Training The Immune System To Remember Hiv
Infection-fighting white blood cells could be a key element in developing an effective vaccine treatment against HIV/AIDS.
When exposed to simian immunodeficiency virus , vaccinated monkeys that produced more CD14+ monocytes than CD16+ monocytes mounted a stronger immune response to the infection overall, indicating that vaccines able to elicit the correct balance of immune response will be more successful.
Veronica Falconieri Hays, Falconieri Visuals
Treatment options for infection with the human immunodeficiency virus have greatly improved over the last 30 years, and current prevention tools, such as pre-exposure prophylaxis , can work well, but the ultimate goal in HIV management remains the development of a preventive vaccine. CCR scientists have discovered that a certain type of white blood cell, known as a CD14+ monocyte, may be crucial in that quest.
In response to a foreign invader like HIV, the immune system can initiate an innate or an adaptive response. In the faster innate response, white blood cells recognize molecules found on a broad array of invaders. Once they home in on an invader, they destroy it and release chemical signals that trigger the longer lasting and more specific adaptive response. The adaptive response involves other types of white blood cells that secrete antibodies that bind to proteins found only on certain invaders.
Respiratory And Cardiovascular Systems
HIV makes it hard to fight off respiratory problems such as the common cold and flu. In turn, an HIV-positive person may develop related infections, such as pneumonia.
Without treatment for HIV, advanced disease puts an HIV-positive person at an even greater risk for infectious complications, such as tuberculosis and a fungal infection called pneumocystis jiroveci pneumonia .
PJP causes trouble breathing, cough, and fever.
The risk of lung cancer also increases with HIV. This is due to weakened lungs from numerous respiratory issues related to a weakened immune system.
According to available research , lung cancer is more prevalent among people with HIV compared to people without it.
People with HIV are more likely to develop high blood pressure. HIV also raises the risk of pulmonary arterial hypertension . PAH is a type of high blood pressure in the arteries that supply blood to the lungs. Over time, PAH will strain the heart and can lead to heart failure.
If a person has HIV with a low CD4 count, theyre also more susceptible to tuberculosis .
TB is an airborne bacterium that affects the lungs. Its a leading cause of death in people who have AIDS. Symptoms include chest pain and a bad cough that may contain blood or phlegm. The cough can linger for months.
Characteristics Of T Cells
The T cell lineage is a unique subset of innate-like T lymphocytes that offer an attractive alternative to conventional T cells, which predominate in current cell-based immunotherapies. Since their discovery in the 1980’s, T cells have been shown to contribute to tumor surveillance, fighting infectious disease, and autoimmunity . Their defining feature is a T-cell receptor comprised of variable and chains that recognizes non-peptidic antigens in the absence of Major Histocompatibility Complex molecules . T cells develop and mature in the thymus and constitute the first T cell population to migrate and populate the periphery during fetal development. Interestingly, there is a correlation between tissue localization and the V chain expression in the TCR indicating a predefined role for T cells before leaving the thymus . Although the specific mechanisms of T cell development and differentiation are still being elucidated, the correlation between V chain expression and tissue localization is well-established .
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How Do People Get Hiv
HIV spreads when infected blood or body fluids enter the body. This can happen:
HIV also can pass from mother to child during pregnancy, childbirth, or breastfeeding.
HIV is NOT spread through:
- pee, poop, spit, throw-up, or sweat
- coughing or sneezing
- sharing eating utensils or drinking glasses
Can Hiv Be Prevented
To reduce the risk of getting HIV, people who are sexually active should:
- use a condom every time they have sex
- get tested for HIV and make sure all partners do too
- reduce their number of sexual partners
- get tested and treated for STDs having an STD increases the risk of HIV infection
- consider taking a medicine every day if they are at very high risk of getting infected
For everyone:
- Do not inject drugs or share any kind of needle.
- Do not share razors or other personal objects that may touch blood.
- Do not touch anyone else’s blood from a cut or sore.
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What Is The First Immune Response
Innate immunity is the first immunological, non-specific mechanism for fighting against infections. This immune response is rapid, occurring minutes or hours after aggression and is mediated by numerous cells including phagocytes, mast cells, basophils and eosinophils, as well as the complement system.
How Is Hiv Treated
Treatments for HIV typically involve antiretroviral therapy. This isnt a specific regimen, but instead a combination of three or four drugs. The U.S. Food and Drug Administration has currently approved nearly 50 different medications to treat HIV.
Antiretroviral therapy works to prevent the virus from copying itself. This maintains immunity levels while slowing the progression of HIV.
Before prescribing medication, a healthcare provider will take the following factors into consideration:
- a persons health history
- the levels of the virus in the blood
HIV doesnt cause a lot of outward or noticeable symptoms until the disease has progressed. For this reason, its important to understand how HIV is transmitted and the ways to prevent transmission.
HIV can be transmitted by:
- having sex, including oral, vaginal, and anal sex
- sharing needles, including tattoo needles, needles used for body piercing, and needles used for injecting drugs
- coming into contact with body fluids, such as semen, vaginal fluid, blood, and breast milk
HIV is not transmitted by:
- breathing the same air as a person living with HIV
- getting bitten by a mosquito or other biting insect
- hugging, holding hands with, kissing, or touching a person living with HIV
- touching a door handle or toilet seat thats been used by an HIV-positive person
Keeping this in mind, some of the ways a person can prevent HIV include:
Symptoms can take years to appear, which is why its so important to get tested regularly.
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Ex Vivo Manipulation Of T Cells
In addition to ex vivo expansion, T cell therapies could stand to benefit from advances in gene editing or inclusion of immunomodulators such as designer antibodies or pro-cytotoxic drug compounds. Transduction of TCRs could bestow T cells with additional antigen recognition of intracellular peptides presented within MHC molecules whereas CARs could be engineered to recognize specific extracellular markers. Traditionally, these modifications have been applied to T cells to target cancer with mixed results, the chief concern being off-target toxicity and ensuing cytokine storm that leads to systemic immune activation . Applying these modifications to T cells has shown promise for eliminating these issues while maintaining antigen-specific effector function and therefore constitute an additional advantageous manipulation to consider when targeting HIV-infected cells .
How Does Hiv Destroy The Immune System
HIV will only attack and reproduce in one cell type. The virus needs to bind to a specific molecule on the cell surface, known as CD4, to access the cell. There are many cell types in the body with CD4 molecules on the surface that can be attacked by HIV. The most important white blood cells are called T4 lymphocytes or helper cells. They play a key role in the immune response because they direct all the other cells and signals.
Healthy people have between 800 and 1,200 CD4 lymphocytes per microlitre of blood. When HIV attacks a CD4 cell and uses it to produce new viruses, the cell is destroyed. HIV destroys a large number of CD4 cells every day and eventually the bone marrow will be unable to maintain the production of new cells. The number of CD4 cells will therefore be gradually reduced. When the CD4 count sinks to 200-300 per microlitre, the immune system is so impaired that the person can contract illnesses that the body would otherwise be able to control.
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Hiv Interferes With Normal Immune Response
With HIV infection, this procedure does not work adequately. Initially, macrophages recognize the HIV, T-helper cells initiate the response, and B cells produce antibodies. However, although effective at first, the antibodies do not eliminate the infection. Although some HIV might get killed, many more viruses will actively infect T-helper cells — the very same cells that are supposed to coordinate the defense against the virus. Infected T cells become virus factories which, if activated, will produce more copies of the virus instead of triggering the production of more antibodies against HIV.
Besides T cells, HIV is capable of infecting other cells and can cross the brain-blood barrier, infecting nervous system cells. Most immune cells cannot cross that barrier, which surrounds the brain and spinal cord, so HIV can retreat where the immune system cannot follow.
The immune system is very complex and many of its processes are still not understood. This brief explanation of the immune response coordinated by the T-helper cells will help you understand issues surrounding immune monitoring and treatment for HIV disease. Some of the tests that are used to monitor the health of HIV positive people show how well the immune system is working , while others show the number of copies of the virus in the body . Monitoring and early treatment can be crucial in determining the course of HIV disease and making informed choices about treatment.
San Francisco AIDS Foundation
Antiretroviral Treatment And The Hiv Lifecycle
Antiretroviral treatment for HIV combines several different types of drugs, each of which targets a different stage in the HIV lifecycle. This means that the replication of HIV is stopped on multiple fronts, making it very effective.
If taken correctly, it keeps the immune system healthy, prevents the symptoms and illnesses associated with AIDS from developing, and means that people can enjoy long and healthy lives.
If someone doesnt take their treatment correctly or consistently , the level of HIV in their blood may increase and the drugs may no longer work. This is known as developing drug resistance.
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Can Hiv Be Prevented Or Avoided
The best way to prevent HIV is to not have sex with a person who has HIV, or share a needle with a person who has HIV. However, there is also a medicine called PrEP that people can take before coming into contact with HIV that can prevent them from getting an HIV infection.
PrEP stands for pre-exposure prophylaxis. It is for people who are at long-term risk of getting HIV either through sexual activity or by injecting drugs. If youre taking PrEP and come into contact with HIV, the medicine makes it difficult for HIV to develop inside your body.
Other ways to prevent HIV include:
- When you have sex, practice safer sex by using a condom. The best condom is a male latex condom. A female condom is not as effective but does offer some protection.
- Do not share needles and syringes.
- Never let someone elses blood, semen, urine, vaginal fluid, or feces get into your anus, vagina, or mouth.
What Is An Hiv Viral Load
A viral load test counts the number of HIV particles in a sample of blood. The result is expressed as the number of copies of HIV RNA per ml of blood. It is now generally accepted that 10,000 copies per ml or less, is considered low and 50,000 copies per ml and above, is considered high.
There are several tests that measure the amount of HIV particles present in the blood, although the tests become unreliable at low levels of infection. Originally this limit was less than 400 or 500 copies per ml. New ultra-sensitive tests are now able to measure to a lower limit of 50 copies per ml and these may become the tests that are more widely used. Depending on the test used, a measurement below the limit of detection may be referred to as undetectable.
The test for viral load is one of the monitoring tests that can indicate disease progression and may give an indication as to the likely course of HIV infection if left untreated. It is generally accepted that a higher viral load may lead to more rapid disease progression. Other indicators such as CD4+ count and symptoms should also be considered when deciding to take treatment.
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Adaptive Immune Response To Hiv
Cellular immune response to HIV. The cellular immune response is induced upon the entry of HIV into the target cells and synthesis of viral proteins . MHC class I on the cell surface displays the intracellularly degraded HIV peptide fragments for recognition by T-cell receptors on CD8+ T cells . CD8+ T cells lyse HIV infected cells and secrete cytokines, i.e. interferon- , tumor necrosis factor , and chemokines, i.e. MIP-1 , MIP and RANTES, that inhibit virus replication and block viral entry into CD4+ T cells. Development of CD8+ T cells is crucial for control of HIV replication. This results in declining viraemia after primary infection. In the early stages of infection, CD4+ T cells lose their proliferative capacity and therefore their contribution to viral control is minor. However, during chronic infection CD4+T cells are present and secrete interleukin-2 or cytokines, such as IFN-, to control viraemia.
Figure 3.
Innate And Adaptive Immune System
There are two subsystems within the immune system, known as the innate immune system and the adaptive immune system. Both of these subsystems are closely linked and work together whenever a germ or harmful substance triggers an immune response.
The innate immune system provides a general defense against harmful germs and substances, so its also called the non-specific immune system. It mostly fights using immune cells such as natural killer cells and phagocytes . The main job of the innate immune system is to fight harmful substances and germs that enter the body, for instance through the skin or digestive system.
The adaptive immune system makes antibodies and uses them to specifically fight certain germs that the body has previously come into contact with. This is also known as an acquired or specific immune response.
Because the adaptive immune system is constantly learning and adapting, the body can also fight or viruses that change over time.
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Questions To Ask Your Doctor
- Is there any sure way to avoid acquiring HIV?
- What is the best treatment for me?
- How can I avoid getting any infections that will make me very sick?
- How can I find support groups in my community?
- What diagnostic tests will you run?
- How often will I need to see my doctor?
- Will there be any side effects to my treatment?
- How does this affect my plans for having a family?
- Is it safe for me to breastfeed my baby?
- Will using a condom keep my sex partners from acquiring HIV?
- Should I follow a special diet?
Normal T Cell Response To Infection
Let’s look first at how the immune response coordinated by the T cells is supposed to work. Please keep in mind that we will be explaining only one of the body’s immune responses.
Any infectious agent that enters your body will eventually be taken up in your lymphatic system.
This may happen very soon after infection, or it may not happen until the invader has found a niche and begun to replicate. In one of your lymph nodes, the infectious agent will bump into a macrophage . The macrophage will ingest the invader .
Then the macrophage takes the invader apart and displays the viral antigens on its surface for other immune cells to read .
Antigens are proteins specific to each particular microorganism. The antigens act as an identity card that allows our immune system to recognize invader organisms that need to be eliminated.
After displaying the agent’s antigens, the macrophage will send out a message to a T-helper cell to read and recognize the antigens .
This message activates T-helper cells and triggers the immune response. Once the T cell has read the antigens, it will send out messages to activate other cells, known as B cells , which will in turn come and read the antigens from the macrophage’s surface .
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Stages Of The Hiv Lifecycle
Binding and fusion
HIV attaches to a T-helper cell. It then fuses to it and releases its genetic information into the cell.
The types of drugs that stop this stage of the lifecycle are called fusion or entry inhibitor drugs because they stop HIV from entering the cell.
Reverse transcription and integration
Once inside the T-helper cell, HIV converts its genetic material into HIV DNA, a process called reverse transcription. The new HIV DNA then enters the nucleus of the host cell and takes control of it.
The types of drugs that stop this stage of the lifecycle are called NRTIs , NNRTIs and integrase inhibitor drugs.
Transcription and translation
The infected T-helper cell then produces HIV proteins that are used to produce more HIV particles inside the cell.
Assembly, budding and maturation
The new HIV is put together and then released from the T-helper cell into the bloodstream to infect other cells and so the process begins again.
The type of drugs that stop this stage of the lifecycle are called protease inhibitor drugs.