ASPECTS OF MALARIAthe synthetic antigens did not associate with the MHC molecules on the macrophages and
hence were not recognised by the antigen receptors on the T cells.
The use of experimental mice produced evidence that suggested that anti-sporozoite
immunity can be cytokine-activated, or a cell-mediated activation, but not antibody-
mediated. The vaccinated mice did not produce any detectable anti-CS antibody.
n 10. 3HOST EFFECTOR MECHANISMS OPERATIVE AT
THE HEPATIC STAGE
Soon after the initial inoculation into the blood stream, the sporozoites penetrate into
hepatocytes (liver cells). The infected hepatocytes stimulate phagocytes in the liver to
release cytokines and in particular gamma interferon (IFN-γ) The IFN-γin the system
activates infected hepatocytes to synthesise reactive nitrogen intermediates. The parasitised
hepatocytes apparently also provide a signal for the generation of reactive nitrogen
intermediates. A further cytokine, known as tumour necrosis factor alpha (TNF-α), is
released from activated cells and induces the reactive nitrogen intermediates to kill
infected cells. It is interesting to note that both IFN-γand TNF-αare similarly needed
to stimulate RNI-mediated killing of Leishmaniaby macrophages.
One of the first cytokines, interleukin-1 (IL-1), released by the activated macro-
phages stimulates the hepatocytes to produce the cytokine interleukin-6 (IL-6). This
cytokine (IL-6) is thought to assist the reactive nitrogen intermediates as well as reactive
oxygen intermediates to kill the intrahepatocytic parasites. However the parasites are still
able to survive in this hostile environment apparently by down-regulating the produc-
tion of IL-6.
n 10.4 EFFECTOR MECHANISMS AGAINST ASEXUAL AND
INTRAERYTHROCYTIC PARASITES
The majority of the in vivo studies of malaria used rodent models; in particular stud-
ies of P. chabaudi, which in many ways resembles human malaria. Severely compromised
immunodeficient (SCID) mice were used in many of these studies.
The transfer of specific lymphocytes, first the T helper cells (CD4+T cells) and then
antibody-producing cells (B cells), into SCID mice infected with the eyrthrocytic forms
of P. chabaudidemonstrated that T helper cells (CD4+) can be protective during the early
stages of infection but the B cells are required to clear the infection.
Normal mice infected with P. chabaudiproduce T helper cells (Th 1 cells) which
secrete the cytokine gamma interferon (IFN-γ) and this prevents the infection from
overwhelming the mouse. As the parasite becomes established within the mouse, the adapt-
ive immune system is stimulated. After about 7 days, the activated B lymphocytes (B cells)
give rise to antibody-secreting plasma cells and, during the later stages of the infection,
the plasma cells secrete the antibody IgG 2 which helps to resolve the infection.
n BOX 10.1
Severely compromised immunodeficient mice (SCID mice) are mice that lack most of the
components of a normal immune system. Most of the missing components are lymphocytes.
The mice are thus a very useful laboratory tool for studying how specific components of
the immune system react to infection. In order to do so, immune cells taken from normal
healthy mice of the same strain are injected into SCID mice. Hence single components or
a combination of the components of the immune system can be investigated.