Studies of cellular immunity in children with measles
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Date
2015-06-10
Authors
Joffe, Max Israel
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Abstract
There have l=eg been two clinical Indications of the significance
of cell-mediated Immunity to measles, namely, the cutaneous delayed
hypersensitivity reaction to tuberculin Is greatly depressed or
even absent during Infection and that Individuals with hypogammaglobullneraia
recover normally from measles.
The experiu- ntal work presented In this dissertation basically
involved the study of the cellular immune status of children
acutely infected with measles virus. Lymphocyte blastogenlsis
and lymphoklne production, two techniques that have been previously
employed In Investigations of clinical conditions known to he
associated with cellular immune defects, were adapted for use in
the present study.
Lymphocyte transformation studies of measles MN cells revealed
the existence of elevated unstloul.ted or •spontaneous' incorporation
of thymidine after overnight incubation, later decreasing to
lower levels. The significance of the latter is speculative but
most probably reflects in vivo activation of MN cell, by measles
antigen. PI1A activation of measles MN cells was essentially
normal over a range of different mitogen concentrations and no
inhibition Of normal lymphocyte transformation was apparent using
measles MN cell supernatants or acute serum. In contrast, allogeneic
stimulation of measles MN cells in the two-way Mi*, resulted in
*1 vt wiw \ xf 4 A m e a a l e s MN
-1 L f _ * V . < , 1 {
cells respond poorly to allogeneic activation, but when mi cornycin
C-treated, they also failed to adequately stimulate control responding
cells. Although no ready explanation for this puzzling finding is
apparent the possibility exists that different lymphocyte subpopulations
are adversely affected by measles virus infection.
To assess lymphok^ne production a two-stage migration assay was
i U 11zed. The first stage consisted of pulsing MN cells with
PHA to induce lymphokine production and the second stage involved
the incubation of indicator cells with and without lymphokinecontaining
supernatants. Using on agarose migration system, it
was snovn that measles MN cells failed to produce LIF while the
capillary tube migration system using guinea-pig PEC, demonstrated
• lack - f MIF activity too.
In contrast to the results obtained by measuring thymidine
incorporation after 18 hours of incubation, measles MN cells aid
not produce LIF 'spontaneously1. In addition, supernatants from
unstimulated measles MN cells did not inhibit the production of
LIF by normal PHA-pulsed MN cells.
These results suggest that a specific lymphokine-producing cell
population may be adversely affected by measles infection. An
attempt at correcting this defect by treatment of measles MN c.11s
in Vitro with levamisole was however, unsuccessful at the concentration
used in this study.
Virological examination of measles MN cell culture supernatants
demonstrated the presence of papovavirus particles in a small
number of patients. Specific immunofluorescent staining for
the virus in MN cell preparations was however unsuccessful. These
results suggest either reactivation of a latent virus infection
during the course of measles or simply, contamination of specimens
during processing in a ’irological laboratory.
The effect of measles on monocyte function was assessed in vitro
using a modified Boyden amber technique. The monocytes of
measles patients were shown to migrate adequately to tbr chemoattractant
casein. Although the migration of measles PMN cells in vivo
was found to be depressed as assessed by the Rebuck skin-window
technique, measles monocytes were found to migrate in sufficient
numbers after 24 hours.
These results imply that the adverse effect? of measles infection
on cellular immunity is probably confined to lymphocytes.
Description
Being a dissertation presented in fulfilment
of the requirements governing the degree of
Master of Science in the School of Medicine,
University of the Witwatersrand.
JOHANNESBURG
September 1978