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Most of us know that it affects the immune system, and that the name is short for Acquired Immune Deficiency Syndrome. Most of us probably also know that the immune system helps protect us from infection. But how many of us know what the immune system actually is, or how it works? The fact is the immune system is no one thing. You can not pinpoint any specific part of the body and say "That's the immune system." It is so complex, that no body of science yet fully understands exactly how it all works. I would like to go through the key points of what we do know, in order to gain a better understanding of this strange condition called AIDS.
The biggest organ of your immune system is your skin. Remember that the microbes that cause infection, whether they are bacteria, viruses or fungi, are all invisible to the human eye. So although we are surrounded by millions of them every day, we can't see them. Your skin helps prevent all those microbes from gaining access to your body. Think of it as fortress walls with electric fencing – that's the immune function of your skin. Your mucous membranes also form part of this fortress that keeps the microbes out.
Of course, no fortress is impenetrable. You may have a cut on your skin, or a wound. And of course, there are doorways into your body through your nose and mouth. Fortunately, these have little alarms that alert the immune system when an intruder tries to make an uninvited entry.
The immune system, of course, has to be very smart. It has to know which cells belong to the body, and which do not. It does this by looking for little markers called antigens. Think of antigens as being uniforms. All the cells in your body wear the same uniform, even though they may have different functions. Microbes coming into the body have their own uniforms, which are usually very different. Maybe they're even dressed in civvies.
Guard cells patrol the body all the time. There are small, quick-footed, lightly armed guards called microphages ("little eaters") which patrol the bloodstream. There are also bigger, slower, better-armed guards called macrophages ("big eaters") which hang around the spleen and lymph nodes, waiting to be called. They also patrol the body tissues.
Microphages are cells with powerful digestive enzymes and antibacterial substances. When a microphage sees a foreign uniform, it rushes over with a baton, bangs the microbe over the head and then gobbles it up to get rid of it. They are always first at the scene of the crime, and call for reinforcements from more powerful immune cells. It's quite possible that the microbes may be more powerful than the microphages, in which case it's the microphage that gets shot before it can wield the baton. The macrophages arrive afterwards, to collect the evidence and destroy any microbes that may have escaped the microphage guards.
Both microphages and macrophages come from the bone marrow. But the bone marrow also makes stem cells, which move to different parts of the body. These include other important immune organs like the thymus gland, spleen, lymph nodes, tonsils, appendix and Peyer's patches in the intestinal wall. Once settled into the organ, the stem cells produce white blood cells called lymphocytes.
Cells produce more cells by dividing into two cells. The daughter cells divide again, and so the process continues. The stem cells that go into the thymus gland divide very quickly, to produce a large number of daughter cells, most of which do not survive. Those that do, then leave the thymus gland and travel between the other immune organs at will. But they never return to the thymus.
These particular cells, formed in the thymus gland, are called T-lymphocytes or T-cells. And they learn special skills in the thymus gland which are very useful in fighting off foreign microbes. When a T-cell reaches the scene of a crime, three things can happen. The foreign microbe can either inactivate or kill the T-cell. If it kills all the T-cells, the body can't see the foreign uniform any more and the microbe can go where it likes.
The T-cells can also start dividing. This means there are more cells that recognise the foreign uniform, which in turn means that if any more of these uniforms try and get into the body, the body can respond quicker and better. The third thing the T-cell can do is release cytokines. This is a bit like casting a magic spell which makes the macrophages in the area stronger and more powerful, so that they can hit the microbes faster and have more chance of devouring them.
T-cells make up about 70% of the lymphocytes in the body. The rest are B-lymphocytes, which never go to the thymus gland. They don't travel as easily as T-cells, and they have different skills, including the ability to make antibodies which inactivate foreign particles. HIV targets mainly the T-cells, specifically those which have a special receptor called a CD4 receptor. The virus attaches onto that receptor so that it can take over the inside of the cell. So we have a virus which looks – and acts like – a CD4 T-cell.
During the first stage of infection with HIV, the virus will kill a number of T-cells as it infects them. The immune system will react to the infection, and the body will display all the symptoms of an immune response such as fever, headache, tender lymph nodes, and generally feeling unwell. However, once the B-cells have formed antibodies, the spread of infection stabilises. The symptoms disappear, and nothing seems to happen for a few months to several years.
But think what happens in the meantime. The virus has not been destroyed, just stabilised. There are antibodies, but not enough. The virus can continue to spread, although at a much slower rate. Now think what happens when a microbe breaches the skin and enters the bloodstream. The immune system sends the T-cells to fight the new microbe. But some of these T-cells are infected with HIV. They've lost their magic spells, and can either die from a microbe attack, or start dividing to make more T-cells. Except that they start making more virus-infected T-cells, which will eventually succumb to the virus. As more and more T-cells die, the body is less able to recognise foreign uniforms.
As time passes, the number of CD4 T-cells slowly drops, and the amount of virus slowly increases until a critical level is reached. Then the number of CD4 T-cells plummets, and the amount of virus in the bloodstream shoots up. Without the T-cells, the immune system becomes virtually useless. The foreign uniforms can march in unchallenged. Even an army of 105 kg. weaklings can come in and create havoc. These diseases – caused by everyday, normally harmless microbes are the ones that usually define the beginning of AIDS.
Scientists have now developed tests to measure the amount of CD4 T-cells and the amount of virus in the body. When the T-cells get too low, or the virus gets too high, they can adjust the HIV treatment to restore a measure of law and order in the body. When pharmaceutical companies test their new anti-HIV drugs, they measure the T-cells and amount of virus in order to measure exactly how effective their drug is.
As a result of understanding the immune system better, people infected with HIV are able to live longer, healthier, productive lives. New research is leading scientists to consider the possibilities of cell transplants. Perhaps one day, our understanding will grow to the point that we know how to rebuild a defective immune system completely.
Glossary
Adherence
The degree to which a patient exactly follows a prescribed treatment regimen. Poor adherence may negatively impact a drug's effectiveness. Compliance is an alternate term.
Amino Acid
A nitrogen-containing molecule that serves as a building block for proteins, including enzymes, muscles, and structural molecules. The human body uses twenty of the eighty amino acids found in nature.
Antiretroviral
A substance that stops or suppresses the activity of a retrovirus such as HIV. AZT (Retrovir), ddC (Hivid), ddI (Videx), and d4T (Zerit) are examples of antiretroviral drugs. Antiviral is sometimes used as an alternate term.
bDNA (branched DNA)
A test for measuring the amount of HIV and other viruses in the blood. Test results are reported in numbers of virus particle equivalents per millilitre of plasma.
Codon
A three-nucleotide genetic subunit that determines which amino acid is placed at one point in a protein chain. Mutations at specific HIV codons are associated with changes in the amino acid sequence of HIV's proteins and enzymes. Such mutations can cause HIV to become resistant to antiretroviral drugs.
Cross-Resistance
The phenomenon by which HIV and other disease-causing organisms become resistant to more than one drug after a single therapy. For example, people who develop resistance from taking one non-nucleoside reverse transcriptase inhibitor (NNRTI) are likely to be cross-resistant to other drugs in the same class.
DNA (Deoxyribonucleic Acid)
A double-stranded molecule that makes up the chromosomes in the centre of a cell and that carries genetic information in the form of genes.
Enzyme
A cellular protein whose shape allows it to hold together several other molecules in close proximity to each other. Enzymes also induce chemical reactions in other substances.
First-Line Treatment
The best starting therapy for someone who has never received therapy before. Because of the potential for the development of cross-resistance by HIV and other microbes, the choice of first-line medication(s) affects the efficacy of subsequent therapies.
Gene
A unit of DNA in the chromosomes that determines the structure of a specific protein or enzyme. Genes regulate the metabolism of individual cells and the development and specialization of body cells and tissues.
The genetic makeup of an individual organism, determined by the sequence of nucleotides in its genes.
Genotypic Assay
A blood test that determines the genetic sequences of an organism. Frequently performed in HIV to establish whether certain mutations conferring drug resistance are present.
HAART (Highly Active Antiretroviral Therapy)
Potent antiretroviral treatment usually including a combination of three or more drugs whose purpose is to reduce viral load to undetectable levels.
IC (Inhibitory Concentration)
The amount of drug in the blood needed to suppress the reproduction of a disease-causing micro-organism such as HIV. For example, IC95 is the drug level needed to block 95% of HIV's normal replication IC50 is the drug level needed to block 50% of HIV's normal replication.
A member of a class of compounds -- including efavirenz (Sustiva), delavirdine (Rescriptor), and nevirapine (Viramune) -- that acts directly to combine with and block the action of HIV's reverse transcriptase to prevent viral RNA from being converted into DNA and integrated into the uninfected cell's nucleus. NNRTIs have suffered from HIV's ability to mutate rapidly and become resistant to their effects.
Nucleoside
The molecular units that serve as the building blocks of DNA and RNA, the genetic material found in living organisms.
Nucleoside Analog
A type of antiviral drug, such as AZT (Retrovir), ddI (Videx), ddC (Hivid), d4T (Zerit), 3TC (Epivir), or abacavir (Ziagen) whose structure constitutes a defective version of a natural nucleoside. Like NNRTIs, these drugs block the viral enzyme responsible for converting HIV RNA into DNA, ultimately preventing the cell from becoming infected.
PCR (Polymerase Chain Reaction)
A sensitive test that amplifies DNA. PCR is a critical part of tests for viral load, genotyping, and phenotyping.
Phenotype
The actual appearance, behaviour, or activity of an organism. HIV's phenotype is affected by its genotype mutations in its genetic structure can alter its behaviour.
Phenotypic Assay
A test that measures the sensitivity of HIV to specific antiretroviral drugs. It is considered more of a direct measure of HIV drug resistance than genotypic tests. See also Genotypic Assay.
Protease
An enzyme that triggers the breakdown of proteins. HIV's protease enzyme breaks apart long strands of viral protein into the separate proteins constituting the viral core and the enzymes it contains. HIV protease acts as new virus particles are budding off a cell membrane.
Protease Inhibitor
A drug that binds to and blocks HIV protease from working, thus preventing the production of new functional viral particles. Examples include saquinavir (Fortovase), ritonavir (Norvir), indinavir (Crixivan), nelfinavir (Viracept), amprenavir (Agenerase), and lopinavir (Kaletra).
Protein
Large molecules made up of long sequences of amino acids. Some hormones and all enzymes and cellular structural components are proteins.
Resistance
Reduction in an organism's sensitivity to a particular drug. Resistance is thought to result mainly from a genetic mutation. In HIV, such mutations can change the structure of viral enzymes and proteins so that an antiviral drug can no longer bind with them. Resistance detected by searching a pathogen's genetic makeup for mutations believed to confer lower susceptibility is called genotypic resistance. Resistance found by successfully growing laboratory cultures of the pathogen in the presence of a drug is called phenotypic resistance.
RNA (Ribonucleic Acid)
A single-stranded molecule composed of nucleotide sequences. It is similar in basic structure to half of the double-stranded DNA. In cells, RNA transmits the code from the DNA-based genes that instruct the cells' chemical machinery to produce structural proteins and enzymes. In retroviruses, RNA is the sole repository of the viral genes.
Sensitivity
The degree to which an organism is affected by a drug.
Wild-Type Virus
Naturally occurring HIV with an optimal genetic makeup and no laboratory-induced mutational defects. The term also refers to HIV that has not been exposed to antiviral drugs and therefore has not accumulated mutations conferring drug resistance.
Ref: Tim Horn. HIV Drug Resistance and Resistance Testing.2001. Text. Queensland HIV research centre. Canberra. 2000.
Disclaimer: All information on this site is provided for informational purposes only! By no means is any
information presented herein intended to substitute for the advice provided to you by any health care or other professional
or organization.
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