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Topic:Immune Response
The immune response in horses involves a complex network of cells, tissues, and molecules that work together to protect the animal from pathogens and other harmful agents. This process includes both innate and adaptive immune mechanisms. Innate immunity provides the first line of defense and involves components such as physical barriers, phagocytic cells, and the complement system. Adaptive immunity, on the other hand, is characterized by the activation of lymphocytes and the production of antibodies, which provide a targeted response to specific antigens. Key components of the equine immune system include T cells, B cells, and various cytokines that facilitate communication between immune cells. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, regulation, and implications of immune responses in equine health.
Modulation of equine articular chondrocyte messenger RNA levels following brief exposures to recombinant equine interleukin-1beta. The effect of recombinant equine IL-1beta (EqIL-1beta) on steady-state mRNA levels of equine articular chondrocytes in high-density monolayer culture was investigated using a customized cDNA array analysis. Total RNA samples isolated from chondrocytes cultured in media alone or with the addition of 1 ng/ml EqIL-1beta for 1-, 3-, and 6-h durations of exposure were reverse transcribed, radiolabeled, and hybridized to a customized 380-target cDNA array. Means of duplicate log base 2 transformed hybridization signals were normalized to equine glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mean s...
In vivo pretreatment with PGG-glucan fails to alter cytokine mRNA expression of equine peripheral blood mononuclear cells exposed to endotoxin ex vivo. Twelve healthy horses were assigned to treatment or control groups. Treated horses received PGG-Glucan[ED-1] (1 mg/kg, IV) 24 hours prior to peripheral blood mononuclear cell (PBMC) isolation. PBMCs were isolated and incubated in the presence of lipopolysachharide (LPS). At 0, 6, 12, 24 and 48 hours messenger RNA (mRNA) was extracted. Reverse transcription polymerase chain reaction (PCR) was performed and cytokine mRNA expression for tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), interleukin 10 (IL-10) and interferon gamma (IFN-gamma) determined using real time PCR. A si...
Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone. Inhaled ozone can induce oxidative injury and airway inflammation. Horses affected by recurrent airway obstruction (RAO) have a decreased pulmonary antioxidant capacity, which may render them more susceptible to oxidative challenge. It is currently unknown whether RAO-affected horses are more susceptible to oxidative stress than those unaffected by RAO. Objective: To determine whether ozone exposure induces greater oxidative stress and airway inflammation in RAO-affected horses in remission than in healthy horses. Methods: Seven healthy control horses and 7 RAO-affected horses were exposed to ...
Genetic immunization with codon-optimized equine infectious anemia virus (EIAV) surface unit (SU) envelope protein gene sequences stimulates immune responses in ponies. In the context of DNA vaccines the native equine infectious anemia virus (EIAV)-envelope gene has proven to be an extremely weak immunogen in horses probably because the RNA transcripts are poorly expressed owing to an unusual codon-usage bias, the possession of multiple RNA splice sites and potential adenosine-rich RNA instability elements. To overcome these problems a synthetic version of sequences encoding the EIAV surface unit (SU) envelope glycoprotein was produced (SYNSU) in which the codon-usage bias was modified to conform to that of highly expressed horse and human genes. In transfect...
Cytokine gene expression in response to SnSAG1 in horses with equine protozoal myeloencephalitis. Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses from the Americas and is mainly caused by Sarcocystis neurona. Recently, a 29-kDa surface antigen from S. neurona merozoites was identified as being highly immunodominant on a Western blot. This antigen has been sequenced and cloned, and the expressed protein has been named SnSAG1. In a previous study, cell-mediated immune responses to SnSAG1 were shown to be statistically significantly reduced in horses with EPM in comparison to EPM-negative control horses. It therefore appears as though the parasite is able to i...
In vivo interaction of pulmonary intravascular macrophages with activated platelets in microvessels of equine lung after multiple exposures to halothane, isoflurane, and thiamylal: a comparative ultrastructural and cytochemical study. The pulmonary intravascular macrophages (PIMs) of equines contain a unique electron-dense surface coat that is predominantly composed of lipoproteins. A single exposure of inhalatory halothane causes mobilization of the surface coat into the endocytotic system of the PIMs, followed by expansion of the Golgi apparatus and its enrichment with acid phosphatase. Simultaneously, the cells of the lymphocytic series show hyperplasia in the form of mitotic changes inside the microvascular compartment of the lung. Halothane is known to cause acute and chronic hepatotoxicity because of its biotransforma...
Nitric oxide levels and nitric oxide synthase expression in uterine samples from mares susceptible and resistant to persistent breeding-induced endometritis. Breeding-induced endometritis (BIE) in the mare is resolved by 36 hr after insemination in resistant mares. However, 10-15% susceptible broodmares fail to do so because of impaired uterine contractility between 7 and 19 hr after exposure to seminal or bacterial challenge, which reduces their fertility. Methods: Nitric oxide (NO) in uterine secretions, and expression of nitric oxide synthase (NOS) in uterine biopsies were compared between susceptible and resistant groups 13 hr after insemination. Results: Susceptible mares had a higher NO in their uterine secretions and greater inducible NOS (i...
Efficacy of a recombinant equine influenza vaccine against challenge with an American lineage H3N8 influenza virus responsible for the 2003 outbreak in the United Kingdom. Fifteen influenza-naive Welsh mountain ponies were randomly assigned to three groups of five. A single dose of a recombinant ALVAC vaccine was administered intramuscularly to five of the ponies, two doses, administered five weeks apart, were administered to five, and the other five served as unvaccinated, challenge controls. Two weeks after the completion of the vaccination programme, the ponies were all challenged by exposure to an aerosol of influenza virus A/eq/Newmarket/5/03. Their clinical signs were scored daily for 14 days according to a standardised scoring protocol, and nasal swabs we...
Serum antibody responses to equine herpesvirus 1 glycoprotein D in horses, pregnant mares and young foals. The envelope glycoprotein D of equine herpesvirus 1 (EHV-1 gD) has been shown in laboratory animal models to elicit protective immune responses against EHV-1 challenge, and hence is a potential vaccine antigen. Here we report that intramuscular inoculation of EHV-1 gD produced by a recombinant baculovirus and formulated with the adjuvant Iscomatrix elicited virus-neutralizing antibody and gD-specific ELISA antibody in the serum of over 90% of adult mixed breed horses. The virus-neutralizing antibody responses to EHV-1 gD were similar to those observed after inoculation with a commercially avai...
Chronic exacerbation of equine heaves is associated with an increased expression of interleukin-17 mRNA in bronchoalveolar lavage cells. Recent finding suggests that T-cells may be involved in the pathogenesis of heaves in horses. However, little is known concerning their possible contribution to pulmonary neutrophilia, a characteristic finding in heaves. Interleukin (IL)-17 is a cytokine secreted by activated T-cells that indirectly promotes the maturation, chemotaxis and activation of neutrophils. We therefore hypothesized that IL-17 may be involved in the recruitment of neutrophils into the airways and that its mRNA expression would be increased in bronchoalveolar lavage (BAL) cells of horses with heaves. Heaves susceptible ...
Rhodococcus equi-specific cytotoxic T lymphocytes in immune horses and development in asymptomatic foals. Rhodococcus equi is an important cause of pneumonia in young horses; however, adult horses are immune due to their ability to mount protective recall responses. In this study, the hypothesis that R. equi-specific cytotoxic T lymphocytes (CTL) are present in the lung of immune horses was tested. Bronchoalveolar lavage (BAL)-derived pulmonary T lymphocytes stimulated with R. equi lysed infected alveolar macrophages and peripheral blood adherent cells (PBAC). As with CTL obtained from the blood, killing of R. equi-infected targets by pulmonary effectors was not restricted by equine lymphocyte all...
Dose responses to inhalation of endotoxin, hay dust suspension and Aspergillus fumigatus extract in horses as measured by levels and activation of matrix metalloproteinase-9. Airway matrix metalloproteinases (MMPs) increase after endotoxin (LPS) exposure, but there are no reports describing dose-dependent increases or activation following exposure. Objective: To study matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) responses in bronchoalveolar lavage fluid (BALF) from heaves-susceptible and control horses following inhalation of hay dust suspension (HDS), LPS and Aspergillus fumigatus extract (AFE). Methods: Heaves-susceptible (n = 7) and control (n = 6) horses received inhalation challenges with 3 different doses of HDS and LPS. Heaves-susceptible horses (n = 6)...
In vivo evaluation of an EIAV vector for the systemic genetic delivery of therapeutic antibodies. Lentiviral-based vectors hold great promise as gene delivery vehicles for the treatment of a wide variety of diseases. We have previously reported the development of a nonprimate lentiviral vector system based on the equine infectious anaemia virus (EIAV), which is able to efficiently transduce dividing and nondividing cells both in vitro and in vivo. Here, we report on the application of EIAV vectors for the systemic delivery of an antibody fusion protein designed for the treatment of cancer. The therapeutic potential of a single chain antibody against the tumour-associated antigen, 5T4, fuse...
Efficacy of DNA vaccination against western equine encephalitis virus infection. The efficacy of a DNA vaccine against western equine encephalitis (WEE) infection in mice was evaluated. The 26S structural region was expressed, in vitro from an internal T7 promoter using a rabbit reticulysate transcription/translation system; and from a CMV promoter after transfection into Vero cell monolayers. The proteins synthesized were reactive with anti-WEE virus (WEEV) antibodies, both in western blot analysis and histochemical staining, respectively. When the DNA vaccine plasmid, pVHX-6, was administered intraepidermally to mice, followed by challenge in a lethal mouse model, the le...
Assessment in mice of vapA-DNA vaccination against Rhodococcus equi infection. There is a need to produce a vaccine against Rhodococcus equi pneumonia in foals in which immunity against infection is largely based on a type 1, cell-mediated, immune response. The VapA protein of the virulence plasmid of R. equi is highly immunogenic. To assess the potential of vapA-DNA to produce immunity, C57BL/6 and BALB/c mice were immunized with a DNA vaccine constructed from vapA incorporated into pcDNA3.1. The plasmid construct expressed VapA in a COS-7 cell line. Intramuscular immunization of mice resulted in enhanced clearance of R. equi from the liver of intravenously challenged m...
Effects of training on phagocytic and oxidative metabolism of peripheral neutrophils in horses exercised in the aerobic-anaerobic transition area. Using simple techniques, the neutrophil function, in its phagocytosis and oxidative metabolism stages, was evaluated in horses. This was done before and after moderate exercise at the aerobic-anaerobic threshold (standardized heart rate 150 beats/min and lactate level of 3.07 +/- 0.21 mmol/L). The objective was to determine whether regular training and moderate exercise improved the neutrophil function. A group of 19 horses was used; 11 of these were untrained and the remainder trained for national jumping events. The exercise test consisted of a 5 min trot followed by a 3 min gallop on a long...
Seasonal reproduction in the mare: possible role of plasma leptin, body weight and immune status. The primary objective of this study was to evaluate the possible role of leptin, body weight and immune status on reproductive activity throughout the transition period from cyclicity to seasonal anestrus, during anestrus and resumption of ovarian activity in Lusitano mares. Mares in good body condition were monthly monitored throughout 2 years (10 mares in each year) for evaluation of their reproductive status by sequential ultrasonography and plasma progesterone determinations. On the second year, all mares were weighed. Progesterone and leptin were assayed by radioimmunoassay (RIA). Paramet...
Ketamine inhibits LPS-induced tumour necrosis factor-alpha and interleukin-6 in an equine macrophage cell line. Ketamine is widely used in equine anaesthesia. Beside its anaesthetic and analgesic properties, ketamine possesses a cytokine-modulating activity. However, to date, no data are available regarding the inhibitory effect of ketamine on the cytokine response in horses. In horses, cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) play a pivotal role in the pathogenesis of equine endotoxaemia following gastrointestinal disorders. Hence, the objective of this study was to assess the influence of ketamine on LPS-induced TNF-alpha and IL-6 formation in an equine macro...
The anamnestic serologic response to vaccination with a canarypox virus-vectored recombinant West Nile virus (WNV) vaccine in horses previously vaccinated with an inactivated WNV vaccine. A new recombinant West Nile virus (WNV) vaccine has been licensed for use in horses. Prior to the availability of the recombinant vaccine in 2004, the only equine WNV vaccine available on the market had been an inactivated vaccine. Since the recombinant vaccine only expresses selected viral genes, the question could be posed as to whether a single dose of the recombinant vaccine would be effective in producing an anamnestic serologic response in horses previously vaccinated with an inactivated WNV vaccine. In this study we demonstrate that vaccination of horses with a canarypox-vectored recomb...
Immune response to vaccines based upon the VapA protein of the horse pathogen, Rhodococcus equi, in a murine model. Rhodococcus equi is a significant pathogen in foals predominantly causing a pyogranulomatous bronchopneumonia. Many vaccine candidates have been tested for the prevention of R. equi disease in foals. However, none of these have been developed for widespread commercial use. Previous studies have shown that a Th1 immune response is imperative for the protection of foals against R. equi disease. In this study a DNA and a protein vaccine based upon the well-characterised R. equi virulence-associated protein VapA were developed. The vaccines were tested in the BALB/c murine model and the results sh...
Immunologic responses to West Nile virus in vaccinated and clinically affected horses. To compare neutralizing antibody response between horses vaccinated against West Nile virus (WNV) and horses that survived naturally occurring infection. Methods: Cross-sectional observational study. Methods: 187 horses vaccinated with a killed WNV vaccine and 37 horses with confirmed clinical WNV infection. Methods: Serum was collected from vaccinated horses prior to and 4 to 6 weeks after completion of an initial vaccination series (2 doses) and 5 to 7 months later. Serum was collected from affected horses 4 to 6 weeks after laboratory diagnosis of infection and 5 to 7 months after the first...
Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy. Among the diverse experimental vaccines evaluated in various animal lentivirus models, live attenuated vaccines have proven to be the most effective, thus providing an important model for examining critical immune correlates of protective vaccine immunity. We previously reported that an experimental live attenuated vaccine for equine infectious anemia virus (EIAV), based on mutation of the viral S2 accessory gene, elicited protection from detectable infection by virulent virus challenge (F. Li et al., J. Virol. 77:7244-7253, 2003). To better understand the critical components of EIAV vaccine e...
Inhibition of lymphocyte proliferation and activation: a mechanism used by equine invasive trophoblast to escape the maternal immune response. At days 36-38 of gestation, the equine invasive trophoblast cells migrate into the endometrium of the pregnant mare to form the endometrial cups. During their migration, they become surrounded by maternal CD4+ and CD8+ T lymphocytes, and stimulate a cytotoxic antibody response to the paternal major histocompatibility complex class I antigens that they express. Nevertheless, endometrial cup cells remain viable at the site of uterine invasion up to days 80-100 of gestation, suggesting the participation of immunomodulatory mechanisms to the maternal cellular immune response. To determine the effe...
Cytokine induced metalloproteinase expression and activity does not correlate with focal susceptibility of articular cartilage to degeneration. To determine whether the focal susceptibility to cartilage degeneration in joints is related to a differential response to cytokine stimulation. Methods: Compare aggrecan and collagen catabolism in in-vitro models of cartilage degradation induced by retinoic acid (RA), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF) and IL-1 plus oncostatin M (OSM). Glycosaminoglycan (GAG) and hydroxyproline (HyPro) quantification and Western immunoblot analyses of aggrecan and collagen degradation products were undertaken in explant cultures of normal cartilage from regions of equine joints with a kno...
Cytokine profiles of peripheral blood and airway CD4 and CD8 T lymphocytes in horses with recurrent airway obstruction. Equine recurrent airway obstruction (RAO) is thought to result from an aberrant immune response to inhaled antigens, modulated by T lymphocytes via the secretion of pro-inflammatory cytokines. However data relating to the phenotypes of the T lymphocytes present in peripheral blood and bronchoalveolar lavage fluid of RAO horses and their cytokine profiles are contradictory. The aim of this study was to further investigate the cytokine (IL-4, IL-5, IL-13 and INF-gamma) mRNA expression profile in peripheral blood lymphocytes and bronchoalveolar lavage lymphocytes from RAO and control horses, befo...
Characterisation and quantification of equine interferon gamma. Interferon-gamma (IFN-gamma) is a key cytokine in cell-mediated immunity. To measure IFN-gamma production of equine lymphocytes (eqIFN-gamma), we developed a quantitative ELISA. Monoclonal antibodies (mAb) were produced against bacterially derived eqIFN-gamma. The mAbs recognised recombinant and lymphocyte-derived eqIFN-gamma in ELISA, Western blotting, as well as flow cytometric and microscopic analysis. In contrast to bacterially derived material, mammalian and insect cell-derived eqIFN-gamma was biologically active but could be neutralised by one of the monoclonal antibodies. Unexpectedly, ...
Histology and ultrastructure of the equine lingual tonsil. I. Crypt epithelium and associated structures. The microstructural and ultrastructural features of the equine lingual tonsil were studied in five young horses. Located at the root of the tongue it presented an irregular surface with rounded elevations, numerous folds and crypts. Stratified squamous non-keratinized epithelium lining its outer surface was modified by heavy infiltration of lymphoid cells to form reticular epithelium within the crypt. The latter implies a role in initiating and maintaining immune responses to incoming infectious agents and antigens. Lamellated structures resembling Hassall's corpuscle were observed towards the...
Effect of type of dietary polyunsaturated fatty acid supplement (corn oil or fish oil) on immune responses in healthy horses. The objective of this study was to compare effects of dietary polyunsaturated fatty acid supplementation (corn oil or fish oil) on selected immune responses in normal horses. Two groups of horses (n = 5) were randomly assigned a dietary supplement with either 3.0% corn oil or fish oil for a period of 14 weeks. Plasma fatty acid profiles were monitored to ensure uptake of dietary fatty acids. Cell-mediated immunity was assessed by a delayed-type hypersensitivity (DTH) skin test to keyhole limpet hemocyanin (KLH), and humoral immunity was assessed by measuring antibody titers to KLH. Production ...
Dietary (n-3) fatty acids from menhaden fish oil alter plasma fatty acids and leukotriene B synthesis in healthy horses. The study objective was to determine the effect of feeding corn oil or fish oil to horses on plasma fatty acid profiles and leukotriene B (LTB) synthesis by stimulated peripheral blood neutrophils. Two groups of horses (n = 5) were randomly assigned to diets supplemented with either 3.0% (by weight) corn oil or fish oil for a period of 14 weeks. The ratio of (n-6) to (n-3) fatty acids in oil supplements was 68.1:1 for corn oil and 0.12:1 for fish oil. Production of LTB4 and LTB, by peripheral blood neutrophils stimulated with calcium ionophore A23187 and plasma cholesterol, triacylglycerol, an...
