Immune regulation and ageing

Question 1

What is immune senescence characterised by?

Answer 1

Failure to down-regulate inflammatory responses

Failure to activate immune responses

Question 2

What does immune senescence trigger?

Answer 2

Loss of protection from pathogens

Inflammatory disease

Autoimmunity

Question 3

What causes age related immune changes?

Answer 3

Changes in immune environment 
Chronic stress 
Changes to innate immunity 
Changes in migration ability
Changes in adaptive immunity

Question 4

What are the changes in the immune environment that trigger inflammageing?

Answer 4

Changes in cytokine expression - more pro-inflammatory cytokines

Decreased levels of cortisol - downregulate the inflammatory response

Question 5

What are the changes in the innate immunity that trigger inflammageing?

Answer 5

Decreased cytotoxicity decreases the killing capacity

Loss in signalling capacity

Question 6

How do changes in migration ability influence inflammageing?

Answer 6

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

Question 7

What are the changes in the adaptive immunity that cause inflammageing?

Answer 7

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

Question 8

What feature of the immune system does age-related immune changes affect the most?

Answer 8

Adaptive immunity

Question 9

What are the features of immune senescence?

Answer 9

Increased severity and frequency of infections

Impaired ability to respond to new antigens

Question 10

What diseases does a low grade chronic inflammatory state lead to?

Answer 10

Cancers
Dementia - Alzheimers, Parkinsons
Musculoskeletal diseases - osteoporosis
CVD - atheroscleorsis, stroke

Question 11

How do infections trigger inflammageing?

Answer 11

Trigger inflammatory responses

Proven that vaccinations decrease incidence of MI

Question 12

What are senescent cells?

Answer 12

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

Question 13

What molecule leads to age-related inflammation?

Answer 13

ROS

Question 14

How do ROSs accumulate with age?

Answer 14

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

Question 15

What is thymic involution?

Answer 15

Progressive shrinking of the thymus with age

Thymus is replaced with fatty tissue

Question 16

When does thymic involution start?

Answer 16

From puberty

Question 17

What is the consequence of thymic involution?

Answer 17

Decreased turnover of T cells

Causes the population of T cells within the thymus to decrease

Question 18

What maintains the T cell population in the body?

Answer 18

Peripheral T cells multiply in response to cytokines instead of pathogens

This is called homeostatic expansion

Question 19

What is the consequence of thymic involution?

Answer 19

Harder to respond to unkown pathogens

Homeostatic expansion means the variability of T cells decreases

Question 20

What are telomeres?

Answer 20

Specialised DNA sequences at the end of chromosomes

Shorten with every cell division

Question 21

Why do T cells have a finite lifespan?

Answer 21

Each T cell division leads to shortening of telomeres

Once the telomeres reach a certain length, the cells become senescent

Question 22

What happens to telomerase when cells enter senescence?

Answer 22

It decreases in concentration

Question 23

What is the role of telomerase:

Answer 23

To make up and elongate the telomere

Question 24

How is inflammation related to telomerase?

Answer 24

Pro-inflammatory cytokines released during inflammation inhibit telomerase

Question 25

What is the relationship between telomere length and disease?

Answer 25

The shorter the telomere, the more likely you will get a disease