The primary focus of my laboratories research has been the innate immune response to HIV in the female genital tract. Specifically, we study antibodies that initiate antibody dependent cell-mediated cytoxicity (ADCC). These antibodies bind in an antigen specific way to the HIV envelope glycoprotein and the Fc region of the antibody bind to the Fc receptor on an innate immune effector cell. The innate immune effector cell is usually a natural killer cell (NK) or a monocyte and it responds by either releasing cytokines or by directly killing the cell that is recognized by the antigen specific arms of the antibody.
Our work
We study ADCC antibodies in the genital tracts of interesting groups of women. Some of these groups include the following:
- Women who either have a high number of sexual partners and do not regularly use protection, highly exposed seronegative women (ESN)
- Individuals who are infected but control viral load, Elite Controllers (EC)
- Women who were being studies as part of a prospective study of HIV who became HIV infected while part of the study, Seroconverters (SC)
Each of these groups of women provides information that contributes to a better understanding of the protective immune response against HIV. Although we have studied ADCC for many years, its importance in host defense against HIV has gained recognition since the Thai vaccine trial known as RV144. Approximately 16,000 low-risk individuals were enrolled in this study; it is the only HIV vaccine trial to date to have any efficacy. Although protection was lower than we would like, around 30 percent of the vaccinated group was protected from natural infection compared to the placebo group. Interestingly, the two major arms of the immune response thought to protect against HIV, cytotoxic T cells (CTL) and neutralizing antibodies, were not responsible for the protection observed in this trial. Subsequent studies revealed that serum IgG antibodies that mediate ADCC against HIV envelope glycoproteins demonstrated significant protection in individuals who did not have HIV specific IgA in their serum. The story is still evolving. IgA is normally an antibody that is protective at mucosal sites, not in the serum. It is usually present as a monomer in the serum and a dimer or trimer in mucosal fluids. Our most recent focus has been to look for mucosal IgA against HIV in genital fluids of these interesting groups of women and measure its ability to mediate ADCC.
Technology
IgA ADCC uses a different Fc receptor and a different innate effector cell than IgG mediated ADCC. Monocytes also require a longer time to kill virus-infected cells than NK cells do. Because of this, it was necessary for us to adapt the assay for IgG mediated ADCC so that we could visualize the activity of mucosal IgA antibodies in ADCC. We use magnetic beads to negatively select CD14+ monocytes from the blood of a healthy individual and incubate these cells with cervical lavage fluid from our subjects. Target cells are then added and killing is measured using one of two standard assays for killing; CD107a expression on the surface of activated effector cells which is measured using flow cytometry or release of 51Cr from target cells.
Funding
Baum has currently taken on the responsibility of directorship of the Integrated Biomedical Sciences graduate program at Rush University Medical Center. Continuation of these studies will occur in collaboration with Mariam Aziz, MD, and is contingent upon their ability to secure NIH funding.
Our team
- Linda Baum, PhD, professor of immunology and microbiology
- Mariam Aziz, MD, associate professor of infectious diseases
- Mariana Mata, research associate
Contact us
Linda Baum, PhD
Professor
Program Director for the Integrated Biomedical Sciences Graduate Program
Rush University
Department of Internal Medicine
Cohn Building
1735 W. Harrison St., Room 314
Chicago, IL 60612
Phone: (312) 942-2881