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.
Longworth KE.Pulmonary intravascular macrophages are an important part of the mononuclear phagocyte system in some species of mammals, mainly sheep and other ruminants, pigs, and horses. These cells phagocytize foreign particles, cell debris and pathogens that pass through the pulmonary circulation. Species with intravascular macrophages localize intravenously injected tracer particles and bacteria predominantly in the lung rather than the liver, and exhibit pulmonary hypertension when these cells are activated. Both in vivo and in vitro studies show that pulmonary intravascular macrophages have distinct s...
Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC.Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been...
Kato H, Ohashi T, Matsushiro H, Watari T, Goitsuka R, Tsujimoto H, Hasegawa A.Equine interleukin-1 receptor antagonist (IL-1ra) was molecularly cloned to establish a basis for cytokine therapy of acute and chronic inflammatory diseases in the horse. cDNA clones encoding the whole coding sequence of equine IL-1ra were isolated from equine peripheral blood mononuclear cells (PBMC) that had been stimulated with lipopolysaccharide (LPS). The equine IL-1ra cDNA obtained in this study contained an open reading frame encoding 177 amino acid residues. The predicted amino acid sequence of equine IL-1ra shared 75.7, 75.3 and 76.3% similarity with sequences of human, murine and ra...
Hu S, Vincenz C, Buller M, Dixit VM.Molluscum contagiosum virus proteins MC159 and MC160 and the equine herpesvirus 2 protein E8 share substantial homology to the death effector domain present in the adaptor molecule Fas-associated death domain protein (FADD) and the initiating death protease FADD-like interleukin-1beta-converting enzyme (FLICE) (caspase-8). FADD and FLICE participate in generating the death signal from both tumor necrosis factor receptor-1 (TNFR-1) and the CD-95 receptor. The flow of death signals from TNFR-1 occurs through the adaptor molecule tumor necrosis factor receptor-associated death domain protein (TRA...
Charan S, Palmer K, Chester P, Mire-Sluis AR, Meager A, Edington N.Up to 21 days after exposure to live or ultraviolet-inactivated equid herpesvirus type-1 (EHV-1) autologous serum from ponies caused an immunosuppressive effect if incorporated into T-cell proliferation assays to EHV-1. The suppressive factor in the sera of ponies also inhibited T-cell response to phytohaemagglutinin. Increased levels of circulating activated transforming growth factor-beta 1 (TGF-beta 1) were detected, and the suppressive activity of the serum could be reversed by antibody to TGF-beta 1. In a challenge experiment the ponies which exhibited circulating TGF-beta 1 activity succ...
Prescott JF, Nicholson VM, Patterson MC, Zandona Meleiro MC, Caterino de Araujo A, Yager JA, Holmes MA.To evaluate use of the virulence-associated protein of Rhodococcus equi in immunizing foals against R equi pneumonia. Methods: Eight (experimental group) and 6 (controls) mares with their foals. Methods: Virulence-associated protein extracted from R equi was used to prepare an acetone-precipitated. Triton X-extracted (APTX) antigen. After determination of the efficacy of passive immunization, in untreated foals or in foals given plasma from a horse vaccinated with APTX antigen or from a nonvaccinated horse, a field trial was done to evaluate the efficacy of vaccination of 8 mares, twice with A...
Schrenzel MD, King DP, McKnight ML, Ferrick DA.Horse (Equus caballus) immunoglobulin mu chain-encoding (IgM) variable, joining, and constant gene segments were cloned and characterized. Nucleotide sequence analyses of 15 cDNA clones from a mesenteric lymph node library identified 7 unique variable gene segments, 5 separate joining segments, and a single constant region. Based on comparison with human sequences, horse variable segments could be grouped into either family 1 of immunoglobulin (Ig) clan I or family 4 of Ig clan II subclan IV. All horse sequences had a relatively conserved 16 base pair (bp) segment in framework 3 which was reco...
Crossett B, Allen WR, Stewart F.Large quantities of an unusual 19 kDa protein (p19) are secreted into the lumen of the uterus of the mare (Equus caballus) during the oestrous cycle and early pregnancy. p19 associates strongly with the acellular capsule that surrounds the young horse conceptus and is believed to be important in maintaining pregnancy. Here we report the complete cDNA sequence encoding p19, its expression patterns in horse tissues and a Southern blot analysis of the gene in horse DNA. The predicted amino acid sequence of the p19 cDNA demonstrated a signal peptide of 18 residues and a mature protein of 162 resid...
Crawford TB, Wardrop KJ, Tornquist SJ, Reilich E, Meyers KM, McGuire TC.The purpose of this study was to identify the mechanisms responsible for the thrombocytopenia that develops following infection of horses by the lentivirus equine infectious anemia virus (EIAV). Immunocompetent Arabian foals and Arabian foals with severe combined immunodeficiency (SCID), which lack functional B and T lymphocytes, were experimentally infected with EIAV. Levels of viremia and a number of clinical and hematologic parameters were examined prior to and following infection. Thrombocytopenia was not dependent on the immune response: SCID foals were affected as severely as immunocompe...
Horohov DW, Keadle TL, Pourciau SS, Littlefield-Chabaud MA, Kamerling SG, Keowen ML, French DD, Melrose PA.Intense exercise affects various parameters of the immune system. The overall effect of exercise on immune function is dependent upon the physical condition of the subject, the intensity and duration of the exercise period, and the immune parameter assessed. Unconditioned horses subjected to a single bout of intensive exercise exhibit multiple alterations in immune function, including an augmentation of lymphokine activated killer (LAK) cell function. This increase in LAK cell activity is not due to an increase in circulating LAK precursors. While peripheral blood mononuclear cells from exerci...
Barton MH, Collatos C, Moore JN.Peritoneal fluid was collected aseptically from 30 healthy adult horses and 115 horses with acute gastrointestinal disease and supernatant was separated from cells by centrifugation followed by freezing until assayed for endotoxin and tumour necrosis factor activity. Peritoneal macrophages obtained from healthy horses were incubated in vitro for 3, 6, 12 or 24 h in the absence (media control) or presence of Escherichia coli 055:B5 endotoxin (final concentrations of 1, 10, 100 or 1000 ng/ml). Macrophages obtained from horses with acute gastrointestinal disease were incubated for 12 h in the abs...
Hines MT, Schott HC, Bayly WM, Leroux AJ.Exercise has been recognized as a stress, which can significantly alter the host's immune response and, therefore, its susceptibility to disease. Whereas research in this area has previously focused primarily on human subjects and laboratory animals, it has more recently extended to domestic animals, especially the equine athlete. Despite several studies, defining the relationship among exercise, the immune response, and disease has proven difficult due to a number of factors, including the complexity of the immune system and the variable nature of exercise itself. It now appears that exercise...
Lunn DP, Schram BR, Vagnoni KE, Schobert CS, Horohov DW, Ginther OJ.Lymphokine activated killing (LAK) is an example of natural cytotoxicity, and as such is a critical means of defense against diseases such as viral infection and neoplasia. Despite this important role, the specific molecular interactions involved in LAK or other forms of natural cytotoxicity are only partially understood. In some species, cells capable of mediating natural cytotoxicity express the CD8 molecule, although no specific role has been demonstrated for CD8 in non-MHC restricted cytotoxicity. In this study the role of the EqCD8 equine homolog of CD8 in LAK cell activity was examined. ...
Dowsett KF, Knott LM, Tshewang U, Jackson AE, Bodero DA, Trigg TE.To investigate the effect of two dose rates (200 and 400 ng) of a gonadotrophin releasing hormone (GnRH) vaccine on testicular function. Methods: A vaccination dose rate experiment. Methods: Two injections were administered 4 weeks apart to six colts in each treatment group. To maintain immunosuppression until the end of the breeding season, a third injection was given if antibody titres fell below 1000. Results: Effective antibody titres were present for 12 to 27 weeks. Testosterone concentrations decreased from 2.22 to 0.31 nmol/L 6 weeks after primary vaccination. Androstenedione concentrat...
Maher JK, Tresnan DB, Deacon S, Hannah L, Antczak DF.Down-regulation of major histocompatibility complex (MHC) genes by trophoblast cells is considered to be a primary mechanism preventing maternal immune rejection of the fetal-placental unit in mammalian pregnancy by rendering these cells, which form the primary barrier between mother and fetus, relatively non-antigenic. In situ hybridization with probes encoding human and horse MHC class I genes was used to characterize the pattern of MHC class I mRNA expression in the various forms of horse trophoblast. Strong hybridization signals were observed in the invasive trophoblast cells of chorionic ...
Knowles DP.Infection of horses with the hemoprotozoan Babesia equi has been reported in southern Florida, US Virgin Islands, part of Asia, Russia, India, the Middle East, Europe, Africa, Australia, South America, Central America, Mexico, Philippine Islands and some Caribbean islands. The restrictions placed on the international movement of infected horses has refocused attention on potential methods to control or eliminate infection. Don Knowles here discusses the primary chemotherapeutic compounds that have been used; the current knowledge concerning immune responses that potentially contribute to contr...
Turner JW, Liu IK, Kirkpatrick JF.Regulation of local overpopulations of free-roaming feral equids is in demand worldwide for ecological balance and habitat preservation. Contraceptive vaccines have proven effective in feral horses, which breed seasonally, but no data are available for equids such as the burro, which is reproductively active all year round. In the present study, 27 individually identified female feral burros (Equus asinus) roaming free in Virgin Islands National Park (St John, US Virgin Islands; Lesser Antilles) were remotely treated with pig zonae pellucidae (PZP) vaccine. Between January and May, 16 burros w...
Hines MT, Palmer GH, Byrne KM, Brassfield AL, McGuire TC.Bronchoalveolar lavage fluid (BALF) and peripheral blood were obtained from each of 17 adult Arabian mares and absolute numbers and relative lymphocyte proportions were determined for total T lymphocytes, using CD2 as a marker, CD4 + T lymphocytes, CD8 + T lymphocytes, CD5 + lymphocytes, and sIgM + B lymphocytes. The marked variation in BALF cell recovery resulted in wide variation in absolute values for each lymphocyte subset. The relative proportions of gated BALF lymphocytes were much less variable and provided a basis for comparison of lymphocyte subsets between the BALF and peripheral blo...
Vatistas NJ, Snyder JR, Hildebrand SV, Harmon FA, Woliner MJ, Barry SJ, Nieto J, Henry P, Enos LR, Magliano D, Brown SA, Drake C.To determine the effects of the 21-aminosteroid, U-74389G, on reperfusion of the equine jejunum, using total (TVO) and partial (PVO) vascular occlusion during the ischemic period. Methods: TVO: 16 healthy horses were randomly allotted to 3 groups-4 horses received the vehicle alone, 6 horses received a low dosage (3 mg/kg o body weight), and 6 horses a high dosage (10 mg/kg) of U-7438G. PVO: 10 healthy horses were randomly allotted to 2 groups--5 horses received the vehicle alone, and 5 horses received the low dosage (3 mg/kg) of U-74389G. Methods: TVO was induced for 1 hour followed by 2 hour...
Esser AF, Tarnuzzer RW, Tomlinson S, Tatar LD, Stanley KK.Lack of hemolytic activity of horse serum is an inherent property of horse C9. To understand the molecular reasons for this deficiency we have cloned C9 cDNA from a horse liver cDNA library and have sequenced the cDNA yielding the complete coding sequence for horse C9. Purification of C9 from horse plasma and microsequencing established the N-terminus of the mature protein and verified that the correct horse C9 cDNA clone had been isolated. The deduced amino acid sequence corresponds to a mature protein of 526 amino acids that is 77% identical to human C9. It has the same domain structure as h...
Sanada Y, Noda H, Nagahata H.The blastogenic response of lymphocytes from 16 newborn foals naturally infected with Rhodococcus equi was investigated, in order to evaluate the relationship between R. equi infection and depressed host response. Naturally infected foals showed evidence of R. equi infection at 5-6 weeks of age, as determined by clinical, haematological, bacteriological and serological methods. The blastogenic response of lymphocytes against phytohaemagglutinin was significantly depressed (stimulation index < 1.80; P < 0.01, P < 0.05) in R. equi-infected foals at 5-6 weeks of age compared with those o...
Coté N, Trout DR, Hayes AM.The electrophoretic position and behavior of the native and activated forms of equine plasma alpha-2-macroglobulin (alpha 2M) were characterized and compared to human alpha 2M by nondenaturing polyacrylamide-gel electrophoresis (PAGE). Plasma alpha 2M was also compared between 6 normal horses and 6 horses with clinical signs of colic and endotoxemia due to volvulus or enteritis. Native and activated forms of alpha 2M were quantified by PAGE and densitometry. Binding of radio-labeled recombinant human tumour necrosis factor-alpha (125I-rhTNF-alpha) to native and activated forms of equine alpha ...
Kirkpatrick JF, Turner JW, Liu IK, Fayrer-Hosken R.A unique application of pig zona pellucida (PZP) immunocontraception is the control of wildlife populations. A native PZP vaccine has been successfully applied to wild horse and donkey populations. A single annual booster inoculation was capable of maintaining contraception. Seven consecutive years of PZP treatment in wild mares resulted in no detectable debilitating side effects, and reversibility of contraception has been documented among mares treated for up to 4 consecutive years. Long-term treatment (5-7 years) is associated with some ovulation failure and depressed urinary oestrogen conc...
Engelhardt H, King GJ.The epitheliochorial placenta represents the least intimate association between maternal and fetal tissues. The best known examples of this form of placentation are the domestic livestock species. Current information on the nature and proposed functions of uterine lymphocyte populations in ruminants (sheep and cattle), horses and pigs is presented. In ruminants unusual gamma delta T cells may play a role in mid to late gestation. During normal horse pregnancy, fetally derived endometrial cup cells invade the uterine stroma and are destroyed by maternal leukocytes midway through gestation. Natu...
Wiler R, Leber R, Moore BB, VanDyk LF, Perryman LE, Meek K.V(D)J rearrangement is the molecular mechanism by which an almost infinite array of specific immune receptors are generated. Defects in this process result in profound immunodeficiency as is the case in the C.B-17 SCID mouse or in RAG-1 (recombination-activating gene 1) or RAG-2 deficient mice. It has recently become clear that the V(D)J recombinase most likely consists of both lymphoid-specific factors and ubiquitously expressed components of the DNA double-strand break repair pathway. The deficit in SCID mice is in a factor that is required for both of these pathways. In this report, we show...
Barlough JE, Madigan JE, DeRock E, Dumler JS, Bakken JS.A Thoroughbred filly that developed clinical signs of equine granulocytic ehrlichiosis following inoculation with the human granulocytotropic ehrlichia was shown to be resistant to challenge with Ehrlichia equi, a closely related agent. This result further substantiates the close and potentially conspecific relationship between these two granulocytotropic ehrlichiae.
Swiderski CE, McClure JJ.The immune system is a complex interactive network. Defects in its function can be characterized broadly as being the result of actual deficiencies in the network or misdirection of normal immunologic functions. The assays that are available to detect deficiencies in the immunologic network barely scrape the surface of the possibilities. These assays primarily evaluate humoral immune function, but undetected defects in innate and cellular immunity are sure to exist. Although assays of humoral immunity have allowed the characterization of a number of immunodeficiency syndromes in horses, closer...
Hurley JR, Begg AP.A trial was conducted on a Thoroughbred stud to determine whether or not the administration of anti-Rhodococcus equi hyperimmune plasma would reduce the prevalence of R equi pneumonia (rattles) in foals born in the 1992 horse breeding season. Hyperimmune plasma was administered to 34 foals; another 57 foals were untreated. There was no significant difference in the number of transfused foals developing R equi pneumonia compared with the untreated foals. The time required for recovery from pneumonia between the 2 groups was not significantly different.
Rule EK, Boyle AG, Stefanovski D, Anis E, Linton J, Lorello O.Equine granulocytic anaplasmosis (EGA) is a common disease in adult horses, but clinical disease in foals is rarely reported. The relationship between equine maternal and neonatal antibodies to Anaplasma phagocytophilum is unclear. Objective: That mares in an endemic region would be seropositive for A. phagocytophilum and that mare and foal serum IgG concentrations for A. phagocytophilum would correlate. Additionally, we hypothesized that foal IgG concentrations for A. phagocytophilum acquired by passive immunity would decline by 6 months of age. Methods: Twenty-two healthy mare-foal pairs. ...
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.
Watson ED.The presence of cytochrome P450C17 within equine follicles and corpora lutea (CL) was detected by immunostaining. Two different antibodies were used which had previously been shown by immunoblotting to cross-react with equine P450C17. Strong positive immunostaining was present in the theca-derived cells of the CL during the estrous cycle and pregnancy. In the CL from mares after Day 40 of pregnancy there were also occasional bands of positively stained cells which resembled the polyhedral-shaped theca cells seen in preovulatory follicles. The pattern of immunostaining suggested compartmentaliz...
Takai S, Morozumi Y, Higashiyama S, Tsubaki S.Equine neutrophil function was studied in 24 newborn foals, 10 adult horses, and a foal infected with R. equi by the quantitative nitroblue tetrazolium (NBT) reduction test. There was no difference between results in newborn foals and adult horses. A foal naturally infected with R. equi showed normal values of NBT reduction test at birth, and after the initial clinical signs, the spontaneous reduction of NBT by neutrophils was found to be remarkably increased until a week before death
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...
Knottenbelt DC.Few skin diseases specifically or exclusively affect older horses and donkeys. Hypertrichosis (hirsutism) associated with pituitary pars intermedia dysfunction is probably the most recognized and best understood exception and is the most common age-related skin condition in equids. Many other conditions are known to be more serious in older horses. Horses affected with immune-compromising conditions can be more severely affected by infectious diseases of the skin or heavy and pathologically significant parasitism. Neoplasia of the skin is probably more prevalent and worse in older horses, alth...
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.
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...
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...
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...