@article{Adaptability:2308,
      recid = {2308},
      author = {Costa Vieira, Marcos},
      title = {Evolution of Adaptability and the Immune Response to  Influenza and HIV},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2020-06},
      pages = {201},
      abstract = {The ability of populations to adapt depends on a complex  suite of traits including mutation and recombination rates  and functional constraints on genes subject to selection.  How much selection can act on these traits to promote  adaptability remains an open question. This dissertation  investigates the ultimate example of evolved adaptability,  the adaptive immune system of jawed vertebrates. Adaptive  immunity has been selected in jawed vertebrates to  recognize pathogens through recombination, mutation and  selection in populations of B cells rapidly evolving during  the immune response within an individual. This short- term  adaptability is enabled by the diversity of immunoglobulin  genes that recombine to produce B cell receptors and by the  receptors’ mutation rate during the immune response,  features that have been shaped by selection in vertebrate  populations over hundreds of millions of years. We explore  how these features contribute to the adaptability of the  immune response through computational and statistical  analyses of the response to influenza and HIV. We ask if  despite possible epistatic interactions among recombining  immunoglobulin genes, specificity for particular pathogens  is associated with individual genes. We find that influenza  infection in mice selects for B cell receptors using  specific immunoglobulin genes during the immune response,  suggesting that selection of immunoglobulin genes in the  long term could lead to their specialization for particular  pathogens. Because the adaptability of B cells depends on  mutations that change affinity for the antigen, we also  investigate the short-term evolution of mutational hotspots  in B cell receptor sequences. While the long-term evolution  of immunoglobulin genes led to an abundance of hotspots in  the antingen-binding loops of the receptor, we find that  selection and neutral mutations disrupt those hotspots over  years of coevolution between B cells and HIV, a loss of  mutability that might limit the adaptability of B cell  responses to chronic or repeated infections. Finally, we  investigate how immunity arises from infection history and  how the resulting protection shapes the ecology of  influenza virus lineages. We conclude by proposing ways to  integrate life-history and ecology into the

study of the  adaptability and specialization of immunity.},
      url = {http://knowledge.uchicago.edu/record/2308},
      doi = {https://doi.org/10.6082/uchicago.2308},
}