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Chapter 25 : Immune Evasion by Parasites

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Abstract:

This chapter examines two paradigms of parasite immune evasion during infection: one is a new theme emerging from a classic paradigm of surface antigen variation by extracellular parasites, and the other is a new paradigm of modified antigen recognition of intracellular parasites. A study was published with newer crystal structure data in a broader sequence survey of VSG molecules related by class (the pattern of Cys residues in the N terminus) and type (sequence similarities within the C terminus). The finding of the study was that the amino acid-hypervariable regions existed among different variant surface glycoprotein (VSG) and that some of these were buried within the surface coat. It was proposed that this represented evidence at the primary sequence level for antigenic variation within potential Th-cell epitope sites, and they made the formal hypothesis that antigenic variation by trypanosomes was done to evade host B- and T-cell responses. Additional evidence that VSG-specific Th-cell responses contribute to host resistance has come from a recent unexpected finding. In this work, C57BL/6-Igh-6 mice that lack mature B cells were infected with LouTat 1. Some parasites reside intracellularly during infection and do not exhibit substantial antigenic variation. In summary, the protozoan parasite Leishmania has developed several powerful strategies to subvert the macrophage signaling system, and this consequently affects the development of protective immune responses to favor parasite survival.

Citation: Mansfield J, Olivier M. 2002. Immune Evasion by Parasites, p 379-392. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch25

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Figure 1

The trypanosome VSG coat presents a T-cell-independent surface “antigen pattern” that activates B cells. The three-dimensional or architectural array of exposed repetitive VSG epitopes is sufficient to activate B cells and produce a rapid immunoglobulin M response during infection in the absence of Th cells. Subsequent exposure of the immune system to VSG molecules liberated from the surface coat induces strong VSG-specific Th1-cell and T-dependent B-cell responses. Adapted from .

Citation: Mansfield J, Olivier M. 2002. Immune Evasion by Parasites, p 379-392. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch25
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Image of Figure 2
Figure 2

VSG molecules are members of a protein superfamily that exhibit a highly conserved structure. Two VSG molecules are shown that differ significantly in primary sequence but display conserved secondary and tertiary structural features; these structural features are retained among different molecules because VSGs contain highly conserved subsequences necessary for proper folding of the molecule. Highlighted in the figure are the minimal structural differences seen between these two VSGs, as well as other molecular landmarks ( ). Reprinted from with permission of the publisher.

Citation: Mansfield J, Olivier M. 2002. Immune Evasion by Parasites, p 379-392. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch25
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Figure 3

Th-cell-reactive sites are found within a buried hyper-variable region conserved among VSG molecules. The relative placement of three different hypervariable (HV) regions found within trypanosome VSGs is shown ( ). HV-2 and HV-3 are predicted to contain amino acids that would be exposed on the surface of the VSG coat, while HV-1 contains amino acids that are predicted to be buried within VSG molecules. The Th-cell-reactive subsequence shown for the LouTat 1 VSG lies within the predicted conserved HV-1 region.

Citation: Mansfield J, Olivier M. 2002. Immune Evasion by Parasites, p 379-392. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch25
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Figure 4

Induction of host cell phosphatases by infection. The Ca-dependent serine / threonine phosphatase PP-2B (calcineurin) activity is increased over the Ser /Thr phosphatase PP- 1 and P-2A activities in -infected macrophages. PTP activity is rapidly triggered by and, in particular, the PTP SHP-1 is recognized for its role as a negative signaling regulator in leukocytes.

Citation: Mansfield J, Olivier M. 2002. Immune Evasion by Parasites, p 379-392. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch25
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