The integrity of all organisms to injury is conserved through intricate mechanisms of response, but none more so than the immune system of the mammals. The complexity and potency of these mechanisms make them both difficult and intriguing to dissect, but more importantly, the study of the immune system can be of benefit both
therapeutically and diagnostically in a range of human diseases. While much have been learnt by studying how the immune system works in both immune and nonimmune diseases in humans and animals, the study of human immunodeficiencies gives an unique opportunity to study the consequences of an immune system inept to work. In this thesis I will present the work done by my colleagues and myself on
innate, inflammatory and regulatory immune mechanisms in Common variable immunodeficiency (CVID), an immunodeficiency named more in keeping with the usual definition of "variable" than "common", but with manifestations highlighting important principles of our current understanding of the immune system. In this introduction I will first briefly outline the normal human immune response before exploring parts of particular interest to my thesis. Thereafter, I will give a brief overview over human immunodeficiencies before examining the particular features of CVID in depth.
LIST OF PAPERS
I. Fevang B, Mollnes TE, Holm AM, Ueland T, Heggelund L, Damås JK, Aukrust P, Frøland SS. Common variable immunodeficiency and the complement system; low mannose-binding lectin levels are associated with bronchiectasis. Clin Exp Immunol 2005 Dec;142(3):576-84. doi:10.1111/j.1365-2249.2005.02951.x
II. Fevang B, Eugen-Olsen J, Yndestad A, Brosstad F, Beiske K, Aukrust P, Frøland SS. Enhanced levels of urokinase plasminogen activator and its soluble receptor in common variable immunodeficiency. Clin Immunol 2009. In press. doi:10.1016/j.clim.2009.01.007
III. Fevang B, Yndestad A, Damås JK, Bjerkeli V, Ueland T, Holm AM, Beiske K, Aukrust P, Frøland SS. Chemokines and common variable immunodeficiency; possible contribution of the fractalkine system (CX3CL1/CX3CR1) to chronic inflammation. Clin Immunol 2009 130, 151-161. doi:10.1016/j.clim.2008.09.002
IV. Fevang B, Yndestad A, Damås JK, Halvorsen B, Holm AM, Beiske K, Aukrust P, Frøland SS. Chemokines and common variable immunodeficiency; possible contribution of CCL19, CCL21 and CCR7 to immune dysregulation. Submitted.
V. Fevang B, Yndestad A, Sandberg WJ, Holm AM, Müller F, Aukrust P, Frøland SS. Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo. Clin Exp Immunol 2007 Mar;147(3):521-5. doi:10.1111/j.1365-2249.2006.03314.x