Imtiaz Khan Professor Dept. of Microbiology, Immunology and Tropical Medicine

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

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.

Intra epithelial lymphocytes first line of defense against pathogens - important role in protective immunity against mucosal pathogens: Toxoplasma gondii (IFN  ) Cryptosporidium muris (IFN  ) 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