Atkinson Lab Research

The complement system defends the host against microbes, being an integral part of the innate and adaptive immune response. It recognizes pathogens and mediates inflammation and instructs adaptive immunity by releasing small peptides that activate cells and by attaching large fragments to a target. The latter serve as opsonins to promote immune adherence and phagocytosis and antigen processing and to educate adaptive immune system.

Many human diseases are mediated by autoantibodies that form complement activating immune complexes which can damage cells and tissues if not properly regulated and disposed of. A more recently recognized function of the complement system is its interaction with altered self such as apoptotic and necrotic cells. Further, debris such as oxidized lipids (atherosclerosis), amyloid proteins (Alzheimer’s), lipofuscin pigments (age-related macular degeneration) and urate crystals (gout) may accumulate in man to cause much morbidity and mortality. Polymorphisms and heterozygous mutations in complement regulatory genes predispose mankind to these conditions which feature chronic inflammation.

To facilitate clinical-pathologic correlations, this laboratory has focused on characterizing a multigene family of receptor and regulatory proteins that regulate complement activation and serve as receptors for complement-coated antigens. Their structure-function relationships, cell signaling, disease associations and pathogen interactions are under investigation. Multiple pathogens, including viruses (measles, pox, adeno and flavi), bacteria (Neisseria, Streptococcus, E. coli) and parasites (malaria), abuse these proteins by employing them as a receptor for cellular attachment or as a regulator to protect themselves from complement attack. These complement regulatory proteins are also in clinical trials as therapeutic agents to thwart undesirable complement activation such as in autoimmune diseases.