The immune response to Togaviridae is characteristic of the classical immune response to a foreign antigen. There are two major pathways by which the virus is cleared from the system: neutralization of circulating virus (humoral) and elimination of infected cells (cell-mediated).
Circulating virus in the blood is randomly engulfed by a macrophage, which digests the virus and presents the viral antigens on its cell membrane as a complex between a major histocompatability complex (HPC) and antigen. The major antigens dispalyed by togaviridae are the envelope proteins. These are also responsible for the specificity of tissue tropism of the virus. This combination is recognized by CD4 lymphocytes, which proliferate and release lymphokines to initiate an inflamatory response. The lymphocytes secrete another lymokine that stimulate the clonal selection of B cells, which differentiate into antibody secreting plasma cells. Circulating antibody binds to, and neutralizes circulating viruses, eliminating the virus from the blood.
Infected cells, as recognized by the presentation of viral antigens in their cell membranes, are recognized by cytotoxic T cells and targetted for destruction. Cytotoxic T-cells secrete perforin into the infected cell membrane, increasing the permeability of the cell, which leads to cell death and termination of viral replication. NK cells can also lyse infected cells, but their specificity is not fully understood.
The two above pathways are quite adept at handling Togaviruses in adult man. Encephalitic alphavirinae have evolved to avoid the immune system through infection of the brain, where little immune activity is present. Because of the reduced encephalitic immune response, the case-fatality rates associated with encephalitic alphavirinae is substantial (10-70%).
Rubivirinae is handled by the adult immune system quite efficiently. Rarely does the virus establish any form of major infection, exhibiting a mortality rate of 0.05%. Once infected, the immune system quickly desposes of the virus and sets up a life-long immunity. The human fetus, however, does not have a mature immune system to combat rubivirinae. Capable of crossing the placenta, rubella is attenuated only by the maternal IgG present in the fetus' blood. Because the level of the immunity is so low in the first trimester fetus, the virus is usually able to set up a succesful infection, resulting in extreme pathogenesis. Teratogenic consequences of maternal rubella infections are not observed in the second and third trimesters because the fetus has developed a slightly more robust immune system, capable of dealing with the rubella onslaught.