Page 920 - Veterinary Immunology, 10th Edition
P. 920
protozoan diseases where the organisms are resistant to
VetBooks.ir intracellular destruction. The most significant destructive molecules
in these M1 cells are reactive nitrogen radicals. However, protozoa
are also experts in surviving within macrophages; for example,
Leishmania, Toxoplasma, and Trypanosoma cruzi can migrate into safe
intracellular vacuoles by blocking phagosome maturation.
Leishmania and T. cruzi can suppress the production of oxidants or
cytokine production, while Toxoplasma gondii can promote
macrophage apoptosis. T. gondii tachyzoites also inhibit
inflammatory cytokine production by preventing nuclear
translocation of NF-κB.
In Theileria parva infection of cattle (East Coast fever), sporozoites
invade α/β and γ/δ T cells as well as B cells. These parasites activate
NF-κB by continuously phosphorylating its inhibitor proteins Iκ-Bα
and Iκ-Bβ (Chapter 8). The persistent NF-κB maintains the cell in an
activated state, and prevents its apoptosis. These activated cells
produce both IL-2 and IL-2R. As a result, a loop is established, by
which infected cells secrete IL-2, which in turn stimulates their
growth. As Theileria schizonts develop within lymphocytes, the
infected cells enlarge and proliferate. The parasite divides with its
host cell and its schizonts bind to the mitotic spindle. Thus they
effectively infect both daughter cells leading to a rapid increase in
parasitized cells, overwhelming infection, and death. Some animals,
however, may recover from infection and become solidly immune.
+
In these animals, CD8 T cells kill infected lymphocytes by
recognizing parasite antigens in association with MHC class I. In
susceptible animals, the parasites interfere with MHC class I
expression.
Infection of chickens or mammals with Eimeria oocysts generally
leads to strong, species-specific immunity that can prevent
reinfection. The immune response inhibits the growth of
trophozoites, the earliest invasive stage, within intestinal epithelial
cells. This growth inhibition is reversible, since if the arrested stages
are transferred to normal animals they can complete their
development. Resistance to primary infection is mediated by
+
multiple mechanisms that involve CD4 T cells, IL-12 and IFN-γ,
macrophages, and NK cells. In contrast, resistance to secondary
+
challenge by Eimeria is mediated by CD8 T cells. In chickens, IFN-
920