IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 16. Antiviral Immunity

■ Viruses are Obligate Intracellular Parasites that vary extremely in Structure and modes of Replication. Some cause acute VIRAL INFECTIONS AND are ultimately eliminated by the host Organism, while others persist indefinitely within it, causing "slow viral infections".

■ Innate Immunity factors, particularly interferons and NK Cells, inhibit infection at its early stages and impede the spread of the virus throughout the body.

■ Antibodies neutralize viral infectivity by preventing their entry into new Cells and Tissues, serving as an important defense mechanism against reinfection.

■ Cytotoxic T lymphocytes are capable of recognizing virus-infected host cells and destroying them during the early stage of viral replication, before a new generation of Viral Particles appears.

■ Viruses can evade recognition by the host immune system due to their properties of latent persistence, antigenic variation, and synthesis of "decoy Proteins" that interfere with host defense mechanisms.

■ Viruses can directly disrupt immune system Functions, causing immunosuppression, immunodeficiency, and autoimmune diseases.

TYPES OF VIRAL INFECTIONS

Viruses are obligate intracellular parasites that use the biochemical machinery of the host Cell to synthesize their proteins. They are extremely diverse in structure and Genome Organization—some have an RNA genome consisting of just a few genes, while others possess DNA genomes with up to two hundred genes. Structurally, a virus is simply a protein "case" (capsid) enclosing packaged nucleic acid. Even simpler forms of living organisms have also been discovered:

✵ Viroids — plant pathogens consisting solely of nucleic acid without a protein coat, and

✵ Prions — "infectious proteins" associated with degenerative neurological diseases in animals and humans, including scrapie in sheep, bovine spongiform encephalopathies, and Creutzfeldt-Jakob disease.

The stages of a typical viral infection at THE CELLULAR LEVEL are shown in Fig. 16.1. Viruses attach to host cells by binding to specific cellular receptors. This Specificity determines the tropism of a given virus for a particular host species or cell type. Examples of cellular receptors utilized by viruses are shown in Fig. 16.2. Following viral entry into The Cell, uncoating occurs—the disassembly of the protein capsid to release the nucleic acid. METABOLISM/31.html">Transcription and viral Protein Synthesis then begin, followed by viral genome replication, and finally, the assembly and maturation of a new "generation" of viral particles. Upon release into the intercellular space, they infect neighboring cells and tissues. Depending on the viral species and host cell metabolic features, this process may vary in detail. For example, Picornaviruses (small RNA viruses) require about 8 hours to form new viral particles, whereas human DNA-containing cytomegalovirus takes up to 48 hours.

Class="center">

Fig. 16.1. To reproduce, a virus must penetrate a host cell.

Fig. 16.2. Viruses attach to cells using specific cellular receptors. Receptor specificity partly determines which cell types will be infected.

The mechanisms of host infection, tissue persistence, and disease Pathogenesis vary widely among different viruses. As a rule, viruses enter the internal environment of the body through mucous membranes. Another highly efficient route of direct entry into the bloodstream is through broken Skin, such as via an insect bite or a hypodermic needle. Viral replication typically occurs in epithelial surfaces; subsequently, in some cases, viruses enter the bloodstream (viremia), leading to their dissemination and infection of other tissues. Recovery may mean the complete elimination of the virus from the host organism. However, certain viruses (notably Herpesviruses) can remain (persist) in the body in a hidden (latent, non-infectious) form after the acute infection subsides and reactivate at some point to produce new infectious viral particles. Other viruses (e.g., hepatitis B virus or lymphocytic choriomeningitis virus) persist in an infectious form despite the host Immune Response. In diseases such as scrapie and Creutzfeldt-Jakob disease, there is no acute phase at all; their agents persist in the body accompanied by a slow infection, manifesting clinical symptoms many years after exposure. Unlike true viral infections, prion infections stimulate neither an immune response nor The production of interferons. The Classification of viral infections according to their clinical course is presented in Fig. 16.3.

Fig. 16.3. Viral infections can be acute or chronic and have various outcomes.