Immunology Flashcards
What is inflammation? (4)
- Swelling
- Redness
- Heat
- Pain
What are the 3 types of inflammation?
Acute: fast., injury, resolves
Chronic: long term, disease process/injury, unresolved
Systemic: long term, low level, unresolved
What are the 4 steps of acute inflammation?
- Pattern recognition and danger signal
- Cytokine and Chemokine production
- Recruitment of cells and phagocytosis
- Resolution of inflammation
What does the immune response do?
Its the ability to detect: self vs non-self and dangerous vs not dangerous
Immune cells reside in tissue: macrophages
What are macrophages? (6)
- grow up in the bone marrow
- live in blood circulation as monocytes
- mature into macrophages as they move into tissue
- phagocytose pathogens and destroy them
- activate and recruit other immune cells
- also have wound healing abilities
How do macrophages detect pathogens?
They have receptors to detect: Self (healthy tissue) vs non-self (bacteria).
The receptors on the surface of the macrophages are called Pattern Recognition Receptors (PRP)
The patterns the macrophages detect are called Pathogen Associated Molecular Patterns on pathogen (PAMP)
How does a macrophage generate an immune response? (3)
- Production of cytokines which bind to receptors on cells
- Active local immune cells to phagocytose and kill pathogens
- Recruit circulating immune cells (neutrophils) via production of chemokines
What are the similarities of Cytokines and Chemokines?
- Proteins released by immune cells
- Bind to specific cell surface receptors
What are the differences of Cytokines and Chemokines?
Cytokines:
- Pleiotropic (Can have more than one main job)
- Activate other cells
- Induce generation of more cytokines
Chemokines:
- Not pleiotropic (more specialised function for inflammation and repair)
- Do not usually induce other chemokines
- Mostly act as a chemoattractant for cells (recruit to site of inflammation)
What are neutrophils?
- Grow up in bone marrow
- Circulate in the blood
- Rapidly produced in bone marrow after infection or injury
Whats the process of neutrophils entering the tissue?
- Neutrophils are recruited out of the blood to an infection site when needed
- Chemokines produced by macrophages attract passing neutrophils
- Neutrophils move towards where the chemokine has been produced (the area of inflammation)
How does a neutrophil fight a pathogen?
- Phagocytosis (eating them)
- Degranulation (release toxic chemicals)
Are inflammatory responses just local?
No, Immune cells are travelling through the blood producing cytokines and chemokines so therefore they end up in the blood and travel to other organs which help fight infection.
Whats the immune response in the liver?
Immediate: actue phase proteins
Outcome: increases phagocytosis
(enter the blood stream and act directly on the immune cells and increase phagocytosis)
Whats the immune response in the bone marrow?
Immediate: mobilise neutrophils
Outcome: phagocytosis
(generates more neutrophils and more cells helping with phagocytosis)
Whats the immune response in the brain?
Immediate: increase body temperature
Outcome: decreased viral and bacterial replication alter immune response
(improve the ability of an immune cell to fight an infection)
Whats the immune response in the muscle?
Immediate: protein and energy mobilisation increase body temperature
Outcome: decreased viral and bacterial replication
How does exercise change the frequency of neutrophils?
- Big increase in cell frequencies following exercise
- Prolonged increase even after exercise
- Exercise less than an hour, immediate increase in circulating immune cells
When does neutrophilia peak?
At 2-3 hours after exercise
What happens to blood during neutrophilia?
More blood
- increased blood flow and cardiac output during exercise = more cells (higher frequency)
What happens to cells made during neutrophilia?
More cells made
- increased plasma cortisol during exercise
- increases neutrophil production and release from bone marrow
What happens to cells released during neutrophilia?
More cells released
- neutrophils need to move into tissues to fight an infection
- neutrophils circulate in blood, but also park along the way (margination; reduced blood flow)
- Demargination from blood vessels in spleen, liver, lung, blood vessels during exercise
What is demargination?
- when the cells release from the cell wall and move through the blood
- without new cells being made, after demargination we have double the amount in the blood
What happens to hormones during neutrophilia?
- Release of catecholamines (adrenaline) and glucocorticoids (cortisol) during exercise
- Cortisol increases neutrophil production in bone marrow = early phase, neutrophilia
Cells mobilised into circulation have:
- increased killing ability (degranulation = release of toxins)
- increased tissue migration potential
- increased ability to respond to catecholamines and glucocorticoids
How does exercise effect phagocytosis?
- After acute exercise, more neutrophils are able to phagocytose (but per cell they are less good at it during infection)
- After chronic exercise, phagocytosis activity decreases
Immune cells in athletes vs normal healthy people at rest:
Resting athletes have about the same number of circulating immune cells as normal healthy people
What does over training or over reaching do to the immune response?
- Over-reaching/over training syndrome causes immune depression
- Immune depression means increased infection risk
What are the effects of under performance syndrome (UPS)?
Decrease in performance after training:
- Malaise
- sleep disturbances
- sore muscles
- gastro disturbance
- slow wound healing
General suppression of immune system
How does temperature effect the immune system in exercise?
Heat: impaired immune cell function
Cold: suppressed immune function
How does altitude effect the immune system in exercise?
Improved immune cells; improved phagocytosis
How does pollution effect the immune system in exercise?
Nobody really knows yet
How does gravity effect the immune system in exercise?
Reduced immune function; reduced phagocytosis
What is systemic inflammation? (4)
- Inflammatory cells (neutrophils, macrophages) infiltrate into adipose tissue
- Accumulate in obesity
- Inflammatory cytokines secreted in high amounts (causes destruction in the area)
- Inflammation leads to tissue degeneration and organ dysfunction
How is systemic inflammation different to acute inflammation? (4)
- Inflammatory trigger is metabolic (caused by excess nutrition)
- mediated by metabolic cells (adipocytes)
- moderate to low grade
- self sustaining (once your in the cycle, its very hard to get out)
Initiation of metabolic syndrome and inflammation: (3)
- nutrients are inflammatory
- feeding couples nutrients with inflammatory molecules
- nutrients engage PRR pathways
How do macrophages detect damage?
- Pattern recognition receptors (PRR)
- Damage associated molecular patterns (DAMP)
cell tries to repair dead cells by killing more cells
Detecting damage in obesity?
- cells recognise damage from obesity effects and induce inflammation
- cells recognise excess nutrition as a pathogen and induce inflammation
Healthy nutrient intake and threshold?
Only over threshold for metabolic pathways so everything is working as it should
Excess nutrient intake and threshold?
Over the threshold for pathogen sensing pathways
Prolonged excess nutrient intake and threshold?
Now over threshold for immune response pathways, so over for everything which puts us into trouble.
Maintenance of systemic inflammation? (3)
- stressed or dying cells: immune cells recruited to repair damage
- nutrient composition alters gut microbiota: start to make more fatty acids which activate PRRs
- bigger adipocytes make more inflammatory cytokines
Effect of diet and microbiome: exercise, obesity and immune response?
- gut microbiome involved in obesity - dysbiosis
- gut microbiome influenced by diet
- exercise increases microbial diversity in obese people
Type 2 diabetes: exercise, obesity and immune response?
- insulin resistance
- crossover between inflammatory cell signalling and insulin signalling
- exercise alone improves insulin sensitivity in obese people
- anti-inflammatory drugs to treat
Obesity and the microbiome in a person who eats different microbes throughout the day?
- Increased diversity
- Flavonoids directly reduce obesity
- Tight junction (how tight our liver is, harder for things to get through)
Obesity and the microbiome in a person who eats the same microbes throughout the day?
- lack of diversity
- flavonoids directly inhibit reduce of obesity
- things can get through the liver easier
Bariatric Surgery: exercise, obesity and immune response?
- best long term weight loss
- attenuation of the metabolic syndrome
