Abstract

Although the neonatal immune system is functionally immature, immune response capabilities are not the same in all newborns. The objective of this thesis was to determine development of immunocompetence and test the hypothesis that activation of maternal inflammatory immunity during pregnancy influences maturation of the neonatal immune system.

Lymphocytes in blood and spleen were immunophenotyped by flow cytometric analysis to determine differentiation characteristics, and splenocytes were assessed for cytokine production capabilities. In normal Th2-prone outbred (CD-1) mice, an adult repertoire of naïve lymphocytes has developed by day 10 and memory cells by day 20, in blood and spleen. However, in Th1-biased inbred (C57BL/6) mice, the development of adult immunophenotypes is accelerated by five days. Adult Th1 capability was established in neonates as early as day 5. These findings indicate that neonatal immune cells have the capability to produce adult-like responses, given an environment demanding such immune reactions.

To test the hypothesis that inducing inflammatory Th1 immune reactions in pregnant CD-1 outbred mice advanceS development of immune cell phenotypes and Th1 response predominance in progeny, dams were inoculated with Leishmania major antigen. As adults, experimental progeny had significantly lower numbers of circulating T (naïve and memory helper, and cytotoxic) cell phenotypes compared to that in control cohorts, while spleens were populated with significantly greater numbers of T and natural killer cells. Contrary to expectations, maternal inoculation led to suppression of Th1 cytokine production in offspring. Thus, developmental pattern of immune phenotypes and Th1 capabilities was Th2-biased in offspring. These data suggest that trafficking of critical numbers of lymphocytes into blood and spleen, and development of a memory cell repertoire, define maturation of immunocompetence and close the window of immaturity. Results support the hypothesis that epigenetic factors (maternal immune reactions during gestation) can modulate maturation of an immune cell repertoire and development of cytokine response capabilities in offspring.

LLU Discipline

Physiology

Department

Physiology

School

Graduate School

First Advisor

Sandra L. Nehlsen-Cannarella

Second Advisor

Steven M. Yellon

Third Advisor

Daila S. Gridley

Fourth Advisor

Charles A. Ducsay

Fifth Advisor

Giuseppe Molinaro

Degree Name

Doctor of Philosophy (Medical Science)

Degree Level

Ph.D.

Year Degree Awarded

1993

Date (Title Page)

6-1999

Language

English

Library of Congress/MESH Subject Headings

Immunity, Maternally-Aquired; Immunophenotyping; Lymphocyte Subsets

Type

Dissertation

Page Count

xii; 136

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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