Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections

Abstract

The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed.

Induction in Humans of CD8+ and CD4+ T Cell and Antibody Responses by Sequential Immunization with Malaria DNA and Recombinant Protein

“…Although vaccines that primarily elicit a specific type of immune response may be effective, it has been the contention of many in the field that a vaccine that elicits protective CD8 ϩ and CD4 ϩ T cell responses and Abs against multiple proteins has the best chance for success (29,30). The most progress with a malaria subunit vaccine has been made with RTS,S in AS02A adjuvant (3,4).…”

Interleukin-18 and Gamma Interferon Production by Oral Epithelial Cells in Response to Exposure toCandida albicansor Lipopolysaccharide Stimulation

“…During the inflammation process, epithelial cells are capable of secreting a variety of proinflammatory cytokines. These cytokines play critical roles in the (7,30). IL-18 is a new entry in the vast epithelial cytokine bank.…”

Memory and effector T cells modulate subsequently primed immune responses to unrelated antigens

“…The Th1/Th2 paradigm provides a useful framework for understanding the pathogenesis of certain infectious diseases as well as tissue-specific autoimmune diseases [4][5][6][7][8][9]. While Th1 responses are necessary to clear infectious virus and intracellular parasitic bacteria, Th2 responses predominantly promote humoral responses that can effectively prevent toxin-related bacterial infection, particularly in the mucosal surface [10][11][12][13]. Thus, the development of the appropriate type of T cell immunity is critical for successful vaccination and eradication of infectious organisms.…”