Many functionally important interactions between genes and proteins involved in immunological diseases and processes are unknown. The exponential growth in public high-throughput data offers an opportunity to expand this knowledge. To unlock human-immunology-relevant insight contained in the global biomedical research effort, including all public high-throughput datasets, we performed immunological-pathway-focused Bayesian integration of a comprehensive, heterogeneous compendium comprising 38,088 genome-scale experiments. The distillation of this knowledge into immunological networks of functional relationships between molecular entities (ImmuNet), and tools to mine this resource, are accessible to the public at http://immunet.princeton.edu. The predictive capacity of ImmuNet, established by rigorous statistical validation, is easily accessed by experimentalists to generate data-driven hypotheses. We demonstrate the power of this approach through the identification of unique host-virus interaction responses, and we show how ImmuNet complements genetic studies by predicting disease-associated genes. ImmuNet should be widely beneficial for investigating the mechanisms of the human immune system and immunological diseases. Display omitted •Interactive web-accessible immunology resource leverages 38,088 experiments•Powerful computational methods generate big-data-driven hypotheses for immunology•Predicts new immune pathway interactions, mechanisms, and disease-associated genes•Flexible, user-friendly platform addresses diverse immunological research questions The large amount of publically available high-throughput data contains, in aggregate, a vast amount of immunologically relevant insight. Sealfon and colleagues report ImmuNet, a web-accessible public resource based on 38,088 experiments that allows researchers to predict gene-gene relationships relevant to the human immune system and immunological diseases.