Biology Reference
In-Depth Information
individuals is also important and intriguing. This is emphasized by an
unpublished study in which a population typed for MHC as part of
a large study on genetic resistance to malaria in the Gambia found that
heterozygotes at MHC loci were more likely to respond to ABA-1 than
expected for their genotypes (A.V. Hill and M.W. Kennedy, unpublished).
Thus, two non-responder MHC allele sets (haplotypes) could come
together in an individual that then exhibits a responder phenotype. The
finding with humans that MHC heterozygotes may be more likely to
respond to a given type of protein antigen than expected should be
explored for pure curiosity if nothing else.
Whether the genetic control of the immune repertoire, so clearly
demonstrated with Ascaris, is of relevance to the development of natural
resistance to the infection remains far from clear. Other chapters in this
topic relate to other correlates with immunity by following the genetics of
humans that are relatively susceptible or resistant to natural infection
with the parasite (see Chapter 12). For instance, whole genome screens
have revealed genetic loci that are associated with natural resistance or
susceptibility, but those genes are not classical MHC loci, although some
may be immune-related.
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But, as argued above, MHC-controlled
immune repertoires are very likely to be important in immunizations
using one or a small number of recombinant protein types, such that
certain individuals may not respond at all to a particular antigen protein.
POLYMORPHISMS IN
ASCARIS
ANTIGENS
It is not yet known whether Ascaris worms are polymorphic in the
antigens they produce. If they were, then this would have important
implications for the acquisition and persistence of immunity in humans
and even for the segregation of A. suum and A. lumbricoides into their
separate host species. Detecting differences in antigen expression in ES
materials of individual larvae would be difficult, though new high reso-
lution techniques will soon be able to analyze the genome, transcriptome,
and proteome of individual larvae. For the moment, it remains worth-
while to consider evidence gained some time ago, using quantitative
immunofluorescence, that A. lumbricoides larvae are diverse in their
surface-exposed antigens.
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This work used serum antibody from infected
people and quantitative immunofluorescence (which has much more
discriminating power for differences in fluorescence emission than the
human eye) on live larvae, and found that there were differences in the
level of binding to the surfaces of larvae of A. lumbricoides raised from
eggs collected from adult worms recovered from the same community in
Nigeria (
Figure 3.5
). Thus, while antibody from one person would bind to
larvae from the same pool with a normal distribution (donor 18), antibody
