Viral Activation of Immunity
Immunity to viral infection is caused by a variety of specific and nonspecific mechanisms. The activation of different immune functions and the duration and magnitude of the immune response depend on how the virus interacts with host cells (on whether it is a cytolytic, steady-state, latent, and/or integrated infection) and on how the virus spreads (by local, primary hematogenous, secondary hematogenous, and/or nervous system spread). Therefore, viral antigens may be present in different parts of the body depending on the route of spread and phase of infection. Local infections at surfaces such as the mucosa can elicit local cell-mediated and humoral (IgA) immune responses, but not necessarily systemic immunity. The host has multiple immune defense functions that can eliminate virus and/or viral disease.
Humoral Immunity: Virus and/or virus-infected cells can stimulate B lymphocytes to produce antibody (specific for viral antigens) Antibody neutralization is most effective when virus is present in large fluid spaces (e.g., serum) or on moist surfaces (e.g., the gastrointestinal and respiratory tracts). IgG, IgM, and IgA have all been shown to exert antiviral activity. Antibody can neutralize virus by: 1) blocking virus-host cell interactions or 2) recognizing viral antigens on virus-infected cells which can lead to antibody-dependent cytotoxic cells (ADCC) or complement-mediated lysis. IgG antibodies are responsible for most antiviral activity in serum, while IgA is the most important antibody when viruses infect mucosal surfaces.
Cell-Mediated Immunity: The term cell-mediated immunity refers to (1) the recognition and/or killing of virus and virus-infected cells by leukocytes and (2) the production of different soluble factors (cytokines) by these cells when stimulated by virus or virus-infected cells. Cytotoxic T lymphocytes, natural killer (NK) cells and antiviral macrophages can recognize and kill virus-infected cells. Helper T cells can recognize virus-infected cells and produce a number of important cytokines. Cytokines produced by monocytes (monokines), T cells, and NK cells (lymphokines) play important roles in regulating immune functions and developing antiviral immune functions.
Virus-Induced Immunopathology
Immune-mediated disease may develop in certain virus infections in which viral antigens and uncontrolled immune hypersensitivity to them persist for a long period. Immune-mediated disease can be mediated by both humoral and cell-mediated immune functions. Immune-complex syndrome can be mediated by virus/virus antigen antibody complexes. T cells (cytotoxic and helper) can also mediate immunopathologic injuries via a number of mechanisms. Immunopathology can result from tissue/organ damage via cytotoxic T cells, inflammation induced via cytokines, antibody plus complement, antibody-antigen complexes and/or ADCC.
Roles of Immune Functions during Viral Infections
The early, nonspecific responses (nonspecific inhibition, natural killer cell activity, and interferon) limit virus multiplication during the acute phase of virus infections. The later specific immune (humoral and cell-mediated) responses function to help eliminate virus at the end of the acute phase, and subsequently to maintain specific resistance to reinfection.
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