The twilight of immunity: emerging concepts in aging

of the immune system

Article Author: Janko Nikolich-Žugich

Presented by: [Edwin Lee] – [Group 8]
MICR270 Journal Article Assignment
Background

Objective of the review and key focus

• Objective: Explore recent developments in the study of age-related
changes of the immune system and how the basic operating rules of the
immune system changes due to age
• Presentation focus: Age-related changes in the immune system that
modifies the rules of operation of the immune system, specifically
concerning secondary lymphoid organs
Background

Terminology
• Lymphocyte: A form of white blood cell that are either B-cells or T-cells, purpose
is to remove antigens
• Secondary lymphoid organs: Organs which include lymph nodes and the spleen,
their function is to create naïve lymphocytes and initiate adaptive immune
responses
• Lymph nodes: Major site and B-cells and T-cells, function is to filter out foreign
particles
• IL-7: Growth factor secreted in the bone marrow and thymus, key maintenance
factor of naïve T-cells
• Naïve T-cells: T-cell that has differentiated in bone marrow, function is to
respond to new pathogens that have not been encountered before
Significance

• This article generates a greater understanding of how the immune

system changes due to age-related defects which can be used to better
develop medications and vaccines for older adult populations
 Key Points

Key point 1: Decreased efficiency of T-cells and B-cells

Age related changes
• Defects in local macrophage TNF production+marking of blood vessel endothelium
for recruitment and extravasation of T cells = poor recruitment of T cells and B cells
• Poor recruitment= inefficient movement of T cells and B cells within lymph nodes
during primary immune response
Overall result:
• Discoordination of human T-cell cutaneous immunity
• Lack of lymphadenopathy
Structural changes:
• Decrease in lymph node size
 Key Points

Key point 2: Shifts from naïve lymphocytes to memory lymphocytes

Age related changes:
• Degradation of lymph nodes= limited access of IL-7 for naïve T-cells
• Insufficient naïve T-cells= CD8+ and CD4+ naïve T-cells change phenotype to become
‘virtual memory T-cells’
• ‘Virtual memory T-cells’ carry out certain immune functions BUT lose ability to fully
expand populations during infections
Overall result:
• Decreased function in immunological defense
• Overall immune system weakened
Key Points
Discussion

Support for current knowledge:

• General consensus is that naïve T-cells decrease numerically but
memory T-cells increase in numbers due to old age
• Article showed support for the theory as it presented a pathway that
explained why and how this change occurs

Future directions:
• Reassessment of the concept of how the immune system ages, need
more focus on how the rules of operations of the immune system
changes and not just the immune response.
Conclusion

• A major contributing factor to a weakened immune response in older adults

is the decreased efficiency of T-cells and B-cells due to inefficient movement
• The immune system in older adults rely more on memory lymphocytes than
naive lymphocytes when compared to younger populations
References

• Nikolich-Žugich, J. (2018). The twilight of immunity: emerging concepts in

aging of the immune system. Nature immunology, 19(1), 10.
Discussion Forum Questions

1. Certain medications such as sirolimus inhibit the activation of T cells and B

cells to suppress the immune system, in your opinion, do you think
sirolimus should be given to older adults considering the age-related
changes of the immune system?

2. Cancer predominantly affects older adults over the age of 50, do you think
age-related changes of the immune system is a factor?

3. In older adults, lymph node swelling is often missing during infections, are
there any problems associated with the lack of swelling?