TY  - JOUR
A1  - Solbach, W.
A1  - Bogdan, C.
A1  - Moll, Heidrun
A1  - Lohoff, M.
A1  - Röllinghoff, M.
T1  - Parasitäre Evasionsmechanismen: Beispiel Leishmanien
T1  - Mechanisms of Parasite Evasion: Leishmania as an Example
N2  - Leishmanien besitzen eine Vielzahl von Mechanismen, die humorale und zelluläre Immunabwehr effektiv zu unterlaufen. Diese hängen eng mit der Expression von hauptsächlich zwei Glykokonjugaten auf der Parasitenoberfläche zusammen, dem gp63 und dem Lipophosphoglykan. Die Parasiten sind einerseits schlechte Aktivatoren des alternativen Komplementweges und umgehen damit ihre eigene extrazelluläre Lyse. Oberflächengebundene Komplementfaktoren fördern andererseits die Aufnahme der Leishmanien durch Makrophagen. Solange diese nicht durch T-Zellen aktiviert sind, dienen sie den Parasiten als "Refugium". Dies gilt insbesondere, als Leishmanien in der Lage sind, 1. den "oxidative burst" zu hemmen; 2. toxische Sauerstoffmetaboliten zu entgiften; 3. abbauende lysosomale Enzyme zu hemmen und 4. das saure Milieu in den Lysosomen für ihren eigenen Metabolismus auszunutzen. Schließlich unterlaufen Leishmanien die zelluläre Immunabwehr des Wirts, indem sie die Aktivierung von T-Lymphozyten hemmen und die Expansion von T-Zell-Sub-populationen bewirken, die für ihr eigenes Überleben nützlich sind.
N2  - Leishmania display a variety of mechanisms for effective evasion of the humoral and cellular immune responses of the host which are strongly associ-ated with the expression of two major surface glycoconjugates, gp63 and lipophosphoglycan. The parasites are poor activators of the alternative com-plement pathway thus avoiding their own extracellular lysis. Complement bound on the surface of promastigotes promotes the uptake of leishmania by macrophages which function as »safe targets« as long as they are not acti-vated by T lymphocytes. This is due to the fact that intracellular parasites are able to 1. decrease the oxidative burst; 2. scavenge toxic oxygen metabolites; 3. inhibit degradative lysosomal enzymes; 4. exploit the acidic milieu of lysosomes for their own metabolism. Finally, leishmania have been shown to evade the host's cellular immune response by down-regulating T cell-activat-ing processes and by initiating the expansion of T cell subpopulations which promote their own survival.
KW  - Leishmanien
KW  - Immunsystem
KW  - Evasionsmechanismen
KW  - Makrophagen
KW  - T-Zellen
KW  - leishmania
KW  - immune System
KW  - evasion mechanisms
KW  - macrophages
KW  - T cells
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30920
ER  - 
TY  - JOUR
A1  - Moll, Heidrun
A1  - Müller, Christoph
A1  - Gillitzer, Reinhard
A1  - Fuchs, Harald
A1  - Röllinghoff, Martin
A1  - Simon, Markus M.
A1  - Kramer, Michael D.
T1  - Expression of T-cell-associated serine proteinase-1 during murine Leishmania major infection correlates with susceptibility to disease
N2  - The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis.
KW  - Biologie
KW  - Immunologie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61311
ER  - 
TY  - JOUR
A1  - Frischholz., S.
A1  - Röllinghoff, M.
A1  - Moll, Heidrun
T1  - Cutaneous leishmaniasis: Co-ordinate expression of granzyme A and lymphokines by CD4\(^+\) T cells from susceptible mice.
JF  - Immunology
N2  - We have recently demonstrated that the frequency ofT cells expressing granzyme A is significantly higher in skin lesions and spleens of susceptible BALB/c mice compared with resistant C57BL/6 mice infected with Leishmania major, a cause of human cutaneous leishmaniasis. In the present study, we have performed in vitro studies to characterize the subpopulation, the antigen responsiveness and the lymphokine production pattern of granzyme A-expressing T cells in L. major-infected mice. Using a limiting dilution system for functional analysis of selected T cells at the clonallevel, we could show that granzyme A activity in infected BALB/c mice can be assigned to L. major-reactive CD4\(^+\) T cells secreting interleukin-2 (IL-2) and IL-4. Granzyme A production was most pronounced in the early phase of infection. On the other hand, granzyme A expression could not be detected in C57BL/6-derived T cells responding to L. major. The da ta support the suggestion that granzyme A is produced by L. major-responsive CD4\(^+\) T cells facilitating lesion formation and the dissemination of infection.
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30954
VL  - 82
SP  - 255
EP  - 260
ER  -