How boosting immunity brings colds


In early fall, a few weeks after the start of school, cold viruses
wing their way from one young nose to another and thence to families
and the workplace, infecting people at three to four times the rate at
other times of year. And so the cold season begins and, with it, the
relentless sneezing, coughing and sniffling that continue well into
Most of us come down with at least a couple of colds a year; children
get up to a dozen. But we all know people who seem never to catch one.
Whats their secret? Do they have extraordinarily robust immune
systems, and the rest of us, pathetically weak ones? You might think
this was key, given the number of nutritional supplements, cold
remedies and fortified cereals on the market that purport to augment
the immune system often with the help of vitamins, zinc or ginseng
and by so doing stave off colds.
But science and experience dont back this up. On the contrary, if
youre keen on tamping down your own cold, boosting your immunity
may be the last thing you want to do.
To understand why this is so requires a bit of knowledge about how
colds work. There are more than 200 cold viruses, the most common of
which are rhinoviruses (from the Greek rin-, for nose). When you
encounter a particular strain, your body eventually produces
antibodies to it, which remain on hand to quash that virus the next
time youre exposed. But with so many flavors of cold virus
circulating, theres always a new one to catch.
From the look of it, these ubiquitous cold bugs are mischief-makers in
our bodies. For decades, people thought this was the case that the
runny nose, sore throat and sneezing we experience with colds resulted
from the destructive effects of the virus itself on the innocent cells
of our noses and throats. After all, flu viruses work this way; they
destroy the cells of our respiratory tract, wreaking havoc in our
But, as medical science has realized over the past few decades, the
most prevalent cold viruses in fact do little direct harm to our
cells. In one experiment in 1984, researchers at the University of
Copenhagen performed biopsies on nasal tissue taken from people
suffering severe colds, then did the same after the subjects had
recovered. To the scientists surprise, none of the samples showed any
sign of damage to the nasal tissue. Further vindicating the viruses
themselves was another study around the same time showing that
rhinoviruses infect only a small number of cells lining the nasal
Here was a new insight in cold science: the symptoms are caused not by
the virus but by its host by the bodys inflammatory response.

Chemical agents manufactured by our immune system inflame our cells
and tissues, causing our nose to run and our throat to swell. The
enemy is us.

Indeed, its possible to create the full storm of cold symptoms with
no cold virus at all, but only a potent cocktail of the so-called
inflammatory mediators that the body makes itself among them,
cytokines, kinins, prostaglandins and interleukins, powerful little
chemical messengers that cause the blood vessels in the nose to dilate
and leak, stimulate the secretion of mucus, activate sneeze and cough
reflexes and set off pain in our nerve fibers.

So susceptibility to cold symptoms is not a sign of a weakened immune
system, but quite the opposite. And if youre looking to quell those
symptoms, strengthening your immune system may be counterproductive.
It could aggravate the symptoms by amplifying the very inflammatory
agents that cause them.

In any case, the supplements, remedies and cereals that claim to
strengthen immunity (and thereby protect you from colds) do no such
thing. It would be one thing if by some magic they made your body
produce antibodies to any particular virus. But they dont. And though
some of these products contain ingredients that have been shown in
studies to affect elements of the immune system, theres scant
evidence that they bolster protection against infection by cold
viruses. No one knows which immune agents other than antibodies
accomplish that.
Theres another intriguing paradox here. Studies suggest that about
one in four people who get infected with a cold virus dont get sick.
The virus gets into their bodies, and eventually they produce
antibodies to it, but they dont experience symptoms. It may be that
people like this are not making the normal amounts of inflammatory
It seems counterintuitive, but there it is: People with more active
immune systems may be especially prone to cold symptoms. So getting a
cold may be a positive sign that your biochemical defenses are working
normally a glass-half-full view of getting the sniffles.
Over-Reactive Immune System Kills Young Adults During Pandemic Flu

ScienceDaily (Dec. 6, 2010) — A hallmark of pandemic flu throughout history, including the 2009 H1N1 pandemic, has been its ability to make healthy young and middle-aged adults seriously ill and even kill this population in disproportionate numbers. In a paper published Dec. 5 in Nature Medicine, Vanderbilt University Medical Center researchers provide a possible explanation for this alarming phenomenon of pandemic flu. The study's findings suggest people are made critically ill, or even killed, by their own immune response.

On November 19, Jason Martin returned to the Medical Intensive Care Unit (MICU) at Vanderbilt University Medical Center for the first time since he nearly died there during last year's H1N1 flu pandemic. The tall and burly Warren County, TN, ambulance worker -- a 30-year-old, father of three young children -- broke down and hugged some of the nurses he recognized.
"I got sick on September 12 and didn't come out of it for the next 20 days. I am just so grateful I came through," Martin said, wiping his eyes.
Martin was among the first wave of critically ill middle Tennesseans, hit hard by the H1N1 flu pandemic in late 2009. A hallmark of pandemic flu throughout history, including the H1N1 pandemic, has been its ability to make healthy young and middle-aged adults seriously ill and even kill this population in disproportionate numbers.
"Every time there is an influenza pandemic there is a large proportion of younger, or middle-aged adults who die. We have always explained these deaths, based on presumed virulence of virus, or getting bacterial infection at the same time. We now have vaccines and antibiotics, but still we see middle-aged individuals who die," Polack said.
Polack directs the INFANT Foundation, a research and clinical institute based in Buenos Aires, in close cooperation with Vanderbilt's Vaccine Center. In Argentina, he had a front row seat for the emergence of the H1N1 flu pandemic, which began in April 2009.
As the H1N1 virus burned its way northward through the southern hemisphere, Polack and his team went to work looking for evidence of a biomarker he had used before. A biomarker is a protein that can be measured in blood or tissue whose concentration reflects the severity or presence of some disease state.
"We have seen this before. Where non-protective antibody responses are associated with an immune-based disease in the lung," Polack said.
Polack has previously published evidence that a first-line immune response, primed by an imperfect antibody, can overreact in a violent and uncontrolled fashion. Patients die from lung damage inflicted by their own immune system. A molecule called C4d, a product of this biochemical cascade (the complement system), is a marker for the strength of the response.
In adults who died during the 2009 H1N1 pandemic, high levels of C4d in lung tissues suggest a massive, potentially fatal activation of the complement system.

Pulmonary and critical care physician, Todd Rice, M.D., assistant professor of Medicine at VUMC, has seen people killed by the "exuberant" and uncontrolled response of the immune system in other diseases -- like sepsis.
"This looked every bit like that," Rice recalled about H1N1 patients, including Jason Martin, who piled into his intensive care unit in mid-September, 2009. "It was impressive. These were as sick as any patients I had ever seen. We tried all sorts of things," Rice said.
Ultimately, Vanderbilt's ICU saw 49 adults with H1N1, most ages 25 to 45. Jason Martin was one of 40 who survived.
But Polack wanted evidence beyond what he saw in patients in 2009. He asked Joyce Johnson, M.D., professor of Pathology with VUMC, to look for evidence this phenomenon may have happened during past flu pandemics. Johnson scanned Vanderbilt's hand-penned autopsy ledgers, dating back to 1925. She was able to locate tissue samples in Vanderbilt's tissue archive and extract half a dozen slices of lung tissue from Nashville patients who died during the 1957 Hong Kong flu pandemic.
Pediatric infectious diseases expert, John Williams, M.D., assistant professor of Pediatrics, Microbiology & Immunology, and his lab found the signature for an influenza infection in 4 of the 53-year-old samples, and were able to confirm the lung tissues had high levels of C4d. These patients too had died from an over-reactive immune response.
"C4d is part of the inflammatory cascade, and while it's really good at killing organisms and protecting us, it's sort of the slash and burn approach, capable of causing lots of tissue damage," Johnson said.
But why did infants and the frail elderly escape this mechanism of death in the H1N1 pandemic?
"We found in 2009, the elderly had good immunity because they had seen a very similar virus sometime before 1957. Babies hadn't seen many viruses at all so there was no trigger. It came down to the young adults -- primed with an ineffective response. Their bodies already had defenses against previous influenza viruses that look like this one but weren't close enough," Polack said.

While the patient sample in the current study is relatively small: 75 patients, including 23 who died in 2009, and 4 from 1957, investigators were able to show that other theories, like dampening of interferon, or the triggering of an inflammatory response called a "cytokine storm," were not supported by the evidence. Even the number of viruses present in a flu patient did not seem to correlate with the severity of illness.
"It suggests this (immune over-reaction) is what happens with pandemic to make young healthy adults seriously ill. There are other things that contribute to threat, but this is one of the main things for this age group," Polack said.
While many questions remain, one thing is clear: the H1N1 vaccine offers protection. Patients who died were overwhelmingly unvaccinated. Many fell ill before a vaccine was even available.

A study of genetics will be among the next steps to explain responses experienced by people like Jason Martin. It may be possible to find out who is susceptible to this over-reactive response so they can actively avoid exposure, or receive a specific regimen of treatment. But until then, vaccination is the best idea.