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==Johne's disease==
*Caused by Mycobacterium avium subsp. paratuberculosis
*Faculative intracellular acid-fast bacillus
*Rule out Nocardia and Corynebacterium – also acid-fast.
*22% of the US dairy herds are infected.
*Infection can be cleared at the early stage, but if colonization takes place, and initial subclinical phase and then a chronic phase.
*Clinical signs – chronic diarrhea, progressive emaciation – diffuse granulomatous enteritis and lymphadenitis.
*Progression to clinical stages associated with reduced expression of IFNgamma at the site of infection.
*Infected at an early age, c/s not apparent until 2yrs+ old.
*Will shed the bacteria in the faeces before c/s apparent.
*Infection mediated by transport of bacteria across the Peyer’s patch by M cells and macrophages – transported inside macrophages
*CMI is mainly by αβ T cells including CD4+ T cells and CD8+ T cells.
*γδ T cells involved in protection of early infectious stage of disease of mycobacteria and other intracellular organisms
*Proliferation and activation of γδ T cells at the site of colonization is mediated by 70kd mycobacterial heat shock protein and cytokines.
*γδ T cells produce proinflammatory cytokines, activate immunoreactive macrophages, αβ T cells and NK cells.
*But much controversy of their protective role or whether they just recruit other inflammatory cells.
This study:
BALB/c mice are susceptible to M.paratuberculosis infection
γδ T cells KO mice produced fewer granulomas than controls and lower numbers of organisms in the spleen.
Therefore γδ T cells may be involved in granuloma formation
γδ T cells in bovines produce TH1 type of cytokines – IFNγ, TNFα and IL-2. May recruit macrophages via production of MCP-1.
TNFα and IFNγ act synergysticly to produce granulomas.
IL-2 induces proliferation of T cells, B cells, macrophages and NK cells, and enhances IFNγ and TNFα production from CD4+ T cells.
Bovines have relatively high proportion of γδ T cells in the GIT compared to man and mice.
[Reduced formation of granulomata in gamma-delta T cell knockout BALB/c mice inoculated with Mycobacterium avium subsp. Paratuberculosis. Tanaka S et al. Vet Path (2000) 37 415-21]
*Can use culture to detect the bacteria in pooled fecal samples from low-level infected herds – as sensitive as detection of Mycobacteria avium subsp. paratuberculosis from feces of an individual animal (about 70%)
[Culture of pooled bovine fecal samples as a method to screen herds for paratuberculosis. JVDI (2000) 12 547-51]
[Immunohistochemical detection of M.paraTB in formalin fixed tissues. JVDI (2000) 12 60-3]
*The subclinical form in sheep – intestinal lymphoid tissue or adjacent lamina propria.
*Numbers of organisms identifiable in macrophages seen in lesions with least CMI response.
*Caused by Mycobacterium avium subsp. paratuberculosis
*Faculative intracellular acid-fast bacillus
*Rule out Nocardia and Corynebacterium – also acid-fast.
*22% of the US dairy herds are infected.
*Infection can be cleared at the early stage, but if colonization takes place, and initial subclinical phase and then a chronic phase.
*Clinical signs – chronic diarrhea, progressive emaciation – diffuse granulomatous enteritis and lymphadenitis.
*Progression to clinical stages associated with reduced expression of IFNgamma at the site of infection.
*Infected at an early age, c/s not apparent until 2yrs+ old.
*Will shed the bacteria in the faeces before c/s apparent.
*Infection mediated by transport of bacteria across the Peyer’s patch by M cells and macrophages – transported inside macrophages
*CMI is mainly by αβ T cells including CD4+ T cells and CD8+ T cells.
*γδ T cells involved in protection of early infectious stage of disease of mycobacteria and other intracellular organisms
*Proliferation and activation of γδ T cells at the site of colonization is mediated by 70kd mycobacterial heat shock protein and cytokines.
*γδ T cells produce proinflammatory cytokines, activate immunoreactive macrophages, αβ T cells and NK cells.
*But much controversy of their protective role or whether they just recruit other inflammatory cells.
This study:
BALB/c mice are susceptible to M.paratuberculosis infection
γδ T cells KO mice produced fewer granulomas than controls and lower numbers of organisms in the spleen.
Therefore γδ T cells may be involved in granuloma formation
γδ T cells in bovines produce TH1 type of cytokines – IFNγ, TNFα and IL-2. May recruit macrophages via production of MCP-1.
TNFα and IFNγ act synergysticly to produce granulomas.
IL-2 induces proliferation of T cells, B cells, macrophages and NK cells, and enhances IFNγ and TNFα production from CD4+ T cells.
Bovines have relatively high proportion of γδ T cells in the GIT compared to man and mice.
[Reduced formation of granulomata in gamma-delta T cell knockout BALB/c mice inoculated with Mycobacterium avium subsp. Paratuberculosis. Tanaka S et al. Vet Path (2000) 37 415-21]
*Can use culture to detect the bacteria in pooled fecal samples from low-level infected herds – as sensitive as detection of Mycobacteria avium subsp. paratuberculosis from feces of an individual animal (about 70%)
[Culture of pooled bovine fecal samples as a method to screen herds for paratuberculosis. JVDI (2000) 12 547-51]
[Immunohistochemical detection of M.paraTB in formalin fixed tissues. JVDI (2000) 12 60-3]
*The subclinical form in sheep – intestinal lymphoid tissue or adjacent lamina propria.
*Numbers of organisms identifiable in macrophages seen in lesions with least CMI response.