Category Archives: Immunology

Want To Boost Your Immune System? Get Vaccinated!

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As an Allergist/Immunologist, I am asked all the time: “how do I boost my immune system?”  This is a great question and will be the subject of a number of posts to this blog.  Today, in part because of the current highly emotional media coverage of a measles outbreak, the focus will be on vaccination.  The scope of this post will be informational: how vaccines were discovered and how vaccines work within the context of the immune system.  I hope that good information of this sort will help people make informed decisions about vaccinations for themselves and their families.

The Discovery of Vaccines

The early history of vaccines and vaccination had to do with smallpox.  This viral disease is believed to have appeared around 12,000 years ago and led to large-scale epidemics.  These epidemics were so severe that they affected the course of history.  For example, the first stages of the decline of the Roman Empire, in the year 108 AD, coincided with an epidemic of smallpox that led to the deaths of almost 7 million people.  But smallpox was also a continual problem in more recent history.  For example, in the 1700s, 400,000 people died every year in Europe of the smallpox.  Aside from death, smallpox left disfiguring scars and one third of survivors lost their sight.

The original attempts at prevention of smallpox were called variolation (inoculation).  In variolation, a lancet wet with pus taken from someone infected with smallpox was subcutaneously introduced on the arm or leg of a non-immune person.  This technique was effective in inducing immunity to smallpox, but 2-3% of variolated people died from the disease, became the source of another smallpox epidemic, or were infected by another disease (such as tuberculosis or syphilis) from the pus used in the variolation.

The incomplete success of variolation led scientifically-minded individuals to begin to consider other methods of preventing smallpox.  Such a person was Edward Jenner, the “Father of Vaccination.” He, and others, had observed that dairy maids who can contracted the cowpox were protected from contracting smallpox.  On May 14, 1796, Jenner used pus from the cowpox lesions of Sarah Nelms (a dairy maid) to inoculate an 8 year old boy.  This boy was later variolated with pus from fresh smallpox lesions and he did not develop smallpox.  This is how the vaccine era began.  In fact, the term “vaccination” was invented by Jenner and was derived from the Latin words for cow (vacca) and cowpox (vaccinia).

How Vaccines Work

How did the process of injecting pus from sick people into perfectly healthy people work?  Why was the pus from smallpox lesions unsafe and the pus from cowpox lesions relatively safe?  To understand the answers to these question, it is first important to understand some basics about how the immune system functions.  Broadly speaking, we have two types of immunity: innate and adaptive immunity.  Innate immunity refers to automatic immunity.  Picture a mousetrap.  This trap will snap shut, in an automatic way, whenever the cheese in the trap is removed by a mouse. But mice find ways to outsmart the mousetrap and get the cheese, anyway.  This is the reason for adaptive immunity.  This concept refers to immunity that is learned. In other words, the immune system has components that can learn to fight off specific infections.

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In the case of smallpox variolation, the adaptive immune system is exposed to the smallpox virus and, if the recipient of the variolation does not get sick and die, learns to become resistant to future infections with the smallpox virus.  Cowpox virus is similar to smallpox virus.  In fact, these viruses are so similar that the adaptive immune system, when learning to fight off cowpox virus, simultaneously learns how to fight off smallpox virus.  The big advantage, here, is that people don’t get sick or die with the cowpox virus.  Therefore, the cowpox virus works in vaccination because it mimics the smallpox virus without causing illness.

Mimicking a real infectious agent without causing illness is the fundamental concept behind every vaccine we have today.  Some modern vaccines use viruses that have been killed, and cannot cause infections, but still can allow the adaptive immune system to learn to fight the live virus.  Some other vaccines use synthetic analogs of infectious agents, but the concept is all the same.

Influenza Vaccine

Influenza virus is an annual challenge, worldwide.  Unlike the smallpox virus, which changes little over time, the influenza virus mutates as it spreads.  Therefore, every year, people need to be re-vaccinated to protect against new strains.  The World Health Organization takes the lead in formulating the components of the influenza vaccine each year.  It holds meetings in February, to recommend viruses for inclusion in vaccines for the northern hemisphere, and in September to recommend viruses for inclusion in vaccines for the southern hemisphere.  A typical trivalent influenza vaccine will contain strains of influenza A subtype H1N1, influenza A subtype H3N2, and influenza B.  In a quadrivalent vaccine, another strain of influenza B is typically added.  The selection of the strains of influenza to be used for vaccines is challenging and the match is better in some years than others.  The concept used by Edward Jenner with smallpox is exactly the same as that used for influenza vaccine: use an alternative, safer agent to teach the adaptive immune system to protect against the influenza virus, without actually causing the disease.  The technology, however, has become very sophisticated and continues to improve.  For example, older types of influenza vaccines contain inactivated influenza virus.  This is essentially “dead” virus that cannot cause influenza infection but that still contains the important elements to trigger the adaptive immune response.  More recently, live attenuated influenza vaccine has become available.  This is the well-known “nasal spray flu vaccine” and it contains virus that is live, but has been weakened so that it cannot cause actual influenza.  In January, 2013, the United States Food and Drug Administration approved a recombinant influenza vaccine.  Influenza viruses are not used at all in the manufacture of this vaccine.  Instead, a protein of the influenza virus is made by genetically modifying a virus that infects insect cells, which, in turn, produce this protein.  When this protein is used in vaccines, it can teach the adaptive immune system to resist live influenza virus.

Boosting the immune system involves making it stronger.  This concept largely has to do with teaching the adaptive part of the immune system to fight off more types of infections.  Vaccines, therefore, are a very effective way to boost our immune systems without forcing us to get sick with epidemic infections.

Posted February 7, 2015

Reference:

Riedel, S. Edward Jenner and the history of smallpox and vaccination. BUMC Proc. 2005; 18:21-25.

Resources for further reading:

www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm

www.fda.gov/consumer

www.immunologyexplained.co.uk/howitworks.aspx

www.nlm.nih.gov/medlineplus/druginfo/meds/a607017.html

www.nlm.nih.gov/medlineplus/druginfo/meds/a607018.html

www.who.int/influenza/vaccines/virus/recommendations/201402_recommendation.pdf

 

 

Is Cycling or Running More Likely to Lead to Colds in Triathletes?

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I train in swimming, cycling, and running multiple times a week.  While I am not as fast or efficient as I want to be in any of these three disciplines, I always feel the most drained after a hard run. Based upon this experience (an “n of 1”, so to speak), I would predict that intense running would make the typical triathlete more vulnerable to colds.  But, what is the evidence?

A recent abstract addresses this question.  My previous post in this blog explained that the level of the antibody, IgA, is affected by intense exercise and that people with lower levels of this antibody are predisposed to get colds (upper respiratory tract infections or URTIs).  In this study, eight male high-level triathletes (average age: 32.8 and average VO2 max: 72.6 ml/kg/min) performed a two hour bout of exercise at 55% of peak power output on both a cycle ergometer and a treadmill, separated by seven days.  Saliva samples were obtained pre- and post- both protocols to measure IgA (salivary IgA or sIgA).  Rates of secretion of sIgA and flow of saliva were also calculated for sIgA based on volume of saliva and time taken to produce a set volume.  Here were the findings (units were omitted for clarity):

sIgA pre sIgA post IgA secretion rate pre IgA secretion rate post saliva flow pre saliva flow post
Treadmill 595 841 (*) 396 223 (*) 658 289 (*)
Cycle Ergometer 594 779 284 216 487 320
(*) statistically significant change

The authors state that “previous studies have shown that with a decrease in sIgA secretion rate and saliva flow rate there is subsequently going to be an increase in URTI episodes [e.g. colds] in the individual. This increase in URTIs can hamper an athlete’s preparation for competition resulting in sub-par performance, which may result in loss of sponsorship deals or contracts.”  They conclude that “the results suggest that long duration running may be more detrimental to immune function than long duration cycling in triathletes.”

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These interesting results must be viewed with caution.  First of all, this report is an abstract, not a peer-reviewed journal article.  This means that the methods and conclusions were not carefully critiqued by experts in the subject, and, also, since abstracts are brief reports, we, the readers, cannot see all the details of the study.  Another area of caution has to do with this study possibly being underpowered.  This means that the sample size (8) may not have been large enough to capture true differences or to filter out “outliers” that can significantly alter results.  For example, suppose that, in the treadmill test, seven of the volunteers showed very similar results to their efforts with the cycle ergometer, but the remaining volunteer had a very high initial flow of saliva.  This would affect the average, but is is really representative of the average person?  Since this is an abstract, we cannot see the individual numbers to decide for ourselves.  Also, please note that the statistically significant changes in secretion of IgA and saliva flow in treadmill participants were related to their very high initial rates and that their post-exercise values were very similar to the participants in cycle ergometry.  Finally, the treadmill participants had statistically significant rises in total sIgA, not falls in sIgA.  Therefore, I am not sure if running is a bigger drain on the immune system than cycling.  For triathletes, we have to train in all three disciplines, anyway.  The practical application of this study to you may, possibly, be to choose cycling over running, if you have a choice, in peak periods of training, if you feel you may be particularly vulnerable to illness, such as after air travel.

Reference:

The effect of exercise mode on salivary IgA secretion in high level triathletes. Barrett, S, Storey, A, and Harrison, M.  J Sci Cycling. Vol. 3(2), 3

 

Does Exercise Lead To Colds?

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IMG_1789

It is not uncommon to feel the symptoms of an upper respiratory tract infection (URTI), especially a sore throat, after periods of exercise.  This is especially true for high-performance athletes.  While I am far from a high-performance athlete, I often feel sore throat and malaise when I am in periods of peak training.  This, for me in the Chicago area, is usually in the summer during our short, but wonderful, triathlon season and not during our usual cold and flu season.  When I experience these symptoms, I usually ascribe them to pre-race nerves.  But, what is the real evidence for a relationship between URTIs, or related symptoms, and exercise?  Is performance in athletic events affected?

The first consideration when exploring the relationship between URTIs and exercise is whether symptoms of URTIs (upper-respiratory symptoms or URS) truly represent infections.  As it turns out, there are only limited studies on this topic.  Furthermore, physicians, like me, may not be very accurate in differentiating between infections and other causes of URS.  The diagnosis of URTI is often based on clinical history and physical exam, so true laboratory confirmation of an infection may be the exception rather than the rule.  However, the few studies that have pursued such laboratory testing have found that about 5% of URS in high-performance athletes arise from bacterial infections, while viral infections appear to account for 30-40%.  The pathogens that have been identified in these studies are typical of URTIs in the general population, and include rhinovirus, influenzae, parainfluenzae, adenovirus, coronovirus, metapneumovirus, epstein barr virus, mycoplasma pneumoniae, streptococus pneumonia, and staphylococus pyogenes.  In further studies, it has appeared that, in athletes with URS, infections account for about one third of cases, non-infectious medical causes account for another third (these include treatable conditions such as asthma, allergy, autoimmune disorders, vocal cord dysfunction, and unresolved non-respiratory infections), and an “unknown etiology” accounts for the final third.  Unproven, speculative, ideas about the causes of URS for athletes with an “unknown etiology” include drying of the airways, psychological impacts of exercise, and the migration to the airways of inflammatory cytokines that had been generated during damage to muscles.

There have been numerous studies examining the association between changes in immune parameters and the risk of URTIs in athletic and non-active populations.  The only immune measures that have shown a consistent relationship between URTIs and level of exercise has been the concentration and rate of secretion of salivary IgA.  Antibodies are divided into different subgroups, including IgM, IgG, IgE, and IgA.  The role of IgA is primarily to provide a first line of defense on internal surfaces of the body (such as the mouth, lungs, and intestines) that come into contact with pathogens.  It has been demonstrated that prolonged high-intensity exercise can reduce levels of salivary IgA whereas moderate exercise can lead to increases in salivary IgA.  This appears to lead to increased susceptibility to URTIs in high-performance endurance athletes undertaking intensive training, but reduced susceptibility to URTIs in people undertaking moderate regular exercise.  However, there is very little evidence to support the commonly-held belief that elite athletes experience more URTIs overall.  In fact, most studies have shown that the rates of URTIs are similar in elite athletes to the general population.  Also of interest is that episodes of URS in elite athletes do not follow the usual seasonal patterns of URTI, but, rather, occur during or around competitions.  For swimmers, URS occur more frequently during high intensity training and the taper before competitions, but in long distance running, URS appear to occur more frequently after competitions.  The limited data about the effects of URS on athletic performance suggests that there can be decrements in performance in athletes with URS.

There appears to be a subset of elite athletes experiencing recurrent URS, associated with long-term fatigue and poor performance.  A high percentage of these individuals have been found to have primary infection with herpes group viruses (such as cytomegalovirus and Epstein-Barr virus (EBV)) or to have reactivation of EBV.  Reactivation of EBV has also been demonstrated in endurance athletes with URS and this may help explain why many athletes with URS have a short duration of symptoms (since symptoms associated with reactivation of virus would be of shorter duration than symptoms associated with an initial, or primary, infection).  However, in a study examining the prophylactic use of an antiviral treatment in elite runners, the expression of EBV was reduced (in other words, the virus appeared to be suppressed), but it was not effective in reducing the frequency of episodes of URS.  This, once more, points to the importance of considering non-infectious cases of URS.

Cytokines, which are proteins that act as regulators all over the body, are also involved in the relationship between exercise and URS.  They are likely to play an important role in modulating post-exercise changes in immune function, which can increase the risk of infection or increase symptoms of inflammation (such as URS).  In athletes prone to frequent URS, there has been shown to be an underlying genetic predisposition to increased expression of the pro-inflammatory cytokine, interleukin-6.  This finding suggests that URS in these athletes may be due to a non-infection-driven inflammatory response.

The bottom line is that many athletes experience URS, especially in periods surrounding very intense exercise.  These symptoms may or may not represent infection.  However, if you are an athlete with URS, especially in a critical phase of your training and racing schedule, it may be helpful to see your health-care provider to determine if your symptoms represent an infection (which may be treatable) or not (which may, still, respond to appropriate treatment).  For athletes with recurrent URS associated with long-term fatigue and poor performance, more thorough clinical investigation may be warranted, including testing for possible involvement of the herpes group viruses.

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Reference:

Position statement.  Part one: Immune function and exercise.  Walsh, NP, Gleeson, M, Shephard, RJ et al.  Exerc Immunol Rev.  2011; 17:6-63.