Immunology of Aging

Question 1

Older adults tend to have a baseline increase in . . .

Answer 1

. . . TNFa, IL-6, CRP, and clotting factors

Question 2

Immunosenescence

Answer 2

refers to changes in the immune system that occur with aging

Question 3

Hematopoietic stem cell population tends to ___ with age

Answer 3

Hematopoietic stem cell population tends to increase with age

Question 4

Aging and HSC transplant

Answer 4

Aging is associated with impaired differentiation and repopulation of blood cell lineages upon transplantation

Question 5

Aged HSC populations tend to be more biased towards ____

Answer 5

Aged HSC populations tend to be more biased towards myelopoiesis

More myelocyte-derived cells, fewer lymphocytes. Some believe that this is why myeloproliferative disorders are often diseases of the elderly.

Question 6

Sex hormone hypothesis

Answer 6

Estrogen and testosterone both suppress the production of IL-6, and a decline in these hormones with advanced age may partially explain the increased baseline inflammatory markers in the enderly.

Question 7

Mitochondrial dysfunction hypothesis

Answer 7

Mitochondrial dysfunction with age is well documented, and it is hypothesized that reactive oxygen species that escape from mitochondria and oxidize cellular components may produce DAMPs that trigger elevated IL-6 and TNFa in older adults.

Question 8

Decline of neutrophil function with aging

Answer 8

• Neutrophils in older adults have:
  
  • impaired chemotaxis
  • impaired phagocytosis/killing
  • impaired NETosis
  • impaired antimicrobial peptide production

Question 9

Dual effect of impaired neutrophil chemotaxis in the elderly

Answer 9

1. Impaired barrier defense and wound healing due to poor neutrophil recruitment
2. Prolonged inflammatory response due to poor neutrophilic inflammation resolution and egress

Question 10

Changes in NK cells with age

Answer 10

• Aged NK cells tend to be CD56^hi , meaning that they are the cytotoxic type rather than the cytokine-producing type
• Despite this, the per-cell killing capability of NK cells is reduced

Question 11

T-cells in older adults are mostly derived from. . .

Answer 11

. . . cell division and expansion of pre-existing T cells. In other words, they have few to no naive T cells.

The capacity of the thymus reduces to about 10% of its childhood capacity by adulthood, and continues to decline from there with age.

Question 12

Decrease in T cell diversity with age

Answer 12

• Driven by two factors:
  
  • The decrease in naive T cells
  • The action of lymphotrophic viruses causing oligoclonal expansion (CMV, EBV, HHV-6)

Question 13

Plasmablasts in older adults

Answer 13

Fewer plasmablasts are produced by older adults 7 days post-challenge