Immune Response From A Resource Allocation Prospective

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Metabolic Cost of The Immune Response

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Introduction

Introduction

Immune defenses are energetically expensive.

The rate at which birds transform energy and nutrients is expected to be elevated as a result of immune system activation.

Infection, trauma, and injury may result in a stereotypical response that includes:

1. Loss of appetite2. Increased sleepiness3. Muscle aches4. Fever

Introduction

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Fever and Energy Cost

Fever and Energy Cost

Fever is an adaptive increase in the set point for body temperature.

Fever and Energy Cost

It is a complex coordinated autonomic, neuro-endocrine, and behavioral adaptive response.

Fever is used by nearly all vertebrates as part of the acute-phase reaction to immune challenge.

Fever and Energy Cost

Fever has been associated with improved survival and shortened disease duration in non-life-threatening infections.

Fever and Energy Cost

Fever is energy intensive, entailing an increased metabolic cost.

Fever and Energy Cost

17 – 25%Increase in body temperature.1°C

for

Increase in caloric energy production

Fever and Energy Cost

In order to meet the accelerated rates of caloric expenditures associated with fever, the body must depend primarily on its stores of metabolizable energy.

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Basal Metabolic Rate In Infected Animals Vs Control

Basal Metabolic Rate In Infected Animals Vs Control

Metabolic rate in infected animals has been investigated in small mammals and birds.

Basal Metabolic Rate In Infected Animals Vs Control

Adult mice immunized with key hole limpet hemocyanin (a relatively mild antigen that causes limited activation of the immune system)

So, the energetic costs is greatly increased with the use of more ecologically relevant antigenic challenges, such as bacteria or parasites.

Expended significantly

More O2 than control mice injected with saline

Basal Metabolic Rate In Infected Animals Vs Control

In male great-tits (type of birds) injected with sheep red blood cells resulted in nearly

9% Basal

Metabolic Rates

Basal Metabolic Rate In Infected Animals Vs Control

Sub- sequent to the immune challenge.

3% Body Weight

Basal Metabolic Rate In Infected Animals Vs Control

Measured during the night when animals were inactive, was 17% higher for flea-invested marsh tit nestlings compared to control nestlings

Nestlings have to depend on their innate immune system to take care of antigens.

17% Mass-specific Resting

Metabolic Rate

Basal Metabolic Rate In Infected Animals Vs Control

House sparrows (birds) injected with phytohaemagglutinin ( a lectin found in raw kidney bean), a commonly used mitogen (a substance that induces or stimulates mitosis) that activates the cell-mediated immune response.

29% Resting

Metabolic Rate

Basal Metabolic Rate In Infected Animals Vs Control

In white cabbage butterfly pupae subsequent to immune challenge with nylon implant.

8% Standard

Metabolic Rate

Basal Metabolic Rate In Infected Animals Vs Control

Other immune activities related to pathogen resistance that require energy include:– The change in size and rate of turnover of cell and protein

pools of the immune system.– Many components of the immune effector responses are

highly proteinaceous in nature.

Basal Metabolic Rate In Infected Animals Vs Control

Barnes et al. (2002) observed that after injection of chicken with Escherichia coli lipopolysaccharide, there were; – 141% increase in fractional rate of protein synthesis (liver)– 161% increase in fractional rate of protein synthesis

(plasma)– 266% hemopexin fractional synthesis rate.

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Tolerating Tissue Damage

Tolerating Tissue Damage

Protein turnover is also involved in immune tolerance in tissue replacement and repair when damage cannot be prevented during infection.

Tolerating Tissue Damage

For example, Mastitis, an inflammatory reaction of the mammary gland

that is usually caused by a microbial infection results in tissue damage induced by either apoptosis or necrosis where both bacterial factors and host immune reactions contribute to epithelial tissue damage.

Larvae of several common species of parasitic nematodes migrate through, and often damage, host lungs.

Wound – Infection Cost Of Protein

The wound is a site of intense metabolic activity characterized by:– Dissolution and removal of necrotic tissue containment – Killing of pathogens– Collagen and elastin synthesis – Wound repair– Cellular proliferation– Restoration of tissue integrity

and all of these steps require both energy and substrates.

Cont. …

Following injury, there is increased activity of:1. Protein, carbohydrate and fat-related metabolic

pathways. 2. Many ion pumps.3. Blood flow to the damaged tissue.

Cont. …

Increased protein turnover and accelerated muscle protein breakdown results in muscle wastage.

This serves to mobilize amino acids for:1. Synthesis of new protein in wounds.2. Proliferation of phagocytes, macrophages, and other

cellular components involved in wound healing.3. Synthesis of acute-phase proteins and glucose in the liver.

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Resource Priority And Homeorhesis

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Resource Priority

Resource Priority

Live creature can be thought of as a resource users.

They have diverse resource management systems to cope with a variety of challenging environmental conditions.

Cont. ….

Because of limited availability of resources, they have evolved priority systems for allocating resources to various activities in a hierarchical fashion.

Resource Priority - Organs

Some organ systems, such as the brain and the heart, have high energetic priority at all times.

Other organs, including the immune system, can be spared when necessary.

Resource Priority – Life Cycle

Since every stage in the life cycle has its own requirements, resource management systems may constrain certain combinations of physiological, behavioral and anatomical states from occurring together.

Cont. …

At every stages of the life cycle various metabolic pathways are;

– Up-regulated– Down-regulated

Resulting in nutrients are divided in various amounts to Different :

1. Tissues2. Biological functions 3. End products

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Homeorhesis

Homeorhesis - Definition

This change in tissue responses to homeostatic controls is called homeorhesis.

It represents “the orchestrated or coordinated changes in metabolism of body tissues to support a physiological state”

Homeorhesis - Lactation

Homeorhesis was initially and extensively described for the physiological state of lactation.

There where marked alterations in:1. Partitioning of nutrients 2. Metabolism of the animal to accommodate demands of the mammary gland.

Cont. …

In addition, the preference of other body tissues for nutrients is altered to allow partitioning of a greater percentage of glucose to the mammary gland.

Homeorhesis – Other Than Lactation

Meanwhile, the general concept of homeorhesis has been extended to include many other physiological states:1. Nutritional 2. Environmental conditions 3. Pathological states as summarized in Collier et al. (2005).

Homeorhesis - Infection

Infection elicits a complete shift in metabolic priorities within the host to those associated with immunity.

Cont. …

Spurlock (1997) discussed the physiological processes that take place during periods of immune challenge, in which pro-inflammatory cytokines orchestrate a homeorhetic response directing nutrients away from tissue growth in support of immune function.

Cont. …

This cytokine mediated “reprogramming” of nutrient uptake and utilization ensures an adequate supply of nutrients for:

1. Proliferation of lymphocyte and macrophage.

2. Antibody production.3. Hepatic synthesis of acute phase

proteins.

Homeorhesis - Growth

A study by Di Angelo et al. (2009) in Drosophila melanogaster suggested that activation of the Toll signaling pathway in fat suppresses insulin signaling, leading to a decrease in nutrient stores and growth.

Cont. …

The authors suggest that communication between these regulatory systems evolved as a means to divert energy in times of need from organism growth to the acute requirement of combating infection.

Homeorhesis - Survival

When animals are given limited food, or are stressed in a way or another, maintenance (survival or longevity) is usually given precedence over growth and reproduction as this will guarantee survival in the short term.

For this reason, maintenance functions are relatively insensitive to (moderate) changes in nutrient supply.

Homeorhesis - Immunity

Traditionally, immune functions have been regarded as part of maintenance.

Some evidence shows that at least some aspects of immunity are sensitive to changes in nutrient intake.

Cont. …

When resources are limited, it could be adaptive for organisms to direct energy away from the immune system toward protecting and restoring other functions which may manifest itself in the form of tradeoffs.

This is also suggested by Segerstrom (2007) who hypothesized that energy used by the immune system represents a lost opportunity to spend that energy remediating resource loss and resolve other demands.

Mobilization & Priority For Nutrients

58

Energy

Physical barriers(skin, mucosa, mucus , etc.)

Innate immune system(macrophages, dendritic cells, APP, etc.)

Adaptive immune system(lymphocytes)

B cells(bursa, antibodies, etc.)

T cells (thymus, lymphocytes T, etc.)

Homeorhesis – Balance

McNamara and Buchanan (2005) hypothesize that under stressful conditions animals must allocate their limited resources between the competing demands of:

Combating the stressor (resistance)

Maintaining condition (tolerance)

Cont. …

Increasing allocation of resources to combating the stressor will: 1. Leave fewer resources for adequate maintenance.2. Increasing the chance of mortality due to the build-up of

damage.

Optimal Strategy

According to the model by McNamara and Buchanan (2005), in a situation of resource restriction, the optimum strategy for resource allocation to combating an immediate physiological threat depends on:

1. The cost to individual condition 2. The threat 3. Duration of the stress period

Cont. …

The optimal strategy concerning the immune system will depend on:

1. The pathogenicity of the environment .2. The body condition. 3. The costs and success of mounting an immune response.

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Genetics – Production – ImmunityTrade Off

Genetics – Production – ImmunityTrade Off

Discrepancies between studies investigating trade-offs may be a result of differing resource availability because energy conflicts may only manifest during resource-intensive times

Cont. …

Doeschl Wilson et al. (2009), who showed in a mathematical model that The relationship between:

Host’s response to pathogen challenge and

Production potential Largely depends on the interaction between its

Genetic capacity for production & disease resistance With the

Nutritional environment.

Cont. …

The observation that selection for high production efficiency has resulted in several undesirable side effects that are mostly related to metabolic imbalance.

In other words, a mismatch between increased output (selection for high production) and decreased input (selection for increased feed efficiency and reduced body fat reserves), suggests that we can expect our farm animals to be restricted by their environment.

Cont. …

Trade-offs may not be found at all if:– Two processes do not share important resources.– Resources are not limited. – Trade-off does not involve the immune parameter being

measured. In addition, several parts of the defense mechanisms may not

incur significant fitness costs.

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals Vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Trade-off Between Immune Function & Growth

Trade-off Between Immune Function & Growth

The negative influence of activation of the immune system on growth results from:

1. Reduced feed intake through anorexia. 2. Redirection of resources toward an immune response

away from other functions.

Cont. …

Chronic immune stimulation in; – Non-vaccinated sows – Farrowed in a non-sanitized

farrowing room and did not receive antibiotics.

resulted in reduced body weight gains in pigs in the study of Williams et al. (1997).

Cont. …

Immune challenge with E. coli lipopolysaccharide resulted in reduced weight gain in weanling pigs in the study of Van Heugten and Spears (1997).

Cont. …

Maucketal. (2005) observed an inverse relationship between growth rate and the development of components of the avian immune system in a wild population of Leach’s Storm-Petrels (Oceanodromaleucorhoa).

Cont. …

Daily injections of the inflammatory agent Sephadex resulted in significantly lower rates of weight gain in chicks in the study of Klasing et al. (1987).

Cont. …

Reciprocally, in the study of Allen and Little (2011), stimulating an increased development rate in juvenile Daphnia resulted in an increased infection rate when exposed to the parasite Pasteuria ramosa,.

This may suggest that allocation of resources to development left the fish lacking the ability to allocate an adequate amount to parasite resistance.

Cont. …

In experimental parasitic infestations Increased metabolizable protein supply reduces fecal egg

counts and worm burdens in ruminants only at later stages. This supports that acquisition, but not expression, of

immunity takes priority over growth.

Conclusion

Coop and Kyriazakis (1999) theorized that;”growing animals that encounter parasites for the first time can be expected to prioritize resources to the acquisition of immunity over growth, whereas once immunity has been acquired, growth and reproduction would be prioritized over expression of immunity to parasites”

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Trade-off Between Immune Function & Stress Response

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Stress Response

Stress Response

Trade-offs may result from resources that are allocated to deal with external stresses.

Cont. …

The stress response includes;1. Metabolic changes 2. Energetic changes 3. Immune changes 4. Endocrine changes 5. Neural changes 6. Behavioral changes

These changes are all aimed to overcoming the stressful situation and compensating the imbalances produced by the stressor.

Cont. …

Stress, through the action of stress hormones such as:1. Glucocorticoids2. Catecholamines3. Prolactin4. Growth hormone 5. Nerve growth factor

have detrimental effects on immune function.

Glucocorticoids

Immune Effect1. Up-regulate the expression of anti-inflammatory proteins.2. Down-regulate the expression of pro-inflammatory proteins.3. Glucocorticoids are also shown to play a role in the

development and homeostasis of T lymphocytes.

Cont. …

Metabolic Effect The name "glucocorticoid" derives from early observations

that these hormones were involved in glucose metabolism. In the fasted state, cortisol stimulates several processes that

collectively serve to increase and maintain normal concentrations of glucose in blood.

Cont. …

Metabolic Effect1. Stimulation of gluconeogenesis in the liver:

– This pathway results in the synthesis of glucose from nonhexose substrates, such as amino acids and glycerol from triglyceride breakdown.

– Enhancing the expression of enzymes involved in gluconeogenesis is probably the best-known metabolic function of glucocorticoids.

2. Mobilization of amino acids from extrahepatic tissues: – These serve as substrates for gluconeogenesis.

3. Inhibition of glucose uptake in muscle and adipose tissue: – A mechanism to conserve glucose.

Cont. …

4. Stimulation of fat breakdown in adipose tissue: – The fatty acids released by lipolysis are used for production of energy

in tissues like muscle, and the released glycerol provide another substrate for gluconeogenesis.

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Stress Module

Stress Module

The stress model developed by Moberg (2000) explains the concept of trade-offs between stress and other functions.

Cont. …

An animal has:– A budget of resources that are

available to serve basal biological functions.

– An available a reserve from which it must draw to deal with stress.

Cont. …

The biological cost of stress depends on:1. The duration of the stress (Acute vs.

Chronic)2. The severity of the stressor3. The number of stressors (single or

repeated exposure to the same stressor).

Cont. …

When the biological cost is met by the reserves, The stressor will have no impact on the other biological functions.

Cont. …

When there are insufficient biological reserves available, Resources must be reallocated away from

other biological functions that now become impaired.

At this time the animal enters a pre-pathological-pathological state due to a reduction in its physiological state, and experiences distress

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Stress and Immune Functions

Stressors

Kelley (1980) identified eight stressors that typically occur in modern livestock production systems:

1. Heat2. Cold3. Crowding4. Mixing5. Weaning6. Limit-feeding7. Noise8. Restraint

All of these stressors have been shown to alter the immune system of animals.

Stress and Immune FunctionsFish

Effects of stress on immune function in fish have been reviewed by Tort (2011).

Stress and Immune FunctionsFish

When the stressor is acute and short- term, – The response pattern is stimulatory and the fish immune

response shows an activating phase that specifically enhances innate responses.

However, if the stressor is chronic, – The immune response shows suppressive effects and

therefore the chances of an infection may be enhanced.

Plan Of Talk

Metabolic Cost of The Immune Response– Introduction– Fever and energy cost– Basal metabolic rate in infected animals vs control

– Tolerating tissue damage Resource priority and homeorhesis– Resource priority– Homeorhesis– Genetics – production – immunity trade off

Trade-off between immune function & growth Trade-off between immune functions and stress response– Stress response– Stress module– Stress and immune functions

Consequences Of Selection For Increased Production On Immune Function

Consequences Of Selection For Increased Production On Immune Function

Genetic Selection

Genetic selection has considerably increased production levels of livestock species.

Animals in a population that have been selected for high production efficiency appear to be more at risk for behavioral, physiological, and immunological problems .

Cont. …

Artificial selection may result in preferential allocation of resources to the traits selected for, leaving animals lacking in ability to respond adequately to other demands.

In particular, those traits that are not specifically included in the breeding goal may be affected, i.e., traits other than production traits, because their importance is not specifically recognized.

Poultry

Genetic selection of poultry for superior growth rate may result in decreased resistance to disease or reduced immunological response.

Cont. …

A meta-analysis by Vander Most et al (2011) indicated that selection for accelerated growth in poultry had a large and significantly negative effect on immune function.

Cont. …

Chickens from a line selected for faster growth were

More susceptible to the development of Marek’s disease

than chickens from a line exhibiting a slower growth rate in the study of Han and Smyth (1972).

Cont. …

Broilers selected for high growth rate showed

Lower antibody responses when challenged with sheep erythrocytes (SRBC) Than animals from a low body weight line and a random bred control line.

Cont. …

Koenen et al. (2002) conclude that: Fast growing broiler chickens are

specialized in the production of a strong short-term humoral response

Slow growing layer- type chickens are specialized in a long-term humoral response in combination with a strong cellular response, which is in conformity with their life expectancy

Cont. …

In the studies of Gross et al. (2002) and Lamont et al. (2003); Reduced body weight was observed in a White Leghorn

population selection for sheep red blood cell anti- body response.

Cont. …

Martin et al. (1990) observed that females from the low line were;

1. Heavier as juveniles 2. Lighter as adult3. Matured at a younger age4. Had higher egg production

Than those from the high line.

Cont. …

In the study of Lamont et al. (2003), A difference in body weight was observed as early as 7 days

after hatch.After 20 generations of selection Animals from the line selected for high antibody response

were 20% lighter and matured 30 days later than animals from the line selected for low antibody response.

Chicken – MD Resistance

Selection for resistance to Marek’s disease in chickens resulted in animals with:

1. Lower adult body weight2. Smaller eggs

Than animals from unselected lines.

Turkey – Fowl Cholera

In the study of Saif et al. (1984), a natural outbreak of erysipelas and fowl cholera resulted in a higher mortality rate in turkeys from a line selected for increased growth rate than in animals from an unselected control line.

Turkey – Fowl Cholera – ND

Mortality of turkeys from the selected line was higher than that of animals from the unselected control line when subsequently experimentally challenged with Pasteurella multocida or with Newcastle disease virus