Chapter 19 : Acquired Immunity against Virus Infections

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The importance of acquired immunity against viruses is demonstrated by fatal or persistent infections of viruses in severe combined immunodeficient (SCID) mice, which lack functional T and B cells, under conditions where normal immunocompetent mice would clear the infection without apparent disease or mortality. Most of our present understanding of antiviral immune mechanisms comes from experiments performed with inbred laboratory mice, because different components of the immune system can be easily manipulated in this animal model. This chapter describes the dynamics of 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. Immunodominant epitopes are highly immunogenic and therefore elicit T-cell responses that are easily detectable, whereas T cells specific for weakly immunogenic, subdominant epitopes are often difficult to detect. Studies with poliovirus have indicated that virus-specific CD8 T cells can recognize antigen presenting cells (APC) class I MHC-presented peptides derived from exogenous proteins. FcγRIII, which are expressed on natural killer (NK) cells in addition to monocytes and macrophages, bind mainly IgG2a, IgG2b, and IgG1 antibodies, and have the potential to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) of virus-infected cells.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2011. Acquired Immunity against Virus Infections, p 239-254. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch19
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Image of FIGURE 1

Kinetics of acquired antiviral immune responses. This shows time kinetics of the antiviral cellular (T and B cell) (Top) and serum antibody (Bottom) responses to a viral infection, progressing from a primary infection to the memory state, followed by a rechallenge with the virus. Innate cytokines include the antiviral IFNs and immunoregulatory and inflammatory cytokines produced by innate immune system cells.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2011. Acquired Immunity against Virus Infections, p 239-254. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch19
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Image of FIGURE 2

Cell interactions during acquired immunity. Infecting viruses encounter DCs, which present processed viral antigens on class I MHC to CD8 T cells and on class II MHC to CD4 T cells. B cells capture unprocessed antigens with their B-cell receptor (surface antibody), internalize them, and present processed antigen on their class II MHC to helper CD4 T cells. CD4 and CD8 T cells proliferate and differentiate into effector cells capable of secreting cytokines, providing help to B cells, or becoming CTL. Others become long-lived memory cells. B cells differentiate into shortlived antibody-secreting plasma cells (PCs) or else enter germinal centers, undergo isotype switching and affinity maturation (somatic hypermutation and selection) and become long-lived PCs or memory B cells. fDC = follicular DC.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2011. Acquired Immunity against Virus Infections, p 239-254. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch19
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Image of FIGURE 3

Presentation of viral antigens. (A) Processing and presentation of MHC class I restricted peptides. (1a) Following virus infection viral gene products are synthesized. (2a) Viral proteins are degraded via cellular proteasomes to produce short peptide fragments. (3a) The viral peptides are transported into the endoplasmic reticulum by the transporters associated with antigen processing. Within the ER, peptides associate with class I molecules that are complexed with the beta-2 microglobulin. (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. (1b) Newly synthesized MHC class II molecules are localized within the ER and are complexed with the invariant chain (li), 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. (2b) APCs internalize exogenous viral proteins by endocytosis. The proteins are localized to the endocytic pathway, where they are degraded by proteases into peptides. (3b) As peptide containing endosomes enter the MIIC, the viral-derived peptides bind to class II molecules. (4b) The class II-peptide complexes migrate to the cell surface for presentation.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2011. Acquired Immunity against Virus Infections, p 239-254. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch19
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Image of FIGURE 4

Progression of virus-induced T cell responses. The T-lymphocyte response to virus infection can be divided into three segments: activation, effector phase, and contraction. 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. 2011. Acquired Immunity against Virus Infections, p 239-254. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch19
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Image of FIGURE 5

Antibody-mediated antiviral effector mechanisms. This figure depicts several antibody-dependent antiviral mechanisms, including (1) prevention of viral attachment by blocking the viral attachment site; (2) prevention of uncoating; (3) aggregation of viral particles; (4) blocking virus absorption by inducing conformational changes in the attachment site; (5) lysis of virionantibody-complement complexes; (6) opsonization; (7) lysis of virus-infected cells by antibody and complement; (8) antibody-dependent cell-mediated cytotoxicity; (9) inhibition of the release of virus particles; (10) intracellular inhibition of the viral life cycle. VR, virus receptor; V-ag, viral antigen; mφ, macrophage; CR2, complement receptor.

Citation: Szomolanyi-Tsuda E, Brehm M, Welsh R. 2011. Acquired Immunity against Virus Infections, p 239-254. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch19
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