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Imtiaz Khan Professor Dept. of Microbiology, Immunology and Tropical Medicine mtmixk@gwumc 994-2863

Imtiaz Khan Professor Dept. of Microbiology, Immunology and Tropical Medicine mtmixk@gwumc.edu 994-2863. Immune response against T.gondii. Innate Immunity Neutrophils (first line of defense). Direct killing of parasites. Dendritic cells (IL-12). NK cells ( IFN g release).

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Imtiaz Khan Professor Dept. of Microbiology, Immunology and Tropical Medicine mtmixk@gwumc 994-2863

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  1. Imtiaz KhanProfessorDept. of Microbiology, Immunology and Tropical Medicinemtmixk@gwumc.edu994-2863

  2. Immune response against T.gondii • Innate Immunity • Neutrophils (first line of defense). Direct killing of parasites. • Dendritic cells (IL-12). • NK cells ( IFNg release). • gd T cells??? (cytokines and CTL activity) • Adaptive Immunity • CD4+ T cells (major source of IFNg during acute infection). Provide help to CD8+ T cell effectors. • CD8+ T cells: Important effector cells (IFNg and CTL).

  3. 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.

  4. Microsporidia • Microsporidia are single celled, obligate intracellular parasites which infect a wide variety of hosts, including vertebrates and non-vertebrates. • 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.

  5. Immune response to Encephalitozoon cuniculi • Protective immunity against E. cuniculi is dependent on immune T cells . • SCID and athymic mice are highly susceptible to infection (Didier et al 1984, 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.

  6. 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)

  7. 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

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