Immunology icon Immunology Notes

Some Topics

Antiviral Defense

Viral infections are the leading cause of transient diseases all over the world. Immune defenses are usually adequate to eradicate most viruses. Some viruses, however, become permanent residents of the host: herpes simplex virus, cytomegalovirus, Epstein-Barr virus, varicella zoster and AIDs virus are well-known residents. These viruses are controlled by protective immune responses. Host immune responses include the rapid proliferation of cytotoxic T lymphocytes that destroy viral-infected cells. A cell infected with a virus produces new viral proteins. Fragments of these proteins are displayed on the cell surface as a signal that a foreign invader is present within the cell. In the best case, Cytotoxic lymphocytes destroy infected cells before new viruses have been produced. Viruses are eliminated only if all infected cells are destroyed.

T-helper-cells that maintain the immune response; and neutralizing antibodies that combine with free virus particles and prevent the spread of infection. Virus-specific CD4+ Th cells appear to be essential for antiviral defense. HIV infection usually causes progressive disease but a few infected people develop sufficient protective immunity to survive the infection. The virus infects lymphocytes that are essential for its control.

An additional problem is that a reservoir of latent HIV virus is established in CD4 cells that may persist even with good drug control of active virus replication. According to Walker: “In most infected patients, the immune system fails to prevent progressive disease. T-helper-cell function appears inadequate, and cytotoxic T lymphocyte responses decline over time. Both host factors (specific HLA class I alleles) and viral factors (mutation leading to immune escape) may contribute to the loss of immunologic control.”

CD4+ cell counts are used to monitor HIV disease progression. Delayed hypersensitivity skin testing is used to assess T-helper-cell responses to common antigens such as tuberculin, mumps and Candida. As AIDS progresses, delayed hypersensitivity skin response decline.

Herpes simplex virus-1 infects mucosal surfaces and remains resident in sensory neurons for the lifetime of the host. Gupta et al described a latency-associated transcript (LAT), the only viral gene expressed during latent infection in neurons. LAT inhibits neuronal apoptosis so that the neuron and the virus survive. The HSV-1 LAT gene encodes a micro RNA that prevents apoptosis in infected cells by modulating TGF-ß signaling.

Dengue Example

This mosquito transmitted virus causes the most severe disease with the second exposure. Dengue is characterized by fever, headache, muscle and joint pain, and rash. “There are four serotypes. Antibodies are serotype-specific and people may have sequential infections. Immunity against a specific serotype is lifelong, but previous infection with one serotype is a risk factor for a more severe form of dengue — dengue hemorrhagic fever — upon subsequent infection with another serotype. Dengue hemorrhagic fever is characterized by the capillary-leak syndrome, thrombocytopenia, hemorrhage, hypotension, and shock. Its incidence has increased dramatically during the past several decades, as multiple dengue serotypes introduced into new environments by air travelers with viremia have become endemic. Approximately 500,000 cases occur annually, with a case fatality rate ranging from 1 to 3% to as high as 10 to 20%, depending on the sophistication of the available fluid management and intensive care.

The virus uses Fc receptors on dendritic cells and macrophages to enter cells. T-cell activation and clearance of infected cells by killer cells and cross-reactive cytotoxic T cells creates a "cytokine storm" that causes endothelial damage and capillary leakage.

See Influenza Virus Defense