Immune regulation and ageing Flashcards
What is immune senescence characterised by?
Failure to down-regulate inflammatory responses
Failure to activate immune responses
What does immune senescence trigger?
Loss of protection from pathogens
Inflammatory disease
Autoimmunity
What causes age related immune changes?
Changes in immune environment Chronic stress Changes to innate immunity Changes in migration ability Changes in adaptive immunity
What are the changes in the immune environment that trigger inflammageing?
Changes in cytokine expression - more pro-inflammatory cytokines
Decreased levels of cortisol - downregulate the inflammatory response
What are the changes in the innate immunity that trigger inflammageing?
Decreased cytotoxicity decreases the killing capacity
Loss in signalling capacity
How do changes in migration ability influence inflammageing?
Young cells are able to migrate in a straight line to target sites
With age the cells meander more and leads to more tissue damage
What are the changes in the adaptive immunity that cause inflammageing?
Decreased presentation of antigens to B cells due to decreased T cell variability
T cell peripheral expansion tiggered by cytokines means the variability between T cells decreases
Loss of costimulation
B cells have lower affinity to antigens
Lower antibody production by B cells
What feature of the immune system does age-related immune changes affect the most?
Adaptive immunity
What are the features of immune senescence?
Increased severity and frequency of infections
Impaired ability to respond to new antigens
What diseases does a low grade chronic inflammatory state lead to?
Cancers
Dementia - Alzheimers, Parkinsons
Musculoskeletal diseases - osteoporosis
CVD - atheroscleorsis, stroke
How do infections trigger inflammageing?
Trigger inflammatory responses
Proven that vaccinations decrease incidence of MI
What are senescent cells?
Cells that secrete pro-inflammatory factors like cytokines
Contributes to inflammageing directly, by secreting cytokines and indirectly, by inducing immune cells to sites of proinflammatory cytokine release
What molecule leads to age-related inflammation?
ROS
How do ROSs accumulate with age?
Mitochondria is a major source of energy and contributes to control of apoptosis
They are also the main source of ROS by oxidative phosphorylation
When we age, build up of ROSs happen as they damage mitochondria progressively
These mitochondria increase in size and reduce their antioxidant production abilities
This leads to mismanagement of apoptosis and an inflammatory state
What is thymic involution?
Progressive shrinking of the thymus with age
Thymus is replaced with fatty tissue
When does thymic involution start?
From puberty
What is the consequence of thymic involution?
Decreased turnover of T cells
Causes the population of T cells within the thymus to decrease
What maintains the T cell population in the body?
Peripheral T cells multiply in response to cytokines instead of pathogens
This is called homeostatic expansion
What is the consequence of thymic involution?
Harder to respond to unkown pathogens
Homeostatic expansion means the variability of T cells decreases
What are telomeres?
Specialised DNA sequences at the end of chromosomes
Shorten with every cell division
Why do T cells have a finite lifespan?
Each T cell division leads to shortening of telomeres
Once the telomeres reach a certain length, the cells become senescent
What happens to telomerase when cells enter senescence?
It decreases in concentration
What is the role of telomerase:
To make up and elongate the telomere
How is inflammation related to telomerase?
Pro-inflammatory cytokines released during inflammation inhibit telomerase
What is the relationship between telomere length and disease?
The shorter the telomere, the more likely you will get a disease
