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Chapter 25 : Immune Evasion by Parasites
Authors:
John M. Mansfield1,
Martin Olivier2
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Affiliations:
1: Department of Bacteriology, University of Wisconsin—Madison, Madison, WI 53706;
2: Infectious Diseases Unit, CHUL, Laval University, Sainte-Foy, Quebec G1V 4G2, Canada
Content Type: Monograph
Publication Year:
2002
Category: Immunology
Book DOI:
10.1128/9781555817978
Chapter DOI:
10.1128/9781555817978.ch25
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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 T. b. rhodesiense 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
Figures
Immune Evasion by Parasites
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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
/content/10.1128/9781555817978.chap25.fig25-1
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 Mansfield (1994) .
10.1128/9781555817978/fig25-1_thmb.gif
10.1128/9781555817978/fig25-1.gif
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 Mansfield (1994) .
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
/content/10.1128/9781555817978.chap25.fig25-2
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 ( Blum et al., 1993 ). Reprinted from Blum et al. (1993) with permission of the publisher.
10.1128/9781555817978/fig25-2_thmb.gif
10.1128/9781555817978/fig25-2.gif
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 ( Blum et al., 1993 ). Reprinted from Blum et al. (1993) 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
/content/10.1128/9781555817978.chap25.fig25-3
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 ( Field and Boothroyd, 1996 ). 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.
10.1128/9781555817978/fig25-3_thmb.gif
10.1128/9781555817978/fig25-3.gif
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 ( Field and Boothroyd, 1996 ). 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
/content/10.1128/9781555817978.chap25.fig25-4
Figure 4
Induction of host cell phosphatases by L. donovani infection. The Ca2+-dependent serine / threonine phosphatase PP-2B (calcineurin) activity is increased over the Ser /Thr phosphatase PP- 1 and P-2A activities in Leishmania-infected macrophages. PTP activity is rapidly triggered by Leishmania, and, in particular, the PTP SHP-1 is recognized for its role as a negative signaling regulator in leukocytes.
10.1128/9781555817978/fig25-4_thmb.gif
10.1128/9781555817978/fig25-4.gif
Figure 4
Induction of host cell phosphatases by L. donovani infection. The Ca2+-dependent serine / threonine phosphatase PP-2B (calcineurin) activity is increased over the Ser /Thr phosphatase PP- 1 and P-2A activities in Leishmania-infected macrophages. PTP activity is rapidly triggered by Leishmania, 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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