Other observations point towards an immune complex (ICX) pathogenesis. Deposition of ICX and subsequent complement activation is thought to cause an intense inflammatory response that may extend across blood vessel walls. The resulting vascular damage would permit leakage of fluid into the intercellular space and eventually lead to the accumulation of thoracic and abdominal exudate. The morphologic features of the vascular lesions (necrosis, polymorphonuclear cell infiltration associated with small veins and venules) strongly indicate an Arthus type reaction. The lesions contain focal deposits of virus, IgG and C3. Moreover, complement depletion and circulating ICX were demonstrated in cats with terminal FIP. In a horizontal study of experimentally infected cats, first clinical signs were accompanied by increased C3 concentrations in the plasma; subsequently antibody titres and circulating ICX increased with a concomitant decrease of complement concentrations. At the time of death, maximum ICX and minimum C3 concentrations were measured.

Although FIP viruses do not infect T-cells, depletion and programmed cell death (apoptosis) was observed in lymphoid organs of infected cats. Apoptosis was mediated by the ICX present in the serum and ascitic fluid of diseased cats and affected only activated T-cells, including lymph node cells, but not unstimulated T-cells. This hitherto unrecognised mechanism of T-cell suppression may operate not only in FIPV infection but also in other ICX diseases [5].

The fatal scenario thus may be as follows: a kitten is born, suckled by its seropositive queen and protected by colostral antibody from infection during the first few weeks. As the maternal antibodies wane, mucosal protection ebbs away and during an episode of maternal FCoV shedding the kitten is infected. A bout of diarrhoea and an occasional sneezing may be the only signs this has happened. It now develops an active immunity, but not a sterilizing one in most cases: virus and antibodies continue to co-exist in the kitten's organism, and an efficient cell-mediated immunity keeps infected macrophages and monocytes in check. In a small, socially stable cat community this animal can live happily ever after.

Problems emerge when our kitten is experiencing any situation of stress, which we want to equate with immune suppression. Infection with the feline leukaemia or immunodeficiency viruses would be the most unmistakable immunosuppressive event, but density (numbers of cats per surface unit), geographic change (displacement into a new environment) and other territorial factors (e.g. change in group hierarchy, dominance) are becoming more and more important - in view of the declining prevalence of retrovirus infections. The failing immune surveillance allows the coronaviral quasispecies cloud of mutants to expand, and more macrophage-tropic mutants emerge in this stochastic process. Amongst them are some that reach high titres and outcrowd the moderate ones. This is the point when immune pathogenesis starts.

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