Host Response to Viral Infections

Host Response to Viral Infections

The main goal of the host response in viral infection is (a) to eliminate the virus and (b) to eliminate the infected cells har-boring or replicating the virus. The host responds by immuno-logic and nonspecific means. The immune response is the best and most important means of controlling virus infections.

Immunity in Viral Infections

Protection against viral infections is induced by both humoral and cell-mediated immunities. Infection by the virus and sub-sequent replication induces immunity in the host against a wide range of virus antigens including the viral internal and surface antigens, nonstructural antigens, and early proteins (Table 51-4).

◗ Humoral immunity

The humoral immunity mediated by antibody plays an impor-tant role against (a) infections caused by extracellular viruses and (b) viremias caused by those viruses. The humoral immu-nity also inhibits multiplication of cytolytic viruses. The cir-culating IgG and IgM antibodies are effective against viruses in blood and tissue spaces while IgA plays an important role against viruses replicating on the mucosal surfaces. The antibodies act against viruses in many ways:

·           They prevent adsorption of virus to the cell receptor at the primary site of infection.

·           They also cause rapid degradation of viruses and also prevent release of the viral progeny from infected cells.

·           The antibodies in combination with complement cause damage to the enveloped viruses resulting in cytolysis of virus infected cells.

The antibodies against surface antigens are usually more effec-tive than against internal antigens. The antibodies produced against surface antigens also vary in their ability to reduce infectivity of viruses. For example, the antihemagglutinin anti-bodies produced against hemagglutinin antigen of influenza virus neutralizes infectivity of the influenza virus, while anti-neuraminidase antibodies against neuraminidase antigen are not effective in neutralizing the infectivity of the virus. The antineuraminidase antibody however is helpful in preventing the release of virion progeny from infected cells.

Humoral antibodies, although are protective, in some instances may cause injuries to host cells and contrib-ute to pathogenesis of disease. For example, antibodies in combination with complement initiate an immune complex disease in infections caused by hepatitis B virus and rubella viruses. Interferons and lymphokines stimulate flu-like symp-toms in respiratory virus infections and in viremia caused by arboviruses.

◗ Cell-mediated immunity

Cell-mediated immunity (CMI) plays a very important role in viral infections:

·           CMI is essential for lysis of target cells in the infections caused by enveloped viruses and also in noncytolytic infec-tions caused by hepatitis A virus. Individuals with deficient cellular immunity are more susceptible to infection by viruses, such as herpes virus, measles virus, and poxvirus.

·           CMI also plays a major role in recovery from viral infections. A deficient CMI results in failure to resolve the infection, which may lead to persistent viral infection, chronic disease, and even death of the patient.

·           CMI also contributes to pathogenesis of diseases by inducing T-cell-induced inflammatory and hypersensitiv-ity reactions. For example, CMI-induced inflammatory response is responsible for the typical clinical manifesta-tion of measles and mumps rather than cytopathologic effect of viruses. In dengue hemorrhagic fever, antigen-specific T cells and specific antibodies induce significant inflammatory and hypersensitivity damage to infected endothelial cells, leading to hemorrhage. Antigen-specific T cells are also responsible for inducing postinfection cytolysis in the infection caused by enveloped viruses, such as measles virus. T cells, macrophages, and polymor-phonuclear leukocytes induce a delayed type hypersensi-tivity and inflammation in many viral infections caused by enveloped viruses.

Infection by some viruses is usually associated with suppressed host immunity; for example, infection by measles virus causes a temporary depression of delayed hypersensitivity to tuberculin antigen and infection by HIV causes a depressed CMI following depletion of CD41 helper T cells.

Once infected by a virus, it usually confers a lifelong immu-nity to reinfection. In some viral infections, such as influenza or common cold, the immunity is not lifelong, because the infection is caused by antigenically different strains of the same virus.

◗ Nonimmunological responses

These include many factors as follows:

Age: Age is the most important factor in determining the sus-ceptibility of the host to viral infections. Most viral infections are common and are more serious in the persons at extremes of age, such as infants, children, and elderly population. Infants and children are more susceptible to a variety of respiratory and exanthematous viral diseases. They are prone to more seri-ous disease caused by paramyxovirus, respiratory infections, etc. Similarly, the elderly people are susceptible to new viral infections (the new strains of influenza A and B virus) and reactivation of the latent viruses (e.g., varicella zoster virus).

Poor nutrition: Poor nutrition or malnutrition affectsthe immune system of the infected person because tissue-regenerating capacity is usually decreased in a person with malnutrition. In such persons, some viral infection (such as measles) causes immunosuppression, thereby facilitat-ing replication of viruses in large numbers. This results in a serious disease associated with more serious and fatal complications.

Genetic make up: Genetic make up of a person also plays animportant role in determining the outcome of viral infection. Genetic differences in immune response genes and genetic defects in other genetic loci affect the susceptibility of the host to viral infection as well as the severity of infection.

Body temperature: Fever is a common manifestation of manyviral infections. Fever acts as a natural defense mechanism against virus infections as many of the viruses are inhibited by a higher temperature above 39°C.

Interferons

Interferons are a family of glycoproteins produced by cells on induction of infection by viral or nonviral microbial agents. These interferons show antiviral activity by inhibiting protein synthesis.