Ehrlichiosis pathophysiology: Difference between revisions
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The pathophysiological process of ehrlichiosis begins with the inoculation of the disease from a tick vector. Following inoculation ehrlichiae and anaplasmosis enter the circulatory system in an attempt to infect a target cell. The infectious agents will then enter the cell via a receptor-mediated endocytosis. This particular endocytosis process is facilitated by a glycophoshoinositol anchored receptor. Both the Ehrlichiae and Anaplasma complete their reproduction process within the host cell's endosome.Infectious agents of both disease are then able to reprogram a host cell's defense mechanisms in order to silently proliferate. | The pathophysiological process of ehrlichiosis begins with the inoculation of the disease from a tick vector. Following inoculation ehrlichiae and anaplasmosis enter the circulatory system in an attempt to infect a target cell. The infectious agents will then enter the cell via a receptor-mediated endocytosis. This particular endocytosis process is facilitated by a glycophoshoinositol anchored receptor. Both the Ehrlichiae and Anaplasma complete their reproduction process within the host cell's endosome.Infectious agents of both disease are then able to reprogram a host cell's defense mechanisms in order to silently proliferate. | ||
== | ==Pathophysiology== | ||
=== | ===Pathogenesis of HME=== | ||
*E. chaffeensis enter into the mononuclear phagocytes. | *E. chaffeensis enter into the mononuclear phagocytes. | ||
*Phagolysosome fusion is inhibited while host genes are suppressed and induced to enable intracellular replication. | *Phagolysosome fusion is inhibited while host genes are suppressed and induced to enable intracellular replication. | ||
| Line 17: | Line 17: | ||
*Organ failure and other pathogenic manifestations resulting in complications or death is a result of immune mediated pathology. | *Organ failure and other pathogenic manifestations resulting in complications or death is a result of immune mediated pathology. | ||
=== | ===Pathogenesis of Human Granulocytotropic Anaplasmosis=== | ||
*A.phagocytophilum successfully resides within the host cells (PMN cells) cytoplasmic vacuoles. | *A.phagocytophilum successfully resides within the host cells (PMN cells) cytoplasmic vacuoles. | ||
*Apoptosis is suppressed due to the upregulation of bfl-1 and inhibiting anti-FAS. Both of which are responsible for inducing apoptosis within neutrophils. | *Apoptosis is suppressed due to the upregulation of bfl-1 and inhibiting anti-FAS. Both of which are responsible for inducing apoptosis within neutrophils. | ||
| Line 28: | Line 28: | ||
*Most of the symptoms of Ehrlichiosis can likely be ascribed to the immune dysfunction that it causes. | *Most of the symptoms of Ehrlichiosis can likely be ascribed to the immune dysfunction that it causes. | ||
*Early in infection, production of [[TNF-alpha]], a cellular product that promotes [[inflammation]] and immune response, is suppressed. | *Early in infection, production of [[TNF-alpha]], a cellular product that promotes [[inflammation]] and immune response, is suppressed. | ||
*Experiments in mouse models further supports this hypothesis, as mice lacking TNF-alpha I/II receptors are resistant to liver injury caused by ehrlichia infection.<ref>{{cite journal|last=McBride|first=Jere W.|coauthors=Walker, David H.|title=Molecular and cellular pathobiology of Ehrlichia infection: targets for new therapeutics and immunomodulation strategies|journal=Expert Reviews in Molecular Medicine|date=31 January 2011|volume=13|doi=10.1017/S1462399410001730}}</ref> | *Experiments in mouse models further supports this hypothesis, as mice lacking TNF-alpha I/II receptors are resistant to liver injury caused by ehrlichia infection. | ||
*Late in infection, however, production of this substance can be upregulated by 30 fold, which is likely responsible for the "[[toxic shock]]-like" syndrome seen in some severe cases of ehrlichiosis.<ref>{{cite journal|last=McBride|first=Jere W.|coauthors=Walker, David H.|title=Molecular and cellular pathobiology of Ehrlichia infection: targets for new therapeutics and immunomodulation strategies|journal=Expert Reviews in Molecular Medicine|date=31 January 2011|volume=13|doi=10.1017/S1462399410001730}}</ref> | |||
==References== | ==References== | ||
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Overview
The pathophysiological process of ehrlichiosis begins with the inoculation of the disease from a tick vector. Following inoculation ehrlichiae and anaplasmosis enter the circulatory system in an attempt to infect a target cell. The infectious agents will then enter the cell via a receptor-mediated endocytosis. This particular endocytosis process is facilitated by a glycophoshoinositol anchored receptor. Both the Ehrlichiae and Anaplasma complete their reproduction process within the host cell's endosome.Infectious agents of both disease are then able to reprogram a host cell's defense mechanisms in order to silently proliferate.
Pathophysiology
Pathogenesis of HME
- E. chaffeensis enter into the mononuclear phagocytes.
- Phagolysosome fusion is inhibited while host genes are suppressed and induced to enable intracellular replication.
- Cytokines IL-12 and IL-18 are downregulated in THP-1 cells.
- Genes that are responsible for upregulation of apoptosis such as SNAP 23, Rab5A and STX16 are downregulated in correlation to the downregulation of IL-12 and IL-18.
- E. chaffeensis secretes an immunoreactive ankyrin protein (200kDa) into the host's nucleus in an attempt to manipulate the gene regulation of the host cell.
- Other methods of E. chaffeensis include inhibiting the signal transduction pathway and circumventing host cell defense mechanisms.
- Organ failure and other pathogenic manifestations resulting in complications or death is a result of immune mediated pathology.
Pathogenesis of Human Granulocytotropic Anaplasmosis
- A.phagocytophilum successfully resides within the host cells (PMN cells) cytoplasmic vacuoles.
- Apoptosis is suppressed due to the upregulation of bfl-1 and inhibiting anti-FAS. Both of which are responsible for inducing apoptosis within neutrophils.
- Host cell gene transcription is controlled through a secreted protein, AnkA, that travels into the host cell's nucleus.
- Research into the pathogensis of HGA has also shown upregulation of pro-inflammatory and IL-8 chemokines.
- The pathogenesis of HGA causes immunosuppression and thus fatality may be attributed to opportunistic pathogens.
Transmission
- Ehrlichia are transported between cells through the host cell filopodia during initial stages of infection, whereas, in the final stages of infection the pathogen ruptures the host cell membrane.[1]
- Most of the symptoms of Ehrlichiosis can likely be ascribed to the immune dysfunction that it causes.
- Early in infection, production of TNF-alpha, a cellular product that promotes inflammation and immune response, is suppressed.
- Experiments in mouse models further supports this hypothesis, as mice lacking TNF-alpha I/II receptors are resistant to liver injury caused by ehrlichia infection.
- Late in infection, however, production of this substance can be upregulated by 30 fold, which is likely responsible for the "toxic shock-like" syndrome seen in some severe cases of ehrlichiosis.[2]
References
- ↑ Thomas S, Popov VL, Walker DH (2010). Kaushal, Deepak, ed. "Exit Mechanisms of the Intracellular Bacterium Ehrlichia". PLoS ONE. 5 (12): e15775. doi:10.1371/journal.pone.0015775. PMC 3004962. PMID 21187937.
- ↑ McBride, Jere W. (31 January 2011). "Molecular and cellular pathobiology of Ehrlichia infection: targets for new therapeutics and immunomodulation strategies". Expert Reviews in Molecular Medicine. 13. doi:10.1017/S1462399410001730. Unknown parameter
|coauthors=ignored (help)