The Natural Killer Cell (NKC) is the cell-mediated cornerstone of innate immunity. The purpose of this reviewis to give a historical perspective of the discovery of the Natural Killer Cell (NKC)and to apply the use of...The Natural Killer Cell (NKC) is the cell-mediated cornerstone of innate immunity. The purpose of this reviewis to give a historical perspective of the discovery of the Natural Killer Cell (NKC)and to apply the use of supplements in the enhancement of NKC in human cancers for the developmentof human health and well-being.Since the discovery of the NKC, as observed by Nomarski optics, scanning (SEM)/transmission electron microscopy (TEM) with cellular numeration and enrichment using bovine serum albumin (BSA) continuous gradients, there have been significant research and clinical studies to increase the effectiveness of NKC in the destruction of cancer cells. Based on significant research and clinical studies, at least 16 components have been identified that enhance or may enhance, based on their immune modulator activity, the NKC. These supplements include Alpha LipoicAcid, Arabinoxylin, Curcumin, Garlic, Genistein, Ginseng, Lentinan, Mistletoe, N-Acetylcysteine, Resveratrol, Selenium, Vitamin B, Vitamin C, Vitamin D3, Vitamin E and zinc.展开更多
The objective of this study was to evaluate the efficacy of the wheat germ oil (WGO) and bone marrow transplantation (BMT) in boosting the immuno response and protecting from oxidative stress in irradiated rats. BM wa...The objective of this study was to evaluate the efficacy of the wheat germ oil (WGO) and bone marrow transplantation (BMT) in boosting the immuno response and protecting from oxidative stress in irradiated rats. BM was given by intravenous injection to male rats, one hour post gamma irradiation at the dose level of 5 Gy. Rats were orally administrated with 54 mg/Kg body wt of wheat germ oil daily for 2 weeks before irradiation. After 14 days, results revealed that total body irradiation induced significant decreases in RBCs, WBCs and lymphocytes, as well as Glutathione (GSH) and zinc superoxide dismutase (Zn/SOD), splenocyte count, bone marrow lymphocyte count and viability. Tumor necrosis factor alpha (TNF-α) and interleukin 2 (IL-2) also recorded significant decrease while interleukin 6 (IL-6) and lipid peroxidation marker malondialdehde (MDA) in serum and spleen were conversely elevated. In irradiated animals receiving BMT and WGO, values of MDA in serum and tissue were significantly depressed as compared with the irradiated group, while lymphocytes, bone marrow viability percentage, splenocytes percentage, IL-2, IL-6 and GSH were significantly elevated. The curative action of WGO enforcing significant innate response could trigger and augment adaptive immune response by BMT, thus protecting immune system from radiation induced damage as well as oxidative stress.展开更多
Despite extensive research efforts, a preventive human immunodeficiency virus (HIV) vaccine remains one of the major challenges in the field of AIDS research. Experimental strategies which have been proven successful ...Despite extensive research efforts, a preventive human immunodeficiency virus (HIV) vaccine remains one of the major challenges in the field of AIDS research. Experimental strategies which have been proven successful for other viral vaccines are not enough to tackle HIV-1 and new approaches to design effective preventive AIDS vaccines are of utmost importance. Due to enormous diversity among global circulating HIV strains, an effective HIV vaccine must elicit broadly protective antibodies based responses;therefore discovering new broadly neutralizing antibodies (bNAbs) against HIV has become major focus in HIV vaccine research. However further understanding of the viral targets of such antibodies and mechanisms of action of bNAbs is required for advancement of HIV vaccine research. This technical note discusses our current knowledge on the bNAbs and immunoprophylaxis using viral vectors with their relevance in designing of new candidates to HIV-1 vaccines.展开更多
Eighty male albino rats of Westar strain (350 ± 10 g), 10 to 12 weeks old were divided into four groups. The groups treated are as following. The first control group (Gp. I) was given intraperitoneally in normal ...Eighty male albino rats of Westar strain (350 ± 10 g), 10 to 12 weeks old were divided into four groups. The groups treated are as following. The first control group (Gp. I) was given intraperitoneally in normal saline (1 mL). The second group (Gp. II) was orally infected with 3 × 1012 CFU of E. coli /Kg. BW. The third group (Gp. III) was infected with E. coli and treated with (0.5%) lactoferrin (LF) 72 hours before E. coli infection in filtered tap water for the duration of the experiment (21 days). The fourth group (Gp. IV) was administrated with LF only (0.5%) in drinking water. Two separate blood samples were collected from heart puncture at the end of 1st, and 3rd week post-treatment for immunological studies. The Leukogram in E. coli treated group was insignificant compared with the control group while lymphocytosis was clear compared with the infected group. Total protein, albumin, α-globulin and β-globulin were展开更多
Vaccination with tumor-antigen pulsed, monocyte-derived dendritic cells (DCs) has emerged as a promising strategy in cancer immunotherapy. The standard DC maturation cocktail consists of a combination of tumor necrosi...Vaccination with tumor-antigen pulsed, monocyte-derived dendritic cells (DCs) has emerged as a promising strategy in cancer immunotherapy. The standard DC maturation cocktail consists of a combination of tumor necrosis factor-α (TNF-α)/interleukin (IL)-1β/IL-6 and prostaglandin E2 (PGE2) for generation of standard DCs (sDCs). In order to improve IL-12p70 production and cytotoxic T-lymphocyte (CTL) induction, a novel cocktail composed of TNF-α/IL-1β/ interferon (IFN)-α/IFN-γ and polyinosinic:polycytidylic acid (Poly-I:C) has been introduced to generate so-called α-Type-1 polarized DCs (αDC1s). We and others have previously performed a comprehensive comparison of sDCs and αDC1s. Here we demonstrate that the viability of αDC1s is lowered compared to sDCs and that DC apoptosis is mediated by Poly-I:C. We speculated that activation of protein kinase R (PKR) could mediate the observed apoptosis, but despite significantly higher PKR expression in αDC1s compared to sDCs and induction of active threonine (Thr)446 autophosphorylation of PKR in αDC1s, Poly-I:C did not influence total PKR expression or autophosporylation, indicating PKR-independent Poly-I:C-induced DC apoptosis.展开更多
In order to assess chicken T cell-mediated responses after immune stress, 200 two-week-old chickens were randomly divided into control group(C) and treatment groups (T1 and T2). The live I-type of Newcastle disease va...In order to assess chicken T cell-mediated responses after immune stress, 200 two-week-old chickens were randomly divided into control group(C) and treatment groups (T1 and T2). The live I-type of Newcastle disease vaccine (ND) was taken as the source of immunological stress. The chickens in group (T2) were injected with overdose of live I-type Newcastle disease vaccine. After vaccination, the dynamic changes of CD4+, CD8+T cells on thymus were detected by immunohisto-chemistry. The ultra-structure of T cells on thymus of the chickens in group (T2) was observed by electron microscopic. The result showed: (1) After immune stress, from day 1 to day 5, the number of the CD4+T cells significantly declined and reached the bottom at day 5, but the number of the CD8+T cells increased dramatically and peaked at day 5. (2) After immune stress, from day 1 to day 5, part of T cells of chicken thymus came with apoptotic and pathological changes of putrescence continually. These results underscore: the immune stress can cause transient immune adjustment. These changes for chickens were the self-protection mechanism of immune system to adapt to survival and avoid immune disorder.展开更多
In 1974, in Nature, we hypothesized that removal of cytokines can be effective in the treatment of certain inflammatory diseases, e.g., rheumatoid arthritis (RA). We call this approach anticytokino-therapy. Later it w...In 1974, in Nature, we hypothesized that removal of cytokines can be effective in the treatment of certain inflammatory diseases, e.g., rheumatoid arthritis (RA). We call this approach anticytokino-therapy. Later it was shown that neutralization of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interferon alpha (IFN-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), leads to a good therapeutic effect. Anticytokinotherapy is currently used around the world for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, and other Th-1-mediated inflammatory diseases. Pro-inflammatory cytokines have also been found in other conditions (myocardial infarctions, strokes, chronic pain syndromes, etc.). This leads us to believe that hyper- production of pro-inflammatory cytokines forms a basis of a variety of pathological conditions and represents a uniform response of the organism to a wide variety of insults in any part of the body. Thus, we propose to add monoclonal antibodies to (or other blockers of) pro-inflammatory cytokines to the treatment regimens for myocardial infarctions, strokes, and possibly other Th-1-mediated diseases.展开更多
Primary cancers can be prevented by immunizations. We suggest immunizing healthy people, especially the ones with genetic predisposition to cancer, with a standard oncoantigen. In patients suffering from cancer, immun...Primary cancers can be prevented by immunizations. We suggest immunizing healthy people, especially the ones with genetic predisposition to cancer, with a standard oncoantigen. In patients suffering from cancer, immunotherapy can be effective only if it is administered during complete remission. Immune competent cells, like T-lymphocytes and bone marrow, are the most important components for cancer prevention and treatment. Because of the dramatic increase in the incidence of cancer, it is important to offer all adults with absolutely healthy immune system an opportunity to donate their own T-lymphocytes and bone marrow cells and preserve them at -196。C. These cells can later be used by the same people in auto-system if they develop cancer. Patients who had their cancerous tumors surgically removed can also have their own T-lymphocytes and bone marrow cells collected during remission and then used in auto-system in case of cancer reoccurrence. It is also possible to impact on cancer development during the process of cancerogenesis by administering large amounts of normal DNA and possibly different types of RNA (displacement) together with nucleases (directly into the tumor or blood). In addition, blockers of cytokines that suppress immune system should be administered as well. It is intriguing to think that injection of large amounts of normal DNA and possibly different types of RNA together with nucleases to patients with chronic and hereditary diseases (diabetes Type II, schizophrenia, and other similar diseases) can lead to therapeutic effect.展开更多
Rheumatoid arthritis (RA) is associated with an HLA-DRB1-coded sequence motif called “shared epitope” (SE). To explore potential mechanisms of RA susceptibility, we analyze in vitro effect of peptides bearing differ...Rheumatoid arthritis (RA) is associated with an HLA-DRB1-coded sequence motif called “shared epitope” (SE). To explore potential mechanisms of RA susceptibility, we analyze in vitro effect of peptides bearing different HLA-DR4 sequences on human peripheral blood-derived cells. Three 15-mer peptides were used: 65-79*0401 (HLA-DRB1*04:01- coded sequence SE motif, QKRAA);65-79*0402 (HLA-DRB1*04:02-coded sequence SE-negative motif, DERAA);65-79*0403 (HLA-DRB1*04:03-coded sequence SE-negative motif, QRRAE). We found that CD4 TH17 cells are regulated by peptide treatment with gender bias. In male-derived T cells, all peptide treatments significantly reduced TH17 cell differentiation in vitro when compared to no peptide treatment, and to female samples. TH17 differentiation in samples not treated with peptides, either in the presence or absence of TH17-polarizing cytokines, was higher in males than in females;however, in unfractionated PBMC after treatment with TH17 polarizing cytokines, IL-17A-positive cells were more abundant in females than in males. In addition, SE-positive females showed a significantly higher percentage of IL-17A-positive cells compared to SE-negative females. In conclusion, donor’s SE status and gender may both influence TH17 immune polarization.展开更多
Background and Aims: In Ivoirian’s school, the management of vaso-occlusive painful crisis in sickle cell disease requires non steroidal anti inflammatory drugs (NSAIDs). Although their effectiveness, these drugs may...Background and Aims: In Ivoirian’s school, the management of vaso-occlusive painful crisis in sickle cell disease requires non steroidal anti inflammatory drugs (NSAIDs). Although their effectiveness, these drugs may be accompanied by intolerance reactions. When these occur, no codified alternative therapeutic seems to be used to our knowledge. Authors aimed to evaluate the induction of tolerance to NSAIDs as an effective alternative therapeutic. Methods: 22 patients (15 men and 7 women aged from 12 to 39 years with mean age: 22.41 ± 7.88) suffering from vaso-occlusive painful crisis were enrolled. They were known to have a history of sickle cell disease and at least one episode of adverse reactions following the Ibuprofen or Diclofenac intake. A rapid protocol of oral challenge was used in patients to induce tolerance to NSAIDs. The first day, initial doses (8.82 mg for Ibuprofen and 2.20 mg for Diclofenac) were given and gradually increased at intervals of 1 hour over a total period of 6 hours. On the second and third days, the therapeutic dose has been orally administrated with an interval of 6 hours over a period of 12 hours. Results: Despite of some cases of failure that might be related to the severity of symptoms or possible patho-physiological mechanism, more than 80% of patients have successfully tolerated Diclofenac and Ibuprofen. Conclusion: This experience appears to be the first in our context. It might be used as a solution in the lack of alternative therapeutic in the management of vaso-occlusive painful crisis of sickle cell disease as well as in other diseases such as HIV infection where patients often develop intolerance to none alternative antibiotics.展开更多
Chronic periodontitis (CP) is a chronic inflammatory condition which destroys the supporting tissues of teeth and increases in prevalence with age. Immune responses against heat shock proteins (HSP) can be cross-react...Chronic periodontitis (CP) is a chronic inflammatory condition which destroys the supporting tissues of teeth and increases in prevalence with age. Immune responses against heat shock proteins (HSP) can be cross-reactive among bacterial and human antigens. There is evidence that microbial HSP65 and human HSP60 are involved in periodontal disease. The aim of this study is to investigate immune responses to the human HSP60 and microbial HSP65 in patients with CP and relate these to the level of inflammation and smoking status. We collected serum samples from 30 patients with chronic gingivitis (CG) and 30 patients with CP. In each group, eight subjects were current smokers. ELISA was used to determine the levels of serum anti-HSP and C-reactive protein (CRP) in each group. Peripheral blood mononuclear cells were also isolated and stimulated with HSPs. Significant lymphoproliferation was seen in CP when stimulated with human HSP60. CRP and serum anti-human HSP60 IgG were elevated in CP compared to the CG, but not serum anti-microbial HSP 65 IgG. In view of the potential confounding effects of smoking in CP, a group of current smokers (n = 16) was also recruited to investigate whether smoking affects HSP immune responses. There was no significant difference in HSP-induced lymphoproliferation between smokers and non-smokers in either the CG or CP. There was a significant correlation between CRP and lymphoproliferative responses to Human HSP60 irrespective of smoking status. This study shows that serum anti-human HSP60 IgG and serum CRP are raised in untreated CP. In CP, serum CRP levels correlated significantly with human HSP60-induced lymphoproliferation, but not with anti-HSP antibody levels.展开更多
Allergic manifestations affect 20% - 30% of the population in industrialized countries. The global market for asthma and allergy medications has been estimated to exceed USD 6 billion, since 40% of the human populatio...Allergic manifestations affect 20% - 30% of the population in industrialized countries. The global market for asthma and allergy medications has been estimated to exceed USD 6 billion, since 40% of the human population has some form of IgE sensitization to diverse proteins. Most therapeutic intervention strategies cope with the symptoms of allergy without eliminating the underlying cause and many are associated with undesirable and often long-term debilitating side effects. We designed a peptide immunogen encompassing sequences of the human Cε2-3 linker region to prime rat (Rattus norvegicus) immune systems, we then designed a chimeric human-dog-human IgE antibody and used it to boost the immune system and produce high-affinity antibodies that targets native IgE. The investigation showed that this peptide immunogen elicit the formation of antibodies recognizing the native IgE of human, canine and equine origin. The current investigation describes novel approaches aimed at the development of safe anti-allergy vaccines based on active immunization with IgE-derived peptides that are involved in the complementary interaction with the high affinity receptor. The immunization strategy was successful but did not fully work as predicted, thus we propose that peptides described in the current study may lead to the development of a pananti-allergy vaccine with applications for the treatment of all IgE-mediated allergic response independent of the nature of the offending allergen.展开更多
A large 7-year vaccination trial was conducted in 15 flocks of goats and 7 flocks of sheep, known to be infected with Mycobacterium avium subsp. paratuberculosis (MAP), in Northern Greece. A total of 3665 kids and 168...A large 7-year vaccination trial was conducted in 15 flocks of goats and 7 flocks of sheep, known to be infected with Mycobacterium avium subsp. paratuberculosis (MAP), in Northern Greece. A total of 3665 kids and 1685 lambs, 7 - 30 days old, were vaccinated during 1995-1999. Seven hundred and seventy-five kids and 413 lambs were kept as unvaccinated controls. For each trial, the Incidence Rate Ratio (IRR), with respective exact 95% confidence intervals, was calculated. All IRR point estimates for young animals were very large (from 5.68 to 11.78 for kids and from 4.28 to 10.08 for lambs), while none of the 95% confidence intervals included 1. The protective effect of vaccination was large and the difference in mortality among vaccinated and unvaccinated animals was more pronounced in young animals. The effect in adult animals was smaller than in young animals;it was, however, still considerable. Upon visual inspection of the K-M curves, it seems that for the young animal trials the vaccinated and control-group curves were diverging increasingly over time, which indicates that the gain from the vaccination (or the loss from non-vaccination) might increase over time during the trial.展开更多
The human 60 kDa and microbial 65 kDa heat shock proteins (HSP) have been implicated in the pathogenesis of chronic periodontitis (CP) and coronary heart disease (CHD). We have studied 100 subjects: Group (a) consiste...The human 60 kDa and microbial 65 kDa heat shock proteins (HSP) have been implicated in the pathogenesis of chronic periodontitis (CP) and coronary heart disease (CHD). We have studied 100 subjects: Group (a) consisted of patients with gingivitis (n = 25), group (b) were patients with CP (n = 25), group (c) patients with CHD and gingivitis (n = 25) and group (d) patients with CHD and CP (n = 25). PBMCs separated from peripheral blood were stimulated with medium, PMA/ionomycin, human HSP60, microbial HSP65, or no stimulus for 18 hours before intracellular IL-2, IFN-γ, TNF-α, IL-4, IL-5, or IL-17 were detected by flow cytometry. The mean fluorescence intensity (MFLI) for intracellular TNF-α was significantly increased when PBMC were stimulated with human HSP60 amongst the four groups (p = 0.001, ANOVA);pairwise comparisons revealed significant differences in MFLI between the gingivitis group and the CP (p = 0.017);between gingivitis and ging/CHD (p = 0.001) as well;but no significant difference between the CP and CP/CHD (p = 0.442). There was no significant difference in intracellular expression of IL-17, or any of the other cytokines tested;and the MFLI for HSP-stimulated were comparable to unstimulated cultures. When heat-labile human HSP60 was heated, intracellular cellular TNF-α expression was abrogated. In contrast, heat-stable LPS elicited TNF-α expression from monocytes in bulk cultures in all groups. These results suggest that the cytokine expression was dependent on human HSP60 and not LPS. Serum CRP was significantly associated with MFLI of intracellular TNF-α in CP patients (rs = 0.665, p = 0.026) and CP/CHD (rs = 0.699, p = 0.011). We conclude that human HSP60 elicits increased monocytic expression of TNF-α in patients with CP, CP/CHD or ging/CHD compared to patients with gingivitis. Since the marker of inflammation, namely CRP correlates with CP with or without CHD and not with mild chronic gingivitis or ging/CHD, this suggests that human HSP60-induced production of TNF-α is associated with CP and not CHD. There was no significant difference in intracellular expression of IL-17.展开更多
Introduction: The existence of receptor-mediated endocytosis (RME) means that selectivity and selectivity occurs in capturing macromolecules. Protein kinase C (PKC) which can be expressed by almost all cells are prote...Introduction: The existence of receptor-mediated endocytosis (RME) means that selectivity and selectivity occurs in capturing macromolecules. Protein kinase C (PKC) which can be expressed by almost all cells are proteins important in signal transduction groove that plays a role in a number of cell activity, e.g. phagocytosis. Aims: The purpose of this study is to determine the expression of RME after modulating the PKC which is characterized by the number of Candida albicans cells attached to the surface of macrophages. Methods: Peritoneal macrophages cultured BALB/c mice are treated with PMA and/or bisindolylmaleimides of providing levels of 5 ng/ml to 100 ng/ml for 10 minutes. Then immediately insert Candida albicans and observe every 30 minutes for 120 minutes. The research design used the same subject. Data collected in the form of number of Candida albicans cells attached to the surface of macrophages are analyzed with ANOVA statistical test (one way) to show the differences between treatments. Results: The test shows statistically significant difference in the number of Candida albicans cells attached to the surface of macrophages after administration of various levels of PMA (p 0.001). The higher level of PMA is given, the more active the PKC is, the more RME are formed, the more Candida albicans cells attached to the surface of macrophages. Another result shows statistically significant difference in the number of Candida albicans cells attached to the surface of macrophages after administration of various levels of bisindolylmaleimides (p 0.001). The higher level of bisindolylmaleimide is given, the less active PKC is, and the less RME are formed, the less Candida albicans cells attached to the surface of macrophages. Conclusion: Research shows that activator PKC (PMA) can increase the expression of RME on macrophages. Another research shows that inhibitor PKC (bisindolylmaleimides) can decrease the expression of RME on macrophages.展开更多
In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases. We were the first to use...In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases. We were the first to use antibodies to IFN-γ and were some of the first to suggest using antagonists of TNF-α in the treatment of autoimmune and inflammatory diseases as well. Our method suppresses one of the main pathogenetic mechanisms of these diseases. Antibodies to IFN-γ and TNF-α exhibit dramatic effects on clinical manifestations of rheumatoid arthritis (RA). However, in our trial ultrasound assessment of the synovial membrane thickness in RA patients showed that only anti-IFN-γ exerted pronounced anti-inflammatory effect. Some patients who underwent treatment with antibodies to TNF-α developed a number of complications. Anticytokine therapy (mono- and poly-) alone or in combination with other drugs can possibly be used not only in the treatment of autoimmune diseases, but also in other pathologies with cytokine synthesis disturbances (a number of neurological, psychiatric, endocrine, and other diseases).展开更多
We determined whether telavancin is as active in experimental immunocompetent murine pneumococcal pneumonia as is vancomycin or ceftriaxone. Experimental murine pneumonia was established by intratracheal administratio...We determined whether telavancin is as active in experimental immunocompetent murine pneumococcal pneumonia as is vancomycin or ceftriaxone. Experimental murine pneumonia was established by intratracheal administration of Streptococcus pneumoniae. Four groups of animals were studied, untreated and treated with vancomycin (110 mg/kg, bid, SQ), telavancin (40 mg/kg, bid, SQ), or ceftriaxone (50 mg/kg, bid, SQ) for 2 days. The untreated animals had a mean of 6.54 ± 0.82 log10 cfu/g lung. The vancomycin-, telavancin-, and ceftriaxone-treated animals had means of 2.01 ± 0.02, 2.00 ± 0.00, and 2.00 ± 0.01 log10 cfu/g lung, respectively (p-values < 0.0001 for each treatment group versus the untreated group). In the model studied, telavancin was as active as vancomycin and ceftriaxone in treating experimental pneumococcal pneumonia in mice.展开更多
Now molecular epidemiology was meaningful. On the surface of the tumor, cells will express its antigen specific as a tumor cell (example: TSA, tumor specific antigen) and can induce cellular immune response. The resul...Now molecular epidemiology was meaningful. On the surface of the tumor, cells will express its antigen specific as a tumor cell (example: TSA, tumor specific antigen) and can induce cellular immune response. The result of interactions between group antigens with the immune system cells of the body will cause a rise in the expression of lymphocytes CD8+. The aim of this research is to find out differences in the number of lymphocytes CD8+ expression between benign and malignant tissues. This research is a laboratory experiment with the approach of cross sectional. Samples are taken from benign and malignant tissue biopsy of the breast and cervical uterine that were got from anatomical pathology laboratory, period January to February 2004. A technique using random sampling, is sample acquiring 30 benign cancer and 30 malignant of the breast or cervical uterine. To find out the significance of the difference in the number of lymphocytes CD8+ between benign and malignant of breast or cervical uterine, we used a statistical analysis Anova in SPSS for Windows 15.0 program. In this research the number of lymphocytes average in the benign cancer is 2.9667 cells (breast) and 4.2667 cells (cervical uterine), on the other side malignant tissue of 23.8000 cells (breast) and 25.0333 cells (cervical uterine). From the statistical analyses with Anova the number of lymphocytes CD8+ was very significant differences between benign and malignant of the breast or cervical uterine tissue (p < 0.001). The conclusion of this research is that there is a significant increase of the number of lymphocytes CD8+ expression in cancer tissue.展开更多
Natural killer (NK) cells play an important role in innate immunity and in mediating antibody and Icon (an antibody-like factor VII/IgG1 Fc immunoconjugate, which, to our best knowledge, was the first therapeutic agen...Natural killer (NK) cells play an important role in innate immunity and in mediating antibody and Icon (an antibody-like factor VII/IgG1 Fc immunoconjugate, which, to our best knowledge, was the first therapeutic agent for dual targeting of both the tumor cells and tumor angiogenic endothelial cells) for cancer immunotherapy. However, a common yet often neglected observation and challenge in antibody immunotherapy is that NK cells are often impaired in cancer patients. Here we hypothesize that the impairment of NK cells significantly contributes to host resistance to antibody immunotherapy for cancer. In order for antibody and Icon to achieve their optimal therapeutic efficacy, we briefly reviewed the current strategies to enhance NK activity, including infusion of cytokines, vaccines or NK cells, and the use of dietary supplements. Moreover, from our point of view we identified some remaining challenges and propose to combine these NK-enhancing strategies with Icon or antibody to overcome NK impairment and ultimately to optimize the efficacy of Icon and antibody immunotherapy for cancer.展开更多
文摘The Natural Killer Cell (NKC) is the cell-mediated cornerstone of innate immunity. The purpose of this reviewis to give a historical perspective of the discovery of the Natural Killer Cell (NKC)and to apply the use of supplements in the enhancement of NKC in human cancers for the developmentof human health and well-being.Since the discovery of the NKC, as observed by Nomarski optics, scanning (SEM)/transmission electron microscopy (TEM) with cellular numeration and enrichment using bovine serum albumin (BSA) continuous gradients, there have been significant research and clinical studies to increase the effectiveness of NKC in the destruction of cancer cells. Based on significant research and clinical studies, at least 16 components have been identified that enhance or may enhance, based on their immune modulator activity, the NKC. These supplements include Alpha LipoicAcid, Arabinoxylin, Curcumin, Garlic, Genistein, Ginseng, Lentinan, Mistletoe, N-Acetylcysteine, Resveratrol, Selenium, Vitamin B, Vitamin C, Vitamin D3, Vitamin E and zinc.
文摘The objective of this study was to evaluate the efficacy of the wheat germ oil (WGO) and bone marrow transplantation (BMT) in boosting the immuno response and protecting from oxidative stress in irradiated rats. BM was given by intravenous injection to male rats, one hour post gamma irradiation at the dose level of 5 Gy. Rats were orally administrated with 54 mg/Kg body wt of wheat germ oil daily for 2 weeks before irradiation. After 14 days, results revealed that total body irradiation induced significant decreases in RBCs, WBCs and lymphocytes, as well as Glutathione (GSH) and zinc superoxide dismutase (Zn/SOD), splenocyte count, bone marrow lymphocyte count and viability. Tumor necrosis factor alpha (TNF-α) and interleukin 2 (IL-2) also recorded significant decrease while interleukin 6 (IL-6) and lipid peroxidation marker malondialdehde (MDA) in serum and spleen were conversely elevated. In irradiated animals receiving BMT and WGO, values of MDA in serum and tissue were significantly depressed as compared with the irradiated group, while lymphocytes, bone marrow viability percentage, splenocytes percentage, IL-2, IL-6 and GSH were significantly elevated. The curative action of WGO enforcing significant innate response could trigger and augment adaptive immune response by BMT, thus protecting immune system from radiation induced damage as well as oxidative stress.
文摘Despite extensive research efforts, a preventive human immunodeficiency virus (HIV) vaccine remains one of the major challenges in the field of AIDS research. Experimental strategies which have been proven successful for other viral vaccines are not enough to tackle HIV-1 and new approaches to design effective preventive AIDS vaccines are of utmost importance. Due to enormous diversity among global circulating HIV strains, an effective HIV vaccine must elicit broadly protective antibodies based responses;therefore discovering new broadly neutralizing antibodies (bNAbs) against HIV has become major focus in HIV vaccine research. However further understanding of the viral targets of such antibodies and mechanisms of action of bNAbs is required for advancement of HIV vaccine research. This technical note discusses our current knowledge on the bNAbs and immunoprophylaxis using viral vectors with their relevance in designing of new candidates to HIV-1 vaccines.
文摘Eighty male albino rats of Westar strain (350 ± 10 g), 10 to 12 weeks old were divided into four groups. The groups treated are as following. The first control group (Gp. I) was given intraperitoneally in normal saline (1 mL). The second group (Gp. II) was orally infected with 3 × 1012 CFU of E. coli /Kg. BW. The third group (Gp. III) was infected with E. coli and treated with (0.5%) lactoferrin (LF) 72 hours before E. coli infection in filtered tap water for the duration of the experiment (21 days). The fourth group (Gp. IV) was administrated with LF only (0.5%) in drinking water. Two separate blood samples were collected from heart puncture at the end of 1st, and 3rd week post-treatment for immunological studies. The Leukogram in E. coli treated group was insignificant compared with the control group while lymphocytosis was clear compared with the infected group. Total protein, albumin, α-globulin and β-globulin were
文摘Vaccination with tumor-antigen pulsed, monocyte-derived dendritic cells (DCs) has emerged as a promising strategy in cancer immunotherapy. The standard DC maturation cocktail consists of a combination of tumor necrosis factor-α (TNF-α)/interleukin (IL)-1β/IL-6 and prostaglandin E2 (PGE2) for generation of standard DCs (sDCs). In order to improve IL-12p70 production and cytotoxic T-lymphocyte (CTL) induction, a novel cocktail composed of TNF-α/IL-1β/ interferon (IFN)-α/IFN-γ and polyinosinic:polycytidylic acid (Poly-I:C) has been introduced to generate so-called α-Type-1 polarized DCs (αDC1s). We and others have previously performed a comprehensive comparison of sDCs and αDC1s. Here we demonstrate that the viability of αDC1s is lowered compared to sDCs and that DC apoptosis is mediated by Poly-I:C. We speculated that activation of protein kinase R (PKR) could mediate the observed apoptosis, but despite significantly higher PKR expression in αDC1s compared to sDCs and induction of active threonine (Thr)446 autophosphorylation of PKR in αDC1s, Poly-I:C did not influence total PKR expression or autophosporylation, indicating PKR-independent Poly-I:C-induced DC apoptosis.
文摘In order to assess chicken T cell-mediated responses after immune stress, 200 two-week-old chickens were randomly divided into control group(C) and treatment groups (T1 and T2). The live I-type of Newcastle disease vaccine (ND) was taken as the source of immunological stress. The chickens in group (T2) were injected with overdose of live I-type Newcastle disease vaccine. After vaccination, the dynamic changes of CD4+, CD8+T cells on thymus were detected by immunohisto-chemistry. The ultra-structure of T cells on thymus of the chickens in group (T2) was observed by electron microscopic. The result showed: (1) After immune stress, from day 1 to day 5, the number of the CD4+T cells significantly declined and reached the bottom at day 5, but the number of the CD8+T cells increased dramatically and peaked at day 5. (2) After immune stress, from day 1 to day 5, part of T cells of chicken thymus came with apoptotic and pathological changes of putrescence continually. These results underscore: the immune stress can cause transient immune adjustment. These changes for chickens were the self-protection mechanism of immune system to adapt to survival and avoid immune disorder.
文摘In 1974, in Nature, we hypothesized that removal of cytokines can be effective in the treatment of certain inflammatory diseases, e.g., rheumatoid arthritis (RA). We call this approach anticytokino-therapy. Later it was shown that neutralization of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interferon alpha (IFN-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), leads to a good therapeutic effect. Anticytokinotherapy is currently used around the world for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, and other Th-1-mediated inflammatory diseases. Pro-inflammatory cytokines have also been found in other conditions (myocardial infarctions, strokes, chronic pain syndromes, etc.). This leads us to believe that hyper- production of pro-inflammatory cytokines forms a basis of a variety of pathological conditions and represents a uniform response of the organism to a wide variety of insults in any part of the body. Thus, we propose to add monoclonal antibodies to (or other blockers of) pro-inflammatory cytokines to the treatment regimens for myocardial infarctions, strokes, and possibly other Th-1-mediated diseases.
文摘Primary cancers can be prevented by immunizations. We suggest immunizing healthy people, especially the ones with genetic predisposition to cancer, with a standard oncoantigen. In patients suffering from cancer, immunotherapy can be effective only if it is administered during complete remission. Immune competent cells, like T-lymphocytes and bone marrow, are the most important components for cancer prevention and treatment. Because of the dramatic increase in the incidence of cancer, it is important to offer all adults with absolutely healthy immune system an opportunity to donate their own T-lymphocytes and bone marrow cells and preserve them at -196。C. These cells can later be used by the same people in auto-system if they develop cancer. Patients who had their cancerous tumors surgically removed can also have their own T-lymphocytes and bone marrow cells collected during remission and then used in auto-system in case of cancer reoccurrence. It is also possible to impact on cancer development during the process of cancerogenesis by administering large amounts of normal DNA and possibly different types of RNA (displacement) together with nucleases (directly into the tumor or blood). In addition, blockers of cytokines that suppress immune system should be administered as well. It is intriguing to think that injection of large amounts of normal DNA and possibly different types of RNA together with nucleases to patients with chronic and hereditary diseases (diabetes Type II, schizophrenia, and other similar diseases) can lead to therapeutic effect.
文摘Rheumatoid arthritis (RA) is associated with an HLA-DRB1-coded sequence motif called “shared epitope” (SE). To explore potential mechanisms of RA susceptibility, we analyze in vitro effect of peptides bearing different HLA-DR4 sequences on human peripheral blood-derived cells. Three 15-mer peptides were used: 65-79*0401 (HLA-DRB1*04:01- coded sequence SE motif, QKRAA);65-79*0402 (HLA-DRB1*04:02-coded sequence SE-negative motif, DERAA);65-79*0403 (HLA-DRB1*04:03-coded sequence SE-negative motif, QRRAE). We found that CD4 TH17 cells are regulated by peptide treatment with gender bias. In male-derived T cells, all peptide treatments significantly reduced TH17 cell differentiation in vitro when compared to no peptide treatment, and to female samples. TH17 differentiation in samples not treated with peptides, either in the presence or absence of TH17-polarizing cytokines, was higher in males than in females;however, in unfractionated PBMC after treatment with TH17 polarizing cytokines, IL-17A-positive cells were more abundant in females than in males. In addition, SE-positive females showed a significantly higher percentage of IL-17A-positive cells compared to SE-negative females. In conclusion, donor’s SE status and gender may both influence TH17 immune polarization.
文摘Background and Aims: In Ivoirian’s school, the management of vaso-occlusive painful crisis in sickle cell disease requires non steroidal anti inflammatory drugs (NSAIDs). Although their effectiveness, these drugs may be accompanied by intolerance reactions. When these occur, no codified alternative therapeutic seems to be used to our knowledge. Authors aimed to evaluate the induction of tolerance to NSAIDs as an effective alternative therapeutic. Methods: 22 patients (15 men and 7 women aged from 12 to 39 years with mean age: 22.41 ± 7.88) suffering from vaso-occlusive painful crisis were enrolled. They were known to have a history of sickle cell disease and at least one episode of adverse reactions following the Ibuprofen or Diclofenac intake. A rapid protocol of oral challenge was used in patients to induce tolerance to NSAIDs. The first day, initial doses (8.82 mg for Ibuprofen and 2.20 mg for Diclofenac) were given and gradually increased at intervals of 1 hour over a total period of 6 hours. On the second and third days, the therapeutic dose has been orally administrated with an interval of 6 hours over a period of 12 hours. Results: Despite of some cases of failure that might be related to the severity of symptoms or possible patho-physiological mechanism, more than 80% of patients have successfully tolerated Diclofenac and Ibuprofen. Conclusion: This experience appears to be the first in our context. It might be used as a solution in the lack of alternative therapeutic in the management of vaso-occlusive painful crisis of sickle cell disease as well as in other diseases such as HIV infection where patients often develop intolerance to none alternative antibiotics.
文摘Chronic periodontitis (CP) is a chronic inflammatory condition which destroys the supporting tissues of teeth and increases in prevalence with age. Immune responses against heat shock proteins (HSP) can be cross-reactive among bacterial and human antigens. There is evidence that microbial HSP65 and human HSP60 are involved in periodontal disease. The aim of this study is to investigate immune responses to the human HSP60 and microbial HSP65 in patients with CP and relate these to the level of inflammation and smoking status. We collected serum samples from 30 patients with chronic gingivitis (CG) and 30 patients with CP. In each group, eight subjects were current smokers. ELISA was used to determine the levels of serum anti-HSP and C-reactive protein (CRP) in each group. Peripheral blood mononuclear cells were also isolated and stimulated with HSPs. Significant lymphoproliferation was seen in CP when stimulated with human HSP60. CRP and serum anti-human HSP60 IgG were elevated in CP compared to the CG, but not serum anti-microbial HSP 65 IgG. In view of the potential confounding effects of smoking in CP, a group of current smokers (n = 16) was also recruited to investigate whether smoking affects HSP immune responses. There was no significant difference in HSP-induced lymphoproliferation between smokers and non-smokers in either the CG or CP. There was a significant correlation between CRP and lymphoproliferative responses to Human HSP60 irrespective of smoking status. This study shows that serum anti-human HSP60 IgG and serum CRP are raised in untreated CP. In CP, serum CRP levels correlated significantly with human HSP60-induced lymphoproliferation, but not with anti-HSP antibody levels.
文摘Allergic manifestations affect 20% - 30% of the population in industrialized countries. The global market for asthma and allergy medications has been estimated to exceed USD 6 billion, since 40% of the human population has some form of IgE sensitization to diverse proteins. Most therapeutic intervention strategies cope with the symptoms of allergy without eliminating the underlying cause and many are associated with undesirable and often long-term debilitating side effects. We designed a peptide immunogen encompassing sequences of the human Cε2-3 linker region to prime rat (Rattus norvegicus) immune systems, we then designed a chimeric human-dog-human IgE antibody and used it to boost the immune system and produce high-affinity antibodies that targets native IgE. The investigation showed that this peptide immunogen elicit the formation of antibodies recognizing the native IgE of human, canine and equine origin. The current investigation describes novel approaches aimed at the development of safe anti-allergy vaccines based on active immunization with IgE-derived peptides that are involved in the complementary interaction with the high affinity receptor. The immunization strategy was successful but did not fully work as predicted, thus we propose that peptides described in the current study may lead to the development of a pananti-allergy vaccine with applications for the treatment of all IgE-mediated allergic response independent of the nature of the offending allergen.
文摘A large 7-year vaccination trial was conducted in 15 flocks of goats and 7 flocks of sheep, known to be infected with Mycobacterium avium subsp. paratuberculosis (MAP), in Northern Greece. A total of 3665 kids and 1685 lambs, 7 - 30 days old, were vaccinated during 1995-1999. Seven hundred and seventy-five kids and 413 lambs were kept as unvaccinated controls. For each trial, the Incidence Rate Ratio (IRR), with respective exact 95% confidence intervals, was calculated. All IRR point estimates for young animals were very large (from 5.68 to 11.78 for kids and from 4.28 to 10.08 for lambs), while none of the 95% confidence intervals included 1. The protective effect of vaccination was large and the difference in mortality among vaccinated and unvaccinated animals was more pronounced in young animals. The effect in adult animals was smaller than in young animals;it was, however, still considerable. Upon visual inspection of the K-M curves, it seems that for the young animal trials the vaccinated and control-group curves were diverging increasingly over time, which indicates that the gain from the vaccination (or the loss from non-vaccination) might increase over time during the trial.
文摘The human 60 kDa and microbial 65 kDa heat shock proteins (HSP) have been implicated in the pathogenesis of chronic periodontitis (CP) and coronary heart disease (CHD). We have studied 100 subjects: Group (a) consisted of patients with gingivitis (n = 25), group (b) were patients with CP (n = 25), group (c) patients with CHD and gingivitis (n = 25) and group (d) patients with CHD and CP (n = 25). PBMCs separated from peripheral blood were stimulated with medium, PMA/ionomycin, human HSP60, microbial HSP65, or no stimulus for 18 hours before intracellular IL-2, IFN-γ, TNF-α, IL-4, IL-5, or IL-17 were detected by flow cytometry. The mean fluorescence intensity (MFLI) for intracellular TNF-α was significantly increased when PBMC were stimulated with human HSP60 amongst the four groups (p = 0.001, ANOVA);pairwise comparisons revealed significant differences in MFLI between the gingivitis group and the CP (p = 0.017);between gingivitis and ging/CHD (p = 0.001) as well;but no significant difference between the CP and CP/CHD (p = 0.442). There was no significant difference in intracellular expression of IL-17, or any of the other cytokines tested;and the MFLI for HSP-stimulated were comparable to unstimulated cultures. When heat-labile human HSP60 was heated, intracellular cellular TNF-α expression was abrogated. In contrast, heat-stable LPS elicited TNF-α expression from monocytes in bulk cultures in all groups. These results suggest that the cytokine expression was dependent on human HSP60 and not LPS. Serum CRP was significantly associated with MFLI of intracellular TNF-α in CP patients (rs = 0.665, p = 0.026) and CP/CHD (rs = 0.699, p = 0.011). We conclude that human HSP60 elicits increased monocytic expression of TNF-α in patients with CP, CP/CHD or ging/CHD compared to patients with gingivitis. Since the marker of inflammation, namely CRP correlates with CP with or without CHD and not with mild chronic gingivitis or ging/CHD, this suggests that human HSP60-induced production of TNF-α is associated with CP and not CHD. There was no significant difference in intracellular expression of IL-17.
文摘Introduction: The existence of receptor-mediated endocytosis (RME) means that selectivity and selectivity occurs in capturing macromolecules. Protein kinase C (PKC) which can be expressed by almost all cells are proteins important in signal transduction groove that plays a role in a number of cell activity, e.g. phagocytosis. Aims: The purpose of this study is to determine the expression of RME after modulating the PKC which is characterized by the number of Candida albicans cells attached to the surface of macrophages. Methods: Peritoneal macrophages cultured BALB/c mice are treated with PMA and/or bisindolylmaleimides of providing levels of 5 ng/ml to 100 ng/ml for 10 minutes. Then immediately insert Candida albicans and observe every 30 minutes for 120 minutes. The research design used the same subject. Data collected in the form of number of Candida albicans cells attached to the surface of macrophages are analyzed with ANOVA statistical test (one way) to show the differences between treatments. Results: The test shows statistically significant difference in the number of Candida albicans cells attached to the surface of macrophages after administration of various levels of PMA (p 0.001). The higher level of PMA is given, the more active the PKC is, the more RME are formed, the more Candida albicans cells attached to the surface of macrophages. Another result shows statistically significant difference in the number of Candida albicans cells attached to the surface of macrophages after administration of various levels of bisindolylmaleimides (p 0.001). The higher level of bisindolylmaleimide is given, the less active PKC is, and the less RME are formed, the less Candida albicans cells attached to the surface of macrophages. Conclusion: Research shows that activator PKC (PMA) can increase the expression of RME on macrophages. Another research shows that inhibitor PKC (bisindolylmaleimides) can decrease the expression of RME on macrophages.
文摘In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases. We were the first to use antibodies to IFN-γ and were some of the first to suggest using antagonists of TNF-α in the treatment of autoimmune and inflammatory diseases as well. Our method suppresses one of the main pathogenetic mechanisms of these diseases. Antibodies to IFN-γ and TNF-α exhibit dramatic effects on clinical manifestations of rheumatoid arthritis (RA). However, in our trial ultrasound assessment of the synovial membrane thickness in RA patients showed that only anti-IFN-γ exerted pronounced anti-inflammatory effect. Some patients who underwent treatment with antibodies to TNF-α developed a number of complications. Anticytokine therapy (mono- and poly-) alone or in combination with other drugs can possibly be used not only in the treatment of autoimmune diseases, but also in other pathologies with cytokine synthesis disturbances (a number of neurological, psychiatric, endocrine, and other diseases).
文摘We determined whether telavancin is as active in experimental immunocompetent murine pneumococcal pneumonia as is vancomycin or ceftriaxone. Experimental murine pneumonia was established by intratracheal administration of Streptococcus pneumoniae. Four groups of animals were studied, untreated and treated with vancomycin (110 mg/kg, bid, SQ), telavancin (40 mg/kg, bid, SQ), or ceftriaxone (50 mg/kg, bid, SQ) for 2 days. The untreated animals had a mean of 6.54 ± 0.82 log10 cfu/g lung. The vancomycin-, telavancin-, and ceftriaxone-treated animals had means of 2.01 ± 0.02, 2.00 ± 0.00, and 2.00 ± 0.01 log10 cfu/g lung, respectively (p-values < 0.0001 for each treatment group versus the untreated group). In the model studied, telavancin was as active as vancomycin and ceftriaxone in treating experimental pneumococcal pneumonia in mice.
文摘Now molecular epidemiology was meaningful. On the surface of the tumor, cells will express its antigen specific as a tumor cell (example: TSA, tumor specific antigen) and can induce cellular immune response. The result of interactions between group antigens with the immune system cells of the body will cause a rise in the expression of lymphocytes CD8+. The aim of this research is to find out differences in the number of lymphocytes CD8+ expression between benign and malignant tissues. This research is a laboratory experiment with the approach of cross sectional. Samples are taken from benign and malignant tissue biopsy of the breast and cervical uterine that were got from anatomical pathology laboratory, period January to February 2004. A technique using random sampling, is sample acquiring 30 benign cancer and 30 malignant of the breast or cervical uterine. To find out the significance of the difference in the number of lymphocytes CD8+ between benign and malignant of breast or cervical uterine, we used a statistical analysis Anova in SPSS for Windows 15.0 program. In this research the number of lymphocytes average in the benign cancer is 2.9667 cells (breast) and 4.2667 cells (cervical uterine), on the other side malignant tissue of 23.8000 cells (breast) and 25.0333 cells (cervical uterine). From the statistical analyses with Anova the number of lymphocytes CD8+ was very significant differences between benign and malignant of the breast or cervical uterine tissue (p < 0.001). The conclusion of this research is that there is a significant increase of the number of lymphocytes CD8+ expression in cancer tissue.
文摘Natural killer (NK) cells play an important role in innate immunity and in mediating antibody and Icon (an antibody-like factor VII/IgG1 Fc immunoconjugate, which, to our best knowledge, was the first therapeutic agent for dual targeting of both the tumor cells and tumor angiogenic endothelial cells) for cancer immunotherapy. However, a common yet often neglected observation and challenge in antibody immunotherapy is that NK cells are often impaired in cancer patients. Here we hypothesize that the impairment of NK cells significantly contributes to host resistance to antibody immunotherapy for cancer. In order for antibody and Icon to achieve their optimal therapeutic efficacy, we briefly reviewed the current strategies to enhance NK activity, including infusion of cytokines, vaccines or NK cells, and the use of dietary supplements. Moreover, from our point of view we identified some remaining challenges and propose to combine these NK-enhancing strategies with Icon or antibody to overcome NK impairment and ultimately to optimize the efficacy of Icon and antibody immunotherapy for cancer.
