Chapter 9 : Innate Immunity to Parasitic Infections

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Traditionally, the control of parasitic infections was thought to be the exclusive domain of the acquired immune system. However, during the past decade it has been recognized that innate immunity can shape the outcome of the host-parasite encounter. Perhaps the simplest forms of innate immunity are represented by the presence of preexisting, soluble factors that can recognize and destroy invading parasites. Importantly, whereas complement-sensitive epimastigotes fail to express gp160, epimastigotes transfected with gp160 are resistant to complement-mediated lysis. Although innate immunity plays an important role in resistance to acute parasitic infections, the adaptive response is required to provide long-term protective immunity. Understanding the cellular and molecular basis of the mechanisms that underlie innate immunity to parasitic diseases may also provide important information for the rational design of immunotherapies or vaccines. At present there is a paucity of vaccines which protect against parasitic diseases, and understanding how innate immunity initiates the development of long-lived, protective responses to these parasites may provide new approaches to vaccination. Perhaps the best example of how understanding the mechanisms of innate immunity to infection can influence the development of new approaches to deal with parasitic infections is provided by IL-12.

Citation: Hunter C, Sher A. 2002. Innate Immunity to Parasitic Infections, p 111-125. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch9

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Image of Figure 1.
Figure 1.

Complement system. The activation of the complement system through either the classical, lectin, or alternative pathways converges on the deposition of C3b on the parasite surface. In the absence of host (or parasite) regulatory proteins, this cascade proceeds to the assembly of the MAC, the opsonization of parasites, and the release of chemotactic peptides. Developmental stages of protozoan parasites found in insects are highly susceptible to lysis via the alternative pathway of complement activation, whereas the stages specific for the mammalian hosts have developed a variety of strategies to evade this mechanism of host resistance. Ag, antigen; Ab antibody.

Citation: Hunter C, Sher A. 2002. Innate Immunity to Parasitic Infections, p 111-125. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch9
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Image of Figure 2.
Figure 2.

Mechanism of TLF killing of TLF binds to high-affinity receptors on the surface of and is endocytosed and targeted to the lysosome. At low lysosomal pH and in the presence of high intracellular concentrations of hydrogen peroxide, TLF facilitates the release of Fe from iron stores. Fe ions react with HO via the Fenton reaction to form hydroxyl radicals. Hydroxyl radicals produced in this reaction attack polyunsaturated fatty acids (LH), causing lipid free-radical formation The lipid free radical forms a lipid (L). peroxyl radical (LOO) in the presence of O, which peroxidates adjacent lipids, creating a chain reaction. The lipid hydroperoxides (LOOH) formed are unstable, resulting in a wide variety of products that can cause membrane breakdown and release of lysosomal contents. This model was supplied by Joseph Bishop and Steve Hajduk from the University of Alabama at Birmingham.

Citation: Hunter C, Sher A. 2002. Innate Immunity to Parasitic Infections, p 111-125. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch9
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Image of Figure 3.
Figure 3.

Regulation of innate cell-mediated immunity to parasites. Infection with various parasites can stimulate the production of proinflammatory cytokines from several sources including neutrophils (PMN), macrophages (Mø), and dendritic cells (DC). IL-12, in combination with other cofactors, plays an important role in stimulating NK-cell production of IFN-γ, which mediates antiparasitic activity and may contribute to the development of Th1-type responses. IL-10 and TGF- are inhibitors of this innate mechanism of immunity, either acting directly on accessory cell populations or NK cells to inhibit the production of proinflammatory cytokines or antagonizing the effector mechanisms required to control parasite replication.

Citation: Hunter C, Sher A. 2002. Innate Immunity to Parasitic Infections, p 111-125. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch9
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Image of Figure 4.
Figure 4.

Activation of splenic dendritic cells by products. The mobilization and activation of dendritic cells are likely to be key steps in the initiation of cell-mediated responses to intracellular pathogens. This figure demonstrates the response of splenic dendritic cells to a soluble extract of tachyzoites (STAg) 6 h after intravenous injection. In the left-hand panels, spleen cells were stained with the DC cell surface marker CD11c, while the right-hand panels show serial sections from the same spleens stained with an anti-IL-12 p40 monoclonal antibody. As can be seen, the products induce a massive mobilization of dendritic cells into the T-cell areas of the spleen, and many of these dendritic cells produce IL-12, a cytokine crucial for the induction of IFN-γ dependent resistance to the parasite.

Citation: Hunter C, Sher A. 2002. Innate Immunity to Parasitic Infections, p 111-125. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch9
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