Thapa, Navin; (2000) Immune parameters in mycobacterioses, other immune disorders and the effects of immunotherapy. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Human anti-mycobacterial immunity is largely successful as more than 90% of people infected with M. tuberculosis remain healthy. Interactions with environmental and pathogenic mycobacteria are believed to be responsible for priming favourable or unfavourable immune responses, respectively. The immune dysfunction in mycobacterioses was investigated by comparing different immune parameters in healthy people and tuberculosis patients. TB patients showed different proliferation and cytokine responses to sonicated mycobacterial antigens. Flow-cytometric analysis confirmed that the lymphocytes of TB patients showed phenotypic as well as functional changes in their properties. Detection of intracellular cytokines showed increased IL-4 but reduced IL-2 and IFN-gamma production by CD4 T cells of TB patients. This confirmed a switch from a Th1 to a Th2 response. The immunotherapy tested in this thesis consisted of an autoclaved preparation of M.vaccae, which was injected intradermally over the deltoid. In patients with mycobacterioses, M.vaccae immunotherapy was given in addition to the antimycobacterial chemotherapy. M.vaccae immunotherapy brought about an overall Th2 to Th1 shift in the majority of patients with drug-resistant pulmonary mycobacterioses which was apparently linked with clinical benefits. Patients with other immune disorders such as hay fever, chronic fatigue syndrome and different types of cancer, also showed similar changes to mycobacterioses in their immune parameters. This study supports the hypothesis that the Th1 to Th2 shift which occur in mycobacterioses and other diseases, can be reversed in some patients by M.vaccae immunotherapy. Greater understanding of immune parameters associated with immunopathological and protective immune processes is required to develop and improve immunotherapy.

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