Aging of the immune system Flashcards
Diseases associated with aging
Arthritis, cancer, CVD, infection, etc
What is immune aging
Alteration of the immune system competence with age increasing susceptibility to disease, and reduced vaccine efficacy
Difference between central memory T cells and effector memory T cells
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
Characteristic of various CD4 subtypes
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
Cellular senescence
Irreversible arrest of cell proliferation triggered to many factors. Mainly due to tumor suppressor mechanism
Most studies on hematopoietic stem cells have been done in mice
True
This has shown that the HST is xterised by decrease in hematatopoiesis, decrease replication, and myeloid differentiation bias with age
Example of HSC marker
CD34+
Which hematopoietic progenitors are more quantitatively affected with age
Lymphoid progenitors
What are the qualitative xtics of HSC
Decrease capacity to produce erythrocyte and leucocyte progenitors
HSC capacity to produced CLP is reduced while MPC is relatively preserved
True
Molecular xtic of HSC in the old
Strong telomeric attrition, reduced hematopoietic capacity, active cell cycling and metabolic state
Mechanisms of HSC dysfxn in thebokd
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
Effects of age on t cells production
1)Decreased production of naive T Cell.This is measured using TRECs which is low with aging
THIS IS DUE TO THYMIC INVOLUTION
Causes of decrease T cells in aging
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
Main changes in the diversity of T lymphocytes in aging
1)Decrease in the repertoire, naive T cells, and diversity of T cells
What are the functional alterations of naive T cells
1) Reduced capacity to be activted
2) decreased IL secretion and expression of IL2R
3) Decreased proliferation
4) incomplete differentiation
Xtics of memory T cells subset in aging
Accumulation of late(CD57+) or highly differentiated memory T cells
Gene expression profiling in Memory T cells in aging
1) increase Genes associated with cell cycling
2) Increase Genes associated with anti apoptosis
3) lncrease genes associated with altered metabolism
Effect of age on central B cell production
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
Mechanisms of B cell depletion in agzing
1)Extrinsic Reduce intake HSC progenitors, Decreased IL7 2)intrinsic Abnormal IL7R signaling BCR rearrangement, and pre BCR signaling
Effects of aging on innate immune system
Stable number
- altered fxn of macrophages and monocytes
2) Altered fxn of NK cells and neutrophils
Consequences of immunosenense in the induction of immune responses
1impaired innate and adaptive immune responsz
Clinical implications of immunosenense
Increased predisposition of new infection(Influenza, VZV, westnile virus), and decreased response to Influenza vaccination
What is immune risk phenotype
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
Approaches to reduce inflammation in aging
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
