Host Immune Response to viruses
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p441-442
2025-10-28
64
The outcome of viral infections reflects the interplay between viral and host factors. Nonspecific host defense mechanisms are usually elicited very soon after viral infection. The most prominent among the innate immune responses is the induction of cytokines such as IFNs. These responses help inhibit viral growth during the time it takes to induce specific humoral and cell-mediated immunity.
A. Innate Immune Response
The innate immune response is largely mediated by IFNs, which are host-coded proteins that are members of the large cytokine family that inhibit viral replication. They are produced very quickly (within hours) in response to viral infection or other inducers and are one of the body’s first responders in the defense against viral infection. IFNs also modulate humoral and cellular immunity and have broad cell growth regulatory activities.
There are multiple species of IFNs that fall into three general groups: designated IFN-α, IFN-β, and IFN-γ (Table 1). Both IFN-α and IFN-β are considered type I or viral IFNs; IFN-γ is type II or immune IFN. Infection with viruses is a potent inducer of IFN-α and IFN-β production; RNA viruses are stronger inducers of IFN than DNA viruses. IFNs also can be induced by double-stranded RNA and bacterial endo toxin. IFN-γ is not produced in response to most viruses but is induced by mitogen stimulation.
Table1. Properties of Human Interferons
IFNs are detectable soon after viral infection in intact animals, and viral production then decreases (Figure 1). Antibody does not appear in the blood of the animal until several days after viral production has abated. This temporal relationship suggests that IFN plays a primary role in the nonspecific defense of the host against viral infections, as well as the fact that agammaglobulinemic individuals usually recover from primary viral infections about as well as normal people.
Fig1. Illustration of kinetics of interferon and antibody synthesis after respiratory viral infection. The temporal relationships suggest that interferons are involved in the host’s early defense system against viral infections.
IFN is secreted and binds to cell receptors, where it induces an antiviral state by prompting the synthesis of other proteins that inhibit viral replication. Several pathways appear to be involved, including: (1) a dsRNA-dependent protein kinase, PKR, which phosphorylates and inactivates cellular initiation factor eIF-2 and thus prevents formation of the initiation complex needed for viral protein synthesis; (2) an oligonucleotide synthetase, 2-5A synthetase, which activates a cellular endonuclease, RNase L, which in turn degrades mRNA; (3) a phosphodiesterase, which inhibits peptide chain elongation; and (4) nitric oxide synthetase, which is induced by IFN-γ in macrophages.
Viruses display different mechanisms that block the inhibitory activities of IFNs on virus replication. Examples include specific viral proteins that block induction of expression of IFN (herpesvirus, papillomavirus, Filovirus, hepatitis C virus, rotavirus), block the activation of the key PKR protein kinase (adenovirus, herpesviruses), activate a cellular inhibitor of PKR (influenza, poliovirus), block IFN-induced signal transduction (adenovirus, herpesviruses, hepatitis B virus), or neutralize IFN-γ by acting as a soluble IFN receptor (myxoma virus).
B. Adaptive Immune Response
Both humoral and cellular components of the adaptive immune response are involved in control of viral infections. Viruses elicit a tissue response different from the response to pathogenic bacteria. Whereas polymorphonuclear leukocytes form the principal cellular response to the acute inflammation caused by pyogenic bacteria, infiltration with mononuclear cells and lymphocytes characterizes the inflammatory reaction of uncomplicated viral lesions.
Virus-encoded proteins serve as targets for the immune response. Virus-infected cells may be lysed by cytotoxic T lymphocytes as a result of recognition of viral polypeptides on the cell surface. Humoral immunity protects the host against reinfection by the same virus. Neutralizing antibody directed against capsid proteins blocks the initiation of viral infection, presumably at the stage of attachment, entry, or uncoating. Secretory IgA antibody is important in protecting against infection by viruses through the respiratory or gastrointestinal tracts.
Special characteristics of certain viruses may have pro found effects on the host’s immune response. Some viruses infect and damage cells of the immune system. The most dramatic example is the human retrovirus HIV that infects T lymphocytes and destroys their ability to function, leading to acquired immunodeficiency syndrome (AIDS).
Viruses have evolved a variety of ways that serve to sup press or evade the host immune response and thus avoid being eradicated. Often, the viral proteins involved in modulating the host response are not essential for growth of the virus in tissue culture, and their properties are realized only in pathogenesis experiments in animals. In addition to infecting cells of the immune system and abrogating their function (HIV), they may infect neurons that express little or no class I major histocompatibility complex (MHC) (herpesvirus), or they may encode immunomodulatory proteins that inhibit MHC function (adenovirus, herpesvirus) or inhibit cytokine activity (poxvirus, measles virus). Viruses may mutate and change antigenic sites on virion proteins (influenza virus, HIV) or may downregulate the level of expression of viral cell surface proteins (herpesvirus). Virus-encoded microRNAs may target specific cellular transcripts and suppress proteins integral to the host innate immune response (polyomavirus, herpesvirus).
The immune response to one virus or vaccine may exacerbate the disease caused by subsequent infection with simi lar strains. For example, dengue virus hemorrhagic fever can develop in persons who already have had at least one prior infection with another dengue serotype due to the intense host response to infection.
Another potential adverse effect of the immune response is the development of autoantibodies through a process known as molecular mimicry. If a viral antigen elicits anti bodies that additionally recognize an antigenic determinant on a cellular protein in normal tissues, cellular injury or loss of function unrelated to viral infection might result. The host may then experience postinfectious autoimmune dis ease, such as Guillain-Barre syndrome associated with prior measles infection.
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