Microbiology & Immunology | Faculty | Keith A. Krolick, Ph.D.
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Microbiology & Immunology Faculty

  Research | Publications | Lab Members


Keith A. Krolick, Ph.D.
Professor

Room 4.025V
Tel: (210) 567-3968
Fax: (210) 567-6612
Email: krolick@uthscsa.edu
 

Research

 

We have entered a new phase in our understanding of cellular and molecular mechanisms that result in immune responsiveness. The players have, for the most part, been identified..... the cells, and the factors that mediate their growth, differentiation, and intercellular interactions have come into clear focus. A challenge that we still face as we enter the next century is to sort through the network of cellular communication pathways that allows immune cells to distinguish between 'self' and 'non-self', a distinction that must be made in order to guarantee beneficial rather than detrimental immunity.

 

Autoimmunity (immunity against one's self) is the focal point of a variety of health problems, and is the central theme of studies performed in this laboratory. To understand autoimmunity is to understand a system of carefully placed biological 'filters' designed to eliminate self-reactive lymphocytes. For more than a decade, this laboratory has used numerous strategies for studying one particular autoimmune disease, myasthenia gravis (MG).

 

In MG, one of 40 or so muscle diseases classified as muscular dystrophy, antibodies produced against muscle by one's own immune system leads to muscle damage and impaired nerve-muscle communication. The symptoms of MG include weakness and rapid-onset fatigue. Extensive experimentation has led our laboratory to the conclusion that, contrary to what was once believed, the relationship between anti-muscle antibody production and disease induction is not simple. Although some anti-muscle antibodies can demonstrate binding to muscle resulting in impaired voluntary contraction, other anti-muscle antibodies can bind to muscle with no resulting effect on contractile function. From patient-to-patient, the severity of disease symptoms and the aggressiveness of disease progression reflect the proportions of these two antibody subsets. It is the identification and characterization of these antibody subsets, as well as of the immunoregulatory pathways that determine which of the antibody subsets dominate in any given patient, that make up some of the ongoing goals of this laboratory.

 

In addition to the pathological influences determined directly by the immune system, the focus of recently initiated studies in this laboratory involves monitoring the production of factors, originating from muscle, with the ability to either amplify or inhibit immune responses. It is very exciting to consider that the various pathological outcomes in MG patients may be based on the fact that the target tissue (i.e., muscle) is not just sitting there getting 'beat up' and that disease severity is not determined simply by the intensity of the immune response itself. Clearly, muscle has the capacity to produce factors that promote resistance to, and repair of, the damage done by the immune system and plays an active, not passive, role in determining disease outcome. Curiously, the stimuli that lead to the production of these muscle-derived factors often come from the stimulated immune system itself. Therefore, a circular communication path back to the immune system exists that determines the composite set and intensities of cells of the immune system that participate in subsequent rounds of immune responsiveness and muscle pathology. This rather complex picture, therefore, leads us to the latest theme of ongoing investigations in this laboratory, that of examining the spectrum of immunologically important molecules produced by muscle cells. From patient-to-patient, the composition of this spectrum may differ, thereby determining disease severity by dictating the nature of immune reactivities that are induced, and the degree to which muscle is damaged.


 

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Publications


 

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Lab Members

  Lab Rooms: 4.025V




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