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SCF (stem cell factor) 637 schistosomiasis vaccines
SCF (stem cell factor)
A substance that promotes growth of hematopoietic precursor
cells and is encoded by the murine SI gene. It serves as
a ligand for the tyrosine kinase receptor family protooncogene
termed c-kit. It apparently has a role in embryogenesis
in cells linked to migratory patterns of hematopoietic stem
cells, melanoblasts, and germ cells.
ScFv
A single chain molecule composed of both heavy and light
chain variable regions fastened together by a flexible linker.
Bela Schick.
Schick, Bela (1877–1967)
Austro-Hungarian pediatrician whose work with von
Pirquet resulted in the discovery and description of serum
sickness. He developed the test for diphtheria that bears his
name. (Refer to Die Serumkrankheit [with Pirquet], 1905.)
Schick test
A test for susceptibility to diphtheria. Standardized
diphtheria toxin is adjusted to contain 1/50 MLD in 0.1
mL, which is injected intracutaneously into the forearm.
Development of redness and induration 24 to 36 hours after
administration constitutes a positive test if the condition
persists 4 days or longer. The presence of 1/500 to 1/250
or more of a unit of antitoxin per milliliter of patient blood
will result in a negative reaction because of neutralization
of the injected toxin. Neither redness nor induration appears
if a test is negative. An individual with a negative test possesses
sufficient antitoxin to protect against infection with
Corynebacterium diphtheria; a positive test denotes susceptibility.
A control is always carried out in the opposite
forearm. For this test, diluted toxin is heated to 70°C for 15
minutes and injected intracutaneously. Heating destroys the
ability of the toxin to induce local tissue injury, but does
not affect the components of the diphtheria bacilli or the
medium that may evoke an allergic response. If the size and
duration of the reaction at the injection site in the control
approximate the reaction in the test arm, the result is negative.
If the reaction is at least 50% larger and of longer duration
on the test arm compared to the control, the individual
is both allergic to the materials in the bacilli or medium and
susceptible to the toxin. A positive Schick reaction suggests
that diphtheria immunization is needed.
Schistosoma immunity
The immune response to the blood flukes classified as
schistosomes is complex. Repeated exposure to schistosome
larval antigens may lead to hypersensitivity and cercarial
dermatitis (swimmer’s itch). Exposure to large numbers of
Schistosoma mansoni or S. japonicum may lead to a serum
sickness or immune complex-like disease, whereas immune
reactions to later stages of the infection may be associated
with resistance against infection. Many of the pathological
changes in schistosome infections are linked to deposition
of eggs that induce granulomatous reactions in tissues,
resulting in fibrosis. The granuloma is a delayed-type
hypersensitivity reaction that is T cell-dependent. In addition
to the cells expected in a granuloma, eosinophils, lymphocytes,
and macrophages are also present. The fibrosis is
also egg antigen-induced. Multiple immune parameters are
activated by these eggs and their antigens, leading to modulation
in chronically infected individuals. Egg antigens
may induce protective and immunopathologic responses.
Whereas the eggs induce mostly immunopathologic effects,
reactions to the schistosomulum are mostly protective of the
host. Adult worms from a primary infection can continue
to survive in individuals resistant to reinfection with fresh
cercariae through “concomitant immunity.” Irradiated
cercariae can be used to induce immunization of mice and
other experimental animals against cercarial challenge.
The main target of destructive immunological attack is the
migrating schistosomulum. Humans develop concomitant
immunity slowly. Resistance is correlated with peripheral
blood eosinophilia in S. haematobium infections. Infectionprotective
immunity may be associated in elderly persons
with IgE antibodies against adult worm antigens. More than
90% of the surface antigens of the young schistosomulum
are carbohydrates. Anti-egg antibodies may cross react
with these antigens. Adult worms activate Th1 responses
and eggs induce Th2 responses. Protection in mice is
mediated mainly by T h1 cells and can be potentiated with
IL12. Tumor necrosis factor α (TNF-α) is associated with
granuloma formation. Adult worms are usually not susceptible
to immune attack, as they either coat themselves with
host-derived macromolecules that mask parasite surface
antigens or shed antigenic macromolecules from the outer
tegument, rendering their outer surfaces immunologically
inert. Although egg identification in human excreta has
long been the method of diagnosis, indirect diagnosis using
antibody detected by the enzyme-linked immunosorbent
assay (ELISA) technique is becoming more common.
Schistosome-derived carbohydrate antigens in the blood are
also helpful in immunodiagnosis. No vaccine is available to
protect against schistosomiasis in humans. Irradiated larvae
have been used to immunize cattle.
schistosomiasis
A schistosome infection characteristically followed by a
granulomatous tissue reaction.
schistosomiasis vaccines
Schistosomiasis (bilharziasis or snail fever) is the worst
human disease induced by a metazoan parasite. Five different
species of Schistosoma produce the disease. Two
isoforms of the schistosome enzyme glutathione-S-transferase
have been investigated as candidates for a vaccine.
They manifest highly effective immunogens in rat models.
Two surface antigens from the migratory larval stage of S.
mansoni parasites or other molecules appear promising in
animal models. Two parasite muscle proteins have also been
tested. None of these antigens has reached clinical trials,
and no immediate prospect for development of an effective
vaccine appears imminent even though the search continues.
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