The immune system in horses is a complex network of cells, tissues, and organs that work together to protect the body from pathogens, such as bacteria, viruses, and parasites. This system includes both innate and adaptive immune responses, which function to identify and eliminate foreign invaders. The innate immune response provides an immediate, non-specific defense, while the adaptive immune response involves a more targeted and long-lasting protection through the production of antibodies. Key components of the equine immune system include white blood cells, such as lymphocytes and macrophages, as well as various signaling molecules like cytokines. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and regulation of the immune system in horses, with an emphasis on understanding its role in maintaining equine health and its response to diseases.
Hammond SA, Cook SJ, Falo LD, Issel CJ, Montelaro RC.Immunization regimens that induce a broadly reactive cytolytic T lymphocyte (CTL) response specific for lentiviral antigens have emerged as the leading candidates in efficacy trials conducted in both animal modelshumans. To date, lentivirus vaccination strategies have overlooked one such immunization strategy, namely the use of particulate antigens. To evaluate the efficacy of targeting antigen into the phagocytic pathway to elicit a cell-mediated immune response to lentiviral antigens, we initiated the first study of a particulate-based vaccination protocol using a large animal model system. ...
Kalsow CM, Dwyer AE.Equine uveitis is a spontaneous disorder of horses that can serve as a model for the study of human uveitis. Although the initial presentation is that of an anterior uveitis, retinal involvement has been noted in some cases. We report here the immunohistopathology of retinas from horses with uveitis. Methods: Sections of eyes recovered from horses with naturally occurring uveitis and from Shetland ponies with experimental leptospira-induced uveitis were stained by hematoxylin and eosin for histopathological evaluation. Immunohistochemistry was used to evaluate retinas for MHC Class II antigen ...
Song L, Porter DG, Coomber BL.Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play very important roles in extracellular matrix (ECM) remodeling in ovarian follicle growth and ovulation. Equine follicles are embedded in cortex that is at the center of the ovary, and they must expand/emigrate to the fossa, the only site in the ovary for ovulation. Therefore, equine ovarian stromal cells (EOSC) are probably involved in ECM remodeling during follicle growth. This study examined whether cultured EOSC synthesize gelatinases and TIMPs, molecules essential for ECM remodeling in other systems. Results showed...
Okumura M, Tagami M, Fujinaga T.Keratan sulphate (KS) concentration and anticollagen type II antibody levels were measured in the serum and synovial fluid (SF) of clinically normal horses and horses with osteoarthritis (OA). Serum KS in OA was significantly higher than that in normal horses, while no significant difference was found in KS levels of SF between normal and OA. Assays of antibody to collagen type II showed no significant increase in sera and SF of OA. It was suggested that levels of serum KS would be of value in the pathological detection of OA in the joint, although there was no evidence that the measurable aut...
Romeike A, Brügmann M, Drommer W.Despite extensive clinical research, the etiology of equine recurrent uveitis (ERU) is still unknown. After an immunologic pathogenesis was established in recurrent uveitis in humans, a similar pathogenic mechanism was assumed to exist in ERU. To investigate whether immunopathologic mechanisms are involved in ERU, 20 eyes of 15 horses with ERU were examined immunohistochemically with a T cell marker, B cell marker, and anti-major histocompatibility complex (MHC) class II antibodies. Twenty-six eyes of 20 horses were used for investigation of MHC class II antigen expression in normal equine eye...
Raidal SL, Bailey GD, Love DN.Flow cytometric techniques were developed for the evaluation of oxidative burst activity in equine peripheral blood neutrophils and lymphocytes, as well as bronchoalveolar lavage derived pulmonary alveolar macrophages and lymphocytes. The oxidation of dichlorofluorescin was measured by the increased fluorescence of cells stimulated with phorbol myristate acetate or a variety of other stimulants. Flow cytometry was a suitable method for the evaluation of the intracellular oxidation in all cell populations evaluated. Analysis was rapid and cell separation before analysis was not required. Hetero...
Leber R, Wiler R, Perryman LE, Meek K.V(D)J rearrangement is the molecular mechanism by which an almost limitless number of unique immune receptors is generated. V(D)J rearrangement involves two DNA breaks and religations resulting in two DNA joints; coding and signal joints. If V(D)J recombination is impaired (as in murine SCID (C.B-17 mouse] or RAG [Recombinase Activating Genes) deficient mice), B lymphocyte and T lymphocyte development is blocked and severe immunodeficiency results. The first animal model of SCID was reported in Arabian foals in 1973. Recently we demonstrated that the mechanistic defect in SCID foals is V(D)J r...
Rubio C, Cubillo MA, Hooghuis H, Sanchez-Vizcaino JM, Diaz-Laviada M, Plateau E, Zientara S, Crucière C, Hamblin C.The mortality rate in susceptible populations of horses during an epizootic of African horse sickness (AHS) may be in excess of 90%. Rapid and reliable assays are therefore essential for the confirmation of clinical diagnoses and to enable control strategies to be implemented without undue delay. One of the major objectives of a recent European Union funded project was the validation of newly developed diagnostic assays which are rapid, sensitive, highly reproducible and inexpensive, for the detection of African horse sickness virus (AHSV) antigens and antibodies. The Laboratorio de Sanidad y ...
Bougrine SI, Fihri OF, Fehri MM.A Western immunoblotting procedure has been developed for the detection of African horse sickness virus (AHSV) protein-specific antibody responses. This assay readily identifies antibodies specific for at least 4 distinct, AHSV proteins, including VP5, NS1, NS2 and NS3/NS3a. By using the AHSV non-structural proteins as 'markers', the Western blotting procedure could be employed to provide a reliable means of discriminating between animals vaccinated with a purified, inactivated AHSV vaccine and those either naturally infected or vaccinated with a live, attenuated AHSV vaccine.
Weiss DJ, Evanson OA, McClenahan D, Fagliari J, Walcheck B.To determine whether platelets become activated and form platelet-platelet or platelet-neutrophil aggregates, or both, when subjected to shear. Methods: Blood obtained from 3 Thoroughbreds. Methods: Blood, with PCV adjusted to 32 (low hematocrit) or 60 (high hematocrit)%, was subjected to shear rates of 11.25, 22.5, 45, 90, 225, and 750/s for 3 minutes by use of a cone-plate viscometer. Flow cytometric techniques were used to identify activated platelets, platelet-platelet aggregates, and platelet-neutrophil aggregates. Results: Shear resulted in decreased platelet count, increased mean platel...
Russell KE, Walker KM, Miller RT, Sellon DC.To determine blood protein concentration, immunoglobulin concentration, and lymphocyte profiles in equine infectious anemia virus (EIAV) seropositive, naturally infected horses without clinical signs of disease. Methods: 26 clinically normal seropositive horses, 6 febrile ponies with experimentally induced EIA, and 52 clinically normal seronegative horses and ponies. Methods: Serum and EDTA-anticoagulated blood were obtained from all horses and ponies, and total serum protein and albumin concentrations, immunoglobulin concentrations, and blood lymphocyte subset counts were determined. Results:...
Anton F, Morales C, Aguilar R, Bellido C, Aguilar E, Gaytán F.The existence of a physiological integration between the immune and endocrine systems has long been recognized. In spite of the abundant literature data on the presence of cells of the immune system in the testis, mast cells and eosinophil leukocytes have received little attention. We have studied the presence, distribution and numbers of mast cells and eosinophils in the testes of 12 mammalian species. Mast cells were frequently found in equine (stallion, ass and mule) and human testis, whereas eosinophils were nearly absent. On the contrary, eosinophils were abundant in the hare testis, whil...
Flaminio MJ, Rush BR, Cox JH, Moore WE.Decreased proportion of CD4+ and CD8+ T lymphocytes in peripheral blood likely contributed to susceptibility to Pneumocystis carinii in a foal. Cytological evaluation of bronchoalveolar lavage was required for identification of the pathogen and serial flow-cytometric analysis of peripheral blood lymphocytes documented transient low expression of CD4+ and CD8+ T lymphocytes. Although immunodeficiency is uncommon, it must be included in the differential diagnosis for patients suffering from chronic or opportunistic infections and may provide an indication for immunostimulant therapy.
Raulo SM, Maisi P.To determine whether gelatinolytic activity in tracheal epithelial lining fluid (TELF), blood neutrophils, and blood lymphocytes from horses was metalloprotease activity, and to compare, for healthy horses and horses with chronic obstructive pulmonary disease, gelatinolytic activity in neutrophils, lymphocytes, and serum with activity in TELF. Methods: 7 horses with chronic obstructive pulmonary disease (COPD) and 4 healthy control horses. Methods: Neutrophils and lymphocytes were obtained by means of Percoll separation. Zymography was used to detect gelatinolytic activity; EDTA inhibition and...
Flaminio MJ, Rush BR, Shuman W.Inactivated Propionibacterium acnes is a biologic response modifier for treatment of non-specific respiratory disease in horses. The objectives of this investigation were to determine alterations in phagocytic activity, phenotypic expression of lymphocyte subpopulations and lymphokine-activated killing cell response in healthy young horses. Samples were collected on day 0, 7 and 14 of the investigation. Blood samples were obtained via jugular venipuncture and pulmonary leukocytes were recovered via bronchoalveolar lavage (BAL). Commercially available P. acnes (Eqstim) was administered intraven...
Gottschalk RD, Reyers F, van den Berg SS.The effects of a commercially available equine hyperimmune anti-endotoxin serum on synovial fluid parameters were evaluated in an induced synovitis model in normal horses. Four groups of 3 horses each received lipopolysaccharide (LPS) plus hyperimmune antiendotoxin (anti-LPS), LPS, anti-LPS, and Ringers lactate (control) respectively injected into the left intercarpal joint. Synovial fluid parameters were measured at 4, 8, 24 and 72 h. It was found that anti-LPS had no attenuating effect on the LPS and that it induced a synovitis almost equivalent to that induced by LPS alone. The introduction...
Sheoran AS, Lunn DP, Holmes MA.This paper describes the production of a panel of monoclonal antibodies (mAbs) identifying the four recognised equine IgG subisotypes IgG, IgGa, IgGb, IgGc and IgG(T). Pure preparations of the subisotypes for use in immunisations and testing were produced using a combination of gel filtration, salt precipitation, ion exchange chromatography and protein A and Protein G affinity chromatography. The specificity of mAbs for the IgG subisotypes was confirmed using ELISA assays, by characterisation of affinity purified proteins recognised by the mAbs, and by Western blotting of equine serum proteins...
Yang GC, Croaker D, Zhang AL, Manglick P, Cartmill T, Cass D.Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bo...
Raabe ML, Issel CJ, Cook SJ, Cook RF, Woodson B, Montelaro RC.We have previously reported that immunization of ponies with a baculovirus-expressed recombinant surface unit envelope protein (rgp90) for equine infectious anemia virus (EIAV) resulted in enhancement of disease symptoms and virus replication in 4 of 4 vaccine recipients subjected to a heterologous virus challenge (rpg90 I vaccine trial) (Wang et al., 1994). To extend these studies of EIAV vaccine enhancement, two additional and independent rgp90 vaccine trials (rgp90 II and rgp90 III) were performed. Combined, a total of 13 ponies were immunized with the rgp90 immunogen using our standard vac...
Jensen-Waern M, Persson SG, Nordengrahn A, Mérza M, Fossum C.Eighty Standardbred horses, originating from 5 training campuses, with decreased athletic performance in association with symptoms such as intermittent fever and mild pharyngitis were examined. As control animals, 10 horses from a stable with normally performing horses were used. Virus isolation and clinico-chemical and serological tests were performed. Lymphocyte proliferation tests were carried out to evaluate the capacity of the cell-mediated immunity. In addition, a bioassay for equine type I interferon, as a marker for early viral infections, was established. No specific microbe could be ...
Coenen M.The control of husbandry by veterinarians with the prospect of animal welfare demands a valuation of the nutritional status of farm animals. The situation of main importance is a suspected undernutrition. A prolonged failure in nutrient and energy supply results in mobilisation of body fat as well as body protein. Especially the protein depletion includes a loss of capacity of several essential functions, e.g. of the immune system or the respiratory tract. Undernutrition is often classified as stress, but the typical parameters for stress related reactions offer no sufficient information to ev...
Smith TA, Davis E, Carpenter S.Lentiviruses replicate in cells of the immune system, and activation of immune cells has been shown to modulate virus replication. To determine the effects of macrophage activation on replication of equine infectious anaemia virus (EIAV), primary horse macrophage cultures (HMCs) were established from 20 different horses, infected with an avirulent strain of EIAV, and stimulated with 5 microg/ml of bacterial endotoxin. Supernatants collected from HMCs were assayed for the presence of tumour necrosis factor (TNF-alpha) and for production of infectious virus. Results indicated that EIAV replicati...
Siedek E, Little S, Mayall S, Edington N, Hamblin A.Despite their important role in initiating T-cell responses in other species, dendritic cells have not been studied in the horse. A method for isolating blood dendritic cells by adherence and metrizamide gradients was adapted to equine cells. A number of monoclonal antibodies (mAbs), including some which label dendritic cells in other species, were tested for immunochemical reactivity with the isolated blood dendritic cells, and sections of lymph node and spleen. 62 +/- 6% of the isolated blood cells were MHC Class II positive and had typical dendritic cell morphology and only 4 +/- 2% contain...
Brazil TJ, Rossi AG, Haslett C, McGorum B, Dixon PM, Chilvers ER.The synthetic formylpeptide fMLP is widely used as a model chemoattractant and secretagogue for mammalian neutrophils. Despite possessing fMLP receptors, equine neutrophils do not produce superoxide anions in response to fMLP and there is no inflammatory reaction in the horse when fMLP is injected intradermally. The functional capability of these receptors was investigated after pretreatment with recognized priming agents. Purified neutrophils were pretreated with lipopolysaccharide (LPS), platelet-activating factor (PAF), or tumor necrosis factor alpha (TNF-alpha) and superoxide anion generat...
Foster AP, Cunningham FM.Equine eosinophils and neutrophils are believed to play an important part in the protection of horses against parasitic and bacterial invasion. Eosinophils may also play a key role in the pathogenesis of equine inflammatory conditions such as the allergic skin disease, insect hypersensitivity. The factors which stimulate the respiratory burst of equine eosinophils and neutrophils are poorly understood. The first aim of the present study was to determine the effects of the phorbol ester, phorbol myristate acetate (PMA), which is believed to activate intracellular protein kinase C, and opsonised...
Sheoran AS, Sponseller BT, Holmes MA, Timoney JF.Equine strangles, caused by the clonal pathogen Streptococcus equi, is a source of serious economic loss despite the widespread use of commercial vaccines. The anti-phagocytic 58 kDa M-like protein (SeM) is an important protective antigen. The objective of this study was to define differences, if any, between SeM-specific convalescent serum and mucosal IgA and IgG subisotypes and those induced by vaccination with commercial strangles vaccine. SeM-specific opsonophagocytic IgGb was the predominant serum antibody in horses intramuscularly vaccinated or recently recovered from infection. Infectio...
Martín E, Molleda JM, Ginel PJ, Novales M, Lucena R, López R.Lacrimal fluid represents a major ocular surface defensive mechanism providing different concentrations of all immunoglobulin classes. In this report, four classes of immunoglobulins (IgA, IgM, IgG and IgGT) have been measured in horse tears. As in others species, IgA is the main immunoglobulin responsible for local protection and constitutes quantitatively, 50% of all lacrimal proteins. The rest of immunoglobulins studied are normally present in equine tear fluid (though in lower concentration) and contribute to ocular surface immune protection. Female and adult horses showed significant high...
Rush BR.Pharmacologic manipulation of pulmonary immunity plays an important role in primary and adjunct therapy for equine respiratory disease. Frequent exposure to respiratory viral pathogens, strenuous exercise, long distance transport, and inhalation of harmful substances destroy various aspects of the pulmonary defense system and predispose performance horses to development of infectious and noninfectious respiratory disease. Pulmonary immunity may be bolstered by nonspecific immunostimulants to combat primary or secondary immunodeficiency. State of the art technology improves active and passive-s...
Baskett A, Barton MH, Norton N, Anders B, Moore JN.To compare effects of a single dose of pentoxifylline (PTX), flunixin meglumine (FM), and their combination (FM/PTX) in a model of equine endotoxemia. Methods: 24 healthy horses, aged 2 to 15 years. Methods: 4 groups (n = 6/group) received 30 ng of Escherichia coli O55:B5 endotoxin/kg of body weight, i.v., over 30 minutes, and 1 of the following preparations 15 minutes before and 8 hours after endotoxin infusion: FM, 1.1 mg/kg; PTX, 8 mg/kg; FM/PTX, 1.1 mg of FM and 8 mg of PTX/kg; and saline solution bolus (ENDO). Clinical and hematologic variables were measured over 24 hours. Results: Compar...
Duckett WM, Matthews HK.Paraneoplastic eosinophilia is reported in dogs, cats, and humans. Hypereosinophilia (an eosinophil count greater than 1.5 x 10(9) L) is often associated with metastasis and a poor prognosis. This report describes a case of paraneoplastic hypereosinophilia in a pony. Neoplasia should be included in the differential diagnoses in a horse with eosinophilia.
Ardans AA, Trommershausen-Smith A, Osburn BI, Mayhew IG, Trees C, Park MI, Sawyer M, Stabenfeldt GH.Immunotherapy was attempted in 2 Arabian foals with combined immunodeficiency. One foal was given a transplant of bone marrow from a selected full sibling, and 1 foal was given a fetal thymus transplant. Both foals died. Genetic evidence was obtained for survival of the transplanted tissues in both cases; however, a graft versus host reaction developed in the foal given the fetal thymus transplant.
Bello K, Lorch G, Kim K, Toribio RE, Yan L, Xie Z, Hill K, Phelps M.Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. Objective: To evaluate the pharmacokinetics (PK) of multiple-day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. Methods: Six healthy Standardbred mares. Methods: Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough sampl...
Ewart S, Brown C, Derksen F, Kufuor-Mensa E.Serratia marcescens was the causative agent of bacterial endocarditis in a 2-year-old Arabian stallion. The horse was treated with broad-spectrum antibiotics for 1 month. The horse died several months after treatment was discontinued. To our knowledge, Serratia marcescens has not been reported as the cause of bacterial endocarditis in horses; however, multiple cases of bacterial endocarditis attributable to Serratia marcescens have been documented in human beings. The bacteria is most commonly isolated in immune-compromised patients.
Flaminio MJ, Rush BR, Cox JH, Moore WE.Decreased proportion of CD4+ and CD8+ T lymphocytes in peripheral blood likely contributed to susceptibility to Pneumocystis carinii in a foal. Cytological evaluation of bronchoalveolar lavage was required for identification of the pathogen and serial flow-cytometric analysis of peripheral blood lymphocytes documented transient low expression of CD4+ and CD8+ T lymphocytes. Although immunodeficiency is uncommon, it must be included in the differential diagnosis for patients suffering from chronic or opportunistic infections and may provide an indication for immunostimulant therapy.
Klei TR.This article will focus on current information available on the equine immune response to helminth parasites as it relates to acquired resistance, hypersensitivity reactions, and vaccine development.
Curran JA, Argyle DJ, Cox P, Onions DE, Nicolson L.Interferon gamma, a cytokine produced by T-lymphocytes and natural killer cells, plays a central role in the modulation of the immune response, and its antiviral and antitumourigenic properties have made it a potential candidate for use in immunoprophylactic and therapeutic regimes. We have cloned the equine IFN gamma cDNA to facilitate production of this cytokine for clinical evaluation in the horse. The predicted equine IFN gamma amino acid sequence is 67% identical to that of the human equivalent and 78% to the bovine equivalent.
Heublein S, Wehner F, Höchsmann B, Hochhaus A, Hartmann M, La Rosée P.Acquired severe aplastic anaemia (AA) is a serious condition caused by immune-triggered bone marrow failure. For patients not eligible for bone marrow transplantation, treatment of choice is immunosuppression by a combined treatment with antithymocyte globulin (ATG) and cyclosporine. The debate on treatment optimization in AA is focused on conflicting data regarding ATG preparations from horse (h-ATG) versus rabbit (r-ATG), recently favouring h-ATG. H-ATG has been withdrawn from the European market in 2007. Reimbursement for imported preparations from outside Europe is frequently denied in neg...
Riggs MW.Currently recognized equine immune deficiency disorders include failure of passive colostral immunoglobulin transfer, combined immunodeficiency, selective IgM deficiency, transient hypogammaglobulinemia, and agammaglobulinemia. Additional equine immune deficiency disorders probably exist. Immune deficiency should be suspected in any horse experiencing persistent or recurrent infections that are not responsive to conventional therapy.
Al-Khalidi NW, Weisbrode SE, Dubey JP.Nine ponies were fed 100,000 infective Toxoplasma gondii oocysts and were given corticosteroid injections before and after feeding the T gondii oocysts. Titers to the Sabin-Feldman dye tests (1:2 to 1:16,384) developed within postinoculation days (PID) 7 to 21 and antibodies persisted to PID 133. Toxoplasma organisms were isolated from the tissues of 4 ponies (heart of 4, brain of 2, spinal cord of 3, diaphragm of 1, skeletal muscle of 1, liver of 1, kidneys of 1) killed between PID 36 and 63, but not from 5 ponies killed between PID 117 and 150. Seemingly, ponies are one of the more resistant...
Forsyth J, Halliwell RE, Harrand R.Identification of environmental allergens in horses with allergic disease facilitates allergen avoidance and targeted immunotherapy. Objective: To evaluate allergenic co-reactivity between 44 environmental allergens. Methods: Horses with suspected allergic disease (n = 344) whose sera were submitted for environmental allergen testing. Methods: Allergen-specific IgE serological assays were performed using 44 allergens divided into six taxonomically related groups: house dust/storage mites, moulds, insects, grass, tree and weed pollens. Using pairwise comparisons, odds ratios (ORs) were calcul...
Widders PR, Stokes CR, David JS, Bourne FJ.The immunoperoxidase technique was adapted for the identification of free immunoglobulin and immunoglobulin producing cells in equine tissues. Staining specific for free IgG, IgA and IgM was detected at all levels of the reproductive tract, and secretory component staining was present in the uterine epithelium but not in the oviduct, cervix or vagina. Immunoglobulin producing cells were present at all levels of the tract, with IgG and IgA cells at equivalent concentrations, but with fewer IgM cells. There was no cyclical trend in free immunoglobulin staining, or plasma cell numbers. IgG and Ig...
Dias MC, Landim-Alvarenga FD, de Moraes CN, da Costa LD, Geraldini CM, de Vasconcelos Machado VM, Maia L.Mesenchymal stromal cells (MSCs) have great therapeutic potential, particularly in the process of tissue repair and immunomodulation through the secretion of biomolecules. Thus, the aim of this study was to evaluate the hypothesis that intramuscular transplantation of allogeneic MSCs obtained from equine umbilical cord (UC-MSCs) is safe, demonstrating that this is a suitable source of stem cells for therapeutic use. Results: For this, UC-MSCs were cultured, characterized and cryopreserved for future transplantation in six healthy mares. On day 0, transplantation of three million UC-MSCs dilute...
Da Silva E, Martín-Cano FE, Gómez-Arrones V, Gaitskell-Phillips G, Alonso JM, Rey J, Becerro L, Gil MC, Peña FJ, Ortega-Ferrusola C.Equine endometritis is one of the main causes of subfertility in the mare. Unraveling the molecular mechanisms involved in this condition and pinpointing proteins with biomarker potential could be crucial in both diagnosing and treating this condition. This study aimed to identify the endometritis-induced changes in the endometrial proteome in mares and to elucidate potential biological processes in which these proteins may be involved. Secondly, biomarkers related to bacterial endometritis (BE) in mares were identified. Uterine lavage fluid samples were collected from 28 mares (14 healthy: ne...