Linked Life Data

12659975

Source:http://linkedlifedata.com/resource/pubmed/id/12659975

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-3-27
pubmed:abstractText
Leishmanial mechanisms of virulence have been proposed previously to involve two different groups of parasite molecules. One group consists of largely surface and secretory products, and the second group includes intracellular molecules, referred to as 'pathoantigens'. In the first group are invasive/evasive determinants, which protect not only parasites themselves, but also infected host cells from premature cytolysis. These determinants help intracellular amastigotes maintain continuous infection by growing at a slow rate in the parasitophorous vacuoles of host macrophages. This is illustrated in closed in vitro systems, e.g. Leishmania amazonensis in macrophage cell lines. Although individual macrophages may become heavily parasitized at times, massive destruction of macrophages has not been observed to result from uncontrolled parasite replication. This is thus unlikely to be the direct cause of virulence manifested as the clinical symptoms seen in human leishmaniasis. Of relevance is likely the second group of immunopathology-causing parasite 'pathoantigens'. These are highly conserved cytoplasmic proteins, which have been found to contain Leishmania-unique epitopes immunologically active in leishmaniasis. How these intracellular parasite antigens become exposed to the host immune system is accounted for by periodic cytolysis of the parasites during natural infection. This event is notable with a small number of parasites, even as they grow in an infected culture. The cytolysis of these parasites to release 'pathoantigens' may be inadvertent or medicated by specific mechanisms. Information on the pathoantigenic epitopes is limited. T-cell epitopes have long been recognized, albeit ill-defined, as important in eliciting CD4+ cell development along either the Th1 or Th2 pathway. Their operational mechanisms in suppressing or exacerbating cutaneous disease are still under intensive investigation. However, immune response to B-cell epitopes of such 'pathoantigens' is clearly futile and counterproductive. Their intracellular location within the parasites renders them inaccessible to the specific antibodies generated. One example is the Leishmania K39 epitope, against which antibodies are produced in exceedingly high titers, especially in Indian kala-azar. Here, we consider the hypothetical emergence of this pathoantigenicity and its potential contributions to the virulent phenotype in the form of immunopathology. Microbial virulence may be similarly explained in other emerging and re-emerging infectious diseases. Attenuation of microbial virulence may be achieved by genetic elimination of pathoantigenicity, thereby providing mutants potentially useful as avirulent live vaccines for immunoprophylasis of infectious diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0001-706X
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
375-90
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Leishmania model for microbial virulence: the relevance of parasite multiplication and pathoantigenicity.
pubmed:affiliation
Department of Microbiology/Immunology, University of Health Sciences/Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA. changk@mail.finchcms.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't