From the above description, it can then be deduced that the main feature of adaptive
immunity involves the recognition of an antigen on a specific cell. This response is
initiated by the pathogen associated molecular patterns (PAMPs) on the pathogen
membrane reacting with pathogen receptors (PRRs) on the phagocytic cells which
will become antigen-presenting cells.
The most important result of all this activity is that the macrophages are activated and
attempt to destroy the invading parasites, and selected B cells are cloned, producing
memory B cells and plasma cells. These then secrete specific antibodies to attach to the
invading parasite.n 5.7.1 LYMPHOCYTES AND CYTOKINES
Naive lymphocytes (lymhoyctes that have not been exposed to an antigen) are pluri-
potent; that is they can differentiate along different pathways and develop into effector
cells. The effector cells have PRRs on their surface membranes and when stimulated secrete
specific cytokines. Cytokines reacting with the T helper cells have a major influence in
determining the direction of the adaptive immune response.n 5.8 PARASITES, CYTOKINES AND T HELPER CELLS
Relatively recent experimental studies on the immune response to parasites have
emphasised the importance of the role of the different T helper cell (CD4+) phenotypes
(Th 0 , Th 1 and Th 2 cells). A T helper precursor cell (ThP) gives rise to a Th 0 cell which
is able to secrete cytokines IL-2, IL-4 and IFN-α. Studies with strains of mice in which
Th 1 cells dominate, when infected with the protozoan intracellular parasite Leishmania major,
have shown that the cytokines they produce are TNF-β, IFN-γand IL-2, and control the
growth of the parasite. Mice with only Th 2 cells, which predominantly secrete IL-4, IL-
5, IL-10 and IL-13, experience unrestrained growth of the parasite. In Leishmaniainfec-
tions the ability to induce Th 1 and Th 2 cell responses respectively is apparently a balance
between IL-12 and IL-4 production.
Parasitic helminths tend to initiate a type II (Th 2 ) response. In mice infected with
Schistosoma mansoniexperimental evidence indicates that the size of egg granulomas in the
liver is modulated by IL-4. The expulsion of the nematode Heligmosomoides polygyrus
from mice has been shown to be controlled by Th 2 cytokines. The majority of parasitic
helminths are extracellular, which apparently does not induce IL-12 production and
seems to favour Th 2 cell production.
From the experimental evidence with both protozoan and helminth parasites it
appears that the Th 2 cell functions are of primary importance in both immunopathologic
and immunoprotective responses to helminth egg granuloma and worm expulsion from
the gut.
The protozoan parasites Toxoplasmaand Leishmania amastigotesinduce significant IL-12
production when they infect macrophages (mfs). However when Leishmania promastigotes
infect macrophages they do not induce IL-12 secretion. Promastigotes are killed by
activated macrophages but the initial invasion allows time for conversion of the pro-
mastigotes to amastigotes without excessive activation of Th 1 cell responses.
On the surface membranes of Leishmaniapromastigotes are molecules of lipophos-
phoglycan (LPG) which are shed during the invasion of macrophages and their conver-
sion to amastigotes. There is evidence that evasion of IL-12 induction by promastigotes
may be due to the presence of the LPG molecules during parasite invasion.
In S. mansoniinfections there are stage-specific differences in cytokine induction. For
example the larvae tend to induce a Th 1 cell response, whilst egg deposition tends to inducePARASITOLOGY