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Imtiaz Khan Professor Dept. of Microbiology, Immunology and Tropical Medicine [email protected] 994-2863 Immune response against T.gondii • Innate Immunity • Adaptive Immunity • Neutrophils (first line of defense). Direct killing of parasites. • CD4+ T cells (major source of IFNg during acute infection). Provide help to CD8+ T cell effectors. • Dendritic cells (IL-12). • NK cells ( IFNg release). • gd T cells??? (cytokines and CTL activity) • CD8+ T cells: Important effector cells (IFNg and CTL). Projects • Population of dendritic cells responsible for initiation of CD8+ T cell response in the gut • Is NK-DC interaction critical for induction of robust CD8+ T cell immunity • Can long term central memory CD8+ T cell response be generated • What is the role of cytokines like IL-7 and IL-15 in the generation and maintenance of CD8+ T cell immunity in the gut and brain. Microsporidia • Microsporidia are single celled, obligate intracellular parasites which infect a wide variety of hosts, including vertebrates and nonvertebrates. • Enterocytozoon bieneusi, the most common microsporidian identified in humans cannot be grown in tissue culture. • Studies related to mammalian Microsporidia most often have utilized Encephalitozoon cuniculi because of its ability to infect laboratory animals and to grow in long-term tissue culture. Immune response to Encephalitozoon cuniculi • Protective immunity against E. cuniculi is dependent on immune T cells . • SCID and athymic mice are highly Hermanek et al 1993). • Adoptive transfer of immune T cells to SCID mice protects against a lethal challenge. • CD4-/- mice can withstand E.cuniculi infection . However, mice lacking CD8+ T cells are highly susceptible (Khan et al J. Immunol. 1999, Moretto et al J. Immunol 2001). • CD8+ T cells are critical for protection against intraperitoneal E. cuniculi infection. susceptible to infection (Didier et al 1984, Intra epithelial lymphocytes first line of defense against pathogens - important role in protective immunity against mucosal pathogens: Toxoplasma gondii (IFNg) Cryptosporidium muris (IFNg) Rotavirus (cytotoxicity) Research focus • Mechanism involved in the priming of IEL response • TLRs involved in this response • Trafficking of IELs • Immune response to the parasite in aged animals