Avian pathogenic Escherichia coli (APEC) are a group of bacteria that cause a variety of diseases in birds. Broiler chickens were challenged with APEC to observe the RNA expression changes in genes involved in the immune response to these bacteria. This study focuses on the bursa of Fabricius, a primary lymphoid tissue that functions to facilitate B cell maturation in chickens. B cells play an important role in the immune response to infection, primarily by antibody production. Some Toll like receptor (TLR) and cluster of differentiation (CD) molecules are expressed on the surface of B cells and are involved in the immune response to infection. We hypothesize expression of these genes to be related to the immune response to APEC. The relative RNA levels of TLR21, TLR15, TLR5, TLR2, CD40, and CD38 were analyzed in the bursa of chickens that were challenged and not challenged with APEC. Vaccination and mock vaccination with increased serum survival protein (Iss) was administered to both groups. We hypothesize these TLR and CD genes in the bursa will have differential RNA expression in broilers challenged with APEC compared to broilers who were not challenged. We found TLR15 to have significant differential RNA levels in the bursa of broilers challenged with APEC compared to broilers that were not challenged. No other genes in this experiment were differentially expressed in any of the other groups. For the first time TLR15 RNA expression was found to be increased in response to APEC challenge in the bursa of broilers.