Transcript Document

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