Immunology Consultation & Research
Smoking and Pulmonary Immunity
Cigarette smoke causes profound changes in the pulmonary immunity, activating innate immunity and suppressing acquired immunity. ClinImmune Labs is actively researching the molecular mechanisms behind these phenomena. We have recently identified two classes of immunosuppressive compounds in cigarette smoke: Dihydroxyphenols found in the particulate phase and α, β-unsaturated aldehydes found in the gas phase. The phenols inhibit T cell proliferation by blocking cell cycle progression in late G1 and S phase. The aldehydes inhibit production of IL-2, IL-10, GM-CSF, IFN-γ and TNF-α by adducting the p50 subunit of NF-κB.
Stringer KA, Freed BM, Dunn JS, Ayers S, Gustafson DL, Flores SC. Particulate phase cigarette smoke increases MnSOD, NQO1 and Cinc-1 in rat lungs. Free Rad Biol Med 37:1527, 2004.
Dunn JS, Freed BM, Gustafson DL, Stringer KA. Inhibition of human neutrophil reactive oxygen species production and p67phox translocation by cigarette smoke extract. Atherosclerosis179:261, 2005.
Lambert C, McCue J, Portas M, Ouyang Y, Li J, Rosano TG, Lazis A, Freed BM. Acrolein in cigarette smoke inhibits T cell activation. J Allergy Clin Immunology 116:916, 2005.
Frazer-Abel A, McCue J, Lazis S, Portas M, Lambert C, Freed BM. Cigarette tar phenols impede T cell cycle progression by inhibiting cyclin-dependent kinases. Mol Immunol 44:488, 2007.
HLA Alleles and Autoimmunity
The HLA system is highly polymorphic and dictates immune responses to foreign organisms and transplanted tissues. In some cases, the HLA system triggers immune responses to self antigens, inducing a variety of autoimmune diseases. ClinImmune Labs is actively investigating the epitopes shared by disparate HLA alleles that trigger immune responses in different diseases.
Bill JR, Mack DG, Falta MT, Maier LA, Sullivan AK, Joslin FG, Martin AK, Freed BM, Kotzin BL, Fontenot AP. Beryllium presentation to CD4+ T cells is dependent on a single amino acid residue of the MHC class II β chain. J Immunology 175:7029, 2005.
Gibney EM, Cagle L, Freed B, Warnell SE, Chan L, Wiseman AC. Detection of donor-specific antibodies using HLA-coated microspheres: another tool for kidney transplant risk stratification. Nephrology Dialysis and Transplantation 21:2625, 2006.
Yang Y, Aubrey M, Zhang G, Ji Y, Freed BM. HLA-B*1586 is a novel hybrid HLA-H15/B22 allele with unique serology and haplotypic associations. Tissue Antigens 67:176, 2006.