Humoral immunity

Humoral immunity involves the interaction of circulating antibodies in blood serum in addition to the actions of B-cells as activated by Th2-cytokine profiled T-cells. In other words, humoral immunity involves the adaptive portion of the immune system response – that which takes a period of days to take effect after infection has begun.

The immunoglobulin complex (1 - Janeway et al, 2005 Figure1-17)

Activation of B-cells:
B-cells are only significantly activated during the immune response by the cytokines produced by Th2 T-cells: specifically, IL-4, Il-5, and Il-10 (2). Furthermore, a Th2-predominant T-cell response implies an ineffectual immune response to the pathogen and results in a severe, often fatal form of leprosy: lepromatous leprosy. This is likely because of the mycobacterium’s unique lifecycle that requires it to replicate inside host cells instead of free in tissue or blood. Having to replicate inside of cells prevents much recognition of the bacterial cell wall and limits any recognition of infection to somatic cell presentation of bacterial epitopes on MHC-I.

Interaction of B-cells and M. leprae:
There is not much information on M. leprae’s interaction with B-cells. It does seem clear, however, that in the specific case of M. leprae, B-cell activation does not play a significant role in clearing the bacteria from the body. As evidenced, IgG and IgM blood serum levels are high during lepromatous leprosy infection, while the immunoglobulin levels are anywhere from high to undetectable levels during tuberculoid leprosy infection, depending on the activity of the disease in the specific patient (3). In general, however, this study found that patients with lepromatous leprosy had a stronger IgG and IgM response than patients with tuberculoid leprosy (3). This trend is indicative of an unnecessary antibody response, given that the milder tuberculoid leprosy causes a wide range of reactions, including no immunoglobulin secreted at all (3). During infection of M. avium (a mycobacterium related to M. leprae which infects the gastrointestinal tract of cattle), an increasing humoral immune response to the pathogen is paired with higher bacterial shedding in the feces and eventually death (4). Researchers further posit that this trend found in M. avium can be applied to similar mycobacterial infections (4).

Infection with M. avium proved to both lower antigen-specific B-cell levels and also to raise unspecific, circulating peripheral B-cells (4). These seemingly contradictory conclusions have not yet been fully described, and their role in promoting further infection by mycobacteria are not understood (4).

Sources:

1. 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.

2. 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.

3. Touw, J., Langendijk, E. M. J., Stoner, G. L., Belehu, A. 1982. Humoral immunity in leprosy: immunoglobulin G and M antibody responses to Mycobacterium leprae in relation to various disease patterns. Infect Imm. 36.3: 885-892.

4. Waters, W. R., Stabel, J. R., Sacco, R. E., Harp, J. A., Pesch, B. A., Wannenmuehler, M. J. 1999. Antigen-specific B-cell unresponsiveness induced by chronic mycobacterium avium subsp. Paratuberculosis infection of cattle. Infect Imm. 67.4: 1593-1598.

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