laser+SWNT-GC treatment could also induce strong expression of heat shock proteins on the surface of tumor cells. This immunologically modified carbon nanotube could be used for selective photothermal interactions in noninvasive tumor treatment.
Winau, Florian; Quack, Christian; Darmoise, Alexandre; Kaufmann, Stefan H E
Stellate cells are star-shaped cells located in the liver and mediate a multitude of primarily non-immunological functions. They play a pivotal role in the metabolism of vitamin A and store 80% of total body retinol. Upon activation, stellate cells differentiate to myofibroblasts for production of extracellular matrix, leading to liver fibrosis. Moreover, activated stellate cells regulate liver blood flow through vasoconstriction implicated in portal hypertension. Earlier work demonstrated stellate cell derived secretion of chemokines and cytokines such as transforming growth factor beta (TGF-beta), suggesting an association with immunological processes. Indeed, recent evidence indicated that hepatic stellate cells perform potent APC function for stimulation of NKT cells as well as CD8 and CD4 T cells. Additionally, stellate cell mediated antigen presentation induced protective immunity against bacterial infection. Current experiments reveal that the presenting ability of stellate cells is the key to antigen-dependent T cell instruction by vitamin A derived retinoic acid. Finally, future studies will show whether in the firmament of immunology stellate cells will represent fixed or falling stars.