Ruminant Diseases and Immunology Research Unit, USDA Agricultural Research Service, National Centers for Animal Health, Ames, IA 50010, USA.
J Dairy Sci. 2012 Jan;95(1):221-39. doi: 10.3168/jds.2011-4712.
Responses of the newborn calf to vaccination are frequently characterized by marginal antibody (Ab) responses. The present study evaluated effects of colostrum ingestion on the adaptive immune response of the preruminant calf to early vaccination. Colostrum-fed (CF) and colostrum-deprived (CD) calves were vaccinated at 2 d of age with Mycobacterium bovis, Pasteur strain of bacille Calmette Guerin (BCG), and ovalbumin (OVA) to track development of the adaptive immune response during the first 8 wk of life. Dams were also vaccinated with BCG prepartum. At wk 0, serum IgG(1), IgG(2), IgA, and IgM were elevated in CF calves, with IgG(1) predominating. In these calves, IgG(2), IgA, and IgM concentrations decreased with age. The CD calves, in contrast, had very low or undetectable serum immunoglobulin concentrations at wk 0 followed by an age-related increase in IgG(1), IgG(2), and IgM concentrations, suggesting endogenous production of these immunoglobulin classes. Immunoblot and ELISA analyses of Ab response to BCG vaccination indicated that colostrum ingestion was associated with measurable serum anti-mycobacterial Ab in CF calves during the first month postpartum, with substantially lower levels at 7 wk of age. Although mycobacteria-specific Ab was undetectable in CD calves at wk 0, it was present at 4 and 7 wk of age, suggesting that these calves, unlike CF calves, were capable of generating an Ab response to BCG vaccination. Antibody responses of CF and CD calves to vaccination with OVA, an antigen not present in the natural environment of dairy cattle, were of comparable magnitude and characterized by a progressive increase in Ab levels from birth (wk 0) to 7 wk of age. The disparate Ab responses of CF calves to BCG and OVA suggest that maternal antigenic experience or exposure influences Ab responses of the colostrum-fed preruminant calf to early vaccination. Ex vivo, antigen [OVA and M. bovis-derived purified protein derivative (PPDb)]-induced IFN-γ and nitric oxide responses of blood mononuclear cells (PBMC) from CF and CD calves were comparable at wk 0 and wk 7. As expected, responses were very low or nonexistent at wk 0. Responses for all calves were greater at wk 7 than at wk 0, suggesting a colostrum-independent maturation of the cell-mediated immune response capacity of the preruminant calf. The consistently greater proliferative responses of antigen-stimulated T-cell subsets at wk 7 versus wk 0 indicate the development of antigen-specific lymphocyte responses to early vaccination. Total numbers of blood leukocytes as well as numbers of lymphocytes and monocytes were unaffected by colostrum feeding; however, granulocyte numbers were higher in CD than in CF calves at wk 0. Granulocyte numbers decreased and monocyte numbers increased with age in all calves. Within the lymphocyte population, only natural killer (NK(+)) cell percentages were affected by colostrum ingestion, with higher percentages of NK(+) cells in CD calves at wk 0 and wk 7. Antigen-induced proliferation of lymphocyte subsets including IgM(+) cells was unaffected by colostrum ingestion. In conclusion, ingestion of colostrum within hours after birth inhibited the capacity of the calf to produce antigen-specific immunoglobulin (i.e., antibody) in response to vaccination, with little or no effect on cell-mediated immune responses. Although colostrum appeared to block endogenous antibody production, certain B-cell functions were retained. These findings will aid in development of new vaccination strategies for improving health of the preruminant calf.
新生牛犊对疫苗的反应通常表现为边缘抗体(Ab)反应。本研究评估了初乳摄入对反刍前小牛对早期疫苗接种的适应性免疫反应的影响。在 2 日龄时,用牛分枝杆菌、巴氏结核分枝杆菌(BCG)和卵清蛋白(OVA)给初乳喂养(CF)和初乳剥夺(CD)小牛接种疫苗,以跟踪在生命的前 8 周内适应性免疫反应的发展。在产前,给母畜接种 BCG。在 0 周时,CF 小牛的血清 IgG(1)、IgG(2)、IgA 和 IgM 升高,以 IgG(1)为主。在这些小牛中,IgG(2)、IgA 和 IgM 浓度随年龄而降低。相比之下,CD 小牛在 0 周时血清免疫球蛋白浓度非常低或无法检测到,随后随着年龄的增长 IgG(1)、IgG(2)和 IgM 浓度增加,表明这些免疫球蛋白类别的内源性产生。对 BCG 疫苗接种的 Ab 反应的免疫印迹和 ELISA 分析表明,在产后第一个月,初乳摄入与 CF 小牛中可测量的抗分枝杆菌 Ab 有关,在 7 周龄时,其水平显著降低。尽管在 0 周时 CD 小牛中未检测到针对结核分枝杆菌的 Ab,但在 4 周和 7 周时存在,这表明与 CF 小牛不同,这些小牛能够对 BCG 疫苗接种产生 Ab 反应。CF 和 CD 小牛对 OVA(奶牛自然环境中不存在的抗原)疫苗接种的抗体反应相当,其特征是从出生(0 周)到 7 周龄时 Ab 水平逐渐增加。CF 小牛对 BCG 和 OVA 的不同 Ab 反应表明,母体抗原经验或暴露会影响反刍前小牛对早期疫苗接种的 Ab 反应。在体外,CF 和 CD 小牛的血液单核细胞(PBMC)对 OVA 和牛分枝杆菌来源的纯化蛋白衍生物(PPDb)诱导的 IFN-γ 和一氧化氮反应在 0 周和 7 周时相当。正如预期的那样,在 0 周时,反应非常低或不存在。与 0 周相比,所有小牛在 7 周时的反应都更大,这表明反刍前小牛的细胞介导免疫反应能力具有初乳独立性成熟。与 0 周相比,7 周时抗原刺激的 T 细胞亚群的增殖反应更大,这表明对早期疫苗接种产生了抗原特异性淋巴细胞反应。血液白细胞的总数以及淋巴细胞和单核细胞的数量不受初乳喂养的影响;然而,在 0 周时,CD 小牛的粒细胞数量高于 CF 小牛。在所有小牛中,粒细胞数量随着年龄的增长而减少,单核细胞数量增加。在淋巴细胞群体中,只有自然杀伤(NK(+))细胞百分比受到初乳摄入的影响,在 0 周和 7 周时 CD 小牛的 NK(+)细胞百分比更高。抗原诱导的淋巴细胞亚群增殖不受初乳摄入的影响,包括 IgM(+)细胞。总之,出生后数小时内摄入初乳抑制了小牛对疫苗接种产生抗原特异性免疫球蛋白(即抗体)的能力,对细胞介导的免疫反应几乎没有影响。尽管初乳似乎阻止了内源性抗体的产生,但保留了某些 B 细胞功能。这些发现将有助于制定新的疫苗接种策略,以改善反刍前小牛的健康状况。