Studies on the protective immune response to Plasmodium chabaudi in mice

McDonald, Vincent (1977) Studies on the protective immune response to Plasmodium chabaudi in mice. PhD thesis, University of Glasgow.

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Abstract

Inbred strains of C5731 and NIH nice infected with the A/S
strain of Plasmodium chaubaudi usually developed high parasitaemias but
infections were rarely fatal in immunocompetent mice and in most mice
the parasites could be eradicated within 53 days or less. The immune
response of C57B1 and NTH mice to infection with the A/S strain of
P. chabaudi was studied. The principle method used in this study for
investigating the immune response of the mice was to examine the immunity
conferred on syngeneic mice, either X-irradiated or non-irradiated, by
transferring to them lymphoid cells or serum from immune or semi-immune
donors. The lymphoid cell populations examined were unfractionated spleen
cells, nylon wool column enriched subpopulations of thymus-derived
lymphocytes (T cells) and the so-called bursa-derived lymphocytes (B cells),
bone marrow cells and phagocytic cells. In the course of these experiments
observations were made on the effect of X-irradiation on the subsequent
growth and multiplication of the parasite.

In addition, an in vitro assay for antibody-dependent cell
mediated cytotoxicity was used to investigate the activity of splenic
K cells during malaria infection. K cells are lymphoid cells which may
include lymphocytes of an undefined category, but possess receptors for
the Fc portion of antibody on their surface and have the ability to non-specifically
lyse target cells coated in antibodies.

a) The adoptive transfer of immunity to P.chabaudi with immune spleen cells.

Spleen cells from mice which had previously been infected with
P.chabaudi were able to confer some immunity on syngeneic mice which had
been irradiated with 600 or 800 rads. The protection was detected as a shortened patent parasitaemia in immune cell recipients compared to
controls. The early experiments indicated the value of using irradiated
recipients rather than non-irradiated recipients. In irradiated mice, a) smaller numbers of immune cells were required to promote detectable immunity than in non-irradiated mice, b) there was an amplification of the difference in the duration of primary parasitaemias in recipients of immune cells and normal cells compared to non-irradiated mice and c) as the irradiated host is immunodepressed, the protective effect of donor cells can be examined with a reduced contribution by the hosts own immune system.
An initial non-specific resistance to P.chabaudi infection was observed in irradiated mice, although the infection in most of these mice was subsequently more severe than in non-irradiated mice. The non-specific resistance could be reduced or abolished by injecting lymphoid cells into mice shortly after irradiation or by infecting irradiated mice more than 15 days after irradiation. Other workers suggest that following irradiation, the reticulo-endothelial system is stimulated at the time that the non-specific resistance to P.chabaudi was observed.

b) the adoptive transfer of immunity in syngeneic mice with enriched
subpopulations of splenic immune T cells, B. cells, bone marrow cells
and phagocytes.
Immunity to P.chabaudi could be adoptively transferred with
enriched spleen subpopulations of immune T cells or immune B cells in
mice which had been irradiated 600 or 300 rads. The protective
effects of unfractionated immune cells was, however, usually better than
that of either immune T or F cell subpopulations. In most experiments
enriched immune T cell recipients were more likely to suffer relapsing patent parasitaemias than either enriched immune B cell recipients or unfractionated immune cell recipients. In one experiment a comparison
was made of the course of P.chabaudi infection in mice which had been
irradiated with either 600 rads or 300 rads and which received injections
of different immune cells. A dose of 600 rads permits the immune
system of mice to recover from the effects of irradiation, but a dose
of 800 rads is lethal to mice unless lymphoid cells are injected after irradiation. It was found that in recipients of enriched immune T or B cells, which had been irradiated with 600 rads, the parasitaemia became subpatent before their equivalents irradiated with 800 rads, but that there was little difference in parasitaemias between recipients of unfractionated immune cells given 600 or 800 rads. Experiments in which enriched immune T cells and B cells were recombined and injected
into syngeneic mice gave inconclusive results as to whether the immune
subpopulations acted synergistically. Similar experiments in which
immune subpopulations of lymphoid cells were recombined with normal
subpopulations of lymphoid cells demonstrated that the latter cells did
not enhance the protective effect of the former cells. Bone marrow
cells from immune mice were able to confer some protection on syngeneic
recipients, but were not as protective as enriched immune T cells or B
cells. The results obtained in adoptive transfer experiments using
phagocytic cells from the spleen of immune mice depended on the length
of time spleen cells were incubated in petri-dishes at 37° C before
harvesting the phagocytes. Using C57B1 mice, phagocytes harvested
after 15 hours incubation were as protective as unfractionated immune
cells in a cell transfer experiment, but phagocytes harvested after 16
hours incubation were not protective. Examination of NIH phagocytic
cells after 2.5 hours incubation at 37°C, which were as protective as
unfractionated immune spleen cells in a cell transfer experiment, demonstrated
that the petri-dish adherent cells may have contained B lymphocytes.
c) The passive transfer of immunity with serum from P.chabaudi infected mice.

The passive transfer of serum from C57B1 mice which had been previously infected with P.chabaudi to normal or irradiated syngeneic mice demonstrated that the serum recipients were initially protected from
infection. Irradiated mice, however, were delayed longer in the onset
of parasitaemia compared to non-irradiated mice. Using NIH mice, sera were collected from unfractionated immune spleen cell recipients, enriched immune T cell recipients and normal spleen recipients on the 11th day of a P.chabaudi infection, just after peak parasitaemia, and also on the 14th day of infection.
On day 14, all immune cells recipients and most of the enriched immune T cell recipients had become subpatent but all normal cell recipients still had patent infections.
Sera collected from the different spleen cell recipients on the 11th day
of infection and passively transferred to irradiated mice demonstrated
little protection. Sera collected on the 14th day of infect ion, however,
reflected the immune status of the donors in their protective properties
in mice infected with P.chabaudi. The serum from unfractionated immune cell
recipients was the most protective of the 3 sera when compared to normal
NIH serum and the serum from enriched immune T cell recipients was
slightly protective, but the serum from normal cell recipients produced
an enhanced infection in mice infected with P.chabaudi.

d) Antibody-dependent cell-mediated cytotoxicity of spleen cells in P.chabaudi infected mice.

In a preliminary investigation of K cell activity in the spleens of P.chabaudi infected mice, it was found that there was an increased activity of K cells collected at around peak parasitaemia compared to the activity of K cells in non-infected mice, and that this increased activity could also be found in mice which had recently become subpatent. As the target cell for antibody-dependent cell-mediated cytotoxicity employed was the thick red blood cell, it is not known whether the K cell is involved in the killing of P.chabaudi parasites.

These results suggest that both T cells and B cells and
antibody may be important in the immune response to P.chabaudi in mice.
Primed T cells may act as helper cells in the production of malarial
antibodies, but, as enriched primed T cells could confer protection on
immunodepressed mice, it is possible that a cell-mediated mechanism of
immunity may also exist.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Supervisor, not known
Date of Award: 1977
Depositing User: Adam Swann
Unique ID: glathesis:1977-7513
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 Aug 2016 15:36
Last Modified: 10 Aug 2016 15:36
URI: http://theses.gla.ac.uk/id/eprint/7513

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