Chapter 25 : Acquired Immunity to Helminths

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The strongest indication that acquired immunity to helminth infections may develop in humans comes from the changing patterns of infection with age. Eosinophils, a characteristic feature of the Th2 response to helminths, have long been associated with enhanced killing of larval schistosomes, with recent studies demonstrating greater immunity in eosinophilic humans. Our understanding of acquired immunity to helminths is based on a rich substrate of animal models, most importantly, the mouse. It is entirely plausible that the halting nature of human immunity to helminths can be ascribed to the strength of regulatory restraints that have evolved to minimize pathological outcomes. The influence of mast cells on immunity to intestinal nematode infection is species specific. In addition to recruitment of inflammatory cells, expulsion of most intestinal nematodes is commonly associated with dramatic alterations in IEC proliferation, turnover, and/or differentiation. Changes in glycosylation status of mucins also occur following intestinal nematode infection, although at present, there is limited evidence to support a direct role for mucins in expulsion of intestinal nematode parasites. Successful resolution of helminth infections requires the appropriate mode and degree of immune responsiveness if full immunity is to be achieved without severe pathological consequences.

Citation: Artis D, Maizels R. 2011. Acquired Immunity to Helminths, p 313-323. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch25
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Initiation and regulation of parasite-specific Th2 cell responses following exposure to intestinal nematode infection. Following infection with intestinal nematode parasites, intestinal epithelial cells express a wide range of chemokines and immunoregulatory cytokines, including IL-17E, thymic stromal lymphopoietin (TSLP), and IL-33. These cytokines can promote expression of IL-4 and/or IL-13 in granulocyte populations including mast cells (MC), eosinophils (EOS), and basophils (BASO). IL-17E and TSLP can also create a permissive environment for Th2 cell differentiation by limiting expression of proinflammatory cytokines in dendritic cells (DCs). Naïve CD4T cells are activated in the draining mesenteric lymph nodes and, in the presence of the appropriate signals, differentiate into host protective Th2 cells that express IL-4, IL-5, IL-9, IL-13, and IL-17E.

Citation: Artis D, Maizels R. 2011. Acquired Immunity to Helminths, p 313-323. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch25
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Th2 cell-mediated immune effector mechanisms in expulsion of intestinal nematode infection. Th2 cell-derived cytokines can promote granulocyte activation including expression of IL-4, MHC class II, costimulatory molecules, and mouse mast cell protease (MMCP). In addition, Th2 cytokines can promote alternative activation of macrophages (AAMac) that express chitinases, chitinase-like molecules (YM-1), arginase-1, and RELMα that can promote parasite expulsion, wound healing, and can limit the magnitude of Th2 cytokine responses. Th2 cells can also influence nonhematopoietic cell lineages, including promoting smooth muscle contractility and alterations in intestinal epithelial cell (IEC) proliferation, differentiation, and migration. Therefore, parasite-specific CD4 T cells elicit nonparasite-specific inflammation and changes in intestinal physiology that create an environment that is unfavorable for parasite persistence. The relative importance of each pathway depends on the particular species of nematode parasite that infects the host.

Citation: Artis D, Maizels R. 2011. Acquired Immunity to Helminths, p 313-323. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch25
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Major human helminth parasites and corresponding model systems

Citation: Artis D, Maizels R. 2011. Acquired Immunity to Helminths, p 313-323. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch25

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