Bovine sire effects on daughters' in vitro blood neutrophil functions, lymphocyte blastogenesis, serum complement and conglutinin levels

Blood neutrophil functions, lymphocyte blastogenic responses, serum complement, and serum conglutinin activity of 98 lactating Holstein cows from two genetic lines were evaluated. The genetic lines were produced in a selection experiment that created and perpetuated genetic differences in milk production for up to seven generations. No significant differences between the two genetic lines of cows were found for neutrophil function, lymphocyte blastogenic responses, serum complement levels, or serum conglutinin levels. Significant differences between sire progeny groups within lines were found for unstimulated and mitogen-stimulated lymphocyte blastogenesis (P less than 0.0001), and almost all neutrophil functions (antibody independent neutrophil cytotoxicity, antibody dependent neutrophil cytotoxicity, ingestion of bacteria, iodination, chemiluminescence, chemokinesis, and chemotaxis (P less than or equal to 0.05)). Sire progeny group differences (P less than or equal to 0.0001) within lines for serum complement and conglutinin activity were also found. Neutrophil chemiluminescence activity (positive relationship; P less than or equal to 0.001), concanavalin A-stimulated lymphocyte blastogenesis (positive relationship; P less than or equal to 0.004), and serum conglutinin activity levels (negative relationship; P less than or equal to 0.01) each had small but significant associations with the total milk somatic cell count. Cows seropositive for bovine leukosis virus had increased resting and mitogen-stimulated lymphocyte blastogenic activity and were associated with increased in vitro neutrophil random migration and production of superoxide anion. Estimates of genetic parameters of various immune cell functions, of serum complement and of conglutinin levels for daughters of 11 sires with 4-6 daughters in the data set were determined. In this report, genetic variation was demonstrated for nonspecific humoral and cellular immunity.     

Effects of ACTH administration on bovine polymorphonuclear leukocyte function and lymphocyte blastogenesis

Yearling steers were treated with ACTH to determine the effect of increased plasma cortisol concentration on bovine lymphocyte and polymorphonuclear leukocyte (PMN) function. The administration of ACTH caused a significant (P less than 0.01) increase in serum cortisol concentration and depression of lymphocyte blastogenesis in response to phytohemagglutinin and concanavalin A. The response to pokeweed mitogen was also depressed, but not significantly. Random migration by PMN was significantly enhanced by ACTH treatment, but there was no effect on ingestion of Staphylococcus aureus, nitroblue tetrazolium reduction, or antibody-dependent cell-mediated cytotoxicity by PMN. The iodination reaction, which evaluates the activity of the myeloperoxidase-hydrogen peroxide-halide antibacterial system of the PMN, was significantly impaired after ACTH treatment. These data indicate that specific parameters of lymphocyte and neutrophil function were impaired directly or indirectly by elevated in vivo concentrations of plasma cortisol.     

Influence of recombinant human interleukin-2 administration on lymphocyte and neutrophil function in clinically normal and dexamethasone-treated cattle

Recombinant human interleukin-2 (rhIL-2) was evaluated for its influence on total and differential WBC counts, lymphocyte blastogenic responsiveness to mitogens, and several measurements of neutrophil function in clinically normal and in dexamethasone-treated cattle. A single dose of rhIL-2 (2.5 X 10(7) U) given SC had no influence on the total or differential WBC count; however, it did cause an inhibition of neutrophil random migration. The other measurements of neutrophil function (Staphylococcus aureus ingestion, cytochrome C reduction, iodination, and antibody-dependent and antibody-independent cell-mediated cytotoxicity) evaluated were not significantly altered. The rhIL-2 treatment was associated with a significant (P less than 0.01) decrease in uptake of [3H]thymidine in unstimulated lymphocytes and a tendency toward enhanced blastogenesis of lymphocytes stimulated with phytohemagglutinin. This enhancement was significant (P less than 0.05) only when the results were expressed as a stimulation index. Lymphocyte responsiveness to concanavalin A and pokeweed mitogen was not significantly influenced by rhIL-2 administration. Dexamethasone (0.04 mg/kg) administered every 24 hours for 3 consecutive days altered the WBC count and several measurements of lymphocyte and neutrophil function. The administration of a single dose of rhIL-2 (2.5 X 10(7) U) 8 hours after the first dose of dexamethasone did not alter the influence of dexamethasone on any of the measurements. These results indicated that rhIL-2 has some biologic activity in cattle, but when used as administered here, did not overcome the influence of dexamethasone on the in vitro measurements of lymphocyte and neutrophil function that were evaluated.     

Suppression of neutrophil and lymphocyte function induced by a vaccinal strain of bovine viral diarrhea virus with and without the administration of ACTH

Effects of a modified live vaccine (MLV) strain of bovine viral diarrhea virus (BVD) on lymphocyte and neutrophil function were determined in cattle with and without increased plasma cortisol (hydrocortisone) concentrations. Cattle were given MLV-BVD vaccine IM and intranasally. Cattle given ACTH received 200 IU every 12 hours for 10 doses. The MLV-BVD virus when administered alone caused no apparent clinical signs or body temperature response. Of 4 MLV-BVD-treated calves that were also given ACTH, 2 developed increased body temperature and respiratory distress. The MLV-BVD virus caused a decrease in circulating lymphocytes and neutrophils, whereas administration of ACTH and MLV-BVD induced a neutrophilia and lymphopenia. The MLV-BVD virus and ACTH when administered separately or in combination caused a depression of lymphocyte blastogenesis in response to selected mitogens. Neutrophils were separated from the peripheral blood and their function was evaluated, using the following procedures: (i) random migration under agarose, (ii) ingestion of 125I-labeled Staphylococcus aureus, (iii) quantitative nitroblue tetrazolium reduction, (iv) iodination, and (v) antibody-dependent cell-mediated cytotoxicity (ADCC). The MLV-BVD virus produced a significant (P less than 0.05) suppression of neutrophil iodination and ADCC. Neutrophils from cattle given MLV-BVD virus and ACTH had enhanced random migration, enhanced S aureus ingestion, suppressed iodination, and suppressed ADCC activity.     

Effect of levamisole on lymphocyte blastogenesis and neutrophil function in dexamethasone-treated cattle

Levamisole was evaluated at 6 dose levels for its ability to prevent the dexamethasone-induced suppression of in vitro lymphocyte blastogenesis or neutrophil function in cattle. Dexamethasone (0.4 mg/kg of body weight, IM) and levamisole hydrochloride (0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg orally) were administered to groups of 4 cattle daily for 3 days. Another group of 4 cattle were given the 3-day dexamethasone treatment and 6.0 mg/kg of levamisole (the recommended anthelmintic dose) was given only once on the 1st day that dexamethasone was given. Results obtained from the dexamethasone-levamisole-treated cattle were compared with results obtained from cattle that were given only dexamethasone. Levamisole had no apparent consistent ability to enhance lymphocyte blastogenic responsiveness (to the mitogens phytohemagglutinin, concanavalin A, or pokeweed mitogen or in a 1-way mixed lymphocyte reaction) or to enhance neutrophil function (random migration, nitroblue tetrazolium reduction, iodination, or antibody-dependent cell-mediated cytotoxicity) in dexamethasone-treated cattle.     

Enhancement of lymphocyte blastogenesis and neutrophil function by avridine in dexamethasone-treated and nontreated cattle

The lipoidal amine, N,N-dioctadecyl-N',N'-bis (2-hydroxyethyl) propanediamine (avridine or CP 20,961), formulated in liposomes, was evaluated for its effect on leukocyte kinetics, lymphocyte blastogenesis, and polymorphonuclear leukocyte (PMN) function in dexamethasone-treated and nontreated cattle. In the 1st experiment, cattle were given avridine in a single IM injection of 0.1, 1.0, or 10 mg/kg of body weight. All doses induced swelling at the injection site, a febrile response, and a leukocytosis due to a neutrophilia. Mononuclear cell numbers were normal. All 3 groups of avridine-treated animals had a higher mean lymphocyte blastogenic response to mitogens on the 4 days after administration than did the control nontreated animals. Avridine administration was associated with an enhanced ability of PMN to ingest Staphylococcus aureus and to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). The highest dose (10 mg/kg) was associated with a depression of the ability of PMN to iodinate protein. An effect of avridine on PMN random migration under agarose or nitroblue tetrazolium (NBT) reduction was not observed. In a 2nd experiment, cattle were given no treatment, 0.04 mg of dexamethasone/kg IM, or 10 mg of avridine/kg IM followed 24 hours later by 0.04 mg of dexamethasone/kg. Dexamethasone administration caused a leukocytosis due to a neutrophilia with normal mononuclear cell numbers, an enhancement of PMN random migration under agarose, and an inhibition of NBT reduction, iodination, and ADCC activity of PMN. Dexamethasone did not have a detectable effect on lymphocyte blastogenesis or on ingestion of S aureus by PMN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lymphocyte blastogenesis and neutrophil function in cattle persistently infected with bovine viral diarrhea virus

Neutrophil function and mononuclear cell proliferative responses to mitogens were determined in healthy cattle and in cattle persistently infected with bovine viral diarrhea (BVD) virus. Uptake of [3H]thymidine by resting and mitogen-stimulated peripheral blood mononuclear cells was significantly lower in cattle persistently infected with BVD virus than in healthy cattle. Neutrophils from cattle persistently infected with BVD virus had significantly impaired capability to ingest Staphylococcus aureus, but were normal in respect to random migration under agarose, cytochrome C reduction, iodination, and antibody-dependent cell-mediated cytotoxicity. Impairment of neutrophil function in cattle persistently infected with BVD virus differs from impairment of neutrophil function reported in healthy cattle mounting an immune response to recent BVD virus infection.     

Alteration of neutrophil function associated with coccidiosis in cattle: influence of decoquinate and dexamethasone

Twenty Holstein steers subclinically infected with coccidia were allotted to 2 groups of 10 steers each. One group received a diet containing 0.5 mg of decoquinate/kg of body weight. After 25 days on the diet, there was no difference between the groups in lymphocyte blastogenic responsiveness to mitogens; however, there were differences in neutrophil function. Lymphocytes from steers of the decoquinate-fed group had decreased random migration under agarose, enhanced cytochrome C reduction, and enhanced iodination activity. Other measures of neutrophil function evaluated (chemotactic index, Staphylococcus aureus ingestion, and antibody-dependent and -independent cell-mediated cytotoxicity) were not affected. After 30 days of decoquinate feeding, half of the cattle in each group received 5 daily IM injections of dexamethasone (0.04 mg/kg of body weight). The dexamethasone-treated steers from the group that did not have decoquinate in the diet developed clinical coccidiosis, whereas the decoquinate-treated steers remained clinically normal. Lymphocyte and neutrophil function were again evaluated for a 3-day period beginning 4 days after dexamethasone treatment was halted. Neutrophils from the steers that developed clinical coccidiosis after dexamethasone administration had significantly (P less than 0.05) inhibited random migration under agarose, cytochrome C reduction, and iodination activity, but significantly (P less than 0.01) enhanced S aureus ingestion. The feeding of decoquinate prevented the inhibition of neutrophil cytochrome C reduction and lessened the inhibition of neutrophil iodination in the dexamethasone-treated group. Dexamethasone treatment was associated with an inhibition of lymphocyte blastogenic responsiveness to phytohemagglutinin in principals as well as controls.     

Alterations in bovine neutrophil function during the periparturient period

Neutrophils from 8 Holstein heifers were evaluated for function during the periparturient period. Random migration, ingestion of bacteria, superoxide anion production, native (nonenhanced) chemiluminescence, iodination, and antibody-dependent, cell-mediated cytotoxicity by neutrophils were determined. Foremilk samples were evaluated for bacteria. Significant (P less than 0.05) increases in random migration of neutrophils, iodination, and chemiluminescence were evident 2 weeks before parturition and then decreased dramatically by the first week after parturition. These impairments of neutrophil function after parturition may be manifested as a severe cumulative deficit in the native defenses afforded by the neutrophil.     

Use of bovine lymphocyte antigens in diagnosis of parentage

Lymphocyte antigens controlled by alleles at the BoLA-A locus were used to indicate which of two bulls could be eliminated as the sire in 18 cases of disputed parentage. The use of bovine lymphocyte antigens (BoLA) significantly increased the exclusion probability over that of the standard red cell and electrophoretic techniques.     

Effects of dexamethasone, levamisole, and dexamethasone-levamisole combination on neutrophil function in female goats

Effects of dexamethasone, levamisole, or combined dexamethasone-levamisole administration on polymorphonuclear neutrophil (PMN) function in healthy, adult female goats were studied. Goats were assigned to treated (n = 6) and control (n = 6) groups. In experiment 1, treated goats were given levamisole (6 mg/kg of body weight, IM). In experiment 2, treated goats were given 0.1 mg of dexamethasone/kg, IV, for 3 consecutive days, 1 mg of dexamethasone/kg, IV, for 6 consecutive days, and 6 mg of levamisole/kg, IM, with a 4th injection of 1 mg of dexamethasone/kg. All injections were administered 12 hours before blood collection. The PMN were evaluated for random migration and chemotaxis under agarose, ingestion of Staphylococcus aureus, cytochrome C reduction, iodination, and antibody-dependent cell-mediated cytotoxicity. Levamisole alone did not alter the function of caprine PMN. Both doses of dexamethasone caused increased random migration and decreased cytochrome C reduction and iodination. Dexamethasone resulted in no changes in chemotaxis, S aureus ingestion, and antibody-dependent cell-mediated cytotoxicity. Random migration and cytochrome C reduction returned toward base line in cells from dexamethasone and levamisole-treated goats. Although iodination activity in cells from dexamethasone-treated goats remained significantly (P less than 0.05) lower than those of controls after levamisole administration, a rebound toward base-line activity occurred.     

In vivo effect of ascorbic acid on neutrophil function in healthy and dexamethasone-treated cattle

Ascorbic acid (20 mg/kg of body weight) administered subcutaneously to otherwise nontreated cattle resulted in enhancement of neutrophil oxidative metabolism and capability of neutrophils to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Random migration, bacterial ingestion, and iodination by neutrophils was unaffected. Three dosage levels of ascorbic acid (10 mg/kg, 20 mg/kg, and 40 mg/kg) were examined for their effects on neutrophil function in cattle treated with dexamethasone (0.04 mg/kg). Dexamethasone administration caused an enhancement of neutrophil random migration and a suppression of neutrophil oxidative metabolism, iodination, and ADCC. None of the dosage levels of ascorbic acid had an effect on the alterations in the WBC count induced by dexamethasone. The ascorbic acid did tend to reverse the effects of dexamethasone on neutrophil random migration, oxidative metabolism, and ADCC in a dose-dependent manner, with the lowest dose having no discernible effect. Ascorbic acid administration also tended to enhance Staphylococcus aureus ingestion by bovine neutrophils. These results indicate that ascorbic acid should be further investigated for its potential to reduce the susceptibility of stressed or glucocorticoid-treated cattle to infective processes.     

Association of increased estradiol and progesterone blood values with altered bovine polymorphonuclear leukocyte function

Polymorphonuclear leukocyte (PMN) function and serum concentrations of estradiol, progesterone, and cortisol (hydrocortisone) were monitored concurrently in clinically normal cows during the estrous cycle. Five parameters were used to evaluate PMN function: (i) random migration under agarose, (ii) ingestion of 125I-labeled Staphylococcus aureus, (iii) nitroblue tetrazolium (NBT) reduction, (iv) iodination, and (v) antibody-dependent cell-mediated cytotoxicity. Increased serum estradiol concentrations were associated with enhanced random migration, but had no apparent effect on NBT reduction, iodination, or ingestion of S aureus by bovine PMN. Increased serum estradiol was also associated with increased serum cortisol. Increased serum progesterone values were associated with a depression of NBT reduction and iodination by PMN, but with enhanced random migration and antibody-dependent cell-mediated cytotoxicity. These results indicate that physiologic changes in steroid hormone values during the normal estrous cycle of the cow are associated with alterations in PMN function.     

Recombinant porcine somatotropin: an immunotoxicology study.

The present study was designed to determine the effect of recombinant porcine somatotropin (rpST; 5, 15, or 25 mg.pig-1.d-1 for 57 d) on a variety of immune function variables. We observed no significant effect of rpST treatment on the gross pathology of the pigs, histopathology of the immune system organs, total and differential white blood cell counts, lymphocyte blastogenic response to mitogens, or the neutrophil functions of chemotaxis, ingestion, reduction of cytochrome C, iodination, and antibody-dependent cell-mediated cytotoxicity. Those variables that were significantly affected by rpST treatment include a decreased hemoglobin and packed red blood cell volume (at some time points for all three rpST dosages), a decrease in plasma protein level at the 25-mg dose, a small increase in neutrophil random migration (at all three rpST dosages), and a decrease in IgG antibody response to tetanus toxoid at 15 d after immunization (but not at d 8, 22, or 29). Additionally, rpST treatment was associated with a decreased rate of BW gain (at 15-mg dose), increased liver and kidney weights (at all three dosage levels), and an increased incidence of renal tubular cytoplasmic vacuolation of minor severity. There were no observed differences in the overall health of the pigs due to rpST treatment, based on clinical observations as well as determination of antibody titer to, and isolation of, common swine pathogens. Therefore, there was no evidence that the observed influence of rpST treatment on immune function would be clinically relevant.     

Genetic variation and responses to vaccines

Disease is a major source of economic loss to the livestock industry. Understanding the role of genetic factors in immune responsiveness and disease resistance should provide new approaches to the control of disease through development of safe synthetic subunit vaccines and breeding for disease resistance. The major histocompatibility complex (MHC) has been an important candidate locus for immune responsiveness studies. However, it is clear that other loci play an important role. Identifying these and quantifying the relative importance of MHC and non-MHC genes should result in new insights into host-pathogen interactions, and information that can be exploited by vaccine designers. The rapidly increasing information available about the bovine genome and the identification of polymorphisms in immune-related genes will offer potential candidates that control immune responses to vaccines. The bovine MHC, BoLA, encodes two distinct isotypes of class II molecules, DR and DQ, and in about half the common haplotypes the DQ genes are duplicated and expressed. DQ molecules are composed of two polymorphic chains whereas DR consists of one polymorphic and one non-polymorphic chain. Although, it is clear that MHC polymorphism is related to immune responsiveness, it is less clear how different allelic and locus products influence the outcome of an immune response in terms of generating protective immunity in outbred animals. A peptide derived from foot-and-mouth disease virus (FMDV) was used as a probe for BoLA class II function. Both DR and DQ are involved in antigen presentation. In an analysis of T-cell clones specific for the peptide, distinct biases to particular restriction elements were observed. In addition inter-haplotype pairings of DQA and DQB molecules produced functional molecules, which greatly increases the numbers of possible restriction elements, compared with the number of genes, particularly in cattle with duplicated DQ genes. In a vaccine trial with several peptides derived from FMDV, BoLA class II DRB3 polymorphisms were correlated with both protection and non-protection. Although variation in immune responsiveness to the FMDV peptide between different individuals is partly explainable by BoLA class II alleles, other genetic factors play an important role. In a quantitative trait locus project, employing a second-generation cross between Charolais and Holstein cattle, significant sire and breed effects were also observed in T-cell, cytokine and antibody responses to the FMDV peptide. These results suggest that both MHC and non-MHC genes play a role in regulating bovine immune traits of relevance to vaccine design. Identifying these genes and quantifying their relative contributions is the subject of further studies.     

Functional and ultrastructural evaluation of neutrophils from foals and lactating and nonlactating mares

Neutrophils from 4 pony foals, 3 lactating pony mares, and 3 nonlactating mares were evaluated ultrastructurally and by in vitro function tests. Neutrophils from foals had significantly (P = 0.05) less random migration than neutrophils from mares; values in tests for iodination and Staphylococcus aureus ingestion were also lower with foal neutrophils. Neutrophils from lactating mares had lower responses to iodination, antibody-dependent cell-mediated cytotoxicity, and random migration tests than did neutrophils from nonlactating mares. Ultrastructurally, granule concentration did not differ significantly among groups. A slight decrease in primary granules and a corresponding increase in granules with a flocculent matrix indicates partial spontaneous neutrophil degranulation in foals and lactating mares.     

Effects of road transportation on lymphocyte subsets in calves

The effect of transportation on peripheral blood lymphocyte subsets in 24 calves was investigated by flow cytometry. Blood was collected before departure, on arrival, at 24h and 1 week after arrival. Highest leucocyte and neutrophil counts, associated with increased concentrations of cortisol and catecholamines, indicated that stress was maximal upon arrival. At this time, a decrease in the percentages of all T lymphocyte subsets was evident, while they did not decrease as absolute counts. The proportion of CD21(+) cells did not change, indicating that the relative reduction of T lymphocyte subsets was not related to an increase in B lymphocytes. These variations may be due to the increase of a natural killer (NK) cell subset. NK cell expansion, together with increasing lymphocyte count and increasing major histocompatibility complex class II expression, may indicate stress-induced stimulation of the immune system.     

Homologies between the major histocompatibility complex of man and cattle: consequences for disease resistance and susceptibility

The major histocompatibility complex (MHC) of mammals contains a large number of mostly duplicated genes. In the HLA system (the MHC of man), which is by far the best-studied major histocompatibility system so far, roughly 20 genes have been defined and mapped. They code for three classes of proteins: HLA-A, -B and -C (Class I), HLA-DP, -DQ and -DR (Class II) and serum complement components C2, C4 and Bf (Class III). Furthermore, the region contains genes for 21-hydroxylase (21-OH) and tumor necrosis factor (TNF). The MHC thus forms a chromosomal segment containing several clusters of genes of only partially defined biological significance, but ondoubtedly playing a role in disease susceptibility. In view of the recently obtained structural information on BoLA, the MHC of cattle, it is hypothesized that susceptibility to diseases in cattle is associated with BoLA in the same way as human diseases. Finally, new technical and conceptual developments in the field of MHC research and their application to the BoLA system are discussed.     

In vivo effects of a thymosin alpha 1-containing colostral whey product on neutrophils and lymphocytes from lactating cows without and with experimentally induced Staphylococcus aureus mastitis

Two separate experiments evaluated ID-1 (a commercial bovine whey product containing 5200 pg of thymosin alpha 1/ml) as an immunotherapeutic agent in lactating cows. In the first experiment, cows without mastitis were evaluated for blood leukogram, milk production, total and differential milk cell counts, lymphocyte (Lc) blastogenesis, and neutrophil (PMN) functions (random and directed migration under agarose, chemiluminescence, ingestion of bacteria, iodination, cytochrome C reduction, antibody-independent neutrophil-mediated cytotoxicity, and antibody-dependent cell-mediated cytotoxicity) before and after ID-1 therapy. ID-1 treatment resulted in a significant treatment group by time period interaction for the relative proportion of mononuclear cells (MNC) in milk (P less than 0.009) and for PMN random migration (P less than 0.01). Based on these interactions, ID-1 treatment appeared to slightly increase the proportion of small MNC in milk and to increase random migration from pretreatment levels by 73% more than increases observed in controls. No significant effect of ID-1 treatment on milk production, total milk somatic cell counts, Lc blastogenesis, or other PMN functions was observed. In cows with experimental Staphylococcus aureus intramammary infections, ID-1 treatment resulted in a significant decline in blood leukocyte count (P less than 0.001) and blood PMN count (P less than 0.02), and maintained PMN random migration (P less than 0.01) while controls declined and abrogated a depression in the ability of Lc to respond to mitogens (P less than 0.05) that developed in controls as a result of S. aureus mastitis. Injection of ID-1 into cows had no adverse effect on their overall health or level of milk production, but did cause subtle and potentially favorable changes in several in vitro immune parameters. In spite of these subtle changes which might indicate increased resistance to mastitis, cows actually developed a more severe S. aureus intramammary infection based on a 9% increase in log 10 bacterial shedding in milk.     

Homologies between the major histocompatibility complex of man and cattle: Consequences for disease resistance and susceptibility

Summary

The major histocompatibility complex (MHC) of mammals number of mostly duplicated contains a large genes. In the HLA system (the MHC of man), which is by far the best‐studied major histocompatibility system so far, roughly 20 genes have been defined and mapped. They code for three classes of proteins: HLA‐A, ‐B and ‐C (Class I), HLA‐DP, ‐DQ and ‐DR (Class II) and serum complement components C2, C4 and Bf (Class III). Furthermore, the region contains genes for 21‐hydroxylase (21‐OH) and tumor necrosis factor (TNF).

The MHC thus forms a chromosomal segment containing seva‐al clusters of genes of only partially defined biological significance, but ondoubtedly playing a role in disease suscepti‐ bility. In view of the recently obtained structural information on BoLA, the MHC of cattle, it is hypothesized that susceptibility to diseases in cattle is associated with BoLA in thesame way as human diseases.

Finally, new technical and conceptual developments in the field of MHC research and their application to the BoLA system are discussed.