Exercise and Immune System, Limits of Performance, Energy balance

Table of Contents

  1. Protection Against Violation of Integrity — Immunity and Inflammatory Regulation
  2. What Are the Limits of Physical Performance?
  3. Energy Balance

Lecture - Slidedeck.


1 Protection Against Violation of Integrity — Immunity and Inflammatory Regulation

Overview of the Immune System

The immune system is the body’s primary defense against pathogens (bacteria, viruses, fungi) and endogenous threats (abnormal cells, debris). It operates through two integrated mechanisms:

Innate Immunity

  • First line of defense — non-specific, immediate response.
  • Components: Skin, mucous membranes, phagocytes (neutrophils, macrophages), natural killer cells, complement system.
  • Responds to: Pathogen-associated molecular patterns (PAMPs).
  • Characteristics: Does not require prior sensitization; activation is rapid.

Adaptive (Acquired) Immunity

  • Second line of defense — specific, delayed response.
  • Components: T lymphocytes (cellular immunity), B lymphocytes (humoral immunity), antibodies.
  • Responds to: Specific antigens.
  • Characteristics: Requires sensitization; activation is slower but generates immune memory.

Inflammation as an Immune Response

Inflammation is a protective response to tissue injury, infection, or immune challenge. It involves:

  1. Immediate phase (0–15 minutes):

    • Mast cells and resident macrophages release histamine and cytokines.
    • Increased vascular permeability — plasma and immune cells enter tissues.
  2. Early phase (15 minutes to 2 hours):

    • Neutrophil recruitment (primary cell type in acute inflammation).
    • Complement activation — enhances phagocytosis and inflammation.
  3. Late phase (2–24 hours):

    • Macrophage infiltration — phagocytosis and cleanup.
    • Lymphocyte recruitment — adaptive immune response initiation.
  4. Resolution phase:

    • Anti-inflammatory cytokines (IL-10, TGF-β) suppress inflammation.
    • Tissue repair and restoration of homeostasis.

Acute Inflammation vs. Chronic Inflammation

Acute inflammation is a protective, self-limiting response lasting hours to days. It is essential for fighting infection and initiating tissue repair.

Chronic inflammation persists for weeks to months or longer. It is detrimental to health and is implicated in:

  • Cardiovascular disease
  • Type 2 diabetes
  • Autoimmune diseases
  • Neurodegenerative diseases
  • Cancer

Inflammatory Markers and Exercise

Key inflammatory markers measured in exercise physiology:

  1. IL-6 (Interleukin-6): Dual role — pro-inflammatory at rest; anti-inflammatory when produced by muscle during exercise (myokine).
  2. TNF-α (Tumor Necrosis Factor-α): Primarily pro-inflammatory; elevated in chronic disease states.
  3. CRP (C-Reactive Protein): Acute phase reactant; elevated with infection and chronic disease.
  4. IL-10: Anti-inflammatory; suppresses pro-inflammatory cytokine production.
  5. Cortisol: Stress hormone with immunosuppressive effects at elevated baseline levels.

Exercise Effects on Immunity and Inflammation

Acute exercise effects:

  • Immune cell mobilization: Transient increase in circulating lymphocytes, neutrophils, and natural killer cells.
  • IL-6 release from muscle (myokine effect): Acts as anti-inflammatory signal despite initial elevation.
  • Immune surveillance enhancement: Mobilized lymphocytes migrate to tissues, enhancing pathogen detection.

Chronic exercise effects:

  • Reduced resting inflammatory markers (IL-6, TNF-α, CRP).
  • Enhanced immune surveillance and function — increased T-cell numbers and improved function.
  • Improved antibody response to vaccination.
  • Reduced infection risk in physically active individuals (U-shaped relationship with extreme endurance exercise).

Practical insight: Regular moderate-to-vigorous physical activity enhances immune competence and reduces chronic inflammation, protecting against age-related immune decline and lifestyle diseases.


2 What Are the Limits of Physical Performance?

2.1 What Influence Does the Ageing Process Have on Exercise?

Physical performance is part of the biological, psychological and social development of humans — subject to a biologically and genetically predetermined change and, on the other hand, to a change influenced to a limited extent by behaviour and circumstances, from the beginning of life to the end of it [1].

Physical performance is an important prerequisite for an active individual lifestyle. Without any noticeable restrictions, performance is accessed almost unnoticed and “as if it were a matter of course”. It is not uncommon for this “obviousness to physical performance” to be equated with vitality, well-being and health [1].

2.2 What Role Does Performance Play in Shaping One’s Life?

Physical performance is part of the biological, psychological and social development of humans throughout the lifespan. Performance capability impacts quality of life, independence, and health status. The decline in physical performance with aging is a significant public health concern, associated with increased disability, reduced autonomy, and higher mortality risk.

2.3 Physiological Definition of Physical Performance

The description of physical performance requires reference points or areas for quantitative classification. Reference ranges are based on empirical studies and on the known physiological minima and maxima. The terms “increase” and “restriction” used in this context are conventions and ostensibly descriptive in nature [1].

2.4 Sports Medical Definition of Physical Performance

From a biological-physical perspective, physical performance is the muscular body work performed in a unit of time — the sum of all determinants currently available for the provision of physical performance [1].

From the perspective of biochemical energy supply, physical performance is the aerobic and/or anaerobic energy provided by high-energy phosphates in a unit of time in order to perform neuromuscular body work [1].

2.5 Determinants of Physical Performance

From a physiological point of view, the primary determinants of performance are:

  1. The biological (anatomical) structure
  2. The physiological functionality of the biological structure

Both primary determinants relate to the level of the entire organism and sub-levels of structures, systems and control circuits. The two primary determinants are essentially influenced by secondary determinants [1]:

  • (Biological) ageing processes
  • Health as physiological functionality
  • Disease and illness as physiological mal-/dysfunctionality
  • Health- and functionality-related lifestyles
  • (Lack of) nutrient supply
  • Movements
  • Physical activity (exercise and training in leisure, occupation and sports)
  • Genetics (genotype, epigenetics)
  • Environmental factors (physical, chemical, ecological, socio-economic)
  • Sensomotorics and perception and psyche

When dealing with the limits of physical performance, a key question is whether the limits are of a physiological nature or caused by pathologies.

2.6 Extended Definition of Physical Performance

Beyond the narrow biological-physical definition, physical performance corresponds to the value created through physical work and energy consumption (movements, exercise, training, sport) and measured against the goal of action with a measurable result and a minimum level. Performance depends on biological, psychological and social resources, external stress and internal stress as well as the willingness to perform [1].

Limits of physical performance capacity — Power and running speed

Figure: Limits of performance with age: Relating MET, V̇O₂max, physical activity behaviour and mortality/morbidity [%] across the lifespan — from physical inactivity (1 MET, 3.5 mL·min⁻¹·kg⁻¹) to very fast running (~26 METs, ~90 mL·min⁻¹·kg⁻¹) — demonstrates age-dependent changes in maximal performance capacity.

Limits of physical performance capacity — Age and mortality

2.7 How Fast Can People Run for How Long?

From a physiological point of view, a high running speed means that muscles have to provide fast and a lot of energy for muscle contractions. A low running speed requires slower contractions and a lower amount of energy per unit time.

The organism has an answer ready for high and low running speeds through different energy supply systems. However, physiological mechanisms also have their limits: after a certain period of time, muscle contraction and energy metabolism become fatigued. The faster you run, the sooner you get tired.

Reference performance parameters (approximate maxima):

ParameterMaximumMeanMinimum
V̇O₂max (mL·min⁻¹·kg⁻¹)~90~45~3.5
Bench press~500 kg~250 kg0 kg
Squats~600 kg~300 kg0 kg
Sprint top speed~12 m·s⁻¹~6 m·s⁻¹0 m·s⁻¹
Marathon mean speed~6 m·s⁻¹~3 m·s⁻¹0 m·s⁻¹

2.8 How Fast Is the Energy Supply at Different Exercise Intensities?

The speed of muscular contraction depends on the speed of energy supply [2]:

DurationEnergy source(s)Examples
Few seconds (<2 s)Available ATPPower lift, high jump, javelin throw, golf swing, tennis serve
Up to 6–8 secondsATP + creatine phosphate (PCr)Sprints, fast breaks, gymnastics routine
Up to ~90 secondsATP + PCr + anaerobic glycolysis (lactate formation)Long sprints 200–400 m, 100 m swimming
~800 m~50 % anaerobic + ~50 % aerobicMiddle-distance running
Longer distancesAerobic glycolysis → β-oxidation (increasing proportion)Long-distance running, endurance events

Energy flow rates:

  • ATP and creatine phosphate capacity: ~5 mmol·g⁻¹ | <2–3 s; ~19 mmol·g⁻¹ | <5–8 s
  • Anaerobic glycolysis capacity: ~50 mmol·g⁻¹ | <60 s
  • Aerobic glycolysis and β-oxidation: limited by substrates | hours to days

Energy flow rate comparison (mmol·kg⁻¹·s⁻¹):

  • ATP and CP: ~3–6
  • Anaerobic glycolytic: ~1.5–3
  • Aerobic glycolytic: ~0.5–0.75
  • Aerobic β-oxidation: ~0.24–0.4
ATP flow rate cycling

Figure: Adenosine-triphosphate (ATP) flow rates versus time. Abbreviations: P—cycling performance on a bicycle ergometer, RPE: Ratings of perceived exertion (Borg scale: 6–20).

Energy time oxygen

Figure: Time course of energy generation.

Performance lactate 4h

Figure: Cycle ergometer exercise of different intensities and duration. Outlined are performance, lactate generation, hormone secretion. Male subjects with a VO2max of 60–65 ml·min⁻¹·kg⁻¹.

Performance energy lactate 4h

Figure: Cycle ergometer exercise of different intensities and duration. Outlined are performance, lactate generation, hormone secretion. Male subjects with a VO2max of 60–65 ml·min⁻¹·kg⁻¹.

Performance energy heart rate 4h

Figure: Cycle ergometer exercise of different intensities and duration. Outlined are performance, lactate generation, hormone secretion. Male subjects with a VO2max of 60–65 ml·min⁻¹·kg⁻¹.

Performance energy 4h

Figure: Cycle ergometer exercise of different intensities and duration. Outlined are performance, lactate generation, hormone secretion. Male subjects with a VO2max of 60–65 ml·min⁻¹·kg⁻¹.

Performance cortisol 4h

Figure: Cycle ergometer exercise of different intensities and duration. Outlined are performance, lactate generation, hormone secretion. Male subjects with a VO2max of 60–65 ml·min⁻¹·kg⁻¹.

Performance cortisol 4h amount

Figure: Cycle ergometer exercise of different intensities and duration. Outlined are performance, lactate generation, hormone secretion. Male subjects with a VO2max of 60–65 ml·min⁻¹·kg⁻¹.

Performance adrenaline 4h

Figure: Cycle ergometer exercise of different intensities and duration. Outlined are performance, lactate generation, hormone secretion. Male subjects with a VO2max of 60–65 ml·min⁻¹·kg⁻¹.

Performance adrenaline 4h amount

Figure: Cycle ergometer exercise of different intensities and duration. Outlined are performance, lactate generation, hormone secretion. Male subjects with a VO2max of 60–65 ml·min⁻¹·kg⁻¹.

Performance 100s lactate adrenaline cortisol

Figure: Cycle ergometer exercise of different intensities and duration. Outlined are performance, lactate generation, hormone secretion. Male subjects with a VO2max of 60–65 ml·min⁻¹·kg⁻¹.

Exercise Strain lactate HPA SNS CHO Fat AA

Figure: Overview of hormonal regulation and energy supply with different loads and durations of load. RPE: Rating of perceived exertion (Borg scale value).

Exercise Strain lactate CHO FAT AA

Figure: Overview of hormonal regulation and energy supply with different loads and durations of load. RPE: Rating of perceived exertion (Borg scale value).


3 Energy Balance

3.1 What Is Energy and What Is It For?

Each of the approximately 80 trillion (80·10¹²) cells in the human body requires energy to maintain structure and function. The key principle of homeostasis allows the energy supplied by food to be used for physiological work.

In the physiological sense, energy is synonymous with the supply and consumption of ATP.

High-energy phosphates, especially adenosine triphosphate (ATP), are the “currency” of energy — for example to perform mechanical muscle work. The task of the physiological regulatory systems is to provide the required amount of ATP at the right place, time and speed. ATP enables muscle tone during physical rest as well as fast and powerful contractions of the skeletal muscles. ATP can be made available under aerobic and anaerobic conditions for both slow and fast physical activity.

Energy exists in either potential or kinetic form. Potential energy refers to energy associated with a substance’s structure or position; kinetic energy refers to energy of motion. The six forms of energy are chemical, mechanical, heat, light, electrical, and nuclear — each can convert to another form.

  • Exergonic reactions release energy to the surroundings.
  • Endergonic reactions store, conserve, or increase free energy.
  • Entropy describes the tendency of potential energy to degrade to kinetic energy with a lower capacity for work.

Enzymes represent highly specific protein catalysts that accelerate chemical reaction rates without being consumed. Coenzymes consist of nonprotein organic substances that facilitate enzyme action. Hydrolysis (catabolism) breaks down complex molecules; condensation (anabolism) synthesises complex biomolecules.

The transport of electrons by specific carrier molecules constitutes the respiratory chain — the final common pathway in aerobic metabolism.

3.2 How Does Energy Get Into the Organism?

Carbon, hydrogen, oxygen, and nitrogen represent the basic structural units for most of the body’s bioactive substances. Less than 40 % of food energy is available as utilisable or stored energy (net available energy, energy-rich phosphates) for skeletal muscle work.

Gross energy values (physical calorific values):

NutrientPhysical energy value (kcal·g⁻¹)Physical energy value (kJ·g⁻¹)Physiological energy value (kcal·g⁻¹)
Fat9.338.99.3
Protein5.523.04.1
Carbohydrate4.117.24.1
Glucose3.815.73.8
Ethanol7.129.77.1

Coefficients of digestibility average 97 % for carbohydrates, 95 % for lipids, and 92 % for proteins. The complete breakdown of 1 mole of glucose liberates 689 kcal of energy; of this, approximately 34 % is conserved in ATP bonds.

Energy transfer pathway:

  • Complete oxidation of a glucose molecule in skeletal muscle yields a net gain of 32 ATP molecules.
  • The complete oxidation of a triacylglycerol molecule yields approximately 460 ATP molecules.
  • During intense exercise when hydrogen oxidation fails to keep pace with its production, pyruvate temporarily binds hydrogen to form lactate, allowing continuation of anaerobic glycolysis.

Energy intake and expenditure must be in balance. Any physical activity consumes energy. Even in an apparently inactive state, the organism needs energy. Physical activity strains the organism — the type and extent of the strain of cells, tissues and organs depends on type, duration, intensity and physiological functional status.

3.3 Energy Transfer — Macronutrients

3.3.1 Carbohydrates

Three major classifications: monosaccharides (glucose, fructose), oligosaccharides (sucrose, lactose, maltose), and polysaccharides (starch, fibre, glycogen). Carbohydrate serves four important functions: (1) major energy source; (2) spares protein breakdown; (3) metabolic primer for fat catabolism; (4) required fuel for the CNS.

Muscle glycogen provides the primary energy substrate during anaerobic exercise. A carbohydrate-deficient diet quickly depletes muscle and liver glycogen, profoundly affecting both all-out exercise capacity and sustained intense aerobic exercise. Individuals who train intensely should consume 60–70 % of daily calories as carbohydrates (400–800 g; 8–10 g·kg⁻¹ body mass).

3.3.2 Lipids

Lipids contain carbon, hydrogen, and oxygen but with a higher ratio of hydrogen to oxygen. Lipids provide the largest nutrient store of potential energy for biological work. Fat contributes 50–70 % of the energy requirement during light- and moderate-intensity physical activity. Stored intramuscular fat and fat derived from adipocytes become important during prolonged exercise, supplying more than 80 % of exercise energy requirements.

Saturated fatty acids exist primarily in animal meat, egg yolk, dairy fats, and cheese — elevated intake promotes coronary heart disease. Unsaturated fatty acids protect against coronary heart disease. Aerobic training increases long-chain fatty acid oxidation during mild-to-moderate intensity exercise.

3.3.3 Proteins

Proteins differ from lipids and carbohydrates because they contain nitrogen in addition to sulfur, phosphorus, and iron. The body requires 20 different amino acids; 8 are essential and must be consumed in the diet. The Recommended Dietary Allowance (RDA) for protein in adults equals 0.83 g·kg⁻¹ body mass. For athletes engaged in intense training, increasing protein intake to 1.2–1.8 g·kg⁻¹ body mass daily is reasonable.

The muscle-derived amino acid alanine plays a key role via gluconeogenesis in supporting carbohydrate availability during prolonged exercise (alanine–glucose cycle accounts for up to 45 % of the liver’s glucose release during long-duration exercise).

References

  • [1] Gabriel H. Bewegung, Leistungsfähigkeit und Aktivität des Menschen. Gestaltungsmöglichkeiten und Grenzen aus physiologischer, sportmedizinischer und gesundheitsförderlicher Perspektive. In Religion und Bildung — Ressourcen im Alter?, pp. 19–40. Beier, Miriam and Gabriel, Holger and Rieger, Hans-Martin and Wermke Michael, 2016.
  • [2] Brixius K. Sport und Leistungsphysiologie. In Brandes R, Lang F, Schmidt RF (eds): Physiologie des Menschen mit Pathophysiologie, chapter 44, pp. 561–579. Springer-Verlag, 32. Auflage, 2019. https://doi.org/10.1007/978-3-662-56468-4

One-Minute-Paper Topics

A One-Minute-Paper (OMP) is a short, focused prompt that students answer in ~60 seconds at the end of a session to consolidate learning, surface misconceptions, and provide formative feedback. When answering, be concise, specific, and use terminology from today’s session.

  1. Compare innate and adaptive immunity on three dimensions: speed of response, specificity, and immunological memory. Give one example of an exercise-relevant cell from each branch.
  2. Outline the four temporal phases of an acute inflammatory response (immediate → early → late → resolution). Which phase is most relevant to exercise recovery, and why?
  3. Why is acute inflammation considered protective while chronic inflammation is pathological? Name two chronic diseases linked to low-grade systemic inflammation.
  4. At rest, IL-6 is primarily pro-inflammatory; during exercise it acts as an anti-inflammatory myokine. What determines which role predominates — the source of IL-6 or its concentration, or both?
  5. Describe the U- (or J-) shaped relationship between exercise volume/intensity and infection risk. What is the “open-window” hypothesis, and how does it explain susceptibility after extreme exercise?
  6. Formulate the sports-medical definition of physical performance from both a biological-physical perspective and a biochemical energy-supply perspective. Which definition is more relevant for exercise prescription?
  7. The lecture distinguishes primary determinants (structure and functionality) from secondary determinants (ageing, health, genetics, lifestyle, etc.). Give two examples where secondary determinants override primary ones.
  8. Why does maximal oxygen uptake decline with ageing even in regularly active individuals? Name two structural and two functional reasons for this trajectory.
  9. Match each exercise duration (< 2 s; up to 8 s; up to 90 s; > 3 min) with its primary energy system and a sport example. What determines the transition point between systems?
  10. Rank the four energy pathways (ATP-PCr, anaerobic glycolysis, aerobic glycolysis, β-oxidation) by their ATP flow rate (mmol·kg⁻¹·s⁻¹). What is the trade-off between power and capacity?
  11. Define basal metabolic rate (BMR) and resting metabolic rate (RMR). Why is RMR always slightly higher than BMR, and which factor has the greatest influence on TDEE in active individuals?
  12. Compare the physical calorific values of fat, protein, carbohydrate, and ethanol (kcal·g⁻¹). Why does fat provide more ATP per gram despite having the same physiological calorific value as carbohydrate per mole of glucose?
  13. Explain why carbohydrates serve as the dominant substrate during high-intensity exercise. What happens physiologically when muscle glycogen is depleted during prolonged effort?
  14. Describe the role of muscle-derived alanine in sustaining blood glucose during prolonged exercise. How does this differ from the Cori cycle, and at what exercise intensity does it become significant?
  15. At which exercise intensity (% V̇O₂max) does fat contribute maximally to total energy supply? Why does its relative contribution decrease at intensities above the anaerobic threshold?
  16. Under what conditions does protein contribute significantly to fuel during exercise? What is the RDA for protein in the general population, and why do intensively training athletes require more?
  17. Using the multi-panel figures from the lecture, describe how blood lactate, cortisol, and adrenaline change across exercise intensities from 50% to maximal effort. What does the cortisol response indicate immunologically?
  18. The extended definition incorporates biological, psychological, and social resources, as well as “willingness to perform.” Give an example from clinical practice where this broader definition is more useful than the physiological one.
  19. At what decade of life does V̇O₂max typically peak in untrained adults? How does regular exercise modify the trajectory of age-related performance decline, and what is the relevance for morbidity/mortality?
  20. Describe the roles of catecholamines, insulin/glucagon, and cortisol in regulating substrate mobilization during exercise. At what exercise intensity do catecholamine levels rise significantly, and what is the immunological consequence?