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1

Evasion of host immune surveillance by hepatitis c virus: potential roles in viral persistence

100%

Moorman J. P., Joo M., Hahn J. S.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 3

189-194

EN

Hepatitis C virus (HCV) is a major human pathogen that causes mild to severe liver disease worldwide. This positive strand RNA virus is remarkably efficient at establishing chronic infections. In order for a noncytopathic virus such as HCV to persist, the virus must escape immune recognition or evade host immune surveillance. Immune escape via the hypervariable region of the E2 envelope protein has been postulated as one mechanism for HCV persistent infection. Such hypervariability within the E2 protein may be under selective pressure from protective B cell or T cell responses and be able to escape immune recognition by rapid mutation of antigenic site. In addition to antigenic variation, HCV may also suppress immune response, leading to dampening of cellular immunity. This is supported by recent studies in our laboratory demonstrating that the HCV core protein can suppress host immune responses to vaccinia virus by downregulating viral specific cytotoxic T lymphocyte (CTL) responses and cytokine production. An understanding of the mechanisms behind HCV persistence will provide a basis for the rational design of vaccines and novel therapeutic agents targeting human HCV infection.

2

Immune reaction to breast cancer: for better or for worse?

88%

Ogmundsdotti H. M.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 2 suppl.

75-82

EN

The infiltration of breast carcinomas with lymphoid cells has often been interpreted as an indication of an active immune response against the tumor and thus a favorable prognostic sign. Several studies have, however, cast doubt on this assumption. In situ breast carcinomas are more common than invasive cancers and it may be speculated that immune surveillance plays a role in preventing some localized cancers from becoming invasive. A secondary type of immune surveillance might be implicated in the long persistence of dormant breast carcinoma cells in the bone marrow. Breast cancer cells can carry tumor-associated antigens, particularly MUC1. These may elicit specific antibody responses but there is less evidence for a CTL response. There are indications that professional antigen presenting cells may be present and active at the edge breast tumours. Breast cancer cells may also interact directly with macrophages and NK cells. In terms of immune effector mechanisms in breast cancer, the communication with potential effector cells is likely to be often faulty because of altered expression of HLA class I molecules. Pleiotrophic cytokines are frequently present and could have a variety of effects ranging from growth inhibition to stimulated proliferation, loss of cell adhesion and activation of matrix degrading enzymes. Fas ligand is unlikely to play a role in the immune evasion of breast cancer. There is thus evidence for a variety of immune reactions to breast cancer. It is possible that they mediate some form surveillance, but growing, invasive tumors have escape routes and may even use cytokines to their advantage.

3

Antigen receptor signaling is subverted by and immunomodulatory product secreted by a filarial nematode

75%

Harnett M. M., Harnett W.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 4

263-270

EN

ES-62 is a phosphorylcholine (PC)-containing glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae which is able to inhibit antigen receptor-stimulated proliferation of B and T lymphocytes in vitro and in vivo. The active component of ES-62 appears to be PC as the results obtained with ES-62 are broadly mimicked by PC conjugated to bovine serum albumin or PC alone. Such desensitization of lymphocyte responsiveness appears to reflect an uncoupling of the antigen receptors from key intracellular proliferative signaling events, such as the phosphoinositide-3-kinase (PI-3K), protein kinase C (PKC) and Ras mitogen-activating protein kinase (RasMAPK) pathways. ES-62 mediates such immunomodulatory effects at concentrations equivalent to those found for PC-containing molecules in the bloodstream of parasitized humans and, thus, ES-62 provides a model system for dissecting the mechanisms of immune evasion induced by related PC-containing glycoproteins expressed by human filarial nematodes.

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3 Archivum Immunologiae et Therapiae Experimentalis

3 2001

1 Hahn J. S.

1 Harnett M. M.

1 Harnett W.

1 Joo M.

1 Moorman J. P.

1 Ogmundsdotti H. M.

Evasion of host immune surveillance by hepatitis c virus: potential roles in viral persistence

Immune reaction to breast cancer: for better or for worse?

Antigen receptor signaling is subverted by and immunomodulatory product secreted by a filarial nematode