Training Your Immune System

The Effects of Exercise on Immune FunctionNoah Hutchinson, BS, EP-C

Summer Self Care July 7, 2020

Who am I?

• Hometown: Mount Pleasant, MI• Truman State University Class of 2019,

Exercise science, biology minor• 2nd year PhD student in the Division of

Nutritional Sciences at UIUC• American College of Sports Medicine Certified

Exercise Physiologist• I study how diet and exercise interact with the

gut microbiome and immune system

Learning Objectives

• How does the immune system work?

• What does exercise do to it (susceptibility and resilience to virus)?

• What can I do to help keep myself safe and healthy?

I am not a doctor, wash your hands

• These strategies should be treated as helpful ADDITIONS to other prophylactic measures, not replacements

• I recommend continuing:• Social Distancing• Proper Hygiene (hand washing, mask wearing, not touching face, etc.)• Be health conscious, watch out for symptoms• Better to be safe than sorry

• Consult your doctor if you are uncertain about anything• Make sure you are clear to begin exercise if not already aware

When I say immunity, what comes to mind?

Innate vs Adaptive Immunity

These are classified separately but important to note that they work together and help orchestrate each other!

Innate Immunity Adaptive Immunity

- Behavioral (disgust of certain smells)

- Physical barriers like skin and mucus

- Inflammation (redness, swelling, fever, pain, loss of function)

- Fast acting- Non specific

- Delayed (hours to days to even weeks)

- Long Lasting- Responsible for continued

immunity- Pathogen specific- Why vaccinations work

Defined• Cytokines and Chemokines

• Secreted signaling proteins that activate or attract other immune cells (Interleukins, Interferons, etc.)

• Antibody (ImmunoGlobulins)• Protein produced by adaptive immune system that is designed to attack a specific

pathogen with high efficiency and effectiveness• Pathogen

• Virus, bacteria, or any micro organism that can cause disease or injury• Antigen

• Portion of the pathogen that triggers immune response• Viral Load

• Amount of virus particles in the body, usually in blood. Indicative of severity of illness

Defined• Leukocytes (white blood cells)

• Innate immune cells that aid in clearance of pathogens and development of adaptive response

• Lymphocytes• Adaptive immune cells

• Resilience• One’s ability to fight off infection

• Surveillance• The presence of leukocytes/lymphocytes, the ability of the immune system to

recognize pathogens quickly• Pathogen Associated Molecular Patterns (PAMPs)

• What leukocytes/lymphocytes recognize and initiate responses to

Innate Immunity, after barriers

Pathogen (coronavirus)

Leukocytes

Cytokines and Chemokines

Inflammation (redness, swelling, etc.)

Innate Immune Response

Janeway’s Immunobiology, 9th edition, (Garland Science 2017)

Inflammation

(Macrophages and neutrophils are types of leukocytes)

Adaptive Immune Response

A relatively similar process occurs with B cells (it takes longer), initiating clonal expansion and ultimately resulting in the production of antibodies

Antigen Presentation

(Dendritic cells are types of leukocytes)

In summaryOnce past anatomical barriers and inside host tissues, leukocytes will recognize the pathogen and attempt to clear it (with the help of some other defense mechanisms) while also sending signals to other immune cells that there is a problem and they need help. While the other leukocytes/lymphocytes come over via an inflammatory response, some leukocytes bring the antigen to the lymph tissue for the maturation of pathogen specific lymphocytes like T cells and plasma cells (which secrete antibodies) and help clear the pathogen.

Effectors = activated lymphocyte/leukocyte subsets (and some other players)

The Peril of COVID-19• A non specific, yet severe response • Immune cells and cells of respiratory tract have delayed release of

cytokines and chemokines early on• Later on will release large amounts of non specific proinflammatory

cytokines and chemokines and small amounts of antiviral cytokines (interferons)

• “Cytokine Storm” that contributes to the development of ARDS (Acute Respiratory Distress Syndrome)

• Your immune system is killing youSymptoms can vary widely in early infection stages, and do not always have to be respiratory related. Be aware!

Illustration of the ultrastructure of the Covid-19 virusCDC/SCIENCE PHOTO LIBRARY

Qing Ye, Bili Wang, Jianhua Mao, 2020

What does this have to do with exercise?

Noticing a Trend: Epidemiology• 5 studies with about 1000 participants each followed individuals for three

months to a year and required them to report physical activity and illness symptoms via questionnaires or periodic interviews

Study Demographic Length of study ResultsElinor et al, 2011 Male and female adults 4 months 18% reduced risk of

reported infection in high vs low activity

Nieman et al., 2011 1002 Male and female adults aged 18-55

12 weeks 46% decrease in days w/ illness in high vs low physical fitness tertile

Matthews et al. 2002 547 Male and female adults around 50 y/o

1 year 29% decreased illness risk in upper quartile of physical activity

Fondell et al., 2011 1509 males and females age 20-60

4 months 18% decreased risk in high vs low activity

Zhou et al., 2011 1413 mle and female adults around 40 y/o

1 year 26% decreased risk in high vs low activity

What does this tell us?• Those who are among the more active portion of the general

population likely to report fewer days with symptoms of upper respiratory infection

• BUT, we do not know if the exercise is the cause of this observation.

Randomized Controlled Trials• Many have resulted in positive effects in illness incidence and days

of illness in the exercise groups.

Split in half

Sedentary control (stretching, etc.)

Exercise intervention (running, aerobics, etc.)

Both groups report outcomes (usually symptom days and severity), and we compare

Grande et al, 2020

Exercise and Vaccination

• Clinical trials of regular exercise in the elderly population have shown increased antibody levels following vaccination

• Not known if this has actual clinical relevance

• Research on this specific topic is inconclusive

Woods, 2009, Grande et al. 2016

Consensus (meta analyses/systematic reviews)• Meta analyses/systematic reviews are difficult due to variations in

study designs and limited sample sizes• Prominent authors in the field agree that regular moderate intensity

aerobic exercise is beneficial for immune health, and can decrease susceptibility to respiratory infection

• These effects are particularly large in the elderly and in individuals with excess fat mass

• More data are needed on resistance training to make conclusions• Exercising regularly/before vaccination may improve their

effectivenessWalsh et al. 2011

Immunosenescence• Immune system gets less effective with age, increasing susceptibility to infection and

decreasing resilience• Exercise has been shown to counteract many aspects of this (many clinical trials are conducted

in elderly population)

Hinderances to immunity

Chronic Inflammation (excess fat mass, chronic stress)• Constant inflammatory signaling in the absence of pathogens or damage throws off the delicate

balance of immunity and results in inappropriate responses to actual threats

Exercise has been shown to reduce chronic inflammation inflicted by both excess fat mass accumulation and chronic stress

Gleeson et al. 2011, Stubbs et al. 2017, Shakh and Ediddin2006, Hu et al. 2014, Hotamisligil 2006, Roediger and Weninger2017

Autoimmune conditions• Regular exercise of all modalities has been shown to reduce fatigue, reduce

systemic inflammation and increase quality of life indices in patients with multiple sclerosis, rheumatoid arthritis, and other autoimmune disorders

Hinderances to immunity

Cancer• Exercise has displayed therapeutic effects in certain cancer patients (if healthy

enough to do so)• Has been shown to prevent many types of cancer, primarily prostate and breast

cancer

Kraschnewski and Schmitz 2017, Biro and Geczji 2019

How do I get these benefits?

• 45 min of moderate intensity exercise 3 to 5 days a week (for healthy individuals)

*Those with health complications should seek advice from medical professionals concerning appropriate amounts and intensities

Do you exercise? If so, how? Put answers in the chat

How do I get these benefits?• Moderate intensity can include:

• Walking, hiking• Jogging• Swimming• Aerobics• Biking• Elliptical• Rowing• Many others, just get your heart rate up (but not too high) and make sure

you can continue your social distancing while doing itSustainability is key! Start easy and work your way up if you don’t already exercise regularly. Find multiple things you enjoy doing, switching it up can help prevent you from getting bored.

*Those with health complications should seek advice from medical professionals concerning appropriate amounts and intensities

Other important factors

If running, make sure to run wide paths around other runners/walkers, keep six feet apart!

Get adequate sleep Eat a balanced diet Make an effort to manage stress Clean AND sanitize any exercise equipment that may have been shared

Can you exercise too much?

Another trend, this time in athletes• 20+ studies have looked into symptoms reported in endurance athletes,

with varying designs, for the most part they report higher than average levels of URTI symptoms, especially around competition time

• Athletes who take part in regular, exhaustive exercise are more likely to report symptoms of infection, especially during time periods close to competition

Conclusion:

But is exercise to blame?Nieman and Wentz, 2019.

This has led to:

Adapted from Nieman and Wentz, 2019

The “J Curve” Hypothesis of susceptibility• Moderate Intensity exercise reduces

susceptibility whereas prolonged, exhaustive exercise and lack of exercise increase susceptibility

• Somewhat controversial (debate article exists)

Criticisms of the J curve hypothesis

• Pathogens not actually lab confirmed, only reported subjectively via questionnaire or interview

• Competitions cause stress and expose athletes to large crowds of people

• High potential for carbohydrate inadequacy• Allergies?

Not all symptoms are due to pathogens• Only about 30% of symptoms were due to actual infections,

per a study by Spence et al. (2007)• Allergy/other inflammatory stimulus is likely the cause• Excessive stress hormone release resulting from exhaustive exercise may be

TOO anti inflammatory, and throw of immune equilibrium (genetic component?)

• “Open Window”, reductions in saliva flow and effectiveness of mucus layers

• BUT, prolonged high intensity exercise does result in a decrease in white blood cells and increase in stress hormone release post exercise

Spence et al, 2007.

What can you do about it? (If you’re competing, etc.)

• Make sure to keep your carbohydrate consumption high before/during exercise

• Low carbohydrate status during exercise induces a much larger stress response and negatively alters many immune biomarkers

• Consistent consumption of polyphenols before exercise has been shown to help

• Dark chocolate, berries, beans, nuts, vegetables, etc.

This Photo by Unknown Author is licensed under CC BY-ND

This Photo by Unknown Author is licensed under CC BY-NC

Nieman and Wentz, 2019

How does regular exercise impact illness severity?

What about illness severity?• Hard to research this in a controlled manner in humans, as

there are obvious ethical concerns with making humans sick

• One such study does exist, Ball state university in 1998• 10 day moderate exercise intervention before infection with

common cold did not alter symptom severity• Longer intervention may have worked

Due to these limitations, we move to animal models

Weidner et al, 1998.

Animal models and moderate intensity exercise• Three studies on mice have shown that moderate intensity

exercise before infection with influenza • reduces mortality by about 40%• Decreases weight loss• Decreases viral load shortly after infection (with equal amounts)• In lean mice, it was found that the presence of proinflammatory

cytokines in the lungs was greatly decreased by exercise, indicating a less severe and more appropriate immune response in exercised mice

We’re not completely sure what is going on here! Lowder et al, 2005, Lowder et al, 2006, Warren et al, 2015.

Animal models are the answer• One study on herpes simplex virus displayed that mice

exercised to exhaustion were about 25% more likely to die

More studies looking at specific biomarkers are needed to ascertain the cause, again most explanations are speculatory

Davis et al, 1997

Take home

Regular moderate intensity exercise has a host of health benefits, and increased immune surveillance and resilience can be added to that list

While all the negative side effects of unfamiliar and exhaustive exercise may not be universal, it is highly recommended to err on the side of caution in the face of a relatively unknown pandemic virus when risk of infection is abnormally high

For the general population, once you have ascertained that it is safe for you to exercise, keeping bouts between 30 to 60 min (about 5 times a week) is recommended and seems the most beneficial based on available evidence

Questions?

References1. Qing Ye, Bili Wang, Jianhua Mao. The pathogenesis and treatment of the `Cytokine Storm' in COVID-

19,Journal of Infection, Volume 80, Issue 6, 2020,Pages 607-613,https://doi.org/10.1016/j.jinf.2020.03.037.

2. Elinor et al. Physical Activity, Stress, and Self-Reported Upper Respiratory Tract Infection. Medicine & Science in Sports & Exercise 2011;43(2):272-279.

3. Nieman DC, Henson DA, Austin MD, Sha W. Upper respiratory tract infection is reduced in physically fit and active adults. British Journal of Sports Medicine 2011;45(12):987-992.

4. Matthews CE, Ockene IS, Freedson PS, Rosal MC, Merriam PA, Hebert JR. Moderate to Vigorous physical activity and risk of upper-respiratory tract infection. Med Sci Sports Exerc 2002;34:1242-48.

5. Fondell E, Lagerros YT, Sundberg CJ, Lekander M, Balter O, Rothman KJ et al. Physical activity, stress, and self-reported upper respiratory tract infection. Med Sci Sports Exerc 2011;43:272-9.

6. Zhou et al. Smoking, leisure-time exercise and frequency of self-reported common cold among the general population in northeastern China: a cross-sectional study. BMC Public Health

7. Nieman DC, Wentz LM. The compelling link between physical activity and the body’s defense system. Journal of Sport and Health Science 2019;8(3):201-217.

8. Spence L, Brown WJ, Pyne DB, et al. Incidence, etiology, and symptomology of upper respiratory illness in elite athletes. Med. Sci. Sports Exerc. 2007;39(4):577-86.

9. Weidner TG, Cranston T, Schurr T, Kaminsky LA. The effect of exercise training on the severity and duration of a viral upper respiratory illness. Medicine & Science in Sports & Exercise 1998;30(11):1578‐83.

2-6: epidemiology for general population

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