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Immune Relevancy (So What?) As related to Pathogenesis, Diagnosis and Vaccine Efficacy. Response correlates to disease or protection? Ag-dependent. Response correlates to disease or protection? Ag-dependent. Environmental mycobacteria, helminths, genetics, age, …. Vaccination.
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Immune Relevancy (So What?) As related to Pathogenesis, Diagnosis and Vaccine Efficacy Response correlates to disease or protection? Ag-dependent Response correlates to disease or protection? Ag-dependent Environmental mycobacteria, helminths, genetics, age, … Vaccination M. bovis challenge Necropsy Environmental mycobacteria, helminths, genetics, age, … Response correlates to disease or protection? Ag-dependent M. bovis challenge Necropsy
Effector Responses - Positive Correlation to Infection IFN-, ng/ml M. bovis PPD rESAT-6:CFP10 Central Memory Responses Prior to Challenge IFN- BCG RD1 Non-vaccinated Central Memory Responses - Positive Correlation to Protection Spearman r = -0.8195 (p <0.0001) IFN- IFN- > 7 < 7 Cumulative Pathology Score
Activation Associated Events • Recall Responses to PPD or RD1 antigens, • After Challenge • Protected versus Non-protected • (BCG- or RD1-vaccinates) versus (non- and/or mc26030-vaccinates): • Decreased Antigen-Specific Response (mRNA) • (IFN-, iNOS, IL-4, IL-5, MIP1-) • Diminished Activation Phenotype, mfi or % • (CD25, CD44, MHCII, CD80/86 and CD62L) • Decreased Antigen Specific Proliferation • primarily w/ CD4 subset • No effect on skin test - vaccines elicit a response to PPD’s
+Ag, +IL-2, 12-14 days Cultured: Central memory ‘CM’: +Ag, +APC, 24 h Cultured ELISPOTs: a method to assess memory T cells PBMC: EM CM ‘ex vivo’: effector and effector memory T cells