2.2 Overview of adaptive immune responses

Viruses are unable to multiply on their own. They depend on the body’s own cells.

To multiply, a virus must first enter the body. One of the ways it does this is through the mucous membranes of the gut or respiratory system. They are not able to infect cells indiscriminately, because they can only attach to cells expressing particular molecules on their surface.

When a virus encounters such a cell, it binds using a complementary surface receptor protein.

The virus is now able to penetrate the cell. The capsid, the part of the virus containing the foreign genetic material, enters the cytoplasm.

There it breaks down, releasing its nucleic acid into the cell. Viruses have genomes which can be either RNA or DNA in single or double stranded forms.

Many viruses replicate in the cytoplasm where their biomolecules are synthesised. These include more viral nucleic acid, nucleocapsid proteins and glycoproteins for the viral envelope if there is one. Some viruses incorporate their DNA into the nucleus.

The components of the virus assemble in the cytoplasm and at the cell membrane. Viral envelope proteins protrude through the plasma membrane, and within the cytoplasm viral nucleic acids associate with capsid proteins to form a new nucleocapsid. The plasma membrane buds off to enclose this new nucleocapsid, causing a new virus to be released into the body. Many virus particles are produced simultaneously in each cell.

Each released virus is potentially capable of infecting another cell. Neighbouring cells in the body are likely to be of the same type, and since the virus targets cells expressing specific host molecules on their surface, propagation of the infection is rapid.

The immune system has several defence mechanisms against viral infection. Here, a virus binds to its target cell.

As we saw, it fuses with the host cell, and releases its genetic material into the cytoplasm.

When the foreign genetic material enters the cell and starts to synthesise viral products, the cell is stimulated to make type 1 interferons.

These interferons can signal to neighbouring cells to directly inhibit viral synthesis. They do this by binding to interferon receptors which signal the production of antiviral proteins. The antiviral proteins can switch the cell into a virus resistant state if it should later become infected.

If a virus now infects that cell, the anti-viral proteins become activated and block viral replication by breaking down the cell’s mRNA and stopping protein synthesis.

The anti-viral proteins put the cell into stasis, which limits further replication of the virus and spread of infection.

This holding action gives the immune system time to mobilise the T cell response.

One consequence of interferon signalling is an increased production of major histocompatibility complex molecules, particularly class I molecules, which are synthesised within the endoplasmic reticulum, where they bind to peptide fragments of proteins synthesised in that cell.

All of the peptides that have bound to MHC class I molecules are carried to the cell surface, including any viral peptides.

Each T cell has an antigen receptor that can potentially recognise an antigenic peptide presented on an MHC class I molecule.

Once attached there may be a direct inter-action between the molecules on the T cell and the infected target cell. An indirect signal may also be sent using, cytokines, such as tumour necrosis factor or lymphotoxin.

In either case, this triggers the release of agents within the cell which disrupt nuclear DNA, and cause cell death by apoptosis. The cytotoxic T cell is now free to seek other similarly infected cells.

Some viruses may attempt to evade immune responses by down-regulating the production of MHC class I molecules. But a cell which lacks MHC class I becomes susceptible to killing by natural killer cells.

The body’s other defence mechanism is carried out by free immunoglobulin. Both infected cells and free virus present viral proteins on their surface.

Antibodies can bind to viral proteins expressed on the surface of infected host cells. In this case they signal to components of the complement system, which attack the cell membrane and damage the cell by membrane attack complexes.

Neutralising antibodies on encountering a virus, can also bind to its surface receptor for the host cells, making it unable to infect them.