The equine immune system is a complex network of cells, tissues, and organs that work collaboratively to defend against pathogens and maintain homeostasis. It consists of innate and adaptive components, each with distinct functions and mechanisms. The innate immune system provides the first line of defense through physical barriers, phagocytic cells, and the complement system. The adaptive immune system involves lymphocytes, such as B cells and T cells, which generate specific responses to antigens and provide immunological memory. Research in equine immunology explores the interactions between these components, the impact of genetic and environmental factors on immune function, and the development of vaccines and therapeutics. This page gathers peer-reviewed studies and scholarly articles focusing on the mechanisms, regulation, and clinical applications of the equine immune system in health and disease.
Okumura M, Tagami M, Fujinaga T.The role of keratan sulphate (KS) as a marker of cartilage metabolism was evaluated by using an in vitro model of equine articular cartilage. Articular cartilage was harvested from clinically healthy 6-month-old foals (n=3). Chondrocytes were centrifuged and cultured as pellets. Chondrocyte pellets were stimulated by insulin-like growth factor (IGF)-Ialpha or interleukin (IL)-1alpha for 2 weeks. The sulfated glycosaminoglycans (GAG) and antigenic KS concentrations in the culture media were measured by a 1,9-dimethyl-methylene blue (DMMB) colorimetric assay and an inhibition ELISA using a 1/14/...
Ikadai H, Kabamoto S, Xuan X, Igarashi I, Nagasawa H, Fujisaki K, Suzuki N, Mikami T.Babesia caballi merozoites were prepared by combining two improved methods of cultivation and purification of merozoites using Percoll-gradiation, and the protein compositions of merozoites were analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. The relative molecular masses of the major proteins and protein masses separated by electrophoresis were >94, 80-70, 50-45, 34-30, 30-28 and 18 kDa. By Western blotting, twelve proteins or protein groups were recognized by pooled sera from two horses experimentally infected with B. caballi. Among...
Lunn DP, Townsend HG.Equine infectious disease remains a constant and important threat to the health of domesticated horses. Vaccination plays a critical role in protecting against such disease, but at the present time the efficacy of some equine vaccination strategies is in doubt. The best strategy for resolving these concerns is an improved knowledge of the immunologic basis of successful vaccination, combined with the appropriate integration of effective vaccines into well-designed disease control policies.
Rush BR, Flaminio MJ.Nonspecific immunomodulators are substances that induce non-antigen-specific enhancement of the body's native or acquired defense mechanisms. Immunomodulant preparations are most often used for treatment of chronic, viral, or bacterial infection with evidence of secondary immunosuppression. The proposed mechanism of action of these products is macrophage activation and subsequent release of cytokines that enhance humoral and cell-mediated immunity. In equine medicine, nonspecific immunostimulant products are used for prevention and treatment of infectious respiratory disease and treatment of s...
Klei TR.Helminths are among the most significant parasites of horses in developed countries. This article examines immune responses against helminth parasites and the implications that immunologic investigations have on vaccine development, improvement of diagnostic procedures, and disease eradication.
Young KM, Lunn DP.Technologic advances in immunodiagnostic testing have enhanced our understanding of the pathogenesis of a broad array of diseases, including infectious diseases, immunodeficiency disorders, and immune-mediated disorders. If applied rationally, with an understanding of the questions the tests answer as well as the limitations that constrain their use, these tests can serve as valuable aids in the diagnosis and management of equine diseases.
Horohov DW.The ultimate reason for better characterizing the immune response to infectious agents is the hope that this knowledge may lead to the development of better preventative or therapeutic measures. As more information becomes available, it becomes possible to incorporate these findings into the design of better vaccines and treatments. Likewise, attempts to either enhance or suppress specific helper T-cell responses may be required to control immunopathologic reactions. Although cytokine intervention in the clinical setting remains theoretic at this time, future manipulation based on the TH1/TH2 ...
Giguère S, Prescott JF.The remarkable ability of the horse and other animals to prevent infection by most bacterial pathogens encountered is the result of a complex set of distinct but overlapping defense mechanisms. This article summarizes the current state of knowledge on innate and adaptive immunity to bacterial pathogens and reviews various ways in which some bacteria have evolved in order to evade components of the host response.
Perryman LE.Primary immunodeficiency disorders are genetically determined failures of immune defense that increase susceptibility to infectious agents. This article reviews the salient features of equine primary immunodeficiency disorders, summarizes the molecular mechanisms of each disorder, and updates information that facilitates diagnosis and management of affected horses. The central theme is to encourage clinicians to ask, "I wonder if this horse has an underlying primary immunodeficiency disorder?" when caring for horses suffering from chronic and recurring infections and responding poorly to stand...
McClure JJ.Although relatively little is known about autoimmunity and autoimmune mechanisms specifically in horses, the similarities between clinical syndromes with identifiable effector mechanisms in horses and other species suggest that comparable mechanisms may be applicable. Our understanding of equine autoimmunity undoubtedly will benefit from the extensive study of autoimmunity in other species.
Swiderski CE.Hypersensitivity is an exaggerated immunologic response to a foreign agent that results in inflammation and organ dysfunction. Hypersensitivity disorders are broadly divided into antibody-mediated and T-cell-mediated reactions. The inflammatory pathways that result in disease are initiated in an antigen-specific manner through Fab portions of antibodies or the T-cell receptor, causing the up-regulation of effector mechanisms designed to clear the offending agent. Effector mechanisms include the generation of inflammatory chemicals such as cytokines and chemokines and the attraction of leukocyt...
Sellon DC.FPT of immunoglobulin in foals is the commonest form of acquired immunodeficiency in horses. FPT predisposes foals to bacterial infections and septicemia and easily is preventable and treatable if breeding farms and veterinarians are attentive to optimum foaling management practices. Other forms of acquired immunodeficiencies are uncommon in horses, although immune function may be transiently suppressed by a wide variety of drugs, infections, or other conditions. As immunologic testing becomes more sophisticated and more readily available to equine practitioners, acquired immunodeficiencies ar...
MacKay RJ.After inflammation is initiated by detection of antigen, plasma components and activated leukocytes are concentrated at the inflammatory site. Cellular and chemical effectors of inflammation are focused on the offending antigen, usually resulting in its destruction and elimination. Activation of endogenous counter-regulatory systems damps down the inflammatory process and is the first stage of repair. In addition to local effects, the inflammatory focus may initiate a continuum of systemic acute phase responses ranging from the systemic inflammatory response syndrome (SIRS) to generalized immu...
Slater J, Hannant D.The identification of some of the adaptive immune responses to infection with equine viruses has been the first step toward rational immunoprophylactic design. Sufficient knowledge of infection-induced immunity and informed estimates of the requirements for long-term immunity for EIV have now been obtained. Thus, the future for inactivated EIV vaccines is promising now that new adjuvants have been applied to induce cellular immunity and safe methods have been designed to stimulate virus-neutralizing (VN) antibody at mucosal surfaces. Adenoviruses induce circulating VN antibody, the presence of...
Nixon AJ, Brower-Toland BD, Sandell LJ.This study cloned and sequenced equine transforming growth factor (TGF)-beta1, yielding a unique nucleotide structure which predicted amino acid substitutions not seen in other mammalian species. The nucleotide sequence homology was 89% to bovine, 91% to man, 90% to ovine, and 86% to rat. Derived amino acid sequence comparison showed that the equine protein was unique, differing by two residues from man, cow, sheep, pig, and dog, and by three residues in the rat. Subsequent use of the cDNA clones to examine the expression of the TGF-beta1 gene in various tissues indicated predominant expressio...
Cantlon JD, Gordy PW, Bowen RA.Vesicular stomatitis (VS) virus causes an important clinical disease of cattle and horses in North America. In order for a vaccine to be useful in the control of VS, it must not only protect against disease, but allow ready differentiation of infected and vaccinated animals. In these studies, we evaluated neutralizing antibody responses in outbred mice, calves, and horses that received a DNA vaccine that expressed the glycoprotein (G) gene of VS New Jersey virus. The vaccine elicited antibody titers in individuals from each species, especially when two doses were administered, but the level of...
Rodger FE, Illingworth PJ, Watson ED.Although the mare corpus luteum (CL) is capable of aromatization, the expression of other enzymes involved in estradiol synthesis is not yet clear. This study examined the localization of P450C17 in the mare CL at different stages of its functional development. In ovaries from follicular phase mares P450C17 was localized in the theca cells of ovarian follicles. Following ovulation, no immunostaining for P450C17 was detected in the mature CLs of nonpregnant mares. In pregnant mares, no immunostaining for P450C17 was identified in the corpus luteum prior to secretion of eCG by the feto placental...
Troedsson MH.The objective of this article is to review the role of uterine defense mechanisms in natural resistance to chronic or persistent endometritis. A breakdown of uterine physical clearance mechanisms is currently believed to play a major role in susceptibility to persistent endometritis. Mares with increased susceptibility to persistent endometritis have impaired myometrial contractility in response to an acute inflammation, resulting in an accumulation of fluid and inflammatory products within the uterine lumen. The origin of this defect remains unknown. Recent studies have demonstrated that sper...
Schröer U, Lange A, Glatzel P, Ludwig H, Borchers K.The aim of the present study was to clarify whether an EHV-1 induced abortion can be prognosticated by an increase of antibody titres, virus shedding and/or viraemia and whether the current abortion diagnostic is suitable. In this context the immune response post immunization and a possible reactivation were of great interest. For this purpose blood samples of 32 mares between the ages of 5-21 years were regularly investigated during a period of two years before and after vaccination and pregnancy. Neutralization tests, indirect immunofluorescence tests as well as PCR and virus isolation were ...
Taniguchi A, Fukushi H, Matsumura T, Yanai T, Masegi T, Hirai K.Pathogenicity of equine herpesvirus 9 (EHV-9), a new type of equine herpesvirus isolated from Gazella thomsoni, in horses was investigated by intranasal inoculation of EHV-9 (10(7) pfu) to two conventionally reared 8-months old half-bred weanling horses. Fever higher than 39 degrees C was recorded. Virus was recovered from nasal swabs and peripheral blood mononuclear cells. Both horses developed neutralizing antibody to EHV-9. Perivascular infiltration of mononuclear cells and glial reaction were found in the olfactory and limbic systems. The results suggested that EHV-9 has a pathogenicity in...
Provitera P, Bouamr F, Murray D, Carter C, Scarlata S.Human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) are closely related lentiviruses that infect immune cells, but their pathogenesis differ. Localization to the cytosolic leaflet of the plasma membrane is critical for replication of both viruses. This localization is accomplished through the matrix (MA) domain of the Gag precursor protein. In HIV-1, association of MA to anionic membranes appears to be primarily driven by a linear cluster of basic residues in the MA domain and an N-myristoylation signal. Interestingly, the MA protein of EIAV does not contain either of ...
Flaminio MJ, Rush BR, Davis EG, Hennessy K, Shuman W, Wilkerson MJ.Studies in infants and foals indicate an age-dependent maturation of peripheral lymphocyte subsets. The age-dependent relationship for maturation of cellular immune responses, such as phagocytosis and lymphocyte responses of the peripheral and pulmonary-derived leukocytes, has not been characterized in foals. Lymphocyte subpopulations, mitogen stimulation response of lymphocytes, lymphokine-activated killing cell activity, phagocytosis and oxidative burst activity, and serum immunoglobulin (Ig) classes G and M concentrations were determined in developing foals. This study illustrates age-depen...
Watson JL, Jackson KA, King DP, Stott JL.Expression of the low-affinity IgE receptor (CD23) on the surface of mononuclear cells is a critical event in the development of IgE-mediated immunologic responses. Using PCR and cDNA library screening, a 2.7kb cDNA encoding equine CD23 and a 627bp PCR fragment of cattle CD23 were sequenced and characterized. The equine CD23 sequence encodes a complete and continuous open reading frame of 327 amino acids, while the shorter cattle fragment encodes 209 amino acids corresponding to nucleotides 325-1098 of the equine CD23 transcript. In addition to high identities in their nucleotides and translat...
Eder C, Crameri R, Mayer C, Eicher R, Straub R, Gerber H, Lazary S, Marti E.Immunoglobulin E antibody (IgE) levels against four recombinant (r) mould allergens (r-Aspergillus fumigatus [rAsp f] 7, 8 and 9; r-Alternaria alternata 1 [rAlta1]) and crude mould (Aspergillus fumigatus, Alternaria alternata, Penicillium notatum) and storage mite extracts were determined by ELISA in sera from 24 pulmonary sound control horses and 26 horses suffering from chronic bronchitis/bronchiolitis (CB), also called chronic obstructive pulmonary disease (COPD). Serum IgG and IgA titres were also determined against Aspergillus fumigatus extract and rAsp f 8.IgE against the crude extracts ...
Barber MR, Fayrer-Hosken RA.Ecological and conservation programs in ecosystems around the world have experienced varied success in population management. One of the greatest problems is that human expansion has led to the shrinking of wildlife habitat and, as a result, the overpopulation of many different species has occurred. The pressures exerted by the increased number of animals has caused environmental damage. The humane and practical control of these populations has solicited the scientific community to arrive at a safe, effective, and cost-efficient means of population control. Immunocontraception using zona pellu...
Olivry T, Borrillo AK, Xu L, Dunston SM, Slovis NM, Affolter VK, Demanuelle TC, Chan LS.Bullous pemphigoid (BP) is an autoimmune subepithelial blistering dermatosis of humans, dogs, cats and pigs. It is characterized by skin-fixed and circulating IgG autoantibodies that target one or both BP antigens. An immunological homologue of BP in humans was diagnosed in two horses with cutaneous and mucosal ulcerations as well as microscopic subepithelial vesiculation. Immunological investigations revealed similar findings for both the horses. Direct immunofluorescence demonstrated the presence of IgG deposited linearly at the dermoepidermal junction in mucosal and skin biopsy specimens. I...
Aggarwal N, Holmes MA.Despite the importance of IgG Fc receptors in the regulation of various immunological mechanisms, these receptors have not been well characterised in the domesticated animals including equines. This paper describes the production of two monoclonal antibodies (CVS 59 and CVS 61) that recognise equine IgG Fc receptors. Fusions were conducted using BALB/c mice hyperimmunised with equine peripheral blood mononuclear cells. Hybridoma supernatants were screened on the basis of their ability to inhibit the rosetting of equine antibody coated sheep erythrocytes with equine peripheral blood mononuclear...
Katz J, Dewald R, Nicholson J.Procedurally similar competitive enzyme-linked immunoassay (cELISA) methods were developed for the serodiagnosis of Babesia equi and Babesia caballi (piroplasmosis), Trypanosoma equiperdum (dourine), and Burkholderia mallei (glanders) infections in horses. Apparent test specificities for the B. equi, B. caballi, T. equiperdum, and B. mallei cELISAs were 99.2%, 99.5%, 98.9%, and 98.9%, respectively. Concordances and kappa values between the complement fixation (CF) and the cELISA procedures for the serodiagnosis of B. equi, B. caballi, T. equiperdum, and B. mallei infections in experimentally e...
Lawler DF, Hopkins J, Watson ED.Recent evidence indicates that the cells of the immune system and their large network of secretory products, or cytokines, play an active role in the ovary throughout the oestrous cycle. In the present study, immune cell populations (T and B lymphocytes, macrophages, granulocytes and eosinophils) and expression of major histocompatibility complex (MHC) class II were investigated in corpora lutea from mares in early (days 2-4), mid- (days 7-10) and late (days 12-14) dioestrus, the post-luteolytic phase (days 16-17) and early pregnancy. The number of T lymphocytes within the corpus luteum increa...
Rossano MG, Mansfield LS, Kaneene JB, Murphy AJ, Brown CM, Schott HC, Fox JC.Equine protozoal myeloencephalitis (EPM) is a neurological disease of horses and ponies caused by the apicomplexan protozoan parasite Sarcocystis neurona. The purposes of this study were to develop the most stringent criteria possible for a positive test result, to estimate the sensitivity and specificity of the EPM Western blot antibody test, and to assess the ability of bovine antibodies to Sarcocystis cruzi to act as a blocking agent to minimize false-positive results in the western blot test for S. neurona. Sarcocystis neurona merozoites harvested from equine dermal cell culture were heat ...
Heskett KA, Mackay RJ.To investigate the use of a specific antibody index (AI) that relates Sarcocystis neurona-specific IgG quotient (Q(SN)) to total IgG quotient (Q(IgG)) for the detection of the anti-S neurona antibody fraction of CNS origin in CSF samples obtained from horses after intragastric administration of S neurona sporocysts. Methods: 18 adult horses. Methods: 14 horses underwent intragastric inoculation (day 0) with S neurona sporocysts, and 4 horses remained unchallenged; blood and CSF samples were collected on days - 1 and 84. For purposes of another study, some challenged horses received intermitten...
Hirayama K, Okamoto M, Sako T, Kihara K, Okai K, Taharaguchi S, Yoshino T, Taniyama H.Histopathologic and immunohistochemical examinations were performed to determine the origin of host cells parasitized by Eimeria in the small intestines collected from five foals. Eimeria organisms at various stages (mainly microgametes and macrogametes) were frequently found in the cytoplasm of hypertrophied host cells in the lamina propria at the tips of villi of the jejunum and ileum. The cytoplasm of the host cell was immunohistochemically positive for cytokeratin AE1/AE3 and cytokeratin 13 and was negative for vimentin, desmin, alpha-smooth muscle actin, chromogranin A, neuron-specific en...
Kim SK, Shakya AK, O'Callaghan DJ.The sole equine herpesvirus 1 (EHV-1) immediate-early protein (IEP) is essential for viral replication by transactivating viral immediate-early (IE), early (E), and late (L) genes. Here, we report that treatment of mouse MH-S, equine NBL6, and human MRC-5 cells with 20 ng/mL of IFN-γ reduced EHV-1 yield by 1122-, 631-, and 10,000-fold, respectively. However, IFN-γ reduced virus yield by only 2-4-fold in mouse MLE12, mouse L-M, and human MeWo cells compared to those of untreated cells. In luciferase assays with the promoter of the EHV-1 early regulatory EICP0 gene, IFN-γ abrogated -activatio...
Loux SC, Fernandes CB, Dini P, Wang K, Wu X, Baxter D, Scoggin KE, Troedsson MHT, Squires EL, Ball BA.Intrauterine infection and inflammation remain a major cause of preterm labour in women and mares, with little known about small RNA (sRNA) expression in tissue or circulation. To better characterise placental inflammation (placentitis), we examined sRNA expression in the endometrium, chorioallantois and serum of mares with and without placentitis. Disease was induced in 10 mares via intracervical inoculation of Streptococcus equi ssp. zooepidemicus, either with moderate or high levels of inoculum; three uninoculated gestationally matched mares were used as controls. Matched chorioallantois an...
Lim WS, Payne SL, Edwards JF, Kim I, Ball JM.Equine infectious anemia virus (EIAV) causes rapid development of acute disease followed by recurring episodes of fever, thrombocytopenia, and viremia. Most infected equid eventually bring the virus under immunological control. We recently reported the development of an equine-specific ribonuclease protection assay (RPA) to quantitate mRNA levels of 10 cytokines. Using this newly developed RPA, we now show significant differences in cytokine induction in equine monocyte-derived macrophages (EMDM) exposed to virulent and avirulent EIAV. Virulent EIAV17 induced significant increases in interleuk...
Vandergrifft EV, Swiderski CE, Horohov DW.We have cloned equine interleukin 4 (IL-4) cDNA using the polymerase chain reaction (PCR) and primers based on the human IL-4 sequence. The cDNA was amplified from mitogen-stimulated equine peripheral blood mononuclear cells (PBMC). The cloned PCR product shares extensive homology ith IL-4 sequences from other species.
Adams AA, Horohov DW.The weaning process of foals involves a period of considerable stress which likely contributes to an increased risk of infectious disease in these young horses. Mechanisms responsible for this heightened risk of infection remain unknown, although likely due to compromised cell-mediated immunity. Parapoxvirus ovis (PPVO), an immmunomodulator, has been shown to limit the severity of infectious disease outbreaks among horses and has been shown to enhance CMI responses. Thus, an objective of this study was to investigate the effect of PPVO therapy on cell-mediated immune (CMI) responses of abruptl...
Beachler TM, Papich MG, Andrews NC, Von Dollen KA, Ellis KE, Withowski K, Bailey CS.Transcervical intrauterine infusion of antibiotics may more effectively treat pathogens associated with fetal and neonatal disease in pregnant mares than standard systemic routes. The objective of this study was to assess the safety of transcervical antibiotic infusion by characterizing the gestational outcome in nine healthy pregnant pony mares following a single transcervical infusion of 2.4 million IU of procaine penicillin and 200 mg of gentamicin in a 10 mL volume during late gestation. Assessment of fetal-placental health was performed through serial measurement of the combined thickness...
Klukowska-Rötzler J, Marti E, Lavoie JP, Ainsworth DM, Gerber V, Zurbriggen A, Janda J.Thymic stromal lymphopoietin (TSLP) is a cytokine involved in lymphocyte development. In humans and mice, TSLP drives the differentiation of T helper 2 (Th2) cells and the development of allergic inflammation. The equine TSLP gene has been previously identified and characterized, but its role in the pathogenesis of equine allergic diseases is not known. Our objective was to assess the expression of TSLP in bronchoalveolar lavage (BAL) cells and in primary bronchial epithelial cells (BEC) isolated from horses with recurrent airway obstruction (RAO). RNA was isolated from BAL cells sampled from ...
Wilkołek PM, Pomorski ZJ, Szczepanik MP, Adamek L, Pluta M, Taszkun I, Gołyński M, Rozwód A, Sitkowski W.The present study was designed to asses specific IgE towards environment allergens in 42 healthy horses. Determination of this immunoglobulin in serum serve as diagnostic tools in allergic diseases to improve efficacy of the treatment and proper allergen selection to specific immunotherapy. Serum levels of allergen specific IgE were measured with equine monoclonal antibody, using 15 individual and 5 mix allergens in North European Panel. The study revealed season dependent increased levels of allergen specific IgE in normal horses. It is noteworthy that healthy horses show high percentage of p...
Justines G, Sucre H, Alvarez O.Transplacental passage of Venezuelan equine encephalitis virus, epizootic strain P-676, occurred in four of nine fetuses studied. The mares were infected near term. Virus was recovered in high titer from fetal blood and organs, while no virus was detected in maternal blood but neutralizing antibodies were present. No evidence of in utero infection was found in two fetuses from mares infected with MF-8, another epizootic strain of Venezuelan equine encephalitis virus.
Berti A, Liguri G, Stefani M, Nassi P, Ramponi G.Horse muscle acylphosphatase antibodies were obtained by immunizing rabbits with the highly purified antigen cross-linked with glutaraldehyde. Specific antibodies were purified from the immunoglobulin fraction by affinity chromatography using a matrix coupled with the pure antigen as immunoadsorbent. The purified antibodies were partially characterized by immunodiffusion and immunoprecipitin techniques. These antibodies could be used to study aspects of the muscle acylphosphatase structure, localization and other biological properties.
Holyoak GR, Smith CM, Boyette R, Montelongo M, Wray JH, Ayalew S, Duggan VE, Confer AW.Actinobacillus equuli is carried in the alimentary tract of mares and can cause severe septicemia of neonatal foals. A hemolytic subspecies, A. equuli subsp. haemolyticus, and a non-hemolytic subspecies, A. equuli subsp. equuli, have been identified. Hemolytic strains produce the RTX toxin Aqx. The purpose of this study was to demonstrate sequentially in two sets of mare-foal pairs antibodies to A. equuli whole bacterial cells, outer membrane proteins, and recombinant Aqx and to compare the transfer of antibodies to these antigens between mares and their foals. Two mare/foal sets of sera were ...
De-Simone SG, Provance DW.Affinity chromatography is a separation method based on a specific binding interaction between an immobilized ligand and its binding partner. An important class of ligands for the effective separation and purification of biotechnologically important substances is lectins, a group of naturally occurring molecules widely found in plants that display a range of specificities to bind different sugars. As sugars are often added to proteins through the process of glycosylation, ∼1/3 of all genetically encoded proteins are glycosylated, numerous cognate pairs of lectins with glycosylation groups ha...