Cells (Immunity) - HIV Flashcards
What is HIV?
Human immunodeficiency virus, which causes the disease acquired immune deficiency syndrome (AIDS). It has a lipid envelope, attachment proteins, a capsid and two single strands of RNA and enzymes. Viruses are not formed of cells and therefore are considered non-living.
What is the structure of HIV?
- On the outside is a lipid envelope, embedded in which are peg-like attachment proteins (glycoproteins used to bind to and to allow entry into a host cell).
- Inside the envelope is a protein layer called the capsid that encloses two single strands of RNA and some enzymes.
- One of these enzymes is reverse transcriptase, so-called because it catalyses the production of DNA from RNA - the reverse reaction to that carried out by transcriptase.
- The presence of reverse transcriptase, and consequent ability to make DNA from RNA, means that HIV belongs to a group of viruses called retroviruses.
- HIV also has a matrix which gives the virus structural strength.
What is reverse transcriptase?
An enzyme in HIV which enables the production of DNA from RNA.
What is a retrovirus?
A group of viruses which have the ability to make DNA from RNA because they have reverse transcriptase.
What is mRNA?
A single stranded polynucleotide found in HIV.
How does the human immunodeficiency virus replicate?
Being a virus, HIV cannot replicate itself. This is as HIV does not have the ribosomes, enzymes and other materials to replicate alone. Instead it uses its genetic material to instruct the host cell’s biochemical mechanisms to produce the components required to make new HIV. HIV infects helper T cells as its primary host cell.
- Following infection HIV enters the bloodstream and circulates around the body.
- A protein on the HIV readily binds to a protein called CD4. While this protein occurs on a number of different cells, HIV most frequently attaches to helper T cells.
- The protein capsid fuses with the cell-surface membrane, releasing its contents - the RNA genome (contains the two RNA copies alongside the protective nucleocapsid) and enzymes (reverse transcriptase and integrase) - into the cytoplasm of the helper T cell.
- The HIV reverse transcriptase uses the viral RNA as a template to make a complementary DNA strand. Eventually, double-stranded DNA is produced from the RNA.
- The enzyme integrase makes a cut in the host DNA and inserts the viral DNA into the host.
- The viral DNA hijacks the cell, and forces it to read the viral DNA to make viral mRNA. This viral mRNA then hijacks the host cells’ ribosomes and forces it to only make viral proteins. Without making its own proteins, the host can’t survive.
- The mRNA passes out of the nucleus through a nuclear pore. The viral proteins assemble at the cell membrane and use the cell’s protein synthesis mechanisms to form new viral HIV particles.
- They exit the cell through budding (exocytosis).
- A portion of the phospholipid bilayer is taken along with it to form the viral coat (their lipid envelope).
- Upon release, each new viral particle infect more helper T cells to replicate more HIV.
How long does it take to develop AIDS after being infected with HIV?
Once infected with HIV, a person is said to be HIV positive. However, the replication of HIV often goes into dormancy and only recommences, leading to AIDS, many years later. The average time between HIV infection and development of AIDS is 10 years.
How does HIV cause the symptoms of AIDS?
HIV specifically attach helper T cells. HIV causes AIDS by killing or interfering with the normal functioning of helper T cells. An uninfected person normally has between 800 and 1200 helper T cells in each mm3 of blood. In a person suffering from AIDS, this number can be as low as 200mm-3.
Helper T cells are important in cell-mediated immunity. Without a sufficient number of helper T cells, the immune system cannot stimulate B cells to produce antibodies or the cytotoxic T cells that kill cells infected by pathogens. Without helper cells, immune cells die. In the absence of activation signals, both cytotoxic T cells and B cells undergo anergy and eventually die. This leads to the overall failure of the immune system, leaving the individual susceptible to infections.
Memory cells may also become infected and destroyed. As a result, the body is unable to produce an adequate immune response and becomes susceptible to other infections and cancers. Many AIDS sufferers develop infections of the lungs, intestines, brain and eyes, as well as experiencing weight loss and diarrhoea. It is these secondary diseases that ultimately cause death.
Does HIV kill individuals?
HIV does not kill individuals directly. By infecting the immune system, HIV prevents it from functioning normally. As a result, those infected by HIV are unable to respond effectively to other pathogens. It is these infections, rather than HIV, that ultimately cause ill health and eventual death.
What is the ELISA test?
ELISA stands for ‘enzyme linked immunosorbant assay’. It uses antibodies to not only detect the presence of a protein in a sample, but also the quantity. It is extremely sensitive and so can detect very small amounts of a molecule.
To understand how the ELISA test works, imagine that we are trying to find whether a particular protein, in this case an antigen, is present in a sample. What is the procedure?
- Apply the sample to a surface, for example a slide, to which all the antigens in the sample will attach.
- Wash the surface several times to remove any unattached antigens.
- Add the antibody that is specific to the antigen we are trying to detect and leave the two to bind together.
- Wash the surface to remove excess antibody.
- Add a second antibody that binds with the first antibody. This second antibody has an enzyme attached to it.
- Add the colourless substrate of the enzyme. The enzyme acts on the substrate to change it into a coloured product.
- The amount of the antigen present is relative to the intensity of colour that develops.
Where can the ELISA test be used?
This basic technique can be used to detect HIV and the pathogens of diseases including tuberculosis and hepatitis. ELISA is especially useful where the quantity of an antigen needs to be measured. In testing for particular drugs in the body for example. The mere presence of a drug is often less important than its quantity as many drugs are found naturally in low concentrations. ELISA is therefore very useful in both drug and allergen tests.
What is an allergen?
An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies.
Why are antibiotics ineffective against viral diseases such as AIDS?
Antibiotics work in a number of different ways. One is by preventing bacteria from making normal cell walls.
In bacterial cells, as in plant cells, water constantly enters by osmosis. This entry of water would normally cause the cell to burst. That it doesn’t burst is due to the wall that surrounds all bacterial cells. This wall is made of murein (peptidoglycan) a tough material that is not easily stretched. As water enters the cell by osmosis, the cell expands and pushes against the cell wall. Being relatively inelastic, the cell wall resists expansion and so halts further entry of water. Antibiotics like penicillin inhibit certain enzymes required for the synthesis and assembly of the peptide cross-linkages in bacterial cell walls. This weakens the walls, making them unable to withstand pressure. As water enters naturally by osmosis, the cell bursts and the bacterium dies.
Viruses rely on the host cells to carry out their metabolic activities and therefore lack their own metabolic pathways and cell structures. As a result, antibiotics are ineffective because there are no metabolic mechanisms or cell structures for them to disrupt. Viruses also have a protein coat rather than murein cell wall and so do not have sites where antibiotics can work. In any case, when viruses are within an organism’s own cells, antibiotics cannot reach them without destroying the body’s own cells.
What is the influenza virus case study?
- The influenza virus evolves quickly so new vaccines need to be developed every year to fight against new strains of the influenza virus.
- New strains can be present each year. Every year there tends to be a new common strain which is present. Therefore an influenza virus is chosen each year based on the most common strain.
- Another issue is people not having the flu vaccine. Whilst the main problem is the antigen variability of influenza, another factor is the number of people who do not vaccinate themselves with the annual flu vaccine. Unvaccinated individuals readily catch the influenza virus, providing it with more opportunities to evolve and develop new strains, which further complicates the development of an influenza vaccine.
