Diseases have been part of human life for generations and evolve within the population, sometimes dying out while other times becoming endemic or the cause of recurrent outbreaks. Co-infection with different pathogens is common, yet little is known about how infection with one pathogen affects the host’s immunological response to another. Immunology-based models of malaria and tuberculosis (TB) are constructed by extending and modifying existing mathematical models in the literature. The two are then combined to give a single nine-variable model of co-infection with malaria and TB. The immunology-based models of malaria and TB give numerical results that agree with the biological observations. The malaria–TB co-infection model gives reasonable results and these suggest that the order in which the two diseases are introduced have an impact on the behavior of both.