Immunity and Aging Flashcards
(45 cards)
Age associated changes in immune function
Immunoescence
Most abundant leukocyte in circulation and provide immediate frontline protection against rapidly dividing bacteria, fungi, and yeast
Neutrophils
How do neutrophils provide anti microbial defense?
1) . Their extravasation from the bloodstream and migration to the site of infection
2) . Neutrophils attempt to contain invading pathogens via phagocytosis
3) . Once phagocytosed, pathogens are exposed to a harsh microbicial environment, the creation of which requires the generation of reactive oxygen species (ROS)
How does age affect neutrophils?
1) . Directional accuracy of neutrophil migration to inflammatory agonists as well as bacterial peptides is greatly reduced
2) . Neutrophils from the elderly exhibit significantly reduced phagocytic activity towards complement and immunoglobulin opsonized pathogens (due to reduced expression of CD16)
3) . Aging results in impaired NET formation (due to decline in ROS production)
What is reduced with age that contributes to reductions in neutrophils?
1) . Recruitment of receptors into lipid rafts is reduced
2) . Specific micro domains enriched for phospholipids and cholesterol that help in signal transduction are reduced
Neutrophils release their nuclear DNA into the extracellular environment
These structures are decorated with an array of granule and cytosol derived peptides and proteases and have been shown to capture and in some cases disarm gram positive and negative bacteria
Neutrophil extracellular traps (NETs)
Large granular lymphocytes
Involved in the direct recognition and elimination of virus infected, stressed, and malignant cells
Natural killer cells (NK)
How does aging affect NK cells?
1) . Aging results in reduction in NK cell production and proliferation
2) . Increase in CD56 dim NK cells and decrease in CD56 bright NK cells
3) . Aberrant NK cell migration
4) . NK cell cytotoxicity decreases with age
5) . When bound to transformed cells, NK cells from elderly exhibit impaired polarization of perforin containing lytic granules to the immunological synapse
6) . Defective signaling proximal to NK cell membrane
7) . NK cells exhibit aberrant cytokine production
What are the two contact dependent mechanisms used by NK cells to eliminate transformed cells?
1) . Granule exocytosis
2) . Death receptor ligation
Characterized by the secretion of the pore forming protein perforin and the serine protease granzyme B
Primary cytotoxic mechanism of NK cells
Granule exocytosis
What are the clinical consequences of reduced NKCC?
1) . A last history of severe infection
2) . Increased risk of future infection
3) . Reduced probability of surviving infectious episodes
4) . Infectious morbidity
A heterogenous population of immune cells
Categorized into three subsets. Asked on the differential surface expression of CD14 and the Fc receptor CD16
Monocytes
What are the 3 subsets of monocytes?
1) . Classical (CD14++16-)
2) . Intermediate (CD14++16+)
3) . Non-classical (CD14+16++)
How does age affect monocytes?
1) . Composition of monocyte pool is markedly different in older adults (increased frequency of non-classical and intermediate monocytes and fewer classical monocytes)
2) .significant reduction in TLR 1/2 induced IL-6 and TNF-alpha synthesis
3) . Reduced LPS induced production of H2O2 and NO2 (ROS production)
4) . Impaired chemotaxis; delayed appearance and reduced expression of adhesion molecules on endothelial surface
5) . Decreased phagocytosis
6) . Decline in TLR1 and TLR4 expression
What are the antimicrobial mechanisms of monocytes and macrophages?
1) . Chemotaxis
2) . ROS generation
3) . Phagocytosis
4) . Antigen presentation
How is pathogen recognition by monocytes and macrophages achieved?
Through their expression of toll like receptors (TLRs), which are a family of endosomal and surface residing receptors that recognize structurally conserved molecules shared by viruses, bacteria, and fungi
What are the effects of age on macrophages?
1) . Decreased antigen presentation
2) . Reduced MHC 2 expression
3) . Increased and decreased phagocytosis
4) . Decreased ROS generation
5) . Decreased and increased chemotaxis
6) . TLR induced cytokine production is reduced
Reside at the interface of innate and adaptive immunity
Heterogenous family of circulating and tissue resident immune cells
Dendritic cells (DCs)
How are dendritic cells classified?
- based on their cellular origins
1) . Myeloid derived DCs (mDCs)
2) . Lymphoid derived DCs (pDCs)
What types of DCs are classified at myeloid derived dendritic cells?
1) . Langerhans cells (LCs) ~ found in the skin
2) . Conventional DCs ( cDCs) ~ in the blood, as in the case of LCs, in the imitation of adaptive immune responses whereas DCs of lymphoid descent, which are represented by blood borne plasmacytoid DCs (pDCs) are involved in anti viral immune responses via their secretion of IFN-alpha
How does age affect pDCs?
1) . Reduction in TLR induced cytokine production ( due to decline is TLR expression and aberrant intracellular signaling)
2) . Impairment of IFN-alpha secretion contributed to increased viral infections
3) . pDCs unable to enhance the cytotoxicity of resting CD8+ T cells
What do mDCs do?
Continually survey and sample their local environment for invading microbes, whose recognition triggers DC maturation and their migration to secondary lymphoid organs
How does age affect mDCs?
1) . Significant impairment in DC migration (due to altered micro environments and impaired signaling from surface expression chemokine receptors)
2) . Stimulatory capacity of mDCs wanes with age
3) . Aged mDCs are less effective at inducing T cell proliferation, IFN-gamma secretion, and T cell cytotoxicity
**all lead to a diminished T cell mediated immune response
4). Decrease in cytokine production due to reduction in TLR expression, impaired intracellular signaling, and an age associated increase in basal cytokine levels
What are the functions of the innate immune system?
1) . Early recognition and elimination of invading pathogens
2) . Immune modulation
3) . Resolution of inflammation
4) . Wound healing
5) . Clearance of senescent cells
