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Immune Response

Innate Immune Response

    The innate immune response to malaria has received little attention until the last few years and is therefore not well understood.  Much of the difficulty stems from Plasmodium’s complex life cycle, its ability to generate vast antigenic variability, and the sophisticated techniques Plasmodium has developed to evade the immune system (Baratin et al., 2005; Khan and Lai, 1999).  In addition, although the genome has been sequenced, over 60% of the 5,400 Plasmodium genes have yet-to-be-discovered functions.  However, experiments suggested that the components of innate immunity detect P. falciparum very early in the course of infection (Baratin et al., 2005).

The Role of Natural Killer Cells
    Natural killer (NK) cells are found in blood, the secondary lymphoid organs, and peripheral nonlymphoid organs such as the lungs.  They play a role in innate effector responses that occur during viral and bacterial infections and aid in the development in antigen-specific responses.  Although the NK response to P. falciparum is still poorly understood, its main role seems to be activation and recruitment of other cells during the innate immune response.  NK cell depletion appeared to lead to increased parasitemia and increased mortality (Baratin et al., 2005).
    Human NK cells appeared to be activated immediately upon recognition of erythrocyte invasion by Plasmodium falciparum.  In both human and mouse malaria, NK cells are an early source of cytokines such as IFN-α, which are produced in the serum about two days before clinical symptoms appear. NK cell activation also induces the expression of CD69 and CD25, as well as the production of CXCL8.  However, there is no degranulation of the NK cell, indicating that NK cells are not cytotoxic against P. falciparum (Baratin et al., 2005). 
    There is some evidence that suggests that macrophages selectively aid NK cells, primarily in the secretion of IL-18.  Data also suggested that full NK cell activation requires activation of the Toll pathway through TLR2, TLR9, and TLR11.  MyD88 indirectly senses P. falciparum infection and is needed on macrophages that aid NK cells (Baratin et al., 2005).   

Humoral Immune Response

    Very little is known about the humoral immune response to malaria is unclear.  Scientists know that in malaria-endemic areas, constant exposure to P. falciparum leads to the development of immunity in adults, but the exact mechanism is still unknown.  Plasmodium is known to excrete soluble exoantigens, which appear to be central to inducing the humoral response, during its asexual stages, but no exoantigens have been isolated from gametocytes (Ramsey, J. M. et al., 2002). Various proteins on the surface of the parasite, such as Spf66, and human blood-stage antigens like gp190 are also believed to contribute to the humoral immune response (Tolle et al., 1993).
    Protective acquired immunity against Plasmodium can reduce the density of malaria parasites within the body, consequently, reduce the duration of the infection. Anti-malaria antibodies are also able to inactivate some gametocytes (Buckling et al., 2001). Acquired humoral immunity, however, is lost in pregnant women and in people infected with HIV/AIDS, and studies are currently underway to determine the reason for this (Tolle et al., 1993). .

Works Cited

Baratin, M., et al.  2005. “Natural killer cell and macrophage cooperation in MyD88-dependent innate response to Plasmodium falciparum.”  PNAS 102: 14747–52.

Buckling, A. and A. F. Read. 2001. "The effect of partial host immunity on the transmission of malaria parasites." Proceedings: Biological Sciences 268: 2325-2330.

Khan, Nasser and Andrew Lai. “The malaria website: pathology/immune response.” 1999. Biology Department, Brown University. <http://www.brown.edu/Courses/Bio_160/Projects1999/malaria/ldpg.html> Accessed 2007 Feb 25.

Ramsey, J. M., et al. 2002. "Plasmodium falciparum and P. vivax gametocyte-specific exoantigens stimulate proliferation of TCRγ:δ+ lymphocytes." The Journal of Parasitology 88.1: 59-68.

Tolle, R. et al. 1993. “Prospective study of the association between the humoral immune response to Plasmoidum falciparum blood stage antigen gp190 and control of malarial antibodies.”  Infection and Immunity 61.1: 40-47.

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