Chapter 18 : Acquired Immunity against Viral Infections

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The importance of acquired immunity against viruses is demonstrated by the fatal outcome of infections with many viruses (such as vaccinia virus, polyomavirus, and influenza virus) in mice with severe combined immunodeficiency (SCID mice), which lack functional T and B cells. This chapter describes the dynamics of the T- and B-cell responses elicited by virus infections and illustrates the functions and importance of these cells with examples from well-studied viral models. While much emphasis has been placed on ascertaining the relative contributions of either T-cell subset to the resolution of viral infections, the optimal control of infection in vivo usually occurs with cooperation between both sets. Recent technologic advances have furthered one's understanding of the dynamics of T-cell responses elicited by virus infection. A substantial enlargement of the CD8 cytotoxic T lymphocytes (CTL) compartment is characteristic of the immune response to viral infections. CTL have two separate systems that mediate cytolytic function. The first is the granule exocytosis pathway, and the second is the interaction of Fas ligand (FasL, expressed on T cells) and Fas (expressed on targets). The specificity of Fas-mediated cell death is enhanced by the fact that FasL expression is upregulated following T-cell receptor (TCR) triggering, so that an infected cell expressing viral antigens would more probably receive the death signal than would an uninfected cell. The induction of antiviral antibody responses in immunocompetent normal mice involves complex interactions of antigen-specific activated CD4 T cells and B cells.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2002. Acquired Immunity against Viral Infections, p 247-266. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch18
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Figure 1

Presentation of viral antigens. (A) Processing and presentation of MHC class I-restricted peptides. (Step 1a) Following virus infection, viral gene products are synthesized. (Step 2a) Viral proteins are degraded via cellular proteasomes to produce short peptide fragments. (Step 3a) The viral peptides are transported into the endoplasmic reticulum (ER) by the transporters associated with antigen processing. Within the ER, peptides associate with class I molecules that are complexed with the -microglobulin. (Step 4a) This newly formed tripartite complex is then shuttled to the cell surface for recognition by virus-specific CTL. (B) Processing and presentation of MHC class II-restricted peptides. (Step 1b) Newly synthesized MHC class II molecules are localized within the ER and are complexed with the invariant chain (Ii), which obstructs the peptide-binding site. The invariant chain also participates in the folding of class II molecules and in their transport to the endocytic pathway. The class II complex is shuttled out of the ER into an endosomal compartment (MIIC), where the invariant chain is degraded by proteases, revealing the peptide-binding site. (Step 2b) APC internalize exogenous viral proteins by endocytosis. The proteins are localized to the endocytic pathway, where they are degraded by proteases into peptides. (Step 3b) As peptide-containing endosomes enter the MIIC, the virus-derived peptides bind to class II molecules. (Step 4b) The class II-peptide complexes migrate to the cell surface for presentation.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2002. Acquired Immunity against Viral Infections, p 247-266. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch18
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Figure 2

Kinetics of virus-induced T-cell responses. The T-lymphocyte response to virus infection can be divided into three segments: activation, effector phase, and silencing. After a virus infection at a peripheral site, viral antigens accumulate within draining lymphoid tissue, where they are processed and presented to virus-specific T cells. Following the activation and proliferation of the T-cell population, the activated lymphocytes migrate to the site(s) of infection to eliminate virus-infected cells. Once the host is cleared of viral antigens, the immune system restores homeostasis by deleting a large portion of the T cells. The remaining virus-specific T cells can acquire a memory phenotype.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2002. Acquired Immunity against Viral Infections, p 247-266. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch18
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Figure 3

Kinetics of antiviral immune responses. (A) Viral replication and clearance. Time is given as days postinfection. (B) Antiviral humoral immune responses. ASC, antibody (IgG)-secreting cells in the spleen; se IgM, virus-specific serum IgM; se IgG, virus-specific serum IgG. (C) Virus-specific and total T-cell responses. The frequency of virus-specific T cells before infection is very low. After infection, the majority of the expanding T-cell population is virus specific, and after the down-regulation of T-cell responses, the host is left with an elevated frequency of the virus-specific T cells.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2002. Acquired Immunity against Viral Infections, p 247-266. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch18
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Figure 4

Antibody-mediated antiviral effector mechanisms. (1) Prevention of viral attachment by blocking the viral attachment site. (2) Prevention of uncoating. (3) Aggregation of viral particles. (4) Blocking of virus absorption by inducing conformational changes in the attachment site. (5) Lysis of virion-antibody-complement complexes. (6) Opsonization. (7) Lysis of virus-infected cells by antibody and complement. (8) ADCC. (9) Inhibition of the release of virus particles. (10) Intracellular inhibition of the viral life cycle. VR, virus receptor; V-ag, viral antigen; mf, macrophage; CR2, complement receptor.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2002. Acquired Immunity against Viral Infections, p 247-266. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch18
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Table 1

Antiviral antibody responses in mice with targeted mutations affecting T-cell helper function

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2002. Acquired Immunity against Viral Infections, p 247-266. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch18

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