Immunity to viruses
Introduction:
Viruses are obligate intracellular parasites. That means that viruses are incapable of reproducing in a free-living state, because they typically lack the means to produce metabolic energy (that it,, to break down sugars and other foodstuffs and to produce ATP as a result) and the means to synthesize protein. In order to reproduce therefore, viruses must be able to attach themselves to the surface of cells (which are provided by some other living organism), to insert their genome into the host cell, and then to commandeer the ATP and protein-synthesizing machinery of the host cell to reproduce themselves.
Some viruses replicate rapidly, leading to the production of large numbers of virus particles inside the cell that are released in a burst by the lysis and death of the host cell. These viruses typically reattach to other host cells (in humans perhaps within 30 minutes) and start this cycle of binding, insertion, commandeering, and bursting all over again. Some viruses actually insert their genome permanently into the host genome, thereby acting like the host cell’s own genetic material. In this “lysogenic” state, the virus directs production of copies of its own nucleic acid and synthesis of necessary viral proteins, at a relatively low rate, and these viral particles typically bud off from the host cell and travel to other cells, without causing death of the host cells. The bursting kind of life history is typical of acutely infectious viruses, like the rhinoviruses that cause the common cold, while the lysogenic/budding mechanism is more typical of viruses that cause chronic disease, such as herpes and hepatitis viruses. It’s an oversimplification to say all viruses adopt one or the other of these “lifestyles”, because there are intermediate life styles, but these are the most common viral strategies.
The defense against viral infections includes both innate immune mechanisms (especially interferons alpha and beta, which induce a number of cellular mechanisms that inhibit viral protein synthesis), as well as both humoral and cellular adaptive responses.
Humoral Response to Virus:
Since viruses typically spend a relatively small fraction of their lives outside a host cell, they are not particularly susceptible to control by the humoral immune system. Antibodies do not cross the membrane of cells, and therefore can only bind to viruses in the period when they have first entered the organism or are moving from one host cell to another. They are vulnerable at that time and antibodies can inactivate them; vaccines often induce a humoral response to viruses, and if the antibody levels are high enough, this can effectively block the virus from reattaching to host cells, and allow it to be opsonized and digested by phagocytic cells like neutrophils and macrophages.
Innate immune response to Viruses:
The early or innate immune defence against virus includes interferons, natural killer cells and macrophages. The viral infection of a cell directly stimulates the production of type 1 IFN (that includes IFN- alpha and a single IFN-beta, as well as less-known IFN-omega) by infected cells.
The type 1 IFN functions to inhibit viral replication in both infected and uninfected cells by inducing an antiviral state. IFN-alpha/ beta bind to receptor present on host cells that trigger IFN signal transduction pathways. Stimulated signal transduction pathways lead to transcriptional activation of 30 or more cellular genes whose products are responsible for inducing the antiviral state.
However, the main means that the immune system uses to control viral infections is the cytotoxic T cell mediated response.
Cytotoxic T cell mediated response:
Once a virus has gained entry into the host cell, antibodies become ineffective and cell mediated immune mechanism come into play to eradicate the infection.
In general, T-cyt cells and T-hi cells are the main components of cell mediated antiviral defence. Antigen- specific recognition mediated by the TCR of T-cyt cells and T-hi cells results in the activation of T-cell effector functions. T-cyt cells identify and destroy virus infected cells. T-cyt cells recognize viral peptides displayed on the surface of infected cells together with class I MHC molecules. These T-cyt cells release granules of the protein-perforin on the target cell membrane. These perforin molecules form transmembrane pores in the target cell membrane, lysing and killing the target cells. Virtually all the cells of the body express class I MHC molecules, making it easier for T-cyt cells to identify and eliminate virus- infected cells. T cells undergo massive proliferation during viral infection.
Destruction of the host cell in which the virus is reproducing is an effective way to interrupt the virus’s reproductive cycle, and thus to control the spread of the infection.
We still get sick from viruses, however, so clearly our immune response is not perfect in preventing disease. What’s more some viruses, like herpes virus, can establish lifelong infections in individuals, so clearly viruses have mechanisms to escape detection and destruction by the immune system.
Strategies of Virus to get into Host cell:
- One is essentially an evolutionary or evasive strategy. That is, the immune system recognizes and attacks particular viral protein structures or “epitopes”. In any given population of viruses some individual virus particles will have undergone some random mutations in their proteins, some of which will change the structure of these epitopes. Thus while the immune system is attacking the viruses which express this dominant epitope, other viruses may escape notice and therefore continue to reproduce. RNA viruses like rhinoviruses or influenza virus often survive by just such a strategy.
- A second group of strategies used by some viruses is actively inhibiting or altering the host’s immune response with viral proteins, and these are some of the most effective viruses. For example some viruses that can be lysed by complement have devised mechanisms to inhibit complement. Vaccinia virus produces a protein that binds and inhibits complement factor C4b, an essential element of the classical pathway.
· One of the most successful groups of human pathogens are the herpes simplex viruses, which cause cold sores, genital herpes (Herpes simplex type II), chicken pox and shingles (Herpes zoster). These viruses establish lifelong infections in their hosts using a variety of ingenious strategies. First, the viruses produce a protein that binds to and inhibits the C3b component of complement, which is essential for the activity of all three complement pathways. Thus, the virus has a self-protective mechanism for those times when it is outside host cells.
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