CSB Faculty

 

Ellen Kraig, Ph.D.
Professor

 

Brandeis University, 1981

 

(210) 567-3818
KRAIG@UTHSCSA.EDU

 

Dr. Kraig is primarily involved in teaching graduate courses and is Co-Director of the Molecular Section of the Graduate Core Course. Dr. Kraig received the UTHSCSA Presidential Award for Teaching Excellence in 1996, the Dean's Award for Exceptional Graduate Teaching in 2000, and was elected to the UT Academy of Health Science Educators in 2006.

 

It has been well documented that immunosenescence is associated with increased susceptibility to infection and cancer as well as with diminished vaccine efficacy in older individuals. Moreover, potentially pathogenic autoimmune responses increase with age, while protective immune responses decline.

 

Our lab is currently focusing on the differential regulation of effector T cells and regulatory cells (Tregs) during aging in order to develop therapies that could potentially enhance immunity and decrease autoimmunity in the elderly. Several different systems are being used in mice, humans, and nonhuman primates, as summarized below.

• First, periodontal disease affects a majority of adults in this country. We are characterizing the interaction between the host and bacterial pathogens, including A. actinomycetemcomitans (Aa), the primary etiological agent of Localized Aggressive Periodontitis (LAP). We have used T-cell hybridoma technology to identify Aa antigens that dominate in orally infected mice; some of these also play a role in LAP patients. Currently, we are testing whether Treg depletion will enhance immune responses in old mice vaccinated with the T-cell antigen, omp34.

 

• Second, we recently demonstrated that old baboons immunized with LcrV, a protein antigen from Y. pestis, the plague bacterium, show unexpectedly vigorous antibody responses (Figure). We are now immunizing other nonhuman primate (NHP) species to determine whether baboon is unique in its ability to evade immunosenescence. These models will provide insights into appropriate NHPs to use in testing vaccines for immunizing elderly humans.

 

• Third, to address the effects of aging on autoimmunity, we have focused on myasthenia gravis (MG), a disease in which antibodies are produced to acetylcholine receptors (AChRs) at the neuromuscular junctions. For many MG patients (40-60%), disease onset occurs after the age of 40. Given that the thymus involutes with aging, we hypothesize that immune dysregulation associated with the loss of thymic controls may play a role in late onset MG and in other autoimmune disorders seen in the elderly. In order to address these questions, we generated a transgenic mouse expressing the T(torpedo)-AChR alpha chain at the neuromuscular junction. These mice develop T cell tolerance which is dependent on Tregs. With this new model, we are asking whether aging and environmental factors might affect tolerance and/or disease.

PUBLICATIONS:
Stacy S, Pasquali A, Sexton VL, Cantwell AM, Kraig E, Dube PH. (2008) An age-old paradigm challenged: old baboons generate vigorous humoral immune responses to LcrV, a plague antigen. J Immunol. 2008 Jul 1;181(1):109-15.

 

Standifer NE, Stacy S, Kraig E, Infante AJ. (2007) Discrete T cell populations with specificity for a neo-self-antigen bear distinct imprints of tolerance. J Immunol. 2007 Mar 15;178(6):3544-50.

 

Stacy S, Infante AJ, Wall KA, Krolick K, Kraig E. (2003) Recall immune memory: a new tool for generating late onset autoimmune myasthenia gravis. Mech Ageing Dev. 2003 Aug-Sep;124(8-9):931-40.

 

Stacy S, Gelb BE, Koop BA, Windle JJ, Wall KA, Krolick KA, Infante AJ, Kraig E. (2002) Split tolerance in a novel transgenic model of autoimmune myasthenia gravis. J Immunol. 2002 Dec 1;169(11):6570-9.

 

 

 

Effects of age on the antibody response to LcrV in baboons and mice. (These data have been published in Journal of Immunology 181:109-115)