Immune activation resulting from the immune system caused by the presence of HIV
There are several emerging concepts that can shed light on these issues. "Perpetual inflammation" - the prolonged state of immune activation resulting from the immune system while the battle with the virus (ad eternum) continues, appears to be a key factor in metabolic disorders and cardiovascular diseases. The research also revealed that the digestive tract may play a much larger role in the progression of HIV disease. In fact, it can be one of the sources of immune activation.
InfecYesthe precocious, the intestine and the vísceras.
Evidence now suggests that by looking only at the céCDXUMUMX, may have underestimated the overall and early impact of this early decline. Just a small fracYeso (2%) of the céCD4 present in the body sãthe effectively found in circulating blood.
Most live on lymph nodes (these include the 'glands' you can sometimes feel in the neck and inguinal region when you have an infection), in the intestines and viscera associated with lymphoid tissue. Where they are present as patches of immune cells lining the entire length and extent of the intestines and lining the mucous membranes as well as other organs liable to be exposed to foreign substances such as the lungs and genitalia. The researchers observed a massive loss of CD4 memory cells in intestinal tissues and viscera surprisingly and immediately after infection.
Danny Douek, a researcher at the US National Institute of Allergy and Infectious Diseases (NIAID), studied the process closely and said,
"We thought CD4 cells were lost slowly and surely during the course of the disease. We have observed that most outer memory T cells - which are the majority of CD4 cells in an adult - are lost extremely rapidly. " About 60% of immune memory cells become infected, and most people can disappear within the first two weeks of infection!
Ideally, HIV treatment may need to beYesagainst immunodeficiencyêinfections, and also against infectious. É prováthat this is a complex objective, and the consensus é that a considerable amount of research toinda é necessária.
In addition to pickling with the tissue of many CD4 cells, HIV also causes structural damage to intestinal immune tissue and to the lymph nodes where many immune cells normally reside. Recent studies have found that these tissues have become marked with collagen tissue during acute infection. Researchers speculate that this damage interferes with normal cell growth and HIV interaction, limiting the ability of the immune system to fully regenerate lost CD4 cells in early infection. Tissue damage in intestines and viscera may also contribute to inflammation that helps lead to later stages of HIV disease.
To infectYesthe crônica: why céCD4 squid die?
After the intense few weeks of acute infection, the body begins to produce antibodies and immune cells that specifically target HIV. During this period (known as immunological window), there is a drop in viral load level and the count of cells CD4 returns to near normal levels. At this point, the disease enters a prolonged phase known as chronic infection.
Is the virus directly that kills CD4 cells? It is easy to assume that it should be the main reason for the eventual drop in counts of CD4. But the truth is more complex. Considerably less than 1% circulating CD4 cells are actually infected by HIV during chronic infection - very little to explain the overall loss - Is millions of new CD4 cells are created every day. In recent years, researchers have discovered possible other means by which HIV leads to the loss of CD4 cells. These include toxic tissue damage to viral proteins, flashes by infected cells, which can kill uninfected cells in the so-called "viewer effect". HIV can also lead to cells in "suicide" in a process called cellular apoptosis,or programmed cell death.
Other mechanisms are likely to be "In this job" as well as including - ironically - the answer itself of the immune system against HIV. The virus can infect only activated CD4 cells - those that have been "linked" to fight the infection. In other words, by the very act of taking action against the virus, all CD4 cells not activated to destroy HIV become targets for infection. This paradox is inevitable to a certain degree, from the activation of immune cells, which is an essential part of immune function.
However, there is growing evidence that prolongation and excessive immune activation - inflammation – underlining much of the ongoing harm caused by HIV disease. (Editor's note: Speculating, I come to believe that in addition to the neuropathic pain, that I threw myself, today, January 5, two thousand and eighteen, literally in bed, that I suffer, along with my wife, from this thing of the inflammation ... a touch more intense and one of us both says there and our spirit is not the same one of old ...)
The idea that inflammation plays an important role in HIV disease was first proposed by the end of the decade. But it has become the center of attention only recently. One of the first great clues came from intelligent study. This large-scale trial investigated whether people who remained on continuous antiretroviral therapy achieved improvement or worsening than those who took structured treatment discontinuations - stopping treatment when their CD4 count rose above 350 cells / mm3 and resumed when the count dropped below 250 cells / mm3.
The SMART study was stopped early after interim results clearly showed that people who discontinued their treatment were more than twice as likely to become seriously ill or die. It is revealing that the facts of treatment switches were not only at risk of "traditional" opportunistic infections. They also had higher rates of heart, liver and kidney disease - metabolic problems that are often associated with inflammation. If HIV was to drive up to levels of immune activation, one would expect to see more inflammation of pollution-related diseases in people whose HIV replication grew freely, allowing them to replicate wildly - just as it was seen in the SMART.
Other studies have confirmed that immune activation is actually a very good way to predict how fast the HIV disease is progressing. People with higher blood pressure levels of a substance called C-reactive protein (CRP) - known to be a sign of immune activation - progress the worst phase of AIDS faster than those with low levels. (PCR is in fact a much better predictor of HIV viral load progression).
So why does immune activation persist after treatment instead of dropping to almost normal levels when HIV replication has been controlled by antiretroviral treatment? So far, this is one of the most speculative areas of the hypothesis. But many researchers are convinced that the answer is back where we started - in infected tissues of the digestive tract.
Back to the ev intestinesísceras
The lymphoid tissue in the intestines and viscera carries "vigilance" on everything that "happens in these places" on the microbes in the digestive tract - whether they are disease-causing organisms from contaminated food or water or "bacteria friends "that colonize the gut and aid digestion and provide" fixation responses that keep the microbes out of the bloodstream. As discussed earlier, the lining of the intestines can sustain long-lasting damage during HIV infection, making it permeable or "dripping".
Danny Douek explains: "The outer wall of most bacteria in the gut contains what is known as endotoxins or lipopolysaccharides (LPS). LPS is extremely immunostimulatory. In people with sepsis or toxic shock, you will see overwhelming immune activation due to huge amounts of LPS in their systems. In people with HIV infection, we have found LPS in the bloodstream - not with the same amounts during sepsis, but sufficient to activate immune cells. We have measured also high levels of other bacterial products, all of which are immune activators, in the bloodstream of people with HIV infection. "
This hypothesis is known as microbial translocation.
Given the complexity of the topic I suggest reading this article that opens in another tab: Progression vs. non-progression of HIV infection: Learning from natural hosts(academic language).
However, many researchers suspect that immune activation has many causes.
"I'm not convinced that the microbial translocation of the intestines and viscera is the only response to HIV-related inflammation," says Robin Weiss, a professor of viral oncology at University College London. "We also see sustained activation immune to malaria, and no one is proposing thatmicrobes intestinal and visceral as a source of immune activation. " Other candidates for HIV infection progression (the disease itself and not AIDS, another stage in the life of people with HIV that is only achieved if not treated.) I Cláudio Souza vos I CALL TO BE TESTED AS THIS CAN BE THE DIFFERENCE BETWEEN LIFE, DEATH OR A LIFE WITH A QUINITY OF FULL SUFFERING.
This may include immune stimulation caused by other infections, and the depletion or deactivation of regulatory T cells, which play a key role in cooling immune activation. Immune cells also produce a variety of 'messenger' chemicals known as cytokines, warning other cells to adjust their immune activity. HIV can confound this immune communication network by disrupting cytokine production. As well as unraveling these complex processes; researchers should also investigate one of the biggest remaining issues: for HIV-positive patients, humans are not able to correct for excessive immune activation, as do other chronic diseases such as viral hepatitis C or simian monkeys.
LTNPs and elite controllers: why reasonãDoes HIV not progress in some people?
For reasons that are not well understood a minority of HIV positive individuals are long-term nonprogressors (Elite controllers), or LTNPs - they maintain high CD4 cell count much longer than most. One particularly fortunate group, the so-called elite controllers, is able to keep HIV's viral load at undetectable levels with no other antiretroviral treatment.
One reason may lie in the immune system of CD8 cells, which control HIV by destroying infected cells. In most infected individuals, CD8 cells are present in high numbers but appear unable to respond adequately to HIV. LTNPs can be blessed with CD8 that remain capable of strongly attacking HIV-infected cells. The reasons for this are probably genetic.
In order to reduce cardiovascular and comprehensive risk for HIV treatment beá necessáto reduce inflammationYesthe control nãthe replica onlyYesor viral.
Jean-Pierre Routy, McGill University
In fact, many genetic differences between individuals can affect the vulnerability to HIV infection and the rate of disease progression. For example, to infect a CD4 cell, HIV needs to lock itself in two specific parts of the cell surface - the CD4 molecule, in addition to one of the two "co-receptors" called either CCR5 or the CXCR4 receptors - most viruses uses CCR5. A small percentage of people lack one or more of the genes needed to generate CCR5. In people with a single missing gene, and HIV develops much more slowly: these people have fewer CCR5 molecules, giving HIV less goals. Those who are entirely lacking ingenes CCR5 seem totally devoid of the vast majority of HIV strains and in fact we now have a drug, Celsentri maraviroc,which mimics this situation by blocking CCR5 receptors.
Other genes called things likeI will watchYeso, and APOBECcontrol other immune defense mechanisms that interfere with the various aspects of the life cycle of viruses (not just HIV). HIV has in turn developed defense antigens asNEF engines, and brightwhich neutralize these cellular defenses - but we could develop drugs that in turn will block those genes and allow the cell to control HIV. Natural variations in these genes may explain why some people have better control over their infection more effectively and can influence the sensitivity of different populations to infection - the mutation that deletes the CCR5 gene, for example, occurs in about 1% of Caucasians in Northern Europe, but virtually none of African blacks. (poor Africa ... And no one cares)
The Future, what our goals and challenges?
Regardless of the immune stimulation that seems to help drive HIV disease, in the end we are trying to avoid the opposite - thedeficiêimmunologyógicawhich leaves people vulnerable to fatal opportunistic infections. Ideally, HIV treatment may need protection against both immunodeficiencies and stimulation. This is likely to be a complex goal, and the consensus is that considerable considerable research is still needed. Editor's Note: I always remember the healing promised and proclaimed in a video that looks more like an overproduction, cure for 2020 !!!!!
McGill University's Jean-Pierre Routy believes that in order to reduce cardiovascular risk is comprehensive for HIV treatment "will be necessary to reduce inflammation and not just viral replication control." As we do this will almost certainly include a push towards starting treatment earlier, but "Adding anti-inflammatory to antiretroviral treatment may be the best way to avoid long-term immune hyperactivation." Clinical assays of anti-inflammatory agents such as chloroquine are defined to begin with, but such assays must be made with caution not to induce the wrong type of immunosuppression.
What is the role and then for "immune activation and enhancement of treatments as with interleukins? Large and very long-lasting trials of interleukin-2 (IL-2) recently concluded that, despite lifting CD4 counts, IL-2 resulted in no long-term improvement. Indeed, people who received IL-2 were more likely to develop serious diseases, namely a blood vessel array and cardiovascular problems that are probably due to inflammation. However, there are dozens of interleukins and other cytokines that regulate the immune system and interact with each other: immune-enhancing and immune suppression, are probably too simplistic forms of visualization as a complex network. Says Routy, "We do not have this understanding of HIV and inflammation when the IL-2 assays were designed twelve years ago. There may be different benefits with IL-7 or other cytokines. "
Asçearly treatment for HIV.
While many details are still being investigated, there is a growing consensus around a key point: the need for antiretroviral treatment. If the course of HIV infection poses greater health risks in the future HIV treatment not - as SMART and other studies suggest - then early treatment would be justified. Large comparisons of cut-off studies are finding that as treatment is initiated at a higher level of CD4 counts, the risk of AIDS-defining illnesses or death steadily declines. The trend is valid until the start of treatment in CD4 counts of 350 cells / mm3, although the benefits of starting treatment at the same higher counts are less clear.
Is the case of prior treatment persuasive enough to change treatment decisions for people with HIV? As an example, Richard Carson, diagnosed in 2005, is uncertain. By the current treatment guidelines, Richard robust CD4 counts (635 cells / mm3 at the last count) and low viral load (1550 copies / ml) allowed him to look at antiretrovirals as a distant prospect. He has heard the arguments but is not fully prepared to make the leap to treatment as a result. "In the end, I'm going to do everything that's best for me," he says. "I have heard many reasons why InãI owestarting treatment yet - the side effects, the risk of resistance. If there is more solid evidence that I should expect, so I could change my position. "
A final challenge may simply be to try to accommodate new evidence and insights into a preexisting model that no longer fits. CD4 cell depletion has often been understood by a simple analogy to "irrigate and drain": Picture the CD4 cell count as the level of water in a heatsink, with the drain open and the touch to work. CD4 cells are destroyed as they are infected with HIV (drainage), but replenished as the body produces more (the tap). When the tap can no longer keep pace with the drain, there is a drop in CD4 cell counts and this is the beginning of the progression of HIV infection to the Acquired Immunodeficiency Syndrome (AIDS would be the correct acronym for us, which we speak Portuguese, I insist, but I also call it AIDS.
As we know there are many factors that affect the progression of the disease, it will be difficult to abandon this simple image and demonstrate a more complex one. Danny Douek thinks not: "I do not necessarily think that more precise means more confusing and complex. The original model of a drain cock is really a good model. I think we have simply realized that there may be more faucets and more drains. I think the model is still very well, but it is becoming more complete and sophisticated. Ultimately it will be simpler because it will make more sense and leave less attended. "
The immune system is a set of different cells that do different jobs.
Some cells assemble non-specific rapid reactions, such as allergies, to get rid of foreign substances.
Others, like monocytes, engulf and digest invaders sometimes (phagocytosis)
B cells secrete antibodies, proteins that surround specific invaders and also block them physically by preventing them from acting on cells or signaling them (the infected and blocked cells) for destruction.
T cells divide into CD8 cells, which destroy already infected cells or CD4 cells, which regulate and amplify other functions of the immune response.
Both B and T-cells can be memory cells, sensitized against specific invaders for rapid response against them in the future. The process similar to that of a vaccine, such as Yellow fever (This link leads to a survey of vaccination posts against yellow fever throughout Brazil) for example.
And the "B" and "T" cells can also be activated. By activating cell work at infection sites, and they are short-lived.
Another theoretical strand tries to explain and test whether and how HIV slowly destroys the immune system, causing T-cells to start living in a stressful state of permanent activation that ultimately leads the immune system to exhaustion.
My thoughts on the text: At first glance, HIV is a rather intricate "viral particle" in relation to processes that are directly or indirectly related to its presence and, despite of everything, so far, after mid-1996 (I still remember reading on the cover of a "scientific" magazine:
HIV - One percent of the cure.
God knows what actions have been taken, in the field of decisions made in relation to the sexual life of each person, endowed, of course, with free will, which may have led them to adopt based on this assertion.
- "Ahhh ... after all only 1% is missing" ...
Do not know. I know that more than twenty years later and this one percent has not been achieved and I have not seen anything that makes me optimistic about healing in 2020, although I very much want to be wrong in my disbelief.
The important thing of all is: Test yourselves.
The sooner you come to know, the better the prognosis and the lesser the damage done.
If you believe you may be infected, run and take the test, window period. After that, whatever the outcome, accept it and take the necessary actions for each of the answers.
And if you have questions about reliability of SUS…