immunoglobulin immunoglobulin two such molecules. In an infection, immunoglobulins usually appear in the order of IgM, IgG, and IgA. B cells first begin to produce IgM, and then some B cells undergo an irreversible switch to those that produce IgG. Later some of this population of cells undergo a switch to become IgA-secreting type B cells. Immunoglobulins persist for varying times; for example, the half-life of particular IgM antibodies is 5 days, while that of IgG can be as long as 21-23 days (Table 14.1).46
Similar to a live microbe, vaccines can also provoke an antibody response. The vaccine can be composed of a live or attenuated microbe, a whole non-proliferating microbe, or an antigenic part of the microbe. Regardless, the intent of the vaccine is to produce protection, often by protective antibodies. Although the half-life of an individual IgG molecule is less than a month, a population of antibodies in the IgG isotype form may persist for life. Memory B cells can sustain these antibodies and retain the ability to quickly generate the appropriate antibodies when challenged. When the immune system encounters another infection or is subjected to a revaccination (booster), the result is an accelerated production of the particular antibody and increase in the levels that circulate in the blood. Figure 14.1 illustrates this.
Perhaps the most discernible pattern of antibody response which has forensic value is the appearance of IgM first, followed by a B-cell switch to the longer lasting IgG. During the early phase of exposure, IgM can be seen first. As time goes on, IgG is seen and predominates, and IgM is no longer found. This is illustrated in Figure 14.2.
The antibody response to a particular agent may be directed to different antigens at different times, that is, early or later after the initial exposure. That response may involve IgM at the early stage and IgG later. Late in the disease or during recovery, only IgG to particular antigens may be seen. A classic example is the human antibody response to Epstein Barr virus (EBV).7 EBV is the virus known to cause mononucleosis. During acute early disease, it is common to find high levels of antibody of the IgM isotype to the viral early
antigen (EA) and viral capsid antigen (VCA). It is rare to find IgG antibody to the VCA or Epstein Barr Nuclear Acid (EBNA) in anything but low titers. As the patient recovers from their first infection with EBV, it is rare to find anything but low levels of IgM to EA or VCA, but IgG to VCA in higher or increasing levels is common. Antibodies to EBNA are often very low during this stage. Then after clinical recovery, that is, several months later, IgM to EA and VCA stay at low levels whereas IgG to VCA and EBNA remain at high levels, often for years. Table 14.3 illustrates this pattern by stage of the immune response to EBV and its particular antigens. Figure 14.3 is a graphic display of this. For the clinician or epidemiologist this provides a framework to determine where in the infectious process a patient may be. Tables 14.2 and 14.3 and Figures 14.2 and 14.3 illustrate how responses to a biothreat agent or its toxin may be used to give some chronological indication of exposure. Combining the antibody response with detection of particular antigens can provide further definition as to the stage of infection or exposure.
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