Infectious bursal disease (IBD) is caused by infectious bursal disease virus (IBDV), a non-enveloped, double-stranded ribonucleic acid virus in the family Birnaviridae. IBDV causes severe immunosuppression with significant economic losses due to poor vaccination responses and subsequent secondary infections. Major histocompatibility complex (MHC) based host genetic resistance has been described against several infectious agents, however the impact of the MHC on host resistance to IBDV has been minimally investigated and is poorly understood. The objectives of the experiments detailed in chapters three and four were to determine if the pathotype of IBDV and the MHC haplotype of the chicken affected the development of IBD, and to characterize the phenotype of infiltrating immune cells in the bursa of Fabricius after challenge with IBDV strains of different pathotypes in chicken lines previously categorized as IBD resistant or susceptible, respectively. B-congenic lines of chickens, which are genetically identical except for their MHC genes, and two lines of chickens with similar B haplotype but differing non-MHC genes, were used in the experiments. The results demonstrated that both the B haplotype of the chicken and the pathotype of IBDV significantly impact the development ofIBD. Significant differences in survival between the chicken lines occurred post-challenge with very virulent (vv) or classical IBDV strains, with the chicken line B*19 continually having the poorest survivability. Similar immune cells infiltrated the bursa of Fabricius post-challenge with classical or vvIBDV strains, but differences in the timing and rate of induction were noted. Two previously undescribed populations of B cells were identified in the bursa of Fabricius which differ in their expression of Bu1 and IgM, and in their response to IBDV infection. Additionally, the IBD susceptible chicken line B*19 had higher concentrations of serum IL-6 compared to the B*21 resistant chicken line after vvIBDV challenge. Collectively, this study demonstrated that both the MHC genes of the host and the pathotype of the IBDV are significant in determining host resistance to IBD, and that the degree of systemic proinflammatory cytokine release as well as the timing of B cell depletion in the bursa of Fabricius may be related to survival post-vvIBDV challenge.