The effects of timing of high immune response phenotyping in relation to weaning on immune responses of crossbred beef calves.

Genetic selection for immune response has the potential to increase the sustainability of the beef industry by breeding cattle that are productive yet with an increased capacity to resist disease. Determining the optimal time to immunophenotype beef cattle is crucial for the accurate prediction of an animal's immune response. The objective of this study was to determine the effect of time of immunophenotyping in relation to weaning on immune responses of beef calves. Antibody- (AMIR) and cell-mediated (CMIR) immune responses were measured on 97 calves on the day of weaning (WEANING, N = 56) or 2 mo post-weaning (POST-WEANING, N = 41). Within each period of immunophenotyping, on day 0, blood was collected, and calves received a 1.0 mL intramuscular injection of type 1 and 2 test antigens. On day 14, blood was collected, and baseline skinfold thickness (SFT) was measured. Calves received an intradermal injection of 0.1 mg of the type 1 antigen suspended in 0.1 mL phosphate buffered saline (PBS) in the right tail fold, and 0.1 mL of PBS in the left. Changes in SFT at 24 h was used to indicate CMIR. To assess AMIR, the titer of type 2 antigen-specific bovine immunoglobulin G in serum from blood collected on day 14 was determined by measuring optical density (OD) using an enzyme-linked immunosorbent assay (ELISA). Among heifers, AMIR was greater for the POST-WEANING group than for the WEANING group (P < 0.01). Among steers, AMIR was not different between the POST-WEANING group and the WEANING group (P = 1.0). Therefore, the AMIR of heifers may be more negatively affected by immunophenotyping at weaning than the AMIR of steers. For steers, CMIR was greater in the POST-WEANING group than the WEANING group (P < 0.001). For heifers, CMIR was not different between the POST-WEANING group and the WEANING group (P = 0.22). The CMIR of steers may be more negatively affected by immunophenotyping at weaning than the CMIR of heifers. Calf age was not associated with AMIR or CMIR for calves phenotyped at weaning or post-weaning. The effect of sire nested within dam age was significant for CMIR for calves in the POST-WEANING group (P < 0.01), but not for calves in the WEANING group (P = 0.67). The results suggest that measuring immunocompetence at weaning may not be representative of a calf's genetic ability to mount an effective immune response, and immunophenotyping should be performed outside the weaning period.

Understanding the optimal time to immunophenotype beef calves is important for the accurate estimation of their genetic ability to resist disease. The compound stressors experienced by a calf during weaning may have a similar impact on the immune system as chronic stress. Therefore, the immune response phenotype of a calf immunophenotyped during the weaning period may not truly reflect the animal's genuine capacity for immune response. To accurately identify cattle with a superior capacity for immune response, with the goal of genetically selecting cattle for immunocompetence, immunophenotypes must be measured accurately. In this study, the effect of time of immunophenotyping in relation to weaning on immune responses of beef calves was determined. Calves immunophenotyped at weaning had lesser antibody-mediated and cell-mediated immune responses than calves immunophenotyped 2 mo post-weaning, this effect was influenced by sex. Sire affected immune responses when calves were immunophenotyped 2 mo post-weaning, but not when calves were immunophenotyped at weaning, indicating that when immunophenotyped post-weaning, the genetic component of a calf's immune response is quantified without being obscured by other environmental factors.

Impact of heat stress on dairy cattle and selection strategies for thermotolerance: a review.

Climate change is a problem that causes many environmental issues that impact the productivity of livestock species. One of the major issues associated with climate change is an increase of the frequency of hot days and heat waves, which increases the risk of heat stress for livestock species. Dairy cattle have been identified as being susceptible to heat stress due to their high metabolic heat load. Studies have shown heat stress impacts several biological processes that can result in large economic consequences. When heat stress occurs, dairy cattle employ several physiological and cellular mechanisms in order to dissipate heat and protect cells from damage. These mechanisms require an increase and diversion in energy toward protection and away from other biological processes. Therefore, in turn heat stress in dairy cattle can lead numerous issues including reductions in milk production and reproduction as well as increased risk for disease and mortality. This indicates a need to select dairy cattle that would be thermotolerant. Various selection strategies to confer thermotolerance have been discussed in the literature, including selecting for reduced milk production, crossbreeding with thermotolerant breeds, selecting based on physiological traits and most recently selecting for enhanced immune response. This review discusses the various issues associated with heat stress in dairy cattle and the pros and cons to the various selection strategies that have been proposed to select for thermotolerance in dairy cattle.

Effect of in-vitro heat stress challenge on the function of blood mononuclear cells from dairy cattle ranked as high, average and low immune responders.

BACKGROUND: The warming climate is causing livestock to experience heat stress at an increasing frequency. Holstein cows are particularly susceptible to heat stress because of their high metabolic rate. Heat stress negatively affects immune function, particularly with respect to the cell-mediated immune response, which leads to increased susceptibility to disease. Cattle identified as having enhanced immune response have lower incidence of disease. Therefore, the objective of this study was to evaluate the impact of in vitro heat challenge on blood mononuclear cells from dairy cattle, that had previously been ranked for immune response, in terms of heat shock protein 70 concentration, nitric oxide production, and cell proliferation. RESULTS: Blood mononuclear cells from dairy cattle classified as high immune responders, based on their estimated breeding values for antibody and cell-mediated responses, produced a significantly greater concentration of heat shock protein 70 under most heat stress treatments compared to average and low responders, and greater cell-proliferation across all treatments. Similarly, a trend was observed where high responders displayed greater nitric oxide production compared to average and low responders across heat treatments. CONCLUSION: Overall, these results suggest that blood mononuclear cells from high immune responder dairy cows are more thermotolerant compared to average and low immune responders.

Immune response phenotype of allergic versus clinically tolerant pigs in a neonatal swine model of allergy.

The prevalence of childhood food allergy and the duration of these allergies, particularly those considered to be transient, like egg and milk allergy, are increasing. The identification of allergic individuals using minimally invasive, non-anaphylaxis-threatening methods is therefore of increasing importance. In this experiment, correlates were sought of an allergic immune response (IR) phenotype in pigs. Using pigs pre-treated with heat-killed bacteria or bacterial components before allergic sensitization with the egg white protein ovomucoid (Ovm), differences were determined in IR phenotype of pigs in the categories treated-allergic, treated-tolerant, control-allergic (CA) and control-tolerant. Phenotype was established by measuring immunoglobulin (Ig)-associated antibody activity (AbA), cytokine profiles and the proportion of blood T-regulatory cells (T-regs) and observing late-phase allergen-specific skin tests (ST). Although 100% of pigs became sensitized to Ovm, only 33% of pigs had clinical signs of allergy after oral challenge with egg white. Pigs without clinical signs were classified as clinically tolerant. Sixty-seven percent of allergic pigs had a positive, late-phase ST classified as very strong or strong, while 84% of clinically tolerant pigs did not have late-phase ST. Treated-allergic pigs and CA pigs had greater total antibody IgG (H+L), IgE and IgG1 AbA than clinically tolerant pigs. Cytokine profiles of allergic pigs and the proportion of circulating T-regs, did not differ significantly between allergic and clinically tolerant pigs. Therefore, measurement of allergen-specific IgG, IgG1 and/or IgE activity and evaluation of late-phase ID ST may be useful in identifying allergic IR phenotypes in swine models of food allergy, which may be extended toward human use.

Effect of heat-killed Escherichia coli, lipopolysaccharide, and muramyl dipeptide treatments on the immune response phenotype and allergy in neonatal pigs sensitized to the egg white protein ovomucoid.

Predisposition to food allergies may reflect a type 2 immune response (IR) bias in neonates due to the intrauterine environment required to maintain pregnancy. The hygiene hypothesis states that lack of early environmental stimulus leading to inappropriate development and bias in IR may also contribute. Here, the ability of heat-killed Escherichia coli, lipopolysaccharide (LPS), or muramyl dipeptide (MDP) to alter IR bias and subsequent allergic response in neonatal pigs was investigated. Three groups of three litters of pigs (12 pigs/litter) were given intramuscular injections of E. coli, LPS, MDP, or phosphate-buffered saline (PBS) (control) and subsequently sensitized to the egg white allergen ovomucoid using an established protocol. To evaluate change in IR bias, immunoglobulin isotype-associated antibody activity (AbA), concentrations of type 1 and 2 and proinflammatory cytokines released from mitogen-stimulated blood mononuclear cells, and the percentage of T-regulatory cells (T-regs) in blood were measured. Clinical signs of allergy were assessed after oral challenge with egg white. The greatest effect on IR bias was observed in MDP-treated pigs, which had a type 2-biased phenotype by isotype-specific AbA, cytokine production, and a low proportion of T-regs. LPS-treated pigs had decreased type 1- and type 2-associated AbA. E. coli-treated pigs displayed increased response to Ovm as AbA and had more balanced cytokine profiles, as well as the highest proportion of T-regs. Accordingly, pigs treated with MDP were more susceptible to allergy than PBS controls, while pigs treated with LPS were less susceptible. Treatment with E. coli did not significantly alter the frequency of clinical signs.

Practical immunoregulation: neonatal immune response variation and prophylaxis of experimental food allergy in pigs.

The importance of environment in immune response is identified and the increase in prevalence of allergic, autoimmune and chronic inflammatory diseases reviewed. In particular, altered opportunity to acquire evolutionarily anticipated commensal microbiota is associated through the "hygiene hypothesis" with defective developmental and response signals to the innate and adaptive immune systems. Evidence of the detrimental effects of such environments is reviewed as is evidence for remediation using controlled exposure to bacteria or their active components such as LPS or peptidoglycan ligands for TLR and NOD-like receptors. Occurrence of major environmentally associated changes in porcine immune response phenotype are described. The prophylactic effects of heat-killed Escherichia coli given intramuscularly or of oral Lactococcus lactis on experimental ovomucoid-induced allergy in piglets are described in the context of altered immune response bias favouring reduced type-2 phenotypes. The high frequency of clinical tolerance to developing allergic signs even in the face of classical sensitization indicates possible function in this pig model of regulatory effectors such as Treg cells.

Porcine allergy and IgE.

Anaphylaxis was reported in 1963 in pigs experimentally sensitized with ovalbumin and was subsequently associated indirectly with IgE-related antibodies by functional assays to confirm heat-labile passive cutaneous anaphylaxis (PCA), reverse passive anaphylaxis (RPA) and Prausnitz-Küstner (PK) reactions to this and other allergens. The immunoglobulin mediating immediate hypersensitivity could be cross-adsorbed with anti-human IgE. Porcine IgE epsilon chain has been cloned and sequenced. Rabbit anti-pig IgE has been described by two groups, as has cross reactivity with pig IgE of various heterologous polyclonal and monoclonal anti-IgEs. Pigs develop transient post-weaning food allergy to soy allergens which can be prevented by pre-weaning feeding of soy proteins in sufficient quantity. Natural hypersensitivity also occurs to nematodes. Recently, experimental allergy has been induced in outbred pigs to peanut and to egg allergens which manifest as respiratory, cutaneous and enteric signs similar to those of human food allergy. These models are platforms for comparative allergy research as realistic alternatives to use of inbred mice or humans for investigation of pathogenesis, prophylaxis and therapy.

Attenuation of allergy to ovomucoid in pigs by neonatal treatment with heat-killed Escherichia coli or E. coli producing porcine IFN-gamma.

Food allergy is epidemic and prompts investigation to reduce allergic predisposition. It was hypothesized that heat-killed Escherichia coli injected intramuscularly (im) with or without interferon gamma (IFN-gamma), reduces neonatal susceptibility to experimental egg allergy. Two litters of Yorkshire pigs were assigned to three intramuscular treatment groups (four/group): control (PBS), heat-killed E. coli with or without IFN-gamma-expressing plasmid. Pigs were sensitized to ovomucoid (Ovm) by intraperitoneal injection with cholera toxin. To assess induction of allergy, pigs were fed egg white in yoghurt and assigned scores for allergic signs. Significantly fewer pigs developed allergy and passive cutaneous anaphylaxis in E. coli and E. coli+IFN-gamma vs control groups. E. coli-treated pigs also had significantly lower frequency of mean clinical scores. E. coli and E. coli+IFN-gamma groups did not differ. Serum antibody associated with IgG (H & L), IgG(1), IgG(2) or IgE all correlated but did not differ by treatment groups. Thus, treatment of neonatal pigs with heat-killed E. coli by im injection reduced susceptibility to allergic sensitization with Ovm. Inclusion of the type-1 cytokine, IFN-gamma, had no additional effect. Results indicate a method for prophylaxis of allergy and suggest support for the "hygiene hypothesis".