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      Neonatal Immune Development in the Calf and Its Impact on Vaccine Response

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      , DVM, PhD a , , , PhD b , , PhD b
      The Veterinary Clinics of North America. Food Animal Practice
      Elsevier Inc.

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          Abstract

          In this article we cover the immunologic response as it develops, the components of passive immunity, and the immune response of young calves. We discuss interference from maternal immunity in the development of specific immunity and vaccine strategies for developing protection against pathogens in calves.

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          Most cited references67

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          Transfer of maternal cytokines to suckling piglets: in vivo and in vitro models with implications for immunomodulation of neonatal immunity.

          Maternal cytokines may play instructive roles in development of the neonatal immune system. However, cytokines in colostrum and milk and their transfer from mothers to neonates have not been well documented, except for TGF-beta. Swine provide a unique model to study lactogenic cytokines because the sow's impermeable placenta prohibits transplacental passage. We investigated IL-6 and TNF-alpha (pro-inflammatory), IFN-gamma and IL-12 (Th1), IL-10 and IL-4 (Th2) and TGF-beta1 (Th3) concentrations in sow serum and colostrum/milk and serum of their suckling and weaned piglets and in age-matched colostrum-deprived gnotobiotic piglets. All cytokines were detected in colostrum/milk and correlated with concentrations in sow serum except for mammary-derived TNF-alpha and TGF-beta1. Detection of IL-12 and TGF-beta1 in pre-suckling and colostrum-deprived gnotobiotic piglet serum suggests constitutive production: other cytokines were undetectable confirming absence of transplacental transfer. Peak median cytokine concentrations in suckling piglet serum occurred at post-partum days 1-2 (IL-4>IL-6>IFN-gamma>IL-10). The effects in vitro of physiologically relevant concentrations of the two predominant lactogenic cytokines (TGF-beta1 and IL-4) on porcine naive B cell responses to lipopolysaccharide (LPS) and rotavirus (RV) were investigated. High (10 ng/ml) TGF-beta1 suppressed immunoglobulin secreting cell responses to LPS and rotavirus; low concentrations (0.1 ng/ml) promoted isotype switching to IgA antibody. Interleukin-4 induced inverse dose-dependent (0.1 ng>10 ng/ml) isotype switching to IgA and enhanced IgM secreting cell responses to LPS and rotavirus. In summary, we documented the transfer and persistence of maternal cytokines from colostrum/milk to neonates and their potential role in Th-2 biased IgA responses and reduced immunologic responsiveness of neonates.
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            Lymphocyte subpopulations and neutrophil function in calves during the first 6 months of life.

            Fifteen clinically healthy calves were sampled every week during the first 5 weeks of life and thereafter every month until the age of 6 months. The percentages and absolute values of CD4+, CD8+ gammadelta TCR+ and WC1+ T cells, CD21+ B cells and NKp46+ NK cells were determined by flow cytometry, and the expression of the interleukin-2 receptor alpha chain (CD25) was measured to assess the level of activation of the lymphocyte subpopulations. Neutrophil phagocytosis, respiratory burst and bactericidal activity were measured in five different neutrophil function assays. Most of the parameters examined reached a stable level during the first 6 months of life. The proportions of CD4+ and CD8+ lymphocytes remained relatively stable during the study period, while there was a moderate decrease in the relative percentage of gammadelta T cells from birth to approximately 5 months of age. However, the absolute numbers of gammadelta T cells per millilitre of blood remained stable throughout the study period and did not display significant variation with age. The percentage of cells expressing the B-cell maturation marker CD21 increased significantly over the first 5 months of life. The proportion of NK cells showed substantial variation during the study. Marked differences in the relative proportions of the lymphocyte subpopulations were noted between the individual calves, and the individual ranking of the animals was largely maintained over time. CD25 expression was detected on a mean of 6.6% of the CD4+ cells, while a lower percentage of the other lymphocyte subpopulations expressed this receptor. Phagocytic activity was demonstrated in approximately 90% of the neutrophils, and this proportion remained stable during the entire study period, while respiratory burst activity showed a moderate decrease during the first 2 months of life. The present study shows that the T-cell subpopulations are present in peripheral blood of calves at levels comparable with adult values, while the B-cell population increases significantly with age. The decrease in the relative percentage of gammadelta T cells appears to be attributable to an increase in the absolute numbers of CD4+ and CD21+ cells, rather than a change in absolute gammadelta T-cell numbers. Furthermore, the results indicate that the neutrophilic granulocytes are functional and able to mount an effective response in young calves from the first week of life.
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              Local and systemic antibody response to bovine respiratory syncytial virus infection and reinfection in calves with and without maternal antibodies.

              Enzyme-linked immunosorbent assays for the detection of immunoglobulin M (IgM), IgA, IgG1, and IgG2 antibodies against bovine respiratory syncytial virus (BRSV) were used to measure antibody responses of calves after experimental or natural infection with BRSV. Serially collected sera, lung lavage samples, nasal and eye secretions, and feces were tested for the presence of these antibodies. Lung lavage fluids and nasal secretions were further examined for the presence of virus. After experimental infection of 3- to 4-week-old, colostrum-deprived (seronegative) calves, the virus was detected from days 3 to 8 post-initial inoculation day (PID). An immune response was first detected 8 to 10 days PID, when BRSV-specific IgM and IgA appeared nearly simultaneously in serum, secretions, and feces. BRSV-specific IgG1 appeared only in serum on days 13 to 17 PID, and IgG2 was first detected in sera from 1 to 3 months PID. Specific IgM and IgA were detectable in the different samples for various periods. In the respiratory and eye secretions, IgA usually remained detectable for long periods, that is, for up to 3.5 months or longer. In lung lavage samples, BRSV-specific IgG1 was only incidentally demonstrated and appeared to be blood derived. The immune response of a 5-month-old calf strongly resembled that of the 3- to 4-week-old calves (feces excepted), indicating that an age effect on the immune response to BRSV is unlikely. After experimental infection of colostrum-fed, seropositive calves, both local and systemic antibody responses were largely or totally suppressed. The degree of suppression seemed to be related to the level of preinoculation virus-specific serum IgG1. Of all isotypes, IgM was least affected. Colostrum-fed animals shed virus in about equal amounts and for the same length of time as colostrum-deprived calves. Clinical signs were mild in both groups. After reinfection, no virus shedding was detected in either colostrum-deprived or colostrum-fed calves. In both groups, a secondary immune response developed, characterized by strong and rapid (from about day 6 PID) mucosal and systemic IgA responses, but reaching higher titers in colostrum-deprived calves. Also, strong mucosal, but not serum, IgM responses were observed, which, however, did not develop faster than those observed after primary infection. Naturally infected calves, showing severe signs of respiratory disease, had various levels of, most likely, maternally derived antibodies on the first day of illness. Mucosal and systemic antibody responses of various heights and durations were observed, but in general these responses were stronger than those observed after experimental infection. The results point to an important role for local IgA, rather for serum IgG1, in the protection against BRSV infection. The capacity to mount a local memory IgA response seems especially important. Priming for such a mucosal memory response is possible even when the primary immune response is severely suppressed because of the presence of material antibodies.
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                Author and article information

                Contributors
                Journal
                Vet Clin North Am Food Anim Pract
                Vet. Clin. North Am. Food Anim. Pract
                The Veterinary Clinics of North America. Food Animal Practice
                Elsevier Inc.
                0749-0720
                1558-4240
                23 February 2008
                March 2008
                23 February 2008
                : 24
                : 1
                : 87-104
                Affiliations
                [a ]Department of Veterinary Science, PO Box 2175, South Dakota State University, Brookings, SD 57007, USA
                [b ]Departments of Large Animal Medicine and Population Health, Bldg 11, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
                Author notes
                []Corresponding author. christopher.chase@ 123456sdstate.edu
                Article
                S0749-0720(07)00077-1
                10.1016/j.cvfa.2007.11.001
                7127081
                18299033
                0bfc562e-2c1a-4f56-8d38-3eea87dc7088
                Copyright © 2008 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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