PhD defence A. (Albert) Dunbar

Summary:

The immune system is a complex and multifaceted system. It consists of several defence mechanisms that protect the body against a wide range of microbial threats from the outside world. If, in a patient, the defence mechanisms are less well function, we speak of an immunocompromised patient. This includes both patients who are born with a weakened immune system (primary immune deficiency), as well as patients who acquired develop a disease during their lifetime (e.g. leukaemia) that affects the immune system (acquired immunodeficiency) and patients who, as a result of treatment with immune suppressive drugs have a weakened immune system. In recent decades, a large number of drugs that suppress the immune system to a lesser or greater extent have come into use but still the long-established corticosteroids are the most widely used. Corticosteroids have various effects on the immune system; they inhibit inflammation and in high doses they inhibit white blood cell function and production. The number of patients with weakened immune system has increased dramatically in recent decades. This is due to a longer
life expectancy, improvement in the treatment of malignancies and autoimmune diseases. In addition more stem cell and organ transplants are taking place that require immune-modulating agents are needed. Immune-compromised patients are also more susceptible to infections that under normal conditions are not pathogenic and which we call 'opportunistic infections'. These infections can be caused by fungi, bacteria, viruses and parasites. Antibiotics, antiviral
drugs and antimycotics have been developed to prevent and/or treat these infections. Some of these infections can be prevented by preventive use of these drugs. When an opportunistic infection occurs, it is crucial that it is detected in time and the treatment is started promptly. This thesis describes a number of studies on prevention, diagnosis and treatment of opportunistic infections in patients with weakened immune systems.