Cell-mediated Immune System Research Articles

Advanced three-dimensional X-ray imaging unravels structural development of the human thymus compartments

BackgroundThe thymus, responsible for T cell-mediated adaptive immune system, has a structural and functional complexity that is not yet fully understood. Until now, thymic anatomy has been studied using histological thin sections or confocal microscopy 3D reconstruction, necessarily for limited volumes.MethodsWe used Phase Contrast X-Ray Computed Tomography to address the lack of whole-organ volumetric information on the microarchitecture of its structural components. We scanned 15 human thymi (9 foetal and 6 postnatal) with synchrotron radiation, and repeated scans using a conventional laboratory x-ray system. We used histology, immunofluorescence and flow cytometry to validate the x-ray findings.ResultsApplication to human thymi at pre- and post-natal stages allowed reliable tracking and quantification of the evolution of parameters such as size and distribution of Hassall’s Bodies and medulla-to-cortex ratio, whose changes reflect adaptation of thymic activity. We show that Hassall’s bodies can occupy 25% of the medulla volume, indicating they should be considered a third thymic compartment with possible implications on their role. Moreover, we demonstrate compatible results can be obtained with standard laboratory-based x-ray equipment, making this research tool accessible to a wider community.ConclusionsOur study allows overcoming the resolution and/or volumetric limitations of existing approaches for the study of thymic disfunction in congenital and acquired disorders affecting the adaptive immune system.

Abstract 6747: Engineering M13 filamentous phages to target dendritic cells and elicit anti-tumor immunity

Abstract Filamentous phage is a safe and effective vaccine vector that can elicit robust immune responses by activating Toll-like receptor pathways. However, engineering neoantigen-displaying phages for cancer vaccines using phage display technology has been challenging and yielded inconsistent results. We developed a dendritic cell (DC)-targeting cancer vaccine platform with M13 filamentous phages using the phage display technology. The engineered phages express DC-targeting peptides (SLS) on p3 sites and spy-catcher proteins on p8 positions, allowing neoantigens and proteins of interest to be linked to the phage vector. We named our platform SCP (SLS-spy catcher phage). Imaging and western blot showed that spy-tagged proteins can be easily attached to SCP by simple mixing. Further studies demonstrated that targeting DCs can enhance antigen presentation and anti-cancer immunity. We tested SCP in MB49 and B16 mouse models and the serum, spleen and tumor tissues were isolated for further investigation of immune response upon treatment. We found that SCP effectively suppressed tumor growth by inducing systemic anti-tumor humoral and cell-mediated immunity. SCP also showed efficacy in late-stage tumor models. SCP treatment triggered particularly robust local anti-tumor response. Histological and flow cytometry analysis revealed increased infiltration of innate and adaptive immune cells, reduced PDL1 expression, and restricted neovascularization in the tumor microenvironment after intratumoral administration of SCP. Our study demonstrated that SCP can induce multifactorial modifications in the tumor microenvironment to impede tumor growth. SCP overcomes the limitations of traditional phage display technology, enabling a wide variety of peptides and proteins to be loaded onto the phage vectors. SCP is also cost-effective and scalable as phage production and purification processes are relatively mature. We propose that SCP can serve as a universal platform for cancer immunotherapy, and may offer novel treatment options for patients. Citation Format: Yee Man Betty Au-Yeung, Zheng Zeng, Jiandong Huang. Engineering M13 filamentous phages to target dendritic cells and elicit anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6747.

Intranasal sensitization model of alopecia areata using pertussis toxin as adjuvant.

Nasopharyngeal Bordetella pertussis (BP) colonization is common, with about 5% of individuals having PCR evidence of subclinical BP infection on nasal swab, even in countries with high vaccination rates. BP secretes pertussis toxin (PTx). PTx is an adjuvant commonly used to induce autoimmunity in multiple animal models of human disease. Colocalization of PTx and myelin from myelinated nerves in the nasopharynx may lead to host sensitization to myelin with subsequent autoimmune pathology. C57BL/6J female adult mice were given varied doses and schedules of intranasal PTx, MOG35-55 antigen, or controls to test whether intranasal administration of PTx and myelin oligodendrocyte peptide (MOG35-55) could induce experimental autoimmune encephalomyelitis (EAE) in mice. While we observed systemic cell-mediated immunity against MOG35-55, we did not observe EAE. Unexpectedly, many mice developed alopecia. We systematically investigated this finding. Patchy alopecia developed in 36.4% of mice with the optimized protocol. Pathology consistent with alopecia areata was confirmed histologically by documenting concomitant reduced anagen phase and increased telogen phase hair follicles (HFs) in biopsies from patches of hair loss in mice with alopecia. We also found reduced CD200 staining and increased CD3+T cells surrounding the HFs of mice with alopecia compared to the mice without alopecia, indicating HF Immune Privilege (HFIP) collapse. Systemic immune responses were also found, with increased proportions of activated T cells and B cells, as well as MHCII+ dendritic cells in peripheral blood and/or splenocytes. Finally, in mice initially exposed to intranasal MOG35-55 and PTx in combination, but not to either agent alone, splenocytes were shown to proliferate after in vitro stimulation by MOG35-55. Consistent with prior investigations, PTx exhibited a dose-response effect on immune cell induction and phenotype, with the lowest PTx dose failing to induce autoimmunity, the highest PTx dose suppressing autoimmunity, and intermediate doses optimizing autoimmunity. We propose that this is the first report of an autoimmune disease in an animal model triggered by colocalization of intranasal PTx and autoantigen. This model parallels a natural exposure and potential intranasal sensitization-to-pathology paradigm and supports the plausibility that nasopharyngeal subclinical BP colonization is a cause of alopecia areata.

Development of HIV Therapeutic Approaches based on Nanotechnology

Acquired Immune Deficiency Syndrome appears to be one of the major threats to humankind and is a serious health problem and a fast-spreading incurable disease. Numerous antiviral medications and nucleic acid therapies, including siRNA, have been researched and assessed for HIV prevention due to the virus' complex structural makeup and the absence of a potential vaccine. The antiviral treatments have considerably improved the quality and hope of life for the infected people, but along with the capacity to adapt to the virus, it has prevented further success. HIV primarily affects the body's cell-mediated immune system. It is concentrated in specific inaccessible areas of the body such as the CNS, lymphatic system and macrophages where the majority of therapeutic drugs cannot reach in sufficient concentrations or for the required period. With the introduction of highly active antiretroviral therapy, the prevalence of HIV/AIDS infections is decreasing. Drug resistance and physical obstacles to antiretroviral therapy are still major problems. Different nanocarriers with the stimuli-responsive release are proposed for antiretroviral agents. These include creating nanoparticles with passive and active targeting capabilities as well as ones that can react to a variety of internal and external triggers. Many of the advantages of the lipid system can also be offered by nanocarriers. For the treatment of HIV/AIDS, drug delivery systems such as liposomes, solid lipid nanoparticles, dendrimers and polymeric nanoparticles are being studied. This study seeks to provide an overview of how nanocarrier technology can offer a logical approach to anti-HIV therapy.

Within-host mathematical model of malaria parasite with cell-mediated and antibody-mediated immune systems

ABSTRACT Malaria is a serious health problem in the world. Nearly half of the world’s population is at risk of disease. In this study, a mathematical model was developed to understand and analyze the dynamics of the malaria parasite within host cells with cell-mediated and antibody-mediated immune systems. The model categorizes the population into six compartments. The study provides a concise representation of the interaction between the parasite and red blood cells, as well as the responses of the immune system, including both antibody-mediated and cell-mediated responses. The research examines the biological visibility and well-posedness of the model, ensuring that the solutions remain bounded and positive. The basic reproduction number, which indicates the potential spread of the parasite is determined. The stability analysis of the parasite-free equilibrium point was also conducted, revealing that the parasite-free state is locally and globally stable if the basic reproduction number, R 0 < 1 . Furthermore, bifurcation and sensitivity analysis are performed. Finally, to complement the theoretical findings and illustrate the impact of immunological effectiveness, numerical simulations are conducted under different scenarios. The result shows that the cell-mediated and antibody-mediated immune response helps to eliminate the parasite within the human host.

Intracardiac Aspergilloma in a Case with Premature Birth: A Case Report

Aspergillus species, which are common in nature, can cause a highly variable spectrum from allergy to invasive disease, depending on the host's immunity and the presence of underlying lung disease. Isolated cardiac aspergilloma is extremely rare without fungal sepsis. In this case, cardiac aspergilloma in a preterm baby has presented. This premature baby born thirty-two weeks and 1000 gr, and hospitalized due to sepsis. She was operated after a mass and thrombus were detected in the echocardiography while receiving antibiotic therapy. During the operation, an intracardiac mass excision was made in the right atrium, starting from the inferior vena cava, measuring 9 x 10 mm (18 mm with the stem). The pathology result was compatible with aspergilloma, and Aspergillus colonization was detected in the myocardial tissue, which was also supported by the pathology laboratory. No growth was detected in blood cultures, and immunological examinations were found to be normal. Low molecular weight heparin and levatirecetam treatments were given to the patient who developed cardiac arrest, seizures, and multiple thrombi during the follow-up. At the end of eight months, the patient was discharged without sequelae, and voriconazole treatment was completed for 12 months. Outpatient follow-up continues. The immaturity of the phagocytic system and T cell-mediated immune system of premature babies, their need for long-term parenteral nutrition, the use of broad-spectrum antibiotics and steroids put these babies at risk for invasive fungal infections

Immunoinformatics Analysis of Citrullinated Antigen as Potential Multi-peptide Lung Cancer Vaccine Candidates for Indonesian Population.

Non-small-cell lung cancer (NSCLC) is the most common lung cancer which has the highest mortality rate in Indonesia. One of the trends in treating cancer is by utilizing peptide vaccines, an immunotherapeutic approach that aims to stimulate the cell-mediated adaptive immune system to recognize cancer-associated peptides. Currently, no peptide vaccines are available in the market for NSCLC treatment. Therefore, this project aims to develop a multi-epitope peptide-based vaccine for NSCLC utilizing citrullinated peptides. Citrullination is a post-translational modification that occurs in cancer cells during autophagy that functions to induce immune responses towards modified self-epitopes such as tumor cells, through activation of PAD enzymes within the APC and target cells. It was found that introducing a common citrullinated neo-antigen peptide such as vimentin and enolase to the immune system could stimulate a higher specific CD4+ T cell response against NSCLC. Moreover, carcinoembryonic antigen (CEA), an antigen that is highly expressed in cancer cells, is also added to increase the vaccine's specificity and to mobilize both CD4+ and CD8+ T cells. These antigens bind strongly to the MHC Class II alleles such as HLA-DRB1*07:01 and HLA-DRB*11:01, which are predominant alleles in Indonesian populations. Through in silico approach, the peptides generated from CEA, citrullinated vimentin and enolase, were analyzed for their MHC binding strength, immunogenicity, ability to induce IFNγ response, and population coverage. It is expected that the immunodominant antigens presentation is able to induce a potent immune response in NSCLC patients in Indonesia, resulting in tumor eradication.

Acute Malaria in Malawian Children and Adults is Characterized by Thrombocytopenia That Normalizes in Convalescence.

BackgroundPlasmodium falciparum malaria has been linked with significant perturbations of the peripheral cell-mediated immune system during acute phase. Some of these changes include lower than normal platelet counts. Although the exact mechanisms that drive thrombocytopenia in P. falciparum malaria are not fully known, a number of hypotheses have been proposed. We conducted two sets of studies with one aimed at determining platelet counts in Malawian children, and the other in adults during acute P. falciparum malaria and a month post treatment.Materials and MethodsWe recruited a total of 113 HIV-uninfected children with acute malaria [n=54 with uncomplicated malaria (UCM), n=30 with severe malarial anemia (SMA), n=29 presenting with cerebral malaria (CM)]. We also recruited 42 HIV-uninfected healthy controls. Out of the 113 participants with malaria, 73 (65%) [n=34 (63%) UCM, n=21 (70%) SMA and n=18 (62%) CM] were successfully followed-up one month after treatment. A 5mL peripheral blood sample was collected for platelet count using HMX Haematological Analyzer analysis both at baseline (acute malaria) and at follow-up a month later. Platelet counts were also determined in blood samples of 106 HIV-uninfected adults, 47 of whom presented with UCM and 29 with severe malaria (SM) and these counts were compared to those of 30 healthy controls. Of the malaria cases, platelet counts for 44 UCM and 21 SM were determined again during follow-up a month after treatment.ResultsIn both children and adults, platelet counts were significantly lower during acute disease compared to the levels in the healthy controls with the lowest levels observed in CM (children) or SM (adults). These lower than normal levels increased close to normal levels a month post treatment.ConclusionP. falciparum malaria in Malawian children and adults was characterized by profound thrombocytopenia which recovered during convalescence.

Chronic Endotoxemia and Peculiarities of Systemic Inflammatory Response in Patients with Osteoarthrosis Requiring Primary Arthroplasty of Large Joints

INTRODUCTION: Infectious complications after the primary arthroplasty of large joints in patients with end-stage osteoarthrosis are often associated with self-opportunistic pathogenic microflora in cases of compromised immune response and systemic inflammatory reactions. Thus, the associated pathogenic mechanisms require additional study.&#x0D; AIM: To examine the peculiarities of signs of endotoxemia and the severity of the systemic inflammatory response (SIR) in patients with osteoarthritis of large joints requiring primary arthroplasty.&#x0D; MATERIALS AND METHODS: A total of 110 patients (67 women, 43 men, average age 49.2 years, age range 41.152.8 years) with stage IIIIV primary osteoarthrosis of the knee joints and 30 healthy individuals (control group) (15 men, 15 women, average age 49.4 years, age range 37.253.1 years) were examined. Analyses were carried out on blood serum concentrations of the endotoxemia parameter lipopolysaccharide (LPS), acute-phase proteins (C-reactive protein [CRP]), lipopolysaccharide-binding protein (LBP), and markers of the proinflammatory activity of cytokine regulation system (interleukine-1 [Il-1]) and activation of cell-mediated immunity (neopterin). Correlation relationships between the studied parameters were evaluated depending on the severity of the SIR.&#x0D; RESULTS: Forty patients were identified (28 women, 12 men) to have signs of high inflammatory activity (CRP concentration 7.59 g/L and erythrocyte sedimentation rate 10 mm/h) and evident synovitis based on the ultrasound data of the joint. The parameters in this group were analyzed: LPS, 12.08 (10.77; 12.65) ng/mL; LBP, 26.31 (25.48; 27. 11) g/mL; Il-1, 8.4 (7.3; 8.7) pg/mL; and neopterin, 9.36 (8.58; 9.62) pg/mL. These values significantly (р 0.05, KruskalWallis test) exceeded the values in the moderate SIR activity and control groups. Correlation analysis (Spearman r-test) in patients with signs of enhanced inflammatory activity revealed a moderate positive relationship between LPS and CRP concentrations, and reduction of positive relationships between LPS and Il-1 and in LPS and LBP.&#x0D; CONCLUSION: Impaired SIR with the underlying excessive proinflammatory activity of the cytokine regulation system, activation of the cell-mediated immunity, and systemic endotoxemia in patients with end-stage osteoarthrosis of large joints requires additional preoperative and postoperative monitoring. The results substantiate the necessity of a detailed investigation of endotoxemia as a probable component of the pathogenesis and sanogenesis of complications following the primary arthroplasty of large joints.

Delay induced interaction of humoral- and cell-mediated immune responses with cancer.

A mathematical model for the quantitative analysis of the interaction between cancer cells and cell-mediated immune system with two discrete-time delays, considering the role of antibodies, is studied in this paper. The model is analyzed both analytically and numerically to understand the dynamics of interaction delay and proliferation enhancement effect delay in the eradication of cancer. Hopf bifurcation occurs when one-time delay crosses the critical value in the absence of the other. It is also observed that as we increase any of the delays, it will increase the cancer burden. The analysis shows that a cancer-free state cannot be obtained solely by the killing rate of cytotoxic T-lymphocytes, but humoral response in combination with cell-mediated immune responses plays an important role to eradicate cancer.

Variants of SARS Coronavirus-2 and Their Potential Impact on the Future of the COVID-19 Pandemic

The emergence of SARS-CoV-2 variants of concern (VOCs), especially the sweeping spread of the delta variant, and differing public health management strategies, have rendered global eradication of SARS-CoV-2 unlikely. The currently available COVID-19 vaccines, including the inactivated whole virus vaccines, mRNA vaccines, and adenovirus-vectored vaccines, are effective in protecting people from severe disease and death from COVID-19, but they may not confer good mucosal immunity to prevent the establishment of infection and subsequent viral shedding and transmission. Mucosal vaccines delivered via intranasal route may provide a promising direction, which, if given as a third dose after a two-dose series of intramuscular vaccination, likely promotes mucosal immunity in addition to boosting the systemic cell-mediated immunity and antibody response. However, immunity induced by vaccination, and natural infection as well, is likely to wane followed by re-infection as in the case of human coronaviruses OC43, 229E, NL63, and HKU1. It is a challenge to prevent and control COVID-19 worldwide with the increasing number of VOCs associated with increased transmissibility and changing antigenicity. Nevertheless, we may seek to end the current pandemic situation through mass vaccination and gradual relaxation of non-pharmaceutical measures, which would limit the incidence of severe COVID-19. Repeated doses of booster vaccine will likely be required, similar to influenza virus, especially for the elderly and the immunocompromised patients who are most vulnerable to infection.

Mucosal immunity to SARS-CoV-2: a clinically relevant key to deciphering natural and vaccine-induced defences

The unusually rapid development of large-scale vaccines against coronavirus disease 2019 (COVID-19) was a historical moment for clinical healthcare. However, it took precedence over the fundamental immunological work needed for a fuller understanding of the critical components of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Consequently, almost all studies of the immune response in COVID-19 have focused exclusively on serum antibodies and systemic cell-mediated immunity including innate responses [1].

A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model.

The use of virus-vectored platforms has increasingly gained attention in vaccine development as a means for delivering antigenic genes of interest into target hosts. Here, we describe a single-cycle influenza virus-based SARS-CoV-2 vaccine designated as scPR8-RBD-M2. The vaccine utilizes the chimeric gene encoding 2A peptide-based bicistronic protein cassette of the SARS-CoV-2 receptor-binding domain (RBD) and influenza matrix 2 (M2) protein. The C-terminus of the RBD was designed to link with the cytoplasmic domain of the influenza virus hemagglutinin (HA) to anchor the RBD on the surface of producing cells and virus envelope. The chimeric RBD-M2 gene was incorporated in place of the HA open-reading frame (ORF) between the 3′ and 5′ UTR of HA gene for the virus rescue in MDCK cells stably expressing HA. The virus was also constructed with the disrupted M2 ORF in segment seven to ensure that M2 from the RBD-M2 was utilized. The chimeric gene was intact and strongly expressed in infected cells upon several passages, suggesting that the antigen was stably maintained in the vaccine candidate. Mice inoculated with scPR8-RBD-M2 via two alternative prime-boost regimens (intranasal-intranasal or intranasal-intramuscular routes) elicited robust mucosal and systemic humoral immune responses and cell-mediated immunity. Notably, we demonstrated that immunized mouse sera exhibited neutralizing activity against pseudotyped viruses bearing SARS-CoV-2 spikes from various variants, albeit with varying potency. Our study warrants further development of a replication-deficient influenza virus as a promising SARS-CoV-2 vaccine candidate.

Oral Vaccination Approaches for Anti-SHIV Immunity.

We modified a Sabin Oral Poliovirus Vaccine (OPV) vector to permit secretion of the antigens of interest with the goal of improving anti-HIV Env humoral responses in a SHIV mucosal immunization composed of DNA and recombinant OPVs. We evaluated stimulation of systemic and mucosal cell-mediated and humoral immunity in Rhesus macaques by two regimens, both involving a prime with a SHIVBG505 DNA construct producing non-infectious particles formulated in lipid nanoparticles, administered in the oral cavity, and two different viral vector boostings, administered in the oral cavity and intestinally. Group 1 was boosted with rMVA-SHIVBG505, expressing SIV Gag/Pol and HIVBG505 Env. Group 2 was boosted with a SHIVBG505-OPV vaccine including a non-secreting SIVmac239CA-p6-OPV, expressing Gag CA, NC and p6 proteins, and a HIVBG505C1-V2-OPV, secreting the C1-V2 fragment of HIV EnvBG505, recognized by the broadly neutralizing antibody PG16. A time course analysis of anti-SHIV Gag and Env CD4+ and CD8+ T-cell responses in PBMC and in lymph node, rectal, and vaginal MNC was carried out. Both regimens stimulated significant cell-mediated responses in all compartments, with SHIVBG505-OPV immunization stimulating more significant levels of responses than rMVA- SHIVBG505. Boolean analysis of these responses revealed predominantly monofunctional responses with multifunctional responses also present in all tissues. Stimulation of antibody responses was disappointing in both groups with negative anti-SHIV IgG in plasma, and IgA in salivary, rectal and vaginal secretions being restricted to a few animals. After repeated rectal challenge with SHIVBG505, two Group 1 animals remained uninfected at challenge termination. No significant differences were observed in post-infection viral loads between groups. After the acute phase decline, CD4+ T cell percentages returned to normal levels in vaccinated as well as control animals. However, when compared to controls, vaccinate groups had more significant preservation of PBMC and rectal MNC Th17/Treg ratios, considered the strongest surrogate marker of progression to AIDS. We conclude that the vaccine platforms used in this study are insufficient to stimulate significant humoral immunity at the tested doses and schedule but sufficient to stimulate significant mucosal and systemic cell-mediated immunity, impacting the preservation of key Th17 CD4+ T cells in blood and rectal mucosa.

The Role of Memory T Cells in Controlling the Covid-19 Pandemic

ABSTRACTEvaluation of changes in antibody orders is a common exclusion in vaccination strategies because of the method ofanalysis. The fact that protection by antibodies produced by the Severe Acute Respiratory Syndrome Coronavirus-2(Sars-Cov-2) infection both naturally and through vaccines will decrease in less than one year, is a challenge for acountry with a large population like Indonesia to run its vaccination program. The main challenge is whether thevaccination strategy adopted will overcome the vaccine barrier and the race between the rate of vaccination and therate of viral mutation and antibody reduction. In addition to antibodies, the adaptive immune system is also run by Tcells that are included in the cell-mediated immune system (CMI) group. In patients with asymptomatic or mildsymptoms of Coronavirus 2019 (Covid-19), T and CMI responses are known to appear in some patients who are notknown to have been exposed to Sars-Cov-2 before. This evidence suggests that the adaptive catastrophe for SarsCov-2 has been acquired by ordering memory T cells and may last longer than previously thought. For countries withlarge populations, this will certainly help overcome the limitations of vaccines and the time needed to implement theirvaccination strategies.

Association between absolute lymphocyte count and overall mortality in patients with surgically resected gastric cancer.

Background/AimsLymphocytes are an important component of the cell-mediated immune system. As lymphopenia is reportedly associated with poor prognoses in patients with various cancers, we investigated this notion in patients who underwent curative gastrectomy.MethodsWe retrospectively analyzed the association between absolute lymphocyte count (ALC) and prognosis in patients with stage I–III gastric cancer who underwent curative surgical resection. Ever lymphopenic patients were defined as those with ALCs < 1,000/μL at any time post-diagnosis except within 30 days post-surgery. Adjusted multivariable regression models were used to evaluate the associations between lymphopenia and overall mortality, gastric cancer-specific mortality, and disease-free survival.ResultsWe investigated 1,222 patients diagnosed between January 2011 and December 2015. Fifty-six patients (4.6%) were lymphopenic at diagnosis and nearly one-quarter (24.8%) were ever lymphopenic with a mean minimum ALC of 640/μL. Older age (odds ratio [OR], 1.02) and higher stage (stage III vs. I; OR, 3.01) were positively associated with ever lymphopenia. On multivariable analysis, ever lymphopenia predicted higher overall mortality (hazard ratio [HR], 1.83; p = 0.008), higher gastric cancer-specific mortality (HR, 1.58; p = 0.048), and shorter disease-free survival (HR, 1.83; p = 0.006). The 5-year gastric cancer-specific mortality rates for ever- and never lymphopenic patients were 10.9% and 3.7%, respectively; their 5-year cumulative recurrence rates were 15.1% and 4.6%, respectively.ConclusionsThis study demonstrate that ever lymphopenia is independent prognostic factor for overall mortality and recurrence in patients with potentially curable gastric cancer; hence, ALCs may be a biomarker for predicting the prognoses of patients with stage I–III gastric cancer who had curative gastrectomy.

Effect of Exercise Intensity on Cell-Mediated Immunity.

Moderate-intensity exercise is considered to enhance immune function and to be useful for preventing acute upper respiratory infections and similar conditions. Many people practice low-intensity short-duration exercise with the expectation of a beneficial effect on immunocompetency. However, it is difficult to affirm the existence of definite evidence of such a benefit. In this article, we discuss the effects of low-intensity short-duration exercise on cell-mediated immunity, and contrast them to the effects of high-intensity and long-duration exercise. Whereas high-intensity exercise induces inflammation and reduces cell-mediated immune system function, low-intensity exercise does not appear to have a large effect on either inflammation or cell-mediated immune function. Low-intensity exercises such as walking and yoga, which are helpful to relieve stress, cannot be considered as harmful to the immune system. Although yoga was shown to impose fewer restrictions on breathing and physical strain, the evidence that yoga enhances cell-mediated immunity remains insufficient. Therefore, further studies are needed to examine the exercise mode that may be most effective for improvement of immune functions.

Immunohistochemical Detection of Aflatoxin in Lesions of Aflatoxin-producing Aspergillus flavus Infection.

To evaluate the presence of aflatoxin in infectious lesions as well as how the toxin is taken up by leukocytes. Pathological specimens from a patient who died from aspergillosis caused by aflatoxin-producing A. flavus were used. Anti-aflatoxin B1 antibody was reacted with paraffin-embedded lesion specimens from the heart, kidney, and thyroid gland of the patient and observed microscopically. Positive reactions were detected in fungal elements and leukocytes (neutrophils and macrophages) in inflammatory lesions. Within the patient's body, A. flavus likely produced aflatoxin, which then was taken up by neutrophils and macrophages.These results suggest that leukocyte function and the immune mechanism are locally suppressed by aflatoxin.

Role of Heat Shock Proteins in Immune Modulation in Malaria.

Malaria is one of the major parasitic killer diseases worldwide. Severe cases of malaria are mostly in children under the age of 5 years due to their naïve immune system and in pregnant women with weakened immune responses. Inflammatory immune responses against the parasite involve complement activation as well as the antibody and effector cell-mediated immune system. However, after an infection with Plasmodium falciparum (P. falciparum), the most dangerous malaria species, the host-derived immunity is often insufficient to completely inhibit the infection cycles of the parasite in red blood cells for yet unknown reasons. In the present chapter we aim to elucidate the role of the host's and the parasite's heat shock proteins (HSPs) in the development of a novel anti-malaria therapeutic approach.

Effect of Deoxycholic Acid on Immune Cells - An Immunophenotyping Analysis of Peripheral Blood and Splenic Lymphocytes in CD57 Female Mice

Background: Deoxycholic acid has been used in Chinese traditional medicine “Niuhuang” that is known to have Immunoregulatory and anti-inflammatory properties. Preliminary evidences have shown that Deoxycholic acid modulates the immune system by way of stimulation and helps in maintaining a disease-free state within an individual. The aim of this study was to investigate the effect of Deoxycholic acid on immunophenotyping analysis of peripheral blood and splenic lymphocytes in CD57 female mice. Methods: Animals were treated with control, 100, 500 and 1000 mg/kg of Deoxycholic acid for 14 days. The animals were euthanized on Day 15 and blood and intact spleens were collected. The homogenized spleens were collected aseptically and prepared single cell suspension of splenocytes. The whole blood and spleen cells were analyzed by flow cytometry. Results: At 100 mg/kg and 500 mg/kg, 2-fold increase in total lymphocytes (CD45) and significant increases in lymphocyte (T-cell) population and sub-populations of T-cell (Helper T-cell, Cytotoxic T-cell) were observed. Increased (up to 77%) proliferation of B-cells was observed at these doses. Similar trends, but at lesser magnitude as compared to 100 and 500 mg/kg, were observed at 1000 mg/kg, this was due to the toxicity observed at this dose. No treatment related changes in the populations of Lymphocytes of spleen. Conclusion: From the results of the present study, it was suggested that Deoxycholic acid treatment modulates the immune system by activating both cell mediated and humoral immune system.