Complement activation, antibody effects

The anti-inflammatory and immunosuppressive effects of glucocorticoids are largely due to the actions described above. In humans, complement activation is unaltered, but its effects are inhibited. Antibody production can be reduced by large doses of steroids, although it is unaffected by moderate doses (eg, 20 mg/d of prednisone). 

The complement system consists of about 20 interacting soluble proteins that circulate in the blood and extracellular fluid. Immunoglobulin molecules bound to the surface of the microorganisms activate Cl, the first component of the complement pathway. The activation occurs through the Fc portion (see Topic D2) of the bound antibody. Only bound antibody can activate complement, soluble antibody not bound to an antigen has no such effect. 

This pathway of complement activation, which starts when antibody has bound to antigen on the microbe surface, is called the classical pathway. An alternative pathway of activation also exists which is activated directly by polysaccharides in the cell wall of microorganisms even in the absence of antibody. The alternative pathway therefore defends the body against attack in the early stages before an immune response can occur and also augments the effects of the classical pathway of complement activation when the immune response has occurred. 

Finally, other factors but the onconeural antibodies may predispose an individual to neuronal damage or contribute to inflammation. We have reported lack of expression of the complement regulator protein CD59 on the surface of Purkinje cells in individuals with PCD, indicating vulnerability to the effects of complement activation [202]. Complement depositis have been found in the brain stem of a patient with paraneoplastic OM [80], Others have found absent or weak complement deposition in postmortem studies of the brain of PEM/SN patients [41, 203, 204], suggesting that... 

Finally, atorvastatin effects were also examined on a class of proteins known to be involved in plaque generation and complement activation, the pentraxins. The pentraxins are acute phase proteins best exemplified by the short variants, C reactive protein and serum amyloid P [113,164]. Both are known to be closely associated with senile plaques in the brain of AD patients [113,164]. Pentraxin expression is stimulated by local inflammatory events and pentraxins are known to activate the classical complement cascade through an antibody independent mechanism [113]. Expression analysis suggest pyramidal neurons can produce amyloid P [164]. Amyloid P is highly resistant to proteolysis and binding of serum amyloid P to proteins, like AP, can protect peptides from subsequent degradation. Indeed, it is possible that serum amyloid P provides the seed for plaque formation. 

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