Displaying publications 21 - 40 of 390 in total

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  1. Fulltext Suppression of Human T Cell Proliferation Mediated by the Cathepsin B Inhibitor, z-FA-FMK Is Due to Oxidative Stress
    Rajah T, Chow SC
    PLoS One, 2015;10(4):e0123711.
    PMID: 25915766 DOI: 10.1371/journal.pone.0123711
    The cathepsin B inhibitor, benzyloxycarbonyl-phenylalanine-alanine-fluoromethyl ketone (z-FA-FMK) readily inhibits anti-CD3-induced human T cell proliferation, whereas the analogue benzyloxycarbonyl-phenylalanine-alanine-diazomethyl ketone (z-FA-DMK) had no effect. In contrast, benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK) was toxic. The inhibition of T cell proliferation mediated by z-FA-FMK requires not only the FMK moiety, but also the benzyloxycarbonyl group at the N-terminal, suggesting some degree of specificity in z-FA-FMK-induced inhibition of primary T cell proliferation. We showed that z-FA-FMK treatment leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in activated T cells. The inhibition of anti-CD3-induced T cell proliferation mediated by z-FA-FMK was abolished by the presence of low molecular weight thiols such as GSH, N-acetylcysteine (NAC) and L-cysteine, whereas D-cysteine which cannot be metabolised to GSH has no effect. The inhibition of anti-CD3-induced up-regulation of CD25 and CD69 expression mediated by z-FA-FMK was also attenuated in the presence of exogenous GSH. Similar to cell proliferation, GSH, NAC and L-cysteine but not D-cysteine, completely restored the processing of caspase-8 and caspase-3 to their respective subunits in z-FA-FMK-treated activated T cells. Our collective results demonstrated that the inhibition of T cell activation and proliferation mediated by z-FA-FMK is due to oxidative stress via the depletion of GSH.
    Matched MeSH terms: T-Lymphocytes/drug effects*; T-Lymphocytes/metabolism; T-Lymphocytes/physiology
  2. The distribution of immunoregulatory cells in the peripheral blood of normal Malaysian adults
    Chin SF, Cheong SK, Lim YC, Ton SH
    Malays J Pathol, 1993 Jun;15(1):49-52.
    PMID: 8277790
    The distribution of immunoregulatory cells in the peripheral blood of an individual has now been established as an important tool in helping the management of several diseases. It is necessary to set the normal ranges of these cells for the laboratory. We have undertaken in this study to establish the reference ranges for normal Malaysian adults. We found that the mean percentages of T cells, B cells, T Helper cells (CD4), T suppressor cells (CD8), NK cells and the ratio of CD4/CD8 were 70.91%, 11.38%, 38.15%, 37.76%, 17.45%, and 1.00 respectively. There was no significant difference between the sexes. In certain parameters, there was significant differences between Malay, Chinese and Indians. The Chinese and Indians were significantly different in the distribution of B cells and in the CD4/CD8 ratio. In the case of CD4 and NK cells, the Indians were different from the other two groups.
    Matched MeSH terms: B-Lymphocytes*; T-Lymphocytes*
  3. Fulltext Aberrancies of human T--and B--lymphocyte populations in peripheral blood
    Gan SC, Yeoh CW
    Med J Malaysia, 1980 Jun;34(4):379-82.
    PMID: 6971393
    Strict precautions were taken in our methodology to exclude any monocytes from being included in the total T and B cell estimation. There is a progressive drop in the percentage of T and B cells with age, but no significant differences between the races nor between the sexes of the same age group. Aberrancies of T and B cell percentages were noted in most infections, malignancies and even malnutrition.
    Matched MeSH terms: B-Lymphocytes*; T-Lymphocytes*
  4. Fulltext TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection
    Amrun SN, Tan JJL, Rickett NY, Cox JA, Lee B, Griffiths MJ, et al.
    Sci Rep, 2020 03 02;10(1):3810.
    PMID: 32123257 DOI: 10.1038/s41598-020-60761-5
    Hand, foot and mouth disease (HFMD), caused by enterovirus A71 (EV-A71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV-A71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterised in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). High resolution transcriptomics was used to decipher EV-A71-host interactions in PBMCs. Ingenuity analyses revealed similar pathways triggered by all EV-A71 isolates, although the extent of activation varied. Importantly, several pathways were found to be specific to the severe isolate, including triggering receptor expressed on myeloid cells 1 (TREM-1) signalling. Depletion of TREM-1 in EV-A71-infected PBMCs with peptide LP17 resulted in decreased levels of pro-inflammatory genes for the moderate and severe isolates. Mechanistically, this is the first report describing the transcriptome profiles during EV-A71 infections in primary human cells, and the potential involvement of TREM-1 in the severe disease pathogenesis, thus providing new insights for future treatment targets.
    Matched MeSH terms: B-Lymphocytes/virology; T-Lymphocytes/virology
  5. Fulltext Dicentric assay technique for the assessment of whole body dose to low let radiation
    Noriah Jamal, Noraisyah Mohd Yusof, Rahimah Abdul Rahim, Juliana Mahamad Napiah, Bo, Nelly Nai Lee, Yahaya Talib, et al.
    Journal of Nuclear and Related Technologies, 2010;2010(1):77-83.
    MyJurnal
    For more than two decades, biodosimetry has been used in biomonitoring of occupational and envir onmental exposure to ionising radiation. Chromosome aberration analysis is a method used to dete ct unstable aberrations in the lymphocytes of irradiated personnel. The Malaysian National Biodosi metry Laboratory is a referance centre for activity relating to biodosimetry in the country. This pap er aims at presenting dicentric assay technique for the assessment of whole body dose to low LET ra diation at the Malaysian National Biodosimetry Laboratory.
    Matched MeSH terms: Lymphocytes
  6. Targeting immunosuppressor cells with nanoparticles in autoimmunity: How far have we come to?
    Ahmad S, Al-Hatamleh MAI, Mohamud R
    Cell Immunol, 2021 10;368:104412.
    PMID: 34340162 DOI: 10.1016/j.cellimm.2021.104412
    Autoimmunity is the assault of immune response towards self-antigens, resulting to inflammation and tissue injury. It is staged into three phases and caused by malfunction of immune tolerance. In our body, immune tolerance is synchronized by several immunosuppressor cells such as regulatory T cells and B cells as well as myeloid-derived suppressor cells, which are prominently dysregulated in autoimmunity. Hence, targeting these cell populations serve as a significant potential in the therapy of autoimmunity. Nanotechnology with its advantageous properties is shown to be a remarkable tool as drug delivery system in this field. This review focused on the development of therapeutics in autoimmune diseases utilizing various nanoparticles formulation based on two targeting approaches in autoimmunity, passive and active targeting. Lastly, this review outlined the approved present nanomedicines as well as in clinical evaluations and issues regarding the lack of translation of these nanomedicines into the market, despite the abundant of positive experimental observations.
    Matched MeSH terms: T-Lymphocytes, Regulatory/immunology*; B-Lymphocytes, Regulatory/immunology*
  7. The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function
    Ramasamy R, Tong CK, Seow HF, Vidyadaran S, Dazzi F
    Cell Immunol, 2008 Feb;251(2):131-6.
    PMID: 18502411 DOI: 10.1016/j.cellimm.2008.04.009
    Mesenchymal stem cells (MSC) are non-haematopoietic stem cells that are capable of differentiating into tissues of mesodermal origin. MSC play an important role in supporting the development of fetal and adult haematopoiesis. More recently, MSC have also been found to exhibit inhibitory effect on T cell responses. However, there is little information on the mechanism of this immunosuppression and our study addresses this issue by targeting T cell functions at various level of immune responses. We have generated MSC from human adult bone marrow (BM) and investigated their immunoregulatory function at different phases of T cell responses. MSC showed the ability to inhibit mitogen (CD3/CD28 microbeads)-activated T cell proliferation in a dose-dependent manner. In order to evaluate the specificity of this immunosuppression, the proliferation of CD4(+) and CD8(+) cells were measured. MSC equally inhibit CD4(+) and CD8(+) subpopulations of T cells in response to PHA stimulation. However, the antiproliferative effect of MSC is not due to the inhibition of T cell activation. The expression of early activation markers of T cells, namely CD25 and CD69 were not significantly altered by MSC at 24, 48 and 72h. Furthermore, the immunosuppressive effect of MSC mainly targets T cell proliferation rather than their effector function since cytotoxicity of T cells is not affected. This work demonstrates that the immunosuppressive effect of MSC is exclusively a consequence of an anti-proliferative activity, which targets T cells of different subpopulations. For this reason, they have the potential to be exploited in the control of unwanted immune responses such as graft versus host disease (GVHD) and autoimmunity.
    Matched MeSH terms: CD4-Positive T-Lymphocytes/cytology; CD4-Positive T-Lymphocytes/immunology*; CD8-Positive T-Lymphocytes/cytology; CD8-Positive T-Lymphocytes/immunology*
  8. Application of Ti3 C2 MXene Quantum Dots for Immunomodulation and Regenerative Medicine
    Rafieerad A, Yan W, Sequiera GL, Sareen N, Abu-El-Rub E, Moudgil M, et al.
    Adv Healthc Mater, 2019 08;8(16):e1900569.
    PMID: 31265217 DOI: 10.1002/adhm.201900569
    Inflammation is tightly linked to tissue injury. In regenerative medicine, immune activation plays a key role in rejection of transplanted stem cells and reduces the efficacy of stem cell therapies. Next-generation smart biomaterials are reported to possess multiple biologic properties for tissue repair. Here, the first use of 0D titanium carbide (Ti3 C2 ) MXene quantum dots (MQDs) for immunomodulation is presented with the goal of enhancing material-based tissue repair after injury. MQDs possess intrinsic immunomodulatory properties and selectively reduce activation of human CD4+ IFN-γ+ T-lymphocytes (control 87.1 ± 2.0%, MQDs 68.3 ± 5.4%) while promoting expansion of immunosuppressive CD4+ CD25+ FoxP3+ regulatory T-cells (control 5.5 ± 0.7%, MQDs 8.5 ± 0.8%) in a stimulated lymphocyte population. Furthermore, MQDs are biocompatible with bone marrow-derived mesenchymal stem cells and induced pluripotent stem cell-derived fibroblasts. Finally, Ti3 C2 MQDs are incorporated into a chitosan-based hydrogel to create a 3D platform with enhanced physicochemical properties for stem cell delivery and tissue repair. This composite hydrogel demonstrates increased conductivity while maintaining injectability and thermosensitivity. These findings suggest that this new class of biomaterials may help bridge the translational gap in material and stem cell-based therapies for tissue repair and treatment of inflammatory and degenerative diseases.
    Matched MeSH terms: CD4-Positive T-Lymphocytes/drug effects; CD4-Positive T-Lymphocytes/metabolism; T-Lymphocytes, Regulatory/drug effects; T-Lymphocytes, Regulatory/metabolism
  9. Fulltext Peripheral immune response in the African green monkey model following Nipah-Malaysia virus exposure by intermediate-size particle aerosol
    Lara A, Cong Y, Jahrling PB, Mednikov M, Postnikova E, Yu S, et al.
    PLoS Negl Trop Dis, 2019 06;13(6):e0007454.
    PMID: 31166946 DOI: 10.1371/journal.pntd.0007454
    The ability to appropriately mimic human disease is critical for using animal models as a tool for understanding virus pathogenesis. In the case of Nipah virus (NiV), infection of humans appears to occur either through inhalation, contact with or consumption of infected material. In two of these circumstances, respiratory or sinusoidal exposure represents a likely route of infection. In this study, intermediate-size aerosol particles (~7 μm) of NiV-Malaysia were used to mimic potential routes of exposure by focusing viral deposition in the upper respiratory tract. Our previous report showed this route of exposure extended the disease course and a single animal survived the infection. Here, analysis of the peripheral immune response found minimal evidence of systemic inflammation and depletion of B cells during acute disease. However, the animal that survived infection developed an early IgM response with rapid development of neutralizing antibodies that likely afforded protection. The increase in NiV-specific antibodies correlated with an expansion of the B cell population in the survivor. Cell-mediated immunity was not clearly apparent in animals that succumbed during the acute phase of disease. However, CD4+ and CD8+ effector memory cells increased in the survivor with correlating increases in cytokines and chemokines associated with cell-mediated immunity. Interestingly, kinetic changes of the CD4+ and CD8bright T cell populations over the course of acute disease were opposite from animals that succumbed to infection. In addition, increases in NK cells and basophils during convalescence of the surviving animal were also evident, with viral antigen found in NK cells. These data suggest that a systemic inflammatory response and "cytokine storm" are not major contributors to NiV-Malaysia pathogenesis in the AGM model using this exposure route. Further, these data demonstrate that regulation of cell-mediated immunity, in addition to rapid production of NiV specific antibodies, may be critical for surviving NiV infection.
    Matched MeSH terms: B-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/immunology
  10. An image processing application for the localization and segmentation of lymphoblast cell using peripheral blood images
    Madhloom HT, Kareem SA, Ariffin H
    J Med Syst, 2012 Aug;36(4):2149-58.
    PMID: 21399912 DOI: 10.1007/s10916-011-9679-0
    An important preliminary step in the diagnosis of leukemia is the visual examination of the patient's peripheral blood smear under the microscope. Morphological changes in the white blood cells can be an indicator of the nature and severity of the disease. Manual techniques are labor intensive, slow, error prone and costly. A computerized system can be used as a supportive tool for the specialist in order to enhance and accelerate the morphological analysis process. This research present a new method that integrates color features with the morphological reconstruction to localize and isolate lymphoblast cells from a microscope image that contains many cells. The localization and segmentation are conducted using a proposed method that consists of an integration of several digital image processing techniques. 180 microscopic blood images were tested, and the proposed framework managed to obtain 100% accuracy for the localization of the lymphoblast cells and separate it from the image scene. The results obtained indicate that the proposed method can be safely used for the purpose of lymphoblast cells localization and segmentation and subsequently, aiding the diagnosis of leukemia.
    Matched MeSH terms: Lymphocytes/pathology*
  11. Fulltext Long term Tai Chi exercise reduced DNA damage and increased lymphocyte apoptosis and proliferation in older adults
    Goon JA, Noor Aini AH, Musalmah M, Yasmin Anum MY, Wan Ngah WZ
    Med J Malaysia, 2008 Oct;63(4):319-24.
    PMID: 19385493 MyJurnal
    Effect of Tai Chi exercise on the level of DNA damage using the comet assay, lymphocyte viability and frequency of sister chromatid exchange (SCE) were determined in adults aged above 45. Tai Chi participants of 7 years (n=35), showed higher level of normal DNA and lower level of mild and severely damaged DNA as compared to the sedentary subjects (n=35). The former are suggested to have effective DNA repair mechanism as their frequency of SCE was markedly lower. Higher lymphocyte apoptosis and proliferation found in the Tai Chi participants also indicated that the exercise promotes renewal and regeneration of lymphocytes.
    Matched MeSH terms: Lymphocytes/physiology*
  12. Fulltext Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer
    Koh CH, Bhoo-Pathy N, Ng KL, Jabir RS, Tan GH, See MH, et al.
    Br. J. Cancer, 2015 Jun 30;113(1):150-8.
    PMID: 26022929 DOI: 10.1038/bjc.2015.183
    Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.
    Matched MeSH terms: Lymphocytes/pathology*
  13. Association of circulatory Tfh-like cells with neutralizing antibody responses among chronic HIV-1 subtype C infected long-term nonprogressors and progressors
    Swathirajan CR, Nandagopal P, Vignesh R, Srikrishnan AK, Goyal R, Qureshi H, et al.
    Pathog Dis, 2019 06 01;77(4).
    PMID: 31505637 DOI: 10.1093/femspd/ftz044
    HIV-1 vaccine functioning relies on successful induction of broadly neutralizing antibodies (bNAbs). CXCR3- circulatory T-follicular helper (cTfh) cells are necessary for inducing B-cells for generating bNAbs. Recent studies have suggested that CXCR3+ Tfh cells might also influence bNAb production. Plasma samples from 34 ART-Naïve HIV-1 infected individuals [long-term nonprogressors (LTNP)-19; Progressors-13] were tested against a heterologous virus panel (n = 11) from subtypes A, B, C, G, AC, BC and AE. Frequencies of CXCR3+ and CXCR3- cTfh-like cells in peripheral circulation were studied using flow cytometry. LTNP showed significantly lower CXCR3+ and higher CXCR3- cTfh-like cell frequencies, while neutralization breadth was observed to be broader in progressors. A positive correlation was observed between bNAb breadth and potency with CXCR3+PD-1+ cTfh-like cells in LTNP. Based on neutralization breadth, 9 HIV-1 infected individuals were classified as 'top neutralizers' and 23 as 'low neutralizers' and they did not show any correlations with CXCR3+ and CXCR3- cTfh-like cells. These preliminary data suggest that CXCR3+ similar to CXCR3- might possess significant functional properties for driving B-cells to produce bNAbs. Hence, an HIV vaccine which is capable of optimal induction of CXCR3+ cTfh cells at germinal centers might confer superior protection against HIV.
    Matched MeSH terms: B-Lymphocytes; T-Lymphocytes, Helper-Inducer
  14. Differential transcriptional expression of PPARalpha, PPARgamma1, and PPARgamma2 in the peritoneal macrophages and T-cell subsets of non-obese diabetic mice
    Yaacob NS, Kaderi MA, Norazmi MN
    J Clin Immunol, 2009 Sep;29(5):595-602.
    PMID: 19472040 DOI: 10.1007/s10875-009-9300-1
    BACKGROUND: The peroxisome proliferator-activated receptors (PPARs) have been implicated in immune regulation. We determined the transcriptional expression of the three isoforms, PPARalpha, PPARgamma1, and PPARgamma2 in the peritoneal macrophages, CD4- and CD8-positive lymphocytes in non-obese diabetic (NOD) mice at 5 and 10 weeks of age as well as at diabetic stage.

    RESULTS: Compared to the non-obese diabetic resistant (NOR) mice, the peritoneal macrophages of NOD mice expressed increased levels of PPARalpha but reduced levels of PPARgamma2, while PPARgamma1 expression was unchanged in all age groups. CD4-positive lymphocytes expressed low levels of PPARalpha in diabetic NOD mice and greatly reduced expression of PPARgamma2 in all age groups. Unlike peritoneal macrophages and CD4-positive cells, the CD8-positive cells expressed low levels of PPARgamma1 in diabetic NOD mice but no difference in PPARalpha and PPARgamma2 expression was observed compared to NOR mice.

    CONCLUSION: The current findings may suggest an important regulatory role of PPARs in the pathogenesis of autoimmune diabetes.

    Matched MeSH terms: CD4-Positive T-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/metabolism; CD4-Positive T-Lymphocytes/pathology; CD8-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/metabolism*; CD8-Positive T-Lymphocytes/pathology
  15. Fulltext Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment
    Looi CK, Chung FF, Leong CO, Wong SF, Rosli R, Mai CW
    J Exp Clin Cancer Res, 2019 Apr 15;38(1):162.
    PMID: 30987642 DOI: 10.1186/s13046-019-1153-8
    BACKGROUND: Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in advanced pancreatic cancer patients. Compared with other cancers, pancreatic cancer exhibits remarkable resistance to conventional therapy and possesses a highly immunosuppressive tumor microenvironment (TME).

    MAIN BODY: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME.

    CONCLUSIONS: It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.

    Matched MeSH terms: T-Lymphocytes/drug effects; T-Lymphocytes/immunology; T-Lymphocytes/metabolism; Lymphocytes, Tumor-Infiltrating/drug effects; Lymphocytes, Tumor-Infiltrating/immunology; Lymphocytes, Tumor-Infiltrating/metabolism
  16. Recent advances on T-cell exhaustion in malaria infection
    Shankar EM, Vignesh R, Dash AP
    Med Microbiol Immunol, 2018 Aug;207(3-4):167-174.
    PMID: 29936565 DOI: 10.1007/s00430-018-0547-0
    T-cell exhaustion reportedly leads to dysfunctional immune responses of antigen-specific T cells. Investigations have revealed that T cells expand into functionally defective phenotypes with poor recall/memory abilities to parasitic antigens. The exploitation of co-inhibitory pathways represent a highly viable area of translational research that has very well been utilized against certain cancerous conditions. Malaria, at times, evolve into a sustained chronic state where T cells express several co-inhibitory molecules (negative immune checkpoints) facilitating parasite escape and sub-optimal protective responses. Experimental evidence suggests that blockade of co-inhibitory molecules on T cells in malaria could result in the sustenance of protective responses together with dramatic parasite clearance. The role of several co-inhibitory molecules in malaria infection largely remain unclear, and here we discussed the potential applicability of co-inhibitory molecules in the management of malaria with a view to harness protective host responses against chronic disease and associated consequences.
    Matched MeSH terms: T-Lymphocytes/immunology*
  17. Effects of low-level laser irradiation on human blood lymphocytes in vitro
    Al Musawi MS, Jaafar MS, Al-Gailani B, Ahmed NM, Suhaimi FM, Suardi N
    Lasers Med Sci, 2017 Feb;32(2):405-411.
    PMID: 28044209 DOI: 10.1007/s10103-016-2134-1
    Low-level laser irradiation (LLLI) has various effects on cultured human lymphocytes in vitro, but little is known about such effects in whole blood. This study investigated whether LLLI affected lymphocyte count in human whole blood in vitro. A total number of 130 blood samples were collected from apparently healthy adult patients through venipuncture into tubes containing EDTA. Each sample was divided into two equal aliquots to be used as a non-irradiated control sample and an irradiated sample. The irradiated aliquot was subjected to laser wavelengths of 405, 589, and 780 nm with different fluences of 36, 54, 72, and 90 J/cm(2), at a fixed irradiance of 30 mW/cm(2). A paired student t test was used to compare between non-irradiated and irradiated samples. The lymphocyte counts were measured using a computerized hematology analyzer and showed a significant (P 
    Matched MeSH terms: Lymphocytes/radiation effects*
  18. Fulltext Cancer immunotherapy: current progress and applications
    Pooi, Pooi Leong, Heng, Fong Seow
    Malaysian Journal of Medicine and Health Sciences, 2006;2(2):1-26.
    MyJurnal
    Cancer immunotherapy is a form of treatment protocol for cancer patients that has been studied intensively over the last two decades. The undesirable side effects during the course of conventional treatment has lead to the development of immunotherapy as an alternative treatment modality. This approach encompasses the use of three different strategies with various immunotherapeutic modalities including (i) cytokines and monoclonal antibodies; (ii) activation of antigen presentation cells (APC) by using antigen-specific peptides or sources of antigens such as tumour lysate; and finally (iii) adoptive transfer of ex vivo activated autologous cytotoxic T-cells. Due to specific-targeting by antigen-specific monoclonal antibodies, dendritic cells and activated CD8+ T-cells, immunotherapy can eliminate tumour
    cells efficiently but the normal tissues are unaffected. Despite years of investigation, the outcome of immunotherapy-based clinical trials are inconsistent with very low response rates from patients. Several mechanisms have been proposed to contribute to this failure including the presence of regulatory T-cells (Treg), immunomodulatory cytokines, and aberrant gene expression in tumour cells. This review summarises information from about 140 articles and review papers. In addition, it also provides an update on recent trends in combinational immunotherapy with conventional therapy and encouraging results have been obtained. Reevaluation of previous studies is necessary to fine-tune the design and approach of immunotherapy to ensure better treatment outcomes.
    Matched MeSH terms: T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory
  19. Trypanosome infections in Orang Aslis (Aborigines) in West Malaysia
    Dissanaike AS, Ong HT, Kan SP
    Trans R Soc Trop Med Hyg, 1974;68(6):494-5.
    PMID: 4460313
    Matched MeSH terms: Lymphocytes/parasitology
  20. Fulltext T Cell Immunity To Enterovirus 71 Infection In Humans And Implications For Vaccine Development
    Yee PTI, Poh CL
    Int J Med Sci, 2018;15(11):1143-1152.
    PMID: 30123051 DOI: 10.7150/ijms.26450
    Enterovirus 71 (EV-A71) is one of the major pathogens causing hand, foot and mouth disease (HFMD). Some strains can lead to neurological disease and fatality in children. Up to date, there is no FDA-approved vaccine to prevent severe HFMD and mortality. Although the inactivated vaccine has advanced to production in China, lack of long-term protection and the requirement of multiple boosters have necessitated the development of other types of vaccines. Recent studies indicate that cellular and not humoral immunity determines the clinical outcome of EV-A71 infections. High levels of cytokines such as IL-1β, IL-6, IL-10 and IFN-γ tend to correlate with clinical severity in patients with pulmonary edema and encephalitis. The live attenuated vaccine may serve as the preferred choice as it can induce excellent humoral and cellular immunity as well as live-long immunity. Expression of certain HLA alleles such as TNF-α promoter type II (-308 allele), HLA-A33 and HLA-DR17 responses have been linked to severe HFMD. However, the high variability of MHC genes could restrict T cell recognition and be a major obstacle in the design of peptide vaccines. Hence, the development of a T cell universal vaccine (incorporating both CD4+ and CD8+ T cell epitopes) that induces broad, multifunctional and cross-reactive CD8+ T cell responses maybe desirable.
    Matched MeSH terms: T-Lymphocytes/immunology*
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