Neonatal Immunity
http://www.100md.com
《新英格兰医药杂志》
During the past 50 years, the field of neonatal immunology has been influenced by such dogmas as "The neonatal age is a window of time when tolerance develops," and "Neonatal immune cells are unresponsive because they are immature." Yet, many questions have been left unanswered: What type of antigen induces immunologic tolerance instead of immunity in neonates? Are neonatal immune cells truly immature? How does neonatal immunity differ from adult immunity? How can safe and effective vaccines for neonates be created? Constantin Bona addresses some of these questions in this book.
After an introduction outlining the elements of the immune system, Bona devotes a remarkable chapter to the ontogeny and development of immune cells. The central point of this chapter is that all cells that mediate innate and adaptive immunity originate from the hematopoietic stem cell and develop through a multistep process involving various cytokines and signaling pathways. The idea that hematopoietic stem cells derive only from the yolk sac is refuted by observations that these cells also originate within the embryo. This is true not only for humans but also for other mammals, fish, birds, and amphibians. The reader will welcome two figures that skillfully summarize this valuable chapter.
Neonatal B and T cells then take the stage. There are subtle differences in the signaling pathways between neonatal and adult B and T cells, whereas the expression of the antigen receptor and costimulatory molecules is similar in neonatal and adult cells. The sequential activation of B-cell precursors during fetal and neonatal life is antigen-independent and genetically programmed by an "internal clock." Mature and functional B and T cells are present in the fetuses and infants of many mammals, but their repertoire of antigen receptors is more restricted than it is in adults. In a section on the effects of maternal antibodies on infants, Bona cautions that such antibodies are beneficial in conferring passive immunity but interfere with active immunization of infants. Maternal transfer of autoantibodies can also cause severe autoimmune diseases in infants. DNA immunization of newborns circumvents the inhibitory effect of maternal antibodies on cellular and humoral responses. Frequent references to the idiotypic network in the regulation of responses of B and T cells in neonates, and to DNA immunization as a successful vaccine tool, reflect the direct interest and expertise of the author.
Although there is evidence to the contrary, Bona describes the cytokine network in neonates by supporting the thesis that T cells in newborn humans and mice are biased to synthesize cytokines produced by type 2 helper T cells. It is interesting to note Bona's acknowledgment of functional type 1 helper T cells in neonatal lymphoid organs. The cytokine microenvironment and the antigen dose and delivery also influence how neonatal T lymphocytes generate effector and memory functions of cytotoxic T lymphocytes. A chapter on neonatal tolerance discusses basic notions of clonal deletion, anergy, and suppression of B and T cells. Bona concludes with a detailed review of existing prophylactic and therapeutic vaccines for neonates.
This book is written for immunologists; it is up to date, and the references are comprehensive. Minor shortcomings include imprecise writing, which makes for difficult reading in a few instances; the number of figures and summary charts, which could be greater; and the language used in many sections, which is too specialized for a general audience, although helpful summary sentences recapitulate the main messages. Notwithstanding these minor limitations, I recommend this book as an excellent source of both old and cutting-edge information on neonatal immunity.
Marcella Sarzotti, Ph.D.
Duke University Medical Center
Durham, NC 27710
msarzott@duke.edu(Constantin Bona. 389 pp.,)
After an introduction outlining the elements of the immune system, Bona devotes a remarkable chapter to the ontogeny and development of immune cells. The central point of this chapter is that all cells that mediate innate and adaptive immunity originate from the hematopoietic stem cell and develop through a multistep process involving various cytokines and signaling pathways. The idea that hematopoietic stem cells derive only from the yolk sac is refuted by observations that these cells also originate within the embryo. This is true not only for humans but also for other mammals, fish, birds, and amphibians. The reader will welcome two figures that skillfully summarize this valuable chapter.
Neonatal B and T cells then take the stage. There are subtle differences in the signaling pathways between neonatal and adult B and T cells, whereas the expression of the antigen receptor and costimulatory molecules is similar in neonatal and adult cells. The sequential activation of B-cell precursors during fetal and neonatal life is antigen-independent and genetically programmed by an "internal clock." Mature and functional B and T cells are present in the fetuses and infants of many mammals, but their repertoire of antigen receptors is more restricted than it is in adults. In a section on the effects of maternal antibodies on infants, Bona cautions that such antibodies are beneficial in conferring passive immunity but interfere with active immunization of infants. Maternal transfer of autoantibodies can also cause severe autoimmune diseases in infants. DNA immunization of newborns circumvents the inhibitory effect of maternal antibodies on cellular and humoral responses. Frequent references to the idiotypic network in the regulation of responses of B and T cells in neonates, and to DNA immunization as a successful vaccine tool, reflect the direct interest and expertise of the author.
Although there is evidence to the contrary, Bona describes the cytokine network in neonates by supporting the thesis that T cells in newborn humans and mice are biased to synthesize cytokines produced by type 2 helper T cells. It is interesting to note Bona's acknowledgment of functional type 1 helper T cells in neonatal lymphoid organs. The cytokine microenvironment and the antigen dose and delivery also influence how neonatal T lymphocytes generate effector and memory functions of cytotoxic T lymphocytes. A chapter on neonatal tolerance discusses basic notions of clonal deletion, anergy, and suppression of B and T cells. Bona concludes with a detailed review of existing prophylactic and therapeutic vaccines for neonates.
This book is written for immunologists; it is up to date, and the references are comprehensive. Minor shortcomings include imprecise writing, which makes for difficult reading in a few instances; the number of figures and summary charts, which could be greater; and the language used in many sections, which is too specialized for a general audience, although helpful summary sentences recapitulate the main messages. Notwithstanding these minor limitations, I recommend this book as an excellent source of both old and cutting-edge information on neonatal immunity.
Marcella Sarzotti, Ph.D.
Duke University Medical Center
Durham, NC 27710
msarzott@duke.edu(Constantin Bona. 389 pp.,)