Importance of use of mycobacterial cells in freunds complete adjuvent
Answers
Answered by
2
Adjuvant- and pristane-induced arthritis
Incomplete Freund adjuvant, which lacks mycobacteria, and the mineral oil pristane, can induce arthritis in susceptible rats and mice, evidence that oil can override natural tolerance.7 The arthritogenic consequences appear to ultimately depend on a reaction against either exogenous or autologous antigens. Heat shock proteins may be regulators in AA.8 A hypothetic mechanism for the development of AA and pristane-induced arthritis is shown in Figure 90.2. In susceptible strains of animals, macrophages phagocytose nondegradable oil components, become intensely activated, and produce large concentrations of proinflammatory cytokines (IL-1, IL-6, TNF, and IFN-γ). This cytokine-rich environment activates T and B cells. The results of polyclonal activation are apparent in pristane-induced arthritis, in which lymphadenopathy and hypergammaglobulinemia precede the onset of disease.
Expansion of autoreactive T- and B-cell populations can occur as a consequence of the adjuvant activation process and result in the migration of cells to the joint and subsequent immune-mediated joint damage and production of a spectrum of autoantibodies against cartilage antigens. Disease onset is rapid in AA (2 weeks), often followed by spontaneous remission. Pristane-induced arthritis is slower (months) and characterized by remissions and relapses, with no indication of B-cell involvement at the onset. The pristane model is highly suited to studying genes controlling onset, severity, and chronicity.9 The spontaneous remission and lack of susceptibility to reinduction make AA a suitable model for studies on the regulation of T-cell tolerance. Histopathologic study of AA shows major involvement of bone marrow, bone erosion, extensive bone apposition, and minor direct cartilage damage in the early stages (Table 90.1).2-4,6,7,10-24 Indirect cartilage damage occurs later, mainly as a consequence of the loss of underlying bone. The latter may explain the cartilage-protective effect of treatment with osteoprotegerin (OPG), which is a selective inhibitor of the osteoclast activator RANKL (receptor activator of nuclear factor κB ligand).10,25Combined blocking of TNF and IL-1 is associated with optimal control of arthritis and joint destruction.
Incomplete Freund adjuvant, which lacks mycobacteria, and the mineral oil pristane, can induce arthritis in susceptible rats and mice, evidence that oil can override natural tolerance.7 The arthritogenic consequences appear to ultimately depend on a reaction against either exogenous or autologous antigens. Heat shock proteins may be regulators in AA.8 A hypothetic mechanism for the development of AA and pristane-induced arthritis is shown in Figure 90.2. In susceptible strains of animals, macrophages phagocytose nondegradable oil components, become intensely activated, and produce large concentrations of proinflammatory cytokines (IL-1, IL-6, TNF, and IFN-γ). This cytokine-rich environment activates T and B cells. The results of polyclonal activation are apparent in pristane-induced arthritis, in which lymphadenopathy and hypergammaglobulinemia precede the onset of disease.
Expansion of autoreactive T- and B-cell populations can occur as a consequence of the adjuvant activation process and result in the migration of cells to the joint and subsequent immune-mediated joint damage and production of a spectrum of autoantibodies against cartilage antigens. Disease onset is rapid in AA (2 weeks), often followed by spontaneous remission. Pristane-induced arthritis is slower (months) and characterized by remissions and relapses, with no indication of B-cell involvement at the onset. The pristane model is highly suited to studying genes controlling onset, severity, and chronicity.9 The spontaneous remission and lack of susceptibility to reinduction make AA a suitable model for studies on the regulation of T-cell tolerance. Histopathologic study of AA shows major involvement of bone marrow, bone erosion, extensive bone apposition, and minor direct cartilage damage in the early stages (Table 90.1).2-4,6,7,10-24 Indirect cartilage damage occurs later, mainly as a consequence of the loss of underlying bone. The latter may explain the cartilage-protective effect of treatment with osteoprotegerin (OPG), which is a selective inhibitor of the osteoclast activator RANKL (receptor activator of nuclear factor κB ligand).10,25Combined blocking of TNF and IL-1 is associated with optimal control of arthritis and joint destruction.
Similar questions