Do maternally derived antibodies and early immune experience shape the adult immune response?

1. Immunological imprinting by maternally derived antibodies has been proposed to have both positive and negative consequences for offspring immunity in early and adult life. However, few studies of maternal effects on immunity have followed individuals past the juvenile stages.

2. Using laboratory Japanese quail, we developed a novel method of directly manipulating yolk antibodies of neonates, and then followed individuals through a series of immune challenges until they were of reproductive age.

3. Our method of directly injecting purified antibodies into the yolk sac of newly hatched chicks successfully elevated the plasma titres of specific anti-KLH IgY in neonates. This allows us to test whether differences in neonatal anti-KLH IgY affect immunity at the juvenile and adult stages of life.

4. We found little evidence for an effect of maternal antibodies on juvenile stage immune response, in contrast to results from previous studies. Adult immune response depended largely on the magnitude of the juvenile immune response regardless of the identity of the antigen in the juvenile immune challenge, and did not depend on neonatal IgY titres. Our results are consistent with a priming effect of early immune experience on adult stage immune responsiveness, but we found no evidence of carryover effects of yolk-derived antibodies on adult immunity.

5. This study employs new methodology for investigation of maternal antibodies and presents results suggesting that further studies of maternal effects on immunity will require careful consideration of the numerous ways maternally derived yolk components can impact the different types of immune response.

Immune response of greenback flounder Rhombosolea tapirina after exposure to contaminanted marine sediment and diet

Non-specific immune response of greenback flounder, Rhombosolea tapirina, exposed to contaminated marine sediments was examined. Reference sediments from Port Sorell and contaminated sediments from Deceitful Cove, Tasmania, Australia were investigated. Hatchery-reared flounder were exposed to reference sediment, contaminated sediment or contaminated sediment and diet for 6 weeks. Phagocytic capacity and lysozyme response in flounder were examined on cessation of exposure trial. Significant differences were found in phagocyticcapacity and lysozyme response between treatments. Exposure to contaminated sediment, irrespective of diet or benthic disturbance elicited inhibition of phagocytic efficiency in flounder. Disturbance of contaminated sediment stimulated lysozyme activity. The immuneresponse in flounder indicates potential immunotoxicity of sediment from Deceitful Cove.

The effects of testosterone on immune function in quail selected for divergent plasma corticosterone response

The immunocompetence handicap hypothesis (ICHH) suggests that the male sex hormone testosterone has a dual effect; it controls the development and expression of male sexually selected signals, and it suppresses the immune system. Therefore only high quality males are able to fully express secondary sexual traits because only they can tolerate the immunosuppressive qualities of testosterone. A modified version of the ICHH suggests that testosterone causes immunosuppression indirectly by increasing the stress hormone corticosterone (CORT). Lines of Japanese quail (Coturnix japonica) selected for divergent responses in levels of plasma CORT were used to test these hypotheses. Within each CORT response line (as well as in a control stock) we manipulated levels of testosterone in castrated quail by treatment with zero (sham), low or high testosterone implants, before testing the birdsʼ humoral immunity and phytohaemagglutinin (PHA)-induced immune response, as well as body condition. The PHA-induced response was not significantly affected by CORT selected line, testosterone treatment or their interaction. There was, however, a significant effect of CORT line on humoral immunity in that the control birds exhibited the greatest antibody production, but there was no significant effect of testosterone manipulation on humoral immunity. The males in the sham implant treatment group had significantly greater mass than the males in the high testosterone group, suggesting a negative effect of high testosterone on general body condition. We discuss these results in the context of current hypotheses in the field of sexual selection.

Optimal immune responses : immunocompetence revisited

The function of the immune system of an animal is to provide defence against infection, in order to maximize fitness. Understanding this and, particularly, how limiting resources are traded off between costly immune responses and other physiological demands, is central to properly understanding life-history traits and their evolution. Here, we propose that functional (rather than immunological) measures of immune responses should be used when investigating this. We further suggest that optimal immune responses are context specific, rather than generic; that is, a maximum immune response is not necessarily optimal. The nature of an optimal immune response will depend on the specific circumstances and infection status of the animal. Identifying and understanding such optimality requires that the effects of different immune strategies on fitness be considered.

An antiviral response directed by PKR phosphorylation of the RNA helicase A

The double-stranded RNA-activated protein kinase R (PKR) is a key regulator of the innate immune response. Activation of PKR during viral infection culminates in phosphorylation of the α subunit of the eukaryotic translation initiation factor 2 (eIF2α) to inhibit protein translation. A broad range of regulatory functions has also been attributed to PKR. However, as few additional PKR substrates have been identified, the mechanisms remain unclear. Here, PKR is shown to interact with an essential RNA helicase, RHA. Moreover, RHA is identified as a substrate for PKR, with phosphorylation perturbing the association of the helicase with double-stranded RNA (dsRNA). Through this mechanism, PKR can modulate transcription, as revealed by its ability to prevent the capacity of RHA to catalyze transactivating response (TAR)–mediated type 1 human immunodeficiency virus (HIV-1) gene regulation. Consequently, HIV-1 virions packaged in cells also expressing the decoy RHA peptides subsequently had enhanced infectivity. The data demonstrate interplay between key components of dsRNA metabolism, both connecting RHA to an important component of innate immunity and delineating an unanticipated role for PKR in RNA metabolism.

Functional similarities between pigeon 'milk' and mammalian milk : induction of immune gene expression and modification of the microbiota

Pigeon ‘milk’ and mammalian milk have functional similarities in terms of nutritional benefit and delivery of immunoglobulins to the young. Mammalian milk has been clearly shown to aid in the development of the immune system and microbiota of the young, but similar effects have not yet been attributed to pigeon ‘milk’. Therefore, using a chicken model, we investigated the effect of pigeon ‘milk’ on immune gene expression in the Gut Associated Lymphoid Tissue (GALT) and on the composition of the caecal microbiota. Chickens fed pigeon ‘milk’ had a faster rate of growth and a better feed conversion ratio than control chickens. There was significantly enhanced expression of immune-related gene pathways and interferon-stimulated genes in the GALT of pigeon ‘milk’-fed chickens. These pathways include the innate immune response, regulation of cytokine production and regulation of B cell activation and proliferation. The caecal microbiota of pigeon ‘milk’-fed chickens was significantly more diverse than control chickens, and appears to be affected by prebiotics in pigeon ‘milk’, as well as being directly seeded by bacteria present in pigeon ‘milk’. Our results demonstrate that pigeon ‘milk’ has further modes of action which make it functionally similar to mammalian milk. We hypothesise that pigeon ‘lactation’ and mammalian lactation evolved independently but resulted in similarly functional products.

The release and induced immune responses of a plant-made and delivered antigen in the mouse gut

This study investigated the site of release of a model vaccine antigen from plant cells and the corresponding induced immune response. Three plant tissues (leaf, fruit and hairy root) and two formulations (aqueous and lipid) were compared in two mouse trials. A developed technique that enabled detection of antigen release by plant cells determined that antigen release occurred at early sites of the gastrointestinal tract when delivered in leaf material and at later sites when delivered in hairy roots. Lipid formulations delayed antigen release from all plant materials tested. While encapsulation in the plant cell provided some protection of the antigen in the gastrointestinal tract and influenced antigen release, formulation medium was also an important consideration with regard to vaccine delivery and immunogenicity. Systemic immune responses induced from the orally delivered vaccine benefited from late release of antigen in the mouse gastrointestinal tract. The influences to the mucosal immune response induced by these vaccines were too complex to be determined by studies performed here with no clear trend regarding plant tissue site of release or formulation medium. Expression and delivery of the model antigen in plant material prepared in an aqueous formulation provided the optimal systemic and mucosal, antigen-specific immune responses.

Older patients are immunocompromised by cytokine depletion and loss of innate immune function after hip fracture surgery

PURPOSE/INTRODUCTION: We have examined the immune status of elderly patients who underwent surgery for a hip fracture, an injury associated with poor postoperative outcomes, to identify specific immune defects. METHODS: In a cohort observational study, 16 patients undergoing surgery for hip fractures had immune function evaluation prior to surgery, and then at 3 and 7 days postoperatively, using flow cytometry for phenotype and for monocyte and granulocyte phagocytic function and respiratory burst. Serum samples were stored and batch analyzed using a human cytokine 25-plex panel. RESULTS: We report significant loss of innate immune function, related specifically to reduced granulocyte numbers by day 7 (P < .0001, flow cytometry; P < .05 white blood cells), and although granulocyte ability to take up opsonized Escherichia coli was increased (P < .05), the ability of those cells to generate a respiratory burst was reduced at days 3 and 7 (P < .05). Monocyte respiratory burst was also significantly reduced (P < .05). Serum cytokine levels indicated very poor T-cell function. CONCLUSION: We have demonstrated that the antimicrobial immune response is profoundly reduced after surgery in elderly patients with hip fractures. The effect was sustained up to 7 days postoperatively, identifying these patients as particularly vulnerable to bacterial infections.