Menu Close

Immune response to viruses

Immunity against viruses
Viruses are a type of microbe that must replicate within the cells they infect, using the biosynthetic machinery of host cells, so they lack characteristic and well-differentiated molecular patterns of eukaryotic cells, making it difficult for the innate immune system to recognize them.1

Viruses infect by binding to specific cell receptors by specific proteins. Depending on what type of receptors they bind to, they will infect one type of cell or another. Within these cells the virus replicates (multiplication of the viral particles) and can produce the death (lysis) of the infected cell, these viruses are the cytopathic viruses. Other viruses do not have a lytic cycle (they do not produce cell death), but rather maintain a balance with the infected cell in which they can even integrate into its genome and remain for a long time in a silent/latent form without being able to be detected by the immune system.1

Innate response
The synthesis of type I interferons (IFN-alpha and IFN-beta) is probably the earliest immune response to viruses. Many cell types are capable of synthesizing type I interferons when infected by viruses and do so in response to the detection of viral RNA and viral DNA by Toll type receptors (TLRs) or by the activation of cytoplasmic kinases (a type of enzyme that modifies other molecules by phosphorylation) by viral RNA. Type I IFNs act by interfering with viral replication through different mechanisms, for example by inhibiting protein synthesis, degrading mRNA or promoting apoptosis of infected cells to prevent the virus from spreading. Type I IFNs are also secreted by infected cells into the environment and act on neighbouring cells, producing a preventive response in these cells that hinders viral replication in case of infection. Type I IFNs also help to enhance the adaptive-type response of T lymphocytes by increasing the synthesis of class I and II MHC molecules.1

The innate cellular response to viruses is mediated by NK lymphocytes. Some viruses, especially of the herpesvirus family, are capable of interfering with the mechanisms of antigen presentation by class I MHCs, which means that the cells infected by these viruses decrease the number of class I MHC molecules on their surface. NK lymphocytes are specialists in detecting cells with low levels of class I MHC through their receptor activators and inhibitors. Some viruses (e.g. cytomegalovirus) also induce the synthesis of proteins such as MIC that activate NK lymphocytes through the NKG2D receptor. The activation of NK lymphocytes leads them to kill infected cells, preventing the spread of the virus to neighboring cells. Activated NK lymphocytes also produce type II interferon (IFN-gamma) that contributes to trigger other cellular responses such as the activation of antigen-presenting cells and Tc (cytotoxic) lymphocytes.1

Adaptive response
In most cases, the innate response to viruses can only delay their growth, but not their effective elimination. This requires an adaptive immune response consisting of the production of antibodies and the activation of Tc lymphocytes. Protective antibodies against viral infections are usually blocking, that is, they bind to the viral particles preventing them from binding to their target cells and, therefore, avoiding replication, as viruses are strict intracellular pathogens. The most suitable type of antibodies to protect us from infections depends on the type of virus, for example against viruses that infect the host through the mucous membranes. The most effective neutralizing antibodies are usually of the igA isotype, as they block the virus in the mucous membrane itself, preventing it from accessing its target cell. Blocking antibodies may also be IgG isotypes, which will be effective in preventing the spread of the virus in the blood. The activation of complement or phagocytes through antibodies attached to viral particles (opsonization) can also be mechanisms of antiviral response. Finally, in some infections, cells expose viral antigens on their plasma membrane that can be recognized by circulating antibodies (e.g. anti EBNA IgG). These antibodies can cause lysis of the infected cell by activation of the classical complement pathway, cell death by antibody-dependent cytotoxicity or phagocytosis by opsonization-dependent mechanisms.1

T lymphocytes are the main cells involved in the defence against viruses. On the one hand, in the vast majority of cases the production of antiviral antibodies depends on T-B cooperation, so it is necessary to activate clones of Th lymphocytes specific to viral peptides, these Th lymphocytes are essential for B lymphocytes, which have immunoglobulins can differentiate into plasma cells that produce the synthesis of antiviral antibodies. On the other hand, the viruses that are already inside the cells are inaccessible to the antibodies. In this case the Tc lymphocytes, which detect the viral infection by inspecting the MHC class I molecules of the cell surface through their membrane receptor (TCR) and respond by secreting perforins and granzymes that kill the infected cells.1

Evasion mechanisms of some viruses
Throughout evolution, pathogens may develop mechanisms or strategies to escape the host’s immune response. These mechanisms are fundamentally of two types: antigenic variation and immune interference.1

Some viruses, such as the influenza virus or the AIDS virus, have an enormous antigenic variation, which can be produced by mutations or by recombinations of their genetic material. The immune response (either antibody or Tc lymphocyte) to a variant of the virus is ineffective when the virus changes these antigens, allowing the selection of virions that resist effector mechanisms. The development of effective vaccines against viruses with high variability is therefore very complex. The mechanisms of viral interference with the immune response are very varied, some viruses, for example the Epstein Barr virus, have developed mechanisms that allow them to block the effect of type I interferons. Poxviruses produce soluble receptors that bind to various cytokines such as IL-1, IL-18, TNF-alpha or IFN-gamma and act as antagonists of these proteins, blocking their effect. The Epstein Barr virus produces a protein with an effect similar to IL-10, a Th2-type cytokine, which inhibits the cellular immune response (Th1-type) effective against the virus. The virus known as vaccinia produces homologous proteins from host complement regulators thus preventing this system from being activated.1

Finally, several virus types have developed strategies to interfere with the presentation of antigens by MHC molecules and thus prevent the activation of the T-lymphocyte response. Some adenoviruses (they are non-encapsulated and bi-catenary DNA viruses) are able to inhibit the transcription of MHC class I molecules and also produce, like the human cytomegalovirus, proteins that bind to MHC class I molecules in the endoplasmic reticulum where they are retained, thus preventing them from surfacing with their peptide load. Some Herpesviruses synthesize proteins that bind to the TAP transporter by blocking it, thus preventing the peptides from passing from the cytosol into the ER to be bound by class I MHC molecules. Kaposi’s sarcoma virus has proteins that bind to class I MHC molecules on the cell surface and cause their internalization into the cytosol.1


  1. Regueiro González J.R., López Larrea C., González Rodriguez S. y Martínez Naves E. Inmunología: Biología y patología del sistema inmunitario. 4ª edición. Editorial Médica Panamerica, 2010.