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					Exercise and Immune system

 Dr. Reza Mazaheri

 Assistant professor of sports medicine
 Department of sports medicine
 Tehran university of medical science
• The relationship between exercise and the immune system.

• Incidence of infection associated with intense exercise.

• When an athlete can train and play with an infection.

• Nutritional consideration to enhance immune function.

• Exercise in cancer survivors.
        Exercise and the immune
• The immune system is a remarkably
  adaptive and complex defense

• It is able to generate an enormous
  variety of cells and molecules
  capable of recognizing and
  eliminating a limitless variety of
  foreign invaders.

•   White blood cells (WBCs or
    leukocytes) are a type of cells in the
    immune system that helps the body
    fight infection and disease.
• There are two complementary parts in the immune
  – The innate immune system,
  Which is non-specific regarding host defense.
     • The skin, mucous membranes, phagocytes, natural killer
       (NK) cells, cytokines and complement factors.
  – The acquired system,
  Protects the body against specific infectious agents during
    both initial and subsequent attacks.
     • T- and B-lymphocytes
• The body's first line of defense,
(skin and mucous membranes) can be impaired by:
   – Temperature, wind, sun, humidity and trauma.

• Exercise can have both,
Positive and negative effects
   On immune function and susceptibility to minor illnesses.
• The circulating numbers and functional capacities of
  leukocytes may be decreased by repeated bouts of intense,
  prolonged exercise.

• The reason is probably related to:
   – Increased levels of stress hormones during exercise and
   – Entry into the circulation of less mature leukocytes from the bone
   – Falls in the blood concentration of glutamine have also been
     suggested as a possible cause of the immunodepression
     associated with heavy training,
       • Although the evidence for this is less compelling.
   – Also, during exercise, an increased production of reactive
     oxygen species, and some immune cell functions can be
     impaired by an excess of free radicals.
• Many upper respiratory pathogens are airborne and affected
   – Airflow patterns, mechanical barriers, and ciliary action in the
     respiratory tract.

• During exercise,
The athlete switches from nasal to mouth breathing,
   – This can increase deposition of harmful articles in the lower
     respiratory tract.
   – It also causes increased cooling and drying of the respiratory
     mucosa, which slows ciliary movement and increases mucous

An increase in gut permeability may also allow increased entry of
  gut bacterial endotoxins into the circulation, particularly during
  prolonged exercise in the heat.
               Natural killer cells
• NK cells express spontaneous cytolytic activity against cells
  infected with viruses.

• After high-intensity exercise,
   – NK cell counts immediately increase 150-300% lasting less than
     1 hour.

• Within 30 minutes of the end of such high-intensity exercise,
   – NK cell counts fall below pre-exercise levels.
• In response to acute exercise of less than 1 hour in duration,
   – NK cell activity increases by 40-100%,
   – And falls to 25-40% below pre-exercise levels 1-2 hours into
     recovery time.

• Intense exercise lasting longer than 1 hour causes,
   – No rise in NK cell activity.
   – There is, however, a more profound and sustained drop in NK
     cell activity in recovery,
       • which is likely to be a cortisol-induced effect.
• Macrophages,
   – Phagocytes foreign particles,
   – Present antigens to lymphocytes, and
   – Produce lymphocyte-stimulating cytokines.

• Acute strenuous exercise
   – Increases the macrophage count and
   – Several aspects of macrophage function.

• Long-term training,
   – Seems to attenuate the macrophage response to acute exercise,
   The resulting macrophage function is still greater than in untrained
• Cytokines are divided into:
   – Pro-inflammatory and
   – Anti-inflammatory types.

• Pro-inflammatory cytokines,
   – Such as tumor necrosis factor (TNF)-α, interleukin (IL)-1 and IL-1ß
Are increased with acute exercise.

• Anti-inflammatory cytokines,
   – such as IL-6, IL-10 and IL-1 receptor antagonist (IL-1ra)
also increase with exercise.
Elevated systemic levels of IL-6 during and following exercise,
   – Could be one of the mechanisms by which regular exercise
     provides protection against the development of chronic diseases.
• Neutrophils are capable of phagocytosis,
   – Both alone and in response to antigen-dependent defenses.

• With acute exercise,
   – Neutrophil counts increases,
       • Most likely due to demargination, and
       • Several hours after exercise, a cortisol-induced phenomenon.

• Moderate training,
   – Increases neutrophil counts,
• Intense training,
   – Decreases them.
• Neutrophil activity,
   – Acute moderate exercise increases, but
   – Acute intense exercise suppresses it.

• Endurance training,
   – Reduces several aspects of neutrophil function compared
     with being sedentary.
  The acquired immune system
• The main components,
   – T- and B- lymphocytes and plasma-cell-secreted antibodies.

• Overall, lymphocyte counts increase with acute exercise.

• Lymphocyte counts and B-cell function,
   – Decreased after intense exercise, but
   – Not after moderate exercise.
               Antibody production
• Intense, prolonged exercise,
   – Impair antibody production, most notably IgA.
       • Cross-country skiers have low baseline salivary IgA levels,
         which further decline after racing.

• In swimmers,
   – Studies of longitudinal changes in salivary IgA levels have
     yielded conflicting results.

• IgG does not seem to be affected as much by intense training,
   – Although some elite athletes show a small decrease during peak
• T-lymphocytes,
   – CD4+ (T-helper) and
   – CD8+ (T-suppressor) cells.

• A ratio of CD4+ to CD8+ cells,
   – 1.5:1 is considered necessary for proper cellular immune function.

• Heavy exercise,
   – Decreases this ratio by
   Decreasing CD4+ cells and increasing CD8+ cells.

• A decreased CD4+ count,
   – Diminishes cytokine output, which
   Decreases NK cell and macrophage activation, and B-cell
• The immunological 'open window',
   – The brief immunosuppression
     after acute, intense physical
      •   When ciliary action,
      •   Mucosal IgA levels,
      •   NK cell count and activity,
      •   T-lymphocyte count, and
      •   CD4+ to CD8' ratio are

During which an athlete may be more
  susceptible to infection.

It may last between 3 and 72 hours,
   depending on the immune measure.
             Exercise and infections
• Are athletes more susceptible to infections?

• The incidence of upper respiratory tract infection and exercise.
   – The results are conflicting,
   There is some evidence that intense training is associated with a
     higher level of infection.

• Athletes engaged in intensive periods of endurance training
   – Appear to be more susceptible to minor infections.
   – URTI risk is elevated during periods of heavy training and in the 1-to
     2- week period after participation in competitive endurance races.

• Once infected, colds may last longer in athletes.
There is relatively little evidence to suggest that,
• There is any clinically significant difference in immune function
   – between sedentary and moderately active persons,
• There is some fairly convincing epidemiological evidence that
   – Moderate habitual physical activity is associated with decreased
     infection incidence.
• Several epidemiological studies involving large numbers of adults
  have shown that,
   – The odds for URTI are reduced by 25% to 50% when comparing
     physically active and inactive participants.

For example,
• It has been reported that the regular performance of ~2 h of
  moderate exercise per day
   – Is associated with a 29% reduction in risk of picking up upper
     respiratory tract infection (URTI) compared with a sedentary lifestyle.
• Nieman has proposed the “J curve”.

• According to this-theory,
Regular moderate exercise,
   – Decreases the risk of upper respiratory tract infection to below
     that of sedentary individuals.

Strenuous intense exercise,
   – Increases the risk above that of sedentary individuals.
The exact frequency, duration, type and intensity of exercise required to
optimally lower one's risk of infection, or to adversely increase the risk
of infection,
                                    Remains to be determined.
 Infection and athletic performance
• Infection may compromise,
   – Muscle enzyme activity and
   – Muscle strength.

• Exercise performed during illness,
   – Requires greater cardiopulmonary effort.

• These findings may theoretically lead to,
   – A detrimental effect of infection on performance.
A number of studies have been performed:

• An initial study in elite swimmers,
   – Did not show any statistically significant decrease in performance.

• In a group of elite middle-distance and distance runners,
   – Illness-affected runners reported a higher perceived training
   – However, laboratory-based measures of performance showed little
     change in physical work capacity.

• A third study in another group of elite swimmers suggested that
   – Mild illness had
       • A trivial effect on the competitive performances of female swimmers,
       • A substantial though small harmful effect in male swimmers.
         Guideline to reduce the risk of
       immunosuppression and infection
• Factors associated with impaired immune function and an
  increased risk of infection:
   –   Poor nutrition
   –   Older age
   –   Cigarette smoking
   –   Mental stress
   –   Lack of sleep
• Athletes should avoid being around sick people before and after
  important events.
• If an athlete is competing during the winter months,
   – An influenza vaccination is recommended.
• Immune function is suppressed during periods of very low caloric
  intake and quick weight reduction, so
   – Weight loss should be gradual to maintain good immunity.
    Should an athlete train during illness?
• It is important to differentiate athletes suffering from viral illness
  into two groups,
    – Those with symptoms restricted to one system, usually the upper
      respiratory tract,
    – Those with generalized symptoms.

• Upper respiratory tract infection manifesting itself as
    – A sore throat, runny nose or headache, who is afebrile,
Should be allowed to continue with mild-to-moderate training below
  80% of Vo2max.
• Modification of the training program may involve,
    – Increased skill training with less anaerobic or endurance training for
      the period of the illness.
• Those athletes with systemic symptoms,
    –   General malaise,
    –   Excessive fatigue,
    –   Muscle pains and tenderness,
    –   Swollen lymph glands,
    –   Temperature in excess of 38°C (100°F) or
    –   A resting heart rate greater than 10 beats above normal,

Should avoid any athletic activity,

• Until the systemic symptoms and signs return to normal or near
(probably 2-4 weeks should be allowed before resumption of intensive training.)

• Activity should then be gradually resumed.
• Engaging in intense exercise during an infection has been
  associated with
   – An increased risk of heat exhaustion, post-viral fatigue syndrome,
     and viral myocarditis.

• This differentiation between the two forms of viral illness is
  known as the 'neck check‘.
In other words,
• If symptoms are above the neck (runny nose, nasal congestion,
   sore throat) and
• Not associated with symptoms below the neck (fever, malaise,
   muscle aches, severe cough, gastrointestinal),
Then the athlete may commence training at half intensity for 10
• If symptoms do not worsen, then the training session can
  continue as tolerated.
              Nutrition concerns
• There are two groups of athletes who may be more at risk of
  nutrition-related immune system disturbance:

   – Those who voluntarily restrict energy and nutrient intake to make
     weight limits or for aesthetic reasons. (females)

   – Athletes who consume large amounts of energy and nutritional
     supplements in the expectation of performance improvement
     and muscle bulking. (males)

• The observations lend support for the notion of a two-way
  interaction between nutrition and infection.
       Long-term recommendations during
•   The macronutrients,
    – Carbohydrate,
    – Fat and
    – Protein
all play critical roles in maintaining immunocompetence.
• Inadequate intake of protein can impair immune function, leading
  to an increased incidence of opportunistic infections.
    – It’s due to impairment of cell replication and protein synthesis necessary
      for the production of key immune cells and soluble factors such as Ig,…

• Athletes who are overtrained or fatigued might benefit from a higher
  protein diet over a 2- or 3-week period.
    – Two specific proteins, glutamine and colostrum, appear to boost immunity.

• Protein intake of ~15% of total energy intake should be sufficient for
  most athletes.
• Dietary carbohydrate is a critical fuel source for both muscle
  and immune cells.

• Glucose has both direct and indirect effects on immune

   – Exercise-induced reduction in blood glucose has been linked to
       • Increased release of cortisol and decreased release of growth

   – Greater perturbations in leukocyte and lymphocyte numbers,
     lymphocyte proliferative responses and cytokine production have
     been linked with exercise undertaken in a carbohydrate-depleted

• There is relatively little information on the importance of fat
  intake in maintaining immune function.
   – Whether manipulations of fat intake modulate the balance of pro-
     and anti-inflammatory cytokines.
• An adequate intake of
   – The minerals (iron, zinc) and
   – Vitamins (A, E, B6, B12)
Is important for maintaining immune function.

• Some researchers have suggested that supplementation with
  anti-oxidant vitamins and trace minerals,
   – Such as vitamins E and C and ß-carotene
may be beneficial.

• Athletes are also advised to consume foods rich in zinc,
   – Supplementation may be indicated for those on low-calorie or
     vegetarian diets.
• Mega-doses of vitamins by athletes may have deleterious
  consequences for immune function.

   – Vitamin E dosages in the range of 300-600 mg are known to
     impair lymphocyte proliferation and increase oxidative and
     inflammatory cytokines during a triathlon.

   – Mega-doses of vitamin A can impair inflammatory responses and
     complement formation.

• Vitamin C is thought to play important roles in various immune

• Probiotics or yoghurt preparations contain so-called “good”
  gut bacteria that are purported to enhance gut health and
      Nutrition to maintain immune function
                  during exercise
• It’s important to achieve appropriate nutritional strategies before, during
  and after single events.
• The primary nutritional strategy during prolonged exercise is to replace
  glycogen and glucose.
    – Current recommendations suggest that 30-60 g per hour of carbohydrate in
      drinks should attenuate various aspects of immunosuppression during
      prolonged exercise.

• The post-event period is also a critical time for nutrient replenishment,
  particularly as it coincides with the so-called window of opportunity for
    – Co-ingestion of carbohydrate and protein should replenish critical sources of
      glucose and glutamine.
        • Although plasma glutamine levels decrease during exercise, it’s unclear whether
          immediate post-exercise supplementation of glutamine has a substantial effect on
          immune function.
     Nutritional intervention during illness
• The need for,
Additional fluids during periods of illness,
Is well established in clinical practice and home remedies.

• A series of studies with marathon and ultramarathon runners
   suggests that,
Vitamin C supplementation can be effective in reducing the
   incidence of illness.
   – There is some evidence that therapeutic ingestion of vitamin C and zinc
     at the onset of upper respiratory tract illness may be helpful in
     alleviating symptoms. (1998).
   – Although other research on this practice is contradictory. (2004).

• There is ongoing interest in the use of phytosupplements,
(herbal preparations) such as Echinacea,
In boosting immune function and reducing signs and symptoms of
   illness in athletes.
               Exercise and cancer
• Most cancers fall into four major classifications
  based on the type of cell from which they arise.
   – Carcinomas
      • Develop from epithelial cells that line the surfaces of the
        body, glands, and internal organs.
      • They comprise 80% to 90% of all cancers and include
        prostate, colon, lunge, cervical and breast.
   – Leukemia
      • Arise from the cells of the blood.
   – Lymphoma
      • Arise from the immune system.
   – Sarcoma
      • Arise from connective tissues such as bones, tendons,
        cartilage, fat, and muscle.
• The 5-year relative survival rate across all cancers and
  disease stages is 62%.

• Physical exercise may play an important role in cancer control
  across the entire cancer experience.
• The evidence indicates that physical activity may significantly
  reduce the risk of developing some cancers.

• The most convincing evidence comes from research on colon
  and breast cancer,
   – In which the risk reduction may be as much as 30% to 50%.

• The American cancer society physical activity guideline for
  cancer prevention:
   – Adults: engage in at least moderate activity for 30 minutes or
     more on 5 or more days of the week;
   45 minutes or more of moderate to vigorous activity on 5 or more
     days per week may further enhance reductions in the risk of
     breast and colon cancer.
   – Children and adolescents: engage in at least 60 minutes per
     day of moderate to vigorous physical activity at least 5 days per
     Exercise in cancer survivors
• Very little human research has been done to examine the
  effects of exercise on cancer.
• For cancers in which exercise has been implicated in their
  primary prevention (colon and breast),
   – It seems reasonable to suggest that exercise may also play a
     role in the recurrence of the disease or second cancers.

• It seems reasonable to suggest that exercise plays a strong
  role in risk reduction of major disease and conditions (heart
  disease, diabetes) in cancer survivors.
• Compelling data suggest that body mass index is an
  independent predictor of cancer recurrence and survival in
  breast and colon cancer survivors.
  Exercise prescription guidelines for
           cancer survivors
• Before initiating an exercise program, it is important
  to have cancer survivors complete,
   – A cancer history questionnaire
   (diagnostic and treatment variables),
       • Time since diagnosis,
       • Type and stage of disease,
       • Type of surgery and adjuvant therapy,
       • Known or suspected side effects of treatment
       (ataxia, cardiomyopathy, pulmonary complications, orthopedic
In addition to other usual exercise and medical history
  questionnaires (PAR-Q).

• One of the most important precaution is
   – The presence of metastatic bone disease, which occurs at some
     point in about 50% of all survivors.
• The most common site of major fracture is the hip.
            Type, volume, and context
• Presently, no evidence suggests that one type of exercise is
  superior to another for the general rehabilitation of cancer

• It is probably safest to prescribe walking or cycle ergometry.

• Walking is the preferred exercise of cancer survivors, and it has
  direct implications for ADLS.

• The advantages of cycle ergometry include:
   – A sitting position with leg exercises that minimize the effects of ataxia
     and limitations in upper extremity movements.

• The optimal rehabilitation program likely combines aerobic and
  weight training.
General aerobic exercise guideline
As a general guideline,
• Fitness professionals should
  prescribe exercise that is,
   – Enjoyable,
   – Builds confidence,
   – Facilitates perceptions of control,
   – Develops new skills,
   – Incorporates social interaction,
   – Takes place in an environment
     that engages the mind and spirit.
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