The Ageing Immune System

Question 1

List 2 ways in which the effects of vaccines change with age of the recipient.

Answer 1

1 - Vaccination efficacy decreases with age.

2 - Vaccination longevity decreases with age.

Question 2

Which microbe causes shingles?

Answer 2

The varicella zoster virus.

Question 3

Which sex is more predisposed to autoimmune conditions?

How does the sex gap of predisposition to autoimmune conditions change with age?

Answer 3

• Females are more predisposed to autoimmune conditions than males.
• As age increases, the gap between males and females initially increases until middle age, where the gap then decreases to ~0.

Question 4

List 4 biological changes that explain age-related inflammation.

Answer 4

Due to changes in the secretions of monocytes:

1 - An increase in TNF alpha.

2 - An increase in IL-6.

3 - An increase in C-reactive protein (CRP).

4 - A decrease in IL-10.

Question 5

List 6 conditions to which an individual suffering from abnormally high inflammation would be at high risk.

Answer 5

1 - Cardiovascular disease.

2 - Diabetes.

3 - Sarcopenia.

4 - Dementia.

5 - Fatigue.

6 - Depression.

Question 6

List 5 causes of age-related inflammation.

Answer 6

1 - Asymptomatic infections.

2 - Reduced physical activity.

3 - Increased adiposity.

4 - Senescent cells.

5 - A decrease in sex hormone production.

Question 7

Which lineage do leukocytes shift towards with increasing age?

Answer 7

The myeloid lineage.

Question 8

List 3 defence mechanisms of neutrophils.

Answer 8

1 - ROS generation.

2 - Degranulation.

3 - NET formation.

Question 9

Define chemokinesis.

Answer 9

The speed of a cell.

Question 10

Define chemotaxis.

Answer 10

The velocity of a cell.

Question 11

Define chemotactic index.

Answer 11

A measure of the accuracy of cell migration.

Question 12

List 4 properties of neutrophil and monocyte migration.

Answer 12

1 - Chemokinesis.

2 - Chemotaxis.

3 - Persistence (changes in direction).

4 - Chemotactic index.

Question 13

Define phagocytic index.

Answer 13

The number of bacteria taken up by phagocytosis by a phagocyte per unit time.

Question 14

List 4 ways in which neutrophil and monocyte function changes with age.

Answer 14

1 - Chemotaxis becomes slower, (although chemokinesis remains the same).

2 - Phagocytic index decreases.

3 - ROS generation decreases.

4 - NET generation decreases.

Question 15

How do neutrophils and monocytes extravasate?

What is the significance of this with regards to increasing age?

Answer 15

• By releasing protease at the leading edge to burrow through the tissue.
• Due to the more convoluted structure of monocytes and neutrophils in an older individual’s immune system, this method of extravasation causes 40% more tissue damage in the older individual’s immune system compared with a younger person’s immune system.

Question 16

List 2 killing mechanisms of NK cells.

Answer 16

1 - Perforin and granzyme release from granules, which result in pore formation.

2 - Inducing apoptosis via binding Fas ligand.

Question 17

List 2 receptors which mediate NK cell cytotoxic activity.

For each receptor, state whether they are excitatory or inhibitory for cytotoxic activity.

Answer 17

1 - NKG2D (excitatory for cytotoxic activity).

2 - KIR (inhibitory for cytotoxic activity).

Question 18

How do NK cell numbers and cytotoxicity change with age?

Answer 18

• NK cells increase in number with age.

- NK cell cytotoxicity decreases with age.

Question 19

What is the reason for the change in cytotoxicity of NK cells with age?

Answer 19

Because perforin release decreases with age.

Question 20

List 2 reasons for the change in efficacy of vaccines with age.

Answer 20

Due to a reduced ability to make memory cells:

1 - 3% of thymus mass is lost per year, meaning fewer naive T cells are produced and the initial pool of varied T cells is decreased.

2 - The ability of cells to replicate decreases with age due to a decrease in telomere size by ~50 base pairs per replication. When the tips of a chromosome is exposed, this is interpreted as DNA damage, which stops cell proliferation (causes senescence).

Question 21

Why are lymphocytes able to replicate a greater number of times than most other cells?

Answer 21

Lymphocytes express the enzyme telomerase, which lengthens the telomere and allows replication to occur for a greater number of times before the telomere becomes too short.

Question 22

What is the consequence of senescence on adaptive immunity to infections that have already been met?

Answer 22

Immune memory of previously met infections decreases with age.

Question 23

Why does the frequency of autoimmune diseases increase with age?

Answer 23

• Due to a decrease in function of T regulatory cells, which normally suppress autoreactive T cells.
• This results in an increase in levels of autoantibodies.

Question 24

Give an example of a drug treatment for decreasing immune function with age.

How does this drug work?

Answer 24

Statins, which improve chemotaxis of neutrophils.

Question 25

Summarise by listing the effects of ageing on the immune system.

Answer 25

1 - Reduced ability to kill pathogens.

2 - Reduces immune memory.

3 - Reduced ability to remove damaged cells (due to changes in monocytes).

4 - Increased autoimmunity.