Cellular response:

Cell mediated immunity is the part of the immune response that involves actions of macrophages, natural killer (NK) cells, activated killer T cells (CD8+), and the actions of various cytokines. Cell mediated immunity is extremely important during the infection process of M. leprae due to the inability of B-cells to mount a useful immune response to pathogen.

Th1 cellular role:
Although Th1 cells are not cytotoxic, they do play a very significant role in cell-mediated immunity. In the case of M. leprae, an important facet of an effective immune response is the delineation of T-cells into Th1 and Th2 cell lines. A Th1-dominant immune response to M. leprae indicates development of tuberculoid leprosy (a milder form of leprosy) (3). Th1 T-cells secrete the cytokines Il-2 and IFN-gamma, which support delayed-type hypersensitivity to the pathogen (3). The Th1 immune response is thought to be chosen through circulation of IFN-gamma and IL-12 (3). Interestingly, IFN-gamma also inhibits the progression of T-cells into Th2 cells (3).
           
A Th2-dominant immune response to M. leprae indicates development of lepromatous leprosy, which is discussed in the section ‘humoral immunity’.
           


An overview of Th cell differentiation. Note that with relatively few differential signals, Th1 and Th2 cells create vastly different immune profiles. (Courtesy and Copyright Becton, Dickinson and Company)

Despite studies that show the importance of a Th1-mediated immune response, studies have shown that up to 50% of patients with various types of leprosy have a mixed cytokine profile, also known as Th0 (3). In this T-cell profile, the cells have not differentiated into Th1 or Th2 cytokine profiles (3). There are a few caveats to this fact; namely, the aforementioned studies only looked at cytokine profiles from the lymph nodes of patients with leprosy, and not closer to the site of infection or lesion (3). Previous studies have shown that T-cells nearer to the actual infection are more likely polarized into the Th1 or Th2 cytokine profile (3).           

 

Macrophage response:
Since M. leprae infects macrophages, their activation proves very important for clearing the bacterial infection. Macrophages are generally activated by Th1 cells, which activate cell-mediated immunity in general (2). When the infected macrophages are inactive, M. leprae is able to evade the cellular immune response and replicates inside of the cell until it bursts. Without any signal from outside sources, macrophages are unable to mount any significant response to the bacterium, and the infection spreads largely unchecked (2). When activated through Th1 cells (and the cytokines secreted by them), macrophages then are more likely to apoptose (thereby killing the residing bacterial load) and also activate their lysosomes to fuse with any phagosomes that might be harboring bacteria (2).

 

NK response:
A Th1 predominant T-cell response usually indicates early movement of the NK cells to the site of infection (1). However, NK cells are also very active in the early stages on infection, before the adaptive immune system has time to kick in (1). In each case, NK cells are very effective at fighting M. leprae infection as long as they are both activated (most likely by Th1 cells) and can recognize the infected macrophages or Schwann cells (2).

 

Sources:
1. Barerra, S. de la., Finiasz, M., Fink, S., Ilarregui, J., Aleman, M., Olivares, L., Franco, M. C., Pizzariello, C., Del Carmen Sasiain, M. 2004. NK cells modulate the cytotoxic activity generated by Mycobacterium leprae-hsp65 in leprosy patients: role of IL-18 and IL-13. Clin Exp Immunol. 135: 105-113.

2. Janeway, C., Travers, P., Walport, M., Shlomchik M. Immuno Biology: the immune system in health and disease. 6th Ed. 2005. New York: Garland Science Publishing.

3. Misra, N., Murtaza, A., Walker, B., Narayan, N. P. S., Misra, R. S., Ramesh, V., Singh, S.,
Colston, M. J., Nath, I. 1995. Cytokine profile of circulating T cells of leprosy patients
reflects both indiscriminate and polarized T-helper subsets: t-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae. Immunology. 86: 97-103.

 

Copyright Alex Greer 2007

For questions/comments, please contact Immunology professor Dr. Sofia Sarafova at Davidson College.