Innate and Adaptive Immunity

Answer #1

The identification of Th1 and Th2 cells has provided a useful model for our understanding the selective induction, polarization, and reciprocal regulation of distinct arms of the immune response (1, 25). Th1 cells are normally induced following infection with intracellular bacteria and viruses, whereas Th2 responses are generated in response to allergens and helminth parasites (1, 10, 28). The early decision to polarize the immune response toward type 1 or type 2 is controlled by a number of factors. Gram-negative bacteria and viruses stimulate the production of interleukin-12 (IL-12) and IL-18 by dendritic cells and macrophages, which favors the induction and expansion of Th1 cells (5, 37). Conversely, early IL-4 acts as a potent stimulus for Th2 differentiation (1, 28).

Th1 and Th2 cells also produce cytokines that are mutually inhibitory for the differentiation and effector functions of the reciprocal subtype. Thus, once a T-cell immune response begins to develop along either a Th1 or Th2 lineage from a common precursor, it tends to become increasingly polarized in that direction. This dichotomy into reciprocally regulated Th1 and Th2 cell type responses provides a simple framework in which we categorize immune responses and their role in dealing with distinct pathogens that require different effector mechanisms for their control. However, the real situation, especially in the developing world, is one where individuals may be exposed to multiple infections or where vaccines may be administered in the face of chronic parasitic infection. The aim of the present investigation was to examine the reciprocal influences of a Th1-inducing bacterial pathogen and a Th2-inducing parasite in vivo.

Answer #2

Several cytokines have been looked at in the context of HIV. Interferon-gamma enhances the function of cells that control mycobacterial infections, including tuberculosis and MAC. It has been studied together with anti-TB treatment in people with TB and HIV. It is also being looked at as an adjunctive therapy to enhance vaccine effects. Early studies suggest that low doses of interferon-gamma may control HIV whereas high doses may promote HIV replication. Interferon-gamma, however, is also associated with cell activation, which isn't necessarily a good thing. Over the years, increased interferon gamma levels have alternately been described as both a good thing and a bad thing.

This point is important when considering the challenges of researching cytokines. In the body, cells are producing these chemicals at very, very small -- nanomolar -- concentrations and together with other cytokines. The combination of cytokines, in varying concentrations, elicits different immune responses. At low doses IL-2 preferentially stimulates natural killer cells, while at higher doses, delivered intermittently, it stimulates CD4+ cells to reproduce. When IL-2 is given at high dose daily it produces no appreciable effect on CD4+ cell count. When it is given for five days every eight weeks, the effect is profound and pronounced. The challenge with cytokine research is not merely to understand the various biologic functions of the cytokine, but also how best to give the therapy to achieve the desired responses.

Interleukin-12 (IL-12) was researched ...