VITAMIN A NUTRITIONAL STATUS AND IMMUNE FUNCTION

Project: Research project

Description

The importance of nutritional factors in the ability to mount an immune
response to bacterial infection is not yet well understood. This proposal
focuses on the role of vitamin A nutritional status early in life on the
immune response to bacterial antigens, particularly to the capsular
polysaccharide antigen of Streptococcus pneumoniae, Type III (designated
SSS-III). Using the young rat as our experimental model, we have conducted
preliminary studies which indicate that young rats fed a retinol-deficient
diet have impaired antibody production when immunized with SSS-III, even
before any clinical signs of vitamin A deficiency are observed. We will
conduct studies under five Specific Aims to test a number of hypotheses.
In Aim 1, we will test the hypothesis that, although nutritional retinol
depletion compromises the young rat's antibody production to SSS-III,
rehabilitation with retinol very near the time of immunization will restore
normal antibody production. We will first determine the minimal length of
time prior to immunization that retinol must be provided in order to
restore immune function, and we will then determine the optimal amount of
retinol needed to effectively restore antibody production. In a limited
manner, we will compare the effects of vitamin A depletion and repletion on
two other antigens of clinical importance, the lipopolysaccharide from
Pseudomonas aeruginosa and meningococcal Type C antigen from Nesseria
meningitidis. In Aim 2, we will develop methods for immunization of spleen
cells with SSS-III, in vitro, in order to investigate which specific cell
types are affected by impaired retinol status. In Aim 3, we will conduct,
in vivo, cell transfer studies in which populations of T cells shown to
either amplify or suppress the antibody response to SSS-III will be
transferred either to or from retinol-depleted animals, after which
antibody production in vivo will be assessed. Together, Aims 2 and 3
should provide a much more detailed understanding of the cell types that
regulate the immune response to SSS-III. In Aim 4, we will determine the
effect of dietary retinol status on the production of interleukin-2 and
gamma-interferon, two molecules that are of particular importance in
modulating the humoral immune response. Finally, the goal of Aim 5 is to
quantitate tissue retinoids in these animals in order to correlate the
concentration of retinol in lymphoid organs, plasma and liver with the
animal's immune response. These studies are expected to provide new
information on the role of retinol status in vivo on antibody production to
clinically relevant bacterial antigens.
StatusFinished
Effective start/end date4/1/895/31/18

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $311,080.00
  • National Institutes of Health: $288,981.00
  • National Institutes of Health: $325,163.00
  • National Institutes of Health: $215,350.00
  • National Institutes of Health: $274,351.00
  • National Institutes of Health: $82,268.00
  • National Institutes of Health: $284,542.00
  • National Institutes of Health
  • National Institutes of Health: $280,893.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $325,163.00
  • National Institutes of Health: $278,084.00
  • National Institutes of Health: $273,921.00
  • National Institutes of Health
  • National Institutes of Health: $94,092.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $305,754.00
  • National Institutes of Health
  • National Institutes of Health: $325,163.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $157,977.00
  • National Institutes of Health: $285,267.00
  • National Institutes of Health

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Nutritional Status
Retinoids
Vitamin A
Antibody Formation
Tretinoin
Vitamin A Deficiency
Antigens
T-Lymphocytes
Immunization
Cytokines
B-Lymphocytes
Interferon Inducers
Bacterial Antigens
Tetanus Toxoid
Tumor Necrosis Factor-alpha
Immune System
Polysaccharides
Poly C
Interferon-gamma
Communicable Diseases