Aging of the immune system

Question 1

Diseases associated with aging

Answer 1

Arthritis, cancer, CVD, infection, etc

Question 2

What is immune aging

Answer 2

Alteration of the immune system competence with age increasing susceptibility to disease, and reduced vaccine efficacy

Question 3

Difference between central memory T cells and effector memory T cells

Answer 3

Central memory T cells circulate through secondary lymphoid tissues, secret more lL2, and exhibit robust proliferation capacity and transition into effector cells
Effector memory T cells circulate and resite in non lymphoid tissue, secret more INFg, and have limited proliferation capacity

Question 4

Characteristic of various CD4 subtypes

Answer 4

1) Central memory. High IL 2,CCR7
2) TH1.secret lFNg, TNF, expresses CXCR3, CCr1-5(cellular immunity)
3) TH2.express lL4/5/13,and CCR4(allergy)
4) TH17 secrets IL17, express CCR4/6(innate immunity)
5) Th21/TFh,Cxcr5(humoral immunity)
6) Tregs.immunosupression

Question 5

Cellular senescence

Answer 5

Irreversible arrest of cell proliferation triggered to many factors. Mainly due to tumor suppressor mechanism

Question 6

Most studies on hematopoietic stem cells have been done in mice

Answer 6

True
This has shown that the HST is xterised by decrease in hematatopoiesis, decrease replication, and myeloid differentiation bias with age

Question 7

Example of HSC marker

Answer 7

CD34+

Question 8

Which hematopoietic progenitors are more quantitatively affected with age

Answer 8

Lymphoid progenitors

Question 9

What are the qualitative xtics of HSC

Answer 9

Decrease capacity to produce erythrocyte and leucocyte progenitors

Question 10

HSC capacity to produced CLP is reduced while MPC is relatively preserved

Answer 10

True

Question 11

Molecular xtic of HSC in the old

Answer 11

Strong telomeric attrition, reduced hematopoietic capacity, active cell cycling and metabolic state

Question 12

Mechanisms of HSC dysfxn in thebokd

Answer 12

1)intrinsic causes. eg Telomeres shortening
2)Extrinsic causes with age.Due to increase inflammatory environment, biased differentiation, and reduced lymphopiesis
Decrease pdtn of growth hormones which has an effect on hematopoiesis

Question 13

Effects of age on t cells production

Answer 13

1)Decreased production of naive T Cell.This is measured using TRECs which is low with aging
THIS IS DUE TO THYMIC INVOLUTION

Question 14

Causes of decrease T cells in aging

Answer 14

1)Thymic involution. Due to decrease pool of thymic precursors
2)Extrinsic causes(eg decrease synthesis of IL17 by stroma cells).
Increase in inflammatory factors like IL6
Decrease in GF, IGF1(antiapoptotic)
Increase in steroid hormones toxic for thymic development

Question 15

Main changes in the diversity of T lymphocytes in aging

Answer 15

1)Decrease in the repertoire, naive T cells, and diversity of T cells

Question 16

What are the functional alterations of naive T cells

Answer 16

1) Reduced capacity to be activted
2) decreased IL secretion and expression of IL2R
3) Decreased proliferation
4) incomplete differentiation

Question 17

Xtics of memory T cells subset in aging

Answer 17

Accumulation of late(CD57+) or highly differentiated memory T cells

Question 18

Gene expression profiling in Memory T cells in aging

Answer 18

1) increase Genes associated with cell cycling
2) Increase Genes associated with anti apoptosis
3) lncrease genes associated with altered metabolism

Question 19

Effect of age on central B cell production

Answer 19

1) reduction in B cell precursor numbers
2) Decreased maturation to pre B cells
3) decrease pre b cell proliferation
4) fewer naive b cells

Question 20

Mechanisms of B cell depletion in agzing

Answer 20

1)Extrinsic
Reduce intake HSC progenitors, 
Decreased IL7
2)intrinsic
Abnormal IL7R signaling 
BCR rearrangement, and pre BCR signaling

Question 21

Effects of aging on innate immune system

Answer 21

Stable number

• altered fxn of macrophages and monocytes
  2) Altered fxn of NK cells and neutrophils

Question 22

Consequences of immunosenense in the induction of immune responses

Answer 22

1impaired innate and adaptive immune responsz

Question 23

Clinical implications of immunosenense

Answer 23

Increased predisposition of new infection(Influenza, VZV, westnile virus), and decreased response to Influenza vaccination

Question 24

What is immune risk phenotype

Answer 24

Immune phenotypes with increased predictability of mortality or vaccine responsibility. This includes

• increased cd8
• decreased cd4/cd8 ratio
• restricted T cell repertoire
• increase in proinflammatory cytokines

Question 25

Approaches to reduce inflammation in aging

Answer 25

1) prevent chronic infections by targeting persistent viruses like CMV
2) hormone or cytokine replacement therapy.
3) adjuvant specifically for old people vaccines
4) stem cell therapy/reprogramming
5) caloric restrictions