In this case, I'm wondering if the immune system, following a large infection fighting event (i.e. a virus) doesn't naturally suffer a tendency to hyper-respond and auto-stimulate responses to all mannor of molecules that it comes across in the main membranes of the body (such asd lungs) and also local pro-inflammatory tendencies caused by recognising our own molecules or naturally beneficial bacteria as threats, and develop an auto-immune dissorder.
Here is just one aspect to this hyper-responsiveness:
http://www.sciencedaily.com/releases/2007/...71107160135.htm
QUOTE
We think genetically predisposed individuals will tend to have this kind of immune reaction to a severe respiratory viral infection," Grayson says. "In those people an allergic-type response could be part of their antiviral immune response. That sets them up to make antibodies against a lot of environmental substances, like pet dander or pollen, and they can go on to develop allergies or asthma."
Reports by the Centers for Disease Control and Prevention indicate that the number of people with asthma in the United States rose from approximately 7 million in 1980 to about 20 million in 2003. The reasons for this trend are unclear, Grayson indicates. But he suggests that a growing population density and the resulting increase in transmission of respiratory viral infections might be a cause.
Respiratory syncytial virus (RSV) is a common source of respiratory infections. In the United States nearly all children have been infected with RSV by two or three years of age. Severe RSV infections, typified by persistent coughing, wheezing and gasping for breath, send many thousands of children to the hospital each year.
To investigate the connection between severe respiratory viral infections and subsequent asthma, the researchers used mice genetically selected to have an asthma susceptibility and infected them with a virus similar to RSV. They found that severe respiratory infections in the mice induced an allergic-type immune response and ultimately caused long-term changes in the airways of the lungs that are hallmarks of chronic asthma.
The researchers discovered that certain immune cells in the mouse lungs reacted to severe viral infections by releasing compounds that instigated an inflammatory response. That in turn induced many lung airway cells to transform into mucus-producing cells, which can cause the obstruction of lung passages and shortness of breath characteristic of asthma.
The researchers found that interfering with this process by altering the immune cells or removing the inflammatory compounds they secreted prevented overgrowth of mucus-producing cells.
The findings promise a new approach to asthma prevention, according to Grayson. "This offers a different way of thinking about what happens in the development of asthma," Grayson says. "It may be possible to prevent many cases of asthma and other chronic inflammatory airway diseases by stopping allergic-type antibody production after a severe viral infection in infants."
Reports by the Centers for Disease Control and Prevention indicate that the number of people with asthma in the United States rose from approximately 7 million in 1980 to about 20 million in 2003. The reasons for this trend are unclear, Grayson indicates. But he suggests that a growing population density and the resulting increase in transmission of respiratory viral infections might be a cause.
Respiratory syncytial virus (RSV) is a common source of respiratory infections. In the United States nearly all children have been infected with RSV by two or three years of age. Severe RSV infections, typified by persistent coughing, wheezing and gasping for breath, send many thousands of children to the hospital each year.
To investigate the connection between severe respiratory viral infections and subsequent asthma, the researchers used mice genetically selected to have an asthma susceptibility and infected them with a virus similar to RSV. They found that severe respiratory infections in the mice induced an allergic-type immune response and ultimately caused long-term changes in the airways of the lungs that are hallmarks of chronic asthma.
The researchers discovered that certain immune cells in the mouse lungs reacted to severe viral infections by releasing compounds that instigated an inflammatory response. That in turn induced many lung airway cells to transform into mucus-producing cells, which can cause the obstruction of lung passages and shortness of breath characteristic of asthma.
The researchers found that interfering with this process by altering the immune cells or removing the inflammatory compounds they secreted prevented overgrowth of mucus-producing cells.
The findings promise a new approach to asthma prevention, according to Grayson. "This offers a different way of thinking about what happens in the development of asthma," Grayson says. "It may be possible to prevent many cases of asthma and other chronic inflammatory airway diseases by stopping allergic-type antibody production after a severe viral infection in infants."
All very interesting, and matches hypotheses made earlier, including that we may be exposed to unnaturally high rates of chronic-infection causing microbes and respiratory diseases.
But thats not the point. The key idea is that auto-proliferative responses to infection would occur due to the bodies natural communication of the virus threat, priming new cells, and which in turn at sites of infection trigger cells that are pro-inflammatory to proliferate and without checks and balances, very quickly a feedback would occur in which cells would learn to attack perfectly harmless, and vital targets of the body, leading to disease. Following Measles, we noted that there is after infection a long period of anergy or reduced antigen presentation:
http://www.bmj.com/cgi/content/full/313/7063/969
QUOTE
Cell mediated immunity after measles in Guinea-Bissau: historical cohort study
Abstract
Objective: To investigate whether children who have had measles have reduced general cell mediated immunity three years later compared with vaccinated children who have not had measles.
Design: Historical cohort study.
Setting: Bissau, Guinea-Bissau.
Subjects: 391 children aged 3-13 years who were living in Bissau during a measles epidemic in 1991 and still lived there. These included 131 primary cases and 139 secondary cases from the epidemic and 121 vaccinated controls with no history of measles.
Main outcome measures: General cell mediated immunity assessed by measurement of delayed type hypersensitivity skin responses to seven recall antigens. Anergy was defined as a lack of response to all antigens.
Results: 82 out of 268 cases of measles (31%) were anergic compared with 20 of the 121 vaccinated controls (17%) (odds ratio adjusted for potential confounding variables 2.2 (95% confidence interval 1.2 to 4.0); P = 0.009). The prevalence of anergy was higher in secondary cases (33% (46/138)) than in primary cases (28% (36/130)), although this difference was not significant. Anergy was more common in the rainy season (unadjusted prevalence 31% (91/291)) than in the dry season (11% (11/98)) (adjusted odds ratio 4.8 (2.2 to 10.3)). This seasonal increase occurred predominantly in the cases of measles.
Conclusions: Reduced general cell mediated immunity may contribute to the higher long term mortality in children who have had measles compared with recipients of standard measles vaccine and to the higher child mortality in the rainy season in west Africa.
Abstract
Objective: To investigate whether children who have had measles have reduced general cell mediated immunity three years later compared with vaccinated children who have not had measles.
Design: Historical cohort study.
Setting: Bissau, Guinea-Bissau.
Subjects: 391 children aged 3-13 years who were living in Bissau during a measles epidemic in 1991 and still lived there. These included 131 primary cases and 139 secondary cases from the epidemic and 121 vaccinated controls with no history of measles.
Main outcome measures: General cell mediated immunity assessed by measurement of delayed type hypersensitivity skin responses to seven recall antigens. Anergy was defined as a lack of response to all antigens.
Results: 82 out of 268 cases of measles (31%) were anergic compared with 20 of the 121 vaccinated controls (17%) (odds ratio adjusted for potential confounding variables 2.2 (95% confidence interval 1.2 to 4.0); P = 0.009). The prevalence of anergy was higher in secondary cases (33% (46/138)) than in primary cases (28% (36/130)), although this difference was not significant. Anergy was more common in the rainy season (unadjusted prevalence 31% (91/291)) than in the dry season (11% (11/98)) (adjusted odds ratio 4.8 (2.2 to 10.3)). This seasonal increase occurred predominantly in the cases of measles.
Conclusions: Reduced general cell mediated immunity may contribute to the higher long term mortality in children who have had measles compared with recipients of standard measles vaccine and to the higher child mortality in the rainy season in west Africa.
....So my thought is this - why did the children get a year of reduced reactivity after the infection? Could this be evidence that, in systemic inflammation resulting from systemic infection, the body woiuld need to check a potentially runaway auto-immune reaction, as local sites contained proliferating colonies of responders / attack cells, and also recogniser cell that in turn have the capacity to change others leading towards increased inflammation, tissue damage and more chance of auto-immune recognition of natural human molecules.
So this process probably needs a powerful mechanism that also can 'proliferate' and spread to sites of damage or in the immune memory cell pools, and surely both, a 'stop fighting' impact that needs to shut down a stage of wide immune hyperactivity and hypersensitivity, connnected to that population inbalancve and multiple sites of injury, which also raise self-proteins, and which due to infiltration of certain cells, ongoing damage and opportunity for macrophages to identifyu thinbgs abnormally, as with other cells, whilst the mechanisms that normally terminate this are also needed to be in balance, which is lost in major infection and at sites of infection. Traffic of these cells, maybe their proliferation and there signals, can spread such a response.
If viruses kill, and have driven so much evolution, we should also ask, wouldn't the over-aggressive immune response, such as a 'cytokine storm', septic shock or slower proliferative disease all be capable of being tremendous selective pressures as well? Thereby, as immune cells must proliferate and escalate rapidly to keep up with the mounting exponential threat of microbial invasion, so must the regulatory response, once infection is cleared. This idea of a natural, systemic anti-inflammatory I posit may have been evolved by selective pressure to prevent various serious diseases resulting after immune activation, and may act for example at local sites of past immune activity, by switching cell fates to T-Regs amongst others. Perhaps this is ultimately regulated by a pathway which activates once an infection 'all clear' status is identified, and which may be effected by length of response (immune cells that regulate these responses usually have a life span of only a few days), and which could say operate by telling dendritic cells and other key cells and APC to divert central and perhaps also local cell fates and activities, towards anergy. Tissue that is damaged and which has an excess of T Regs may be much more prone to become cancerous as well, so that may be an even longer term disease risk, along with infection.
Heres the Wiki overview http://en.wikipedia.org/wiki/Th2
Well, onec wonders as the immune response that is systemic must need post infection regulation of you'll end up with a potentially run way response, no?
Can anyone comment on this idea?I am not certain from what I have read that the natural defenses against auto-immunity or excessive immune responses would be well functioning and in propper balance after a full on inflammatory event fighting severe infection. A period of anergy might, perhaps 'switch off' this response and put the immune back towards balance, and have been selected for in at least some people, as excess reaction is also a major killer. It may be that this is not seen at major sites of infection, which could have a very different local management.