Page 925 - Veterinary Immunology, 10th Edition
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                             FIG. 28.5  A diagram showing how repeated antigenic variation
                                 accounts for the cyclical parasitemia observed in African
                           trypanosomiasis. Each peak represents the growth and destruction
                                               of a new antigenic variant.


                  The major antigens of these trypanosomes are known as variant
               surface glycoproteins (VSGs). The VSGs form a thick coat on the
               surface of the trypanosome that hides other cell surface antigens.

               VSGs are therefore targeted by host antibodies. As previous VSGs
               are recognized by the immune system and the organisms
               destroyed, new VSGs emerge giving rise to waves of parasitemia.
               The VSGs produced early in trypanosome infections tend to

               develop in a predictable sequence. However, as the infection
               progresses, the production of VSGs becomes more random. When
               antigenic change occurs, the VSGs in the old coat are shed and
               replaced by a different VSG. These trypanosomes possess about

               2000 VSG genes, with an additional 1600 silent genes, of which two-
               thirds are pseudogenes. Antigenic variation occurs as a result of
               repeated DNA breaking and repair, replacing an active VSG gene
               with one from the silent gene pool. Each parasite expresses one

               VSG at a time. Since only a small part of the tightly packed VSG is
               exposed to host antibodies, it is not even necessary for the complete
               molecule to change. Replacement of exposed epitopes by gene
               conversion is sufficient for effective variation (Chapter 17). Early in

               infections, complete VSG gene replacement occurs. Later on, partial
               replacement and point mutations can create new antigenic
               specificities. In some cases, the expressed VSG gene can be a mosaic
               derived from several archival pseudogenes. The potential for

               recombination-based variation is therefore absolutely enormous.





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