TY - JOUR
T1 - Defence mechanisms and immune evasion in the interplay between the humane immune system and Plasmodium falciparum
AU - Theander, T G
N1 - Keywords: Animals; Defense Mechanisms; Host-Parasite Interactions; Humans; Immune System; Malaria, Falciparum; Plasmodium falciparum
PY - 1992
Y1 - 1992
N2 - Immunity to P. falciparum malaria is developed as a result of long term exposure to the parasite and depends on immunological memory. The key directors in immune recognition and regulation of the immunological responses are the T-cells. It seems reasonable to propose that immunity is acquired when a critical mass of T-cells, recognizing relevant malaria antigens, has been developed. These T-cells mediate immunity by regulating macrophage and B-cell activity, but they may also act directly as cytotoxic cells on infected hepatocytes and through production of parasite-toxic cytokines. The potential immune effector mechanisms against P. falciparum are many. The relative importance of each in protection is unknown and protection seems to be mediated through different mechanisms according to the degree of exposure to malaria and the pattern of malaria transmission. Since immunity to malaria is not an absolute phenomenon, many effector mechanisms are probably working together in (partially) protected individuals. Immunity to P. falciparum is acquired after years of exposure to the parasite and several disease episodes. The protracted course to clinical immunity indicates that the parasite interfere with development of immunity. Several mechanisms seem to be operating. 1) Induction of the immune response to some macromolecules is avoided because the parasites are living inside host cells during part of their life cycle, and the reaction to other molecules is apparently avoided by mimicry of host molecules. 2) Immune recognition is hampered by the extraordinary diversity of antigen phenotypes in the parasite population. 3) Immune regulation is obstructed by immune suppression. During P. falciparum malaria such suppression is characterized by a profoundly diminished in vitro proliferative response to malaria antigens, which probably is precipitated by defects in the early events of T-cell activation and inhibition of IL-2 function elucidated, but soluble factors secreted either by the parasites, or by host cells as a result of exposure to the parasite, seem to be involved. 4) Immune effector mechanisms in the liver and the spleen are avoided by sequestration of the mature parasites to the vascular endothelium. The interplay between the human defence system and the malaria parasite governs the symptomatology, the pathology and the development of immunity to the disease. These interactions are extremely complex, and only partly understood. Figure 1 summarizes my view on how these interactions could explain the characteristics of acquired immunity to P. falciparum.(ABSTRACT TRUNCATED AT 400 WORDS)
AB - Immunity to P. falciparum malaria is developed as a result of long term exposure to the parasite and depends on immunological memory. The key directors in immune recognition and regulation of the immunological responses are the T-cells. It seems reasonable to propose that immunity is acquired when a critical mass of T-cells, recognizing relevant malaria antigens, has been developed. These T-cells mediate immunity by regulating macrophage and B-cell activity, but they may also act directly as cytotoxic cells on infected hepatocytes and through production of parasite-toxic cytokines. The potential immune effector mechanisms against P. falciparum are many. The relative importance of each in protection is unknown and protection seems to be mediated through different mechanisms according to the degree of exposure to malaria and the pattern of malaria transmission. Since immunity to malaria is not an absolute phenomenon, many effector mechanisms are probably working together in (partially) protected individuals. Immunity to P. falciparum is acquired after years of exposure to the parasite and several disease episodes. The protracted course to clinical immunity indicates that the parasite interfere with development of immunity. Several mechanisms seem to be operating. 1) Induction of the immune response to some macromolecules is avoided because the parasites are living inside host cells during part of their life cycle, and the reaction to other molecules is apparently avoided by mimicry of host molecules. 2) Immune recognition is hampered by the extraordinary diversity of antigen phenotypes in the parasite population. 3) Immune regulation is obstructed by immune suppression. During P. falciparum malaria such suppression is characterized by a profoundly diminished in vitro proliferative response to malaria antigens, which probably is precipitated by defects in the early events of T-cell activation and inhibition of IL-2 function elucidated, but soluble factors secreted either by the parasites, or by host cells as a result of exposure to the parasite, seem to be involved. 4) Immune effector mechanisms in the liver and the spleen are avoided by sequestration of the mature parasites to the vascular endothelium. The interplay between the human defence system and the malaria parasite governs the symptomatology, the pathology and the development of immunity to the disease. These interactions are extremely complex, and only partly understood. Figure 1 summarizes my view on how these interactions could explain the characteristics of acquired immunity to P. falciparum.(ABSTRACT TRUNCATED AT 400 WORDS)
M3 - Journal article
C2 - 1563295
SN - 0907-8916
VL - 39
SP - 49
EP - 63
JO - Danish Medical Bulletin
JF - Danish Medical Bulletin
IS - 1
ER -
